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Acquired C1 esterase inhibitor deficiency	Causes	Infections Human immunodeficiency virus (HIV) is a transmissible retrovirus that can predispose individuals carrying the virus to acquired immunodeficiency syndrome (AIDS) which leads to opportunistic infections. Hepatitis B viral infection (HBV) is a transmissible DNA virus that can potentially lead to liver injury. In a series of cases studies with patients reporting symptoms of angioedema, some of these individuals were found to have positive markers of HBV. Metabolic disorders Xanthomatosis is a systemic metabolic disorder marked by fatty deposits in the presence of hypercholesterolemia, or high cholesterol. Idiopathic causes Idiopathic etiology is considered when well-understood and known causes are excluded after a thorough medical evaluation.
Acquired C1 esterase inhibitor deficiency	Pathophysiology	The C1 esterase inhibitor (C1-INH) enzyme plays a role in the classical pathway of the complement cascade, which is a component of the immune system response that acts to protect the human body from a variety of foreign substances. As shown in the figure above, the complement cascade starts with the C1q protein which binds to an antibody-antigen complex that arises during an immune response to an invading substance. When the complex is signaled for activation, or turned on, then downstream proteins in the complement cascade are activated, including complement component 2 (C2), complement component 3 (C3), and complement component 4 (C4). When these particular enzymes such as C3 and C4 are activated, their subsequent signals lead to an inflammatory response that involves localized edema, or swelling. The role of C1-INH is to regulate and control the activities of the complement cascade, such that complement proteins remain in check and do not lead to unnecessary activity. When there is a deficiency of C1-INH due to one of the previously mentioned causes, then the complement cascade remains continuously activated and can lead to potentially life-threatening swelling.
Acquired C1 esterase inhibitor deficiency	Clinical Presentation	Acquired angioedema presents as mucosal swelling on external and/or internal surfaces of the body. Typical areas of swelling include the face, arms, and legs, while internally some individuals have swelling of the tongue and upper airways. In contrast to hereditary angioedema, there tends to be less symptoms of the abdomen or gastrointestinal tract, but symptoms of nausea, vomiting, and diarrhea have been seen in acquired angioedema. Although this condition appears similar to other skin conditions in which swelling occurs, acquired angioedema does not lead to itchy skin (pruritus) or hives (urticaria).
Acquired C1 esterase inhibitor deficiency	Diagnosis	Acquired angioedema is diagnosed through a supportive clinical examination usually in addition to laboratory evaluation. The clinical history consists of recurrent angioedema episodes, symptom onset after 30 years of age, and negative family history of hereditary angioedema.Laboratory evaluation typically consists of complement studies, genotyping, and/or checking for antibodies against C1INH. The most useful complement studies obtained are as follows: To help confirm cases of acquired angioedema, the following pattern of complement studies are observed: low C4 level, low C1-INH protein level, low C1q level, and decreased C1-INH protein function.Using the diagnostic approach mentioned here and in the figure shown above, acquired angioedema is categorized into subtypes for targeted management. The following subtypes include: AAE-I, AAE-II, sex-hormone dependent AAE, and drug-induced AAE. AAE-I subtype groups paraneoplastic syndrome or B-cell malignancies that lead to destruction of the C1-INH enzyme causing acquired angioedema. AAE-II subtype groups autoimmune disorders, such as systemic lupus, causing acquired angioedema. Sex-hormone dependent AAE is associated with case reports of individuals with abnormally elevated estrogen levels or in cases where physiologically elevated estrogen is expected as in pregnancy. Drug-induced AAE can be triggered by certain medications, including ACE inhibitors or angiotensin receptor blockers.Furthermore, additional laboratory testing can be done to consider other causes of swelling that appear similar to angioedema. Some of the common differential diagnoses for angioedema include: allergic reactions, contact dermatitis, skin and soft tissue infections (i.e. cellulitis), lymphedema, and foreign body aspiration.
Acquired C1 esterase inhibitor deficiency	Management	Treatment of acquired angioedema is separated into two main parts. First controlling acute symptoms during angioedema attacks is crucial for preventing and lowering the risk of mortality. Second, managing AAE chronically with prophylactic treatment is important to improve prognosis and quality of life. Both pharmacologic therapies (i.e. medications) and symptom management can be used in both acute and chronic treatment of AAE.Pharmacologic treatment in acute situations consists of replacing the enzyme concentrate that is deficiencent or dysfunctional in this disease process. In life-threatening situations, including cases of oral and pharyngeal swelling, it is important to manage these symptoms and to protect the airways in order to lower the risk of mortality. Typical treatments for anaphylaxis and allergic reactions, such as epinephrine, corticosteroids, and antihistamines, are often used in acute cases of AAE with variable resolution. C1-INH concentrates are available in intravenous (IV) and intramuscular (IM) methods of delivery. C1-INH concentrate therapy has shown considerable efficacy (or effect) in acute and prophylactic treatments of hereditary angioedema, but has varying levels of efficacy in AAE.For prophylaxis, clinicians focus on controlling underlying disorders, such as those mentioned under causes, that could be contributing to AAE pathophysiology. Beyond controlling comorbidities, angioedema is usually managed through medications to prevent attacks and to reduce the number of attacks. C1-INH concentrate can be used to replace deficient or abnormal C1-INH enzyme with considerable efficacy. The following list of medical therapies have been used for prophylaxis, including androgens, tranexamic acid, and monoclonal antibody such as rituximab. These agents all have varying roles, efficacy, and potential risks through their use.
Acquired C1 esterase inhibitor deficiency	Prognosis	The evaluation of acquired angioedema usually prompts an investigation into the underlying cause. As mentioned in the causes section, malignancy or autoimmune disorders are the more common causes, which must be further explored and considered for treatment if found in an individual. Prognosis depends on the underlying disorder, which may be found at the time of initial diagnosis or through ongoing monitoring. Additionally, successful treatment of the underlying disorder has been observed in some cases to resolve acquired angioedema from partial to complete remission.
Anti-CRISPR	Anti-CRISPR	Anti-CRISPR (Anti-Clustered Regularly Interspaced Short Palindromic Repeats or Acr) is a group of proteins found in phages, that inhibit the normal activity of CRISPR-Cas, the immune system of certain bacteria. CRISPR consists of genomic sequences that can be found in prokaryotic organisms, that come from bacteriophages that infected the bacteria beforehand, and are used to defend the cell from further viral attacks. Anti-CRISPR results from an evolutionary process occurred in phages in order to avoid having their genomes destroyed by the prokaryotic cells that they will infect.Before the discovery of this type of family proteins, the acquisition of mutations was the only way known that phages could use to avoid CRISPR-Cas mediated shattering, by reducing the binding affinity of the phage and CRISPR. Nonetheless, bacteria have mechanisms to retarget the mutant bacteriophage, a process that it is called "priming adaptation". So, as far as researchers currently know, anti-CRISPR is the most effective way to ensure the survival of phages throughout the infection process of bacteria.
Anti-CRISPR	History	Anti-CRISPR systems were first seen in Pseudomonas aeruginosa prophages, which disabled type I-F CRISPR–Cas system, characteristic of some strains of these bacteria. After analysing the genomic sequences of these phages, genes codifying five different Anti-CRISPR proteins (also named Acrs) were discovered. Such proteins were AcrF1, AcrF2, AcrF3, AcrF4 and AcrF5. Research found none of these proteins disrupted the expression of Cas genes nor the assembling of CRISPR molecules, so it was thought that those type I-F proteins directly affected the CRISPR–Cas interference.Further investigation confirmed this hypothesis with the discovery of 4 other proteins (AcrE1, AcrE2, AcrE3 and AcrE4), which were shown to impede Pseudomonas aeruginosa’s CRISPR-Cas system. Furthermore, the locus of the genes codifying these type I-E proteins was really close to the one responsible for the type I-F proteins expression in the same group of phages, leading to the conclusion that both types of proteins worked together. However, these first nine proteins shared no common sequence motifs, which would have made easier the identification of new Anti-CRISPR protein families.
Anti-CRISPR	History	Later on, it was seen that phages that produced such proteins also encoded a putative transcriptional regulator named Aca 1 (anti-CRISPR associated 1) which was genetically located really close to the anti-CRISPR genes. This regulatory protein is supposed to be the responsible for the anti-CRISPR gene expression during the infectious cycle of the phage, therefore, both types of proteins (anti-CRISPR and Aca1) seem to work together as a single mechanism.After some studies, a similar amino-acid sequence to that of Aca1 was found, leading to the discovery of Aca2, a new family of Aca proteins. Aca2 also revealed the existence of five new groups of type I-F anti-CRISPR proteins due to their genomic proximity: AcrF6, AcrF7, AcrF8, AcrF9 and AcrF10. These proteins were not only present in Pseudomonas aeruginosa’s phages, as they also affected other cells of the Pseudomonadota (formerly Proteobacteria).Thanks to the use of bioinformatic tools, in 2016, AcrIIC1, AcrIIC2 and AcrIIC3 protein families were discovered in Neisseria meningitidis (which had been infected by phages previously). Such proteins were the first inhibitors of type II CRISPR–Cas to be found (concretely, they impeded II-C CRISPR–Cas9, the type of mechanism used in the genetic edition of human cells). A year later, a study confirmed the presence of type II-A CRISPR–Cas9 inhibitors (AcrIIA1, AcrIIA2, AcrIIA3 and AcrIIA4) in Listeria monocytogenes (infected by bacteriophages which introduced the anti-CRISPR proteins). Two of those proteins (AcrIIA2 and AcrIIA4) were demonstrated to work properly against Streptococcus pyogenes type II-A defensive CRISPR system.
Anti-CRISPR	History	The result of all this research has been the discovery of 21 different Anti-CRISPR protein families, despite other inhibitors may exist due to the quick mutational process of phages. Thus, more research is needed to unravel the complexity of anti-CRISPR systems.
Anti-CRISPR	Types	Anti-CRISPR genes can be found in different parts of the phage DNA: in the capsid, the tail and at the extreme end. Moreover, it has been found that many MGEs have two or even three Acr genes in a single operon, which suggest that they could have been exchanged between MGEs.As all proteins, Acr family proteins are formed by the translation and transduction of the genes, and their classification is based on the type of CRISPR-Cas system they inhibit, due to the fact that each anti-CRISPR protein inhibits a specific CRISPR-Cas system. Although not many anti-CRISPR proteins have been discovered, these are the ones that have been found so far: So far, genes encoding anti-CRISPR proteins have been found in myophages, siphophages, putative conjugative elements and pathogenicity islands.
Anti-CRISPR	Types	Attempts have been made to find common surrounding genetic features of anti-CRISPR genes, but without any success. Nevertheless, the presence of an aca gene just below anti-CRISPR genes has been observed.The first Acr protein families to be discovered were AcrF1, AcrF2, AcrF3, AcrF4 and AcrF5. These inhibitors are mainly found in Pseudomonas phages, which are capable of infecting Pseudomonas aeruginosas possessing a type I‑F CRISPR–Cas system. Then, in another study, AcrE1, AcrE2, AcrE3 and AcrE4 protein families were found to also inhibit the type I‑F CRISPR–Cas in Pseudomonas aeruginosas.Later on, AcrF6, AcrF7, AcrF8, AcrF9 and AcrF10 protein families, which were also able to inhibit type I‑F CRISPR–Cas, were found to be very common in Pseudomonadota MGEs.The first inhibitors of a type II CRISPR–Cas system were then discovered: AcrIIC1, AcrIIC2 and AcrIIC3, that block the type II‑C CRISPR–Cas9 activity of Neisseria meningitidis.Finally, AcrIIA1, AcrIIA2, AcrIIA3 and AcrIIA4 were found. These protein families have the ability to inhibit the type II‑A CRISPR–Cas system of Listeria monocytogenes.As for the naming convention of Acr family proteins, it is established as follows: firstly, the type of system inhibited, then a numerical value referring to the protein family and finally the source of the specific anti-CRISPR protein. For example, AcrF9Vpa is active against the type I-F CRISPR–Cas system. It also was the ninth anti-CRISPR described for this system, and it is encoded in an integrated MGE in a Vibrio parahaemolyticus genome.
Anti-CRISPR	Structure	As exposed above, there is a wide spectrum of anti-CRISPR proteins, but few of these have been deeply studied. One of the most studied and well-defined Acrs is AcrIIA4, which inhibits Cas9, thus blocking the II-A CRISPR-Cas system of Streptococcus pyogenes.
Anti-CRISPR	Structure	AcrIIA4 The protein was solved using nuclear magnetic resonance (NMR); it contains 87 residues and its molecular weight is 10.182 kDa. AcrIIA4 contains: 3 antiparallel β-strands (the first, from residues 16 to 19, the second, from 29 to 33, and the third, from 40 to 44) that form a β-sheet. This represents a 16,1% of the total number of amino acids, as 14 of them form the β-strands.
Anti-CRISPR	Structure	3 α-helices (the first, 2–13 residues, the second, 50–59 residues, and the third, 68–85 residues). 1 310 helix placed between the first (β1) and second (β2) β-strands, which starts at residue 22 and end in residue 25. The total helical part is composed of 40 residues, which is a 50,6% of the protein.
Anti-CRISPR	Structure	Loops joining the different secondary structures.There is a good definition of the secondary structures, as the three α-helices are packed near the three β-strands. Strikingly, between β3 strand, α2 and α3 helices, there is a hydrophobic core, originated by a cluster of aromatic side chains which are attracted by non-covalent interactions, such as pi stacking. Moreover, as it is an acidic protein, there is a high concentration of negatively charged residues in the loops between β3 and α2, between α2 and α3, and in the first part of α3, which may play an important role in the inhibition of Cas9, as negative charges might imitate phosphates of nucleic acids.
Anti-CRISPR	Structure	AcrF1 On the other hand, there is another Acr, AcrF1, which may not have been as studied as the explained above, although there is a good description of its structure. It inhibits the I-F CRISPR-Cas system of Pseudomonas aeruginosa. Maxwell et al. solved the 3D structure using NMR.
Anti-CRISPR	Structure	The protein contains 78 residues, between which interact to form secondary structures. The structure of AcrF1 is formed of two anti-parallel α-helices and a β-sheet, which contains four anti-parallel β-strands. This β-sheet is placed in the contrary side of the α-helical part, which creates a hydrophobic core formed of 13 amino acids. Turns can also be found in different parts of the protein, for instance, joining the β-strands.There are surface residues which actively participate in the active site of AcrF1, two of which are tyrosines (Y6 and Y20) and the third amino acid is a glutamic acid (E31), as their mutation by an alanine causes a 100-fold decrease in the activity of the protein (with Y20A and E31A mutations), and a 107-fold decrease when Y6 is mutated.
Anti-CRISPR	Structure	The different structures that form the protein create a strange combination, as Maxwell et al. conducted a DALI search in order to find similarities between other proteins, and they found no informative similarities.
Anti-CRISPR	Function	Avoiding destruction of the phage DNA The principal function of anti-CRISPR proteins is to interact with specific components of CRISPR-Cas systems, such as the effector nucleases, to avoid the destruction of the phage DNA (by binding or cleavage).A phage introduces its DNA into a prokaryotic cell, usually the cell detects a sequence known as "target", that activates CRISPR-Cas immune system, but the presence of an initial sequence (before the target) encoding the formation of Acr proteins, avoids phage destruction. Acr proteins are formed before the target sequence is read. This way, the CRISPR-Cas system is blocked before it can develop a response.
Anti-CRISPR	Function	The procedure starts with the CRISPR locus being transcribed into crRNAs (CRISPR RNA). CrRNAs combine with Cas proteins forming a ribonucleoprotein complex called Cascade. This complex surveys the cell to find complementary sequences of the crRNA. When this sequence is found, the Cas3 nuclease is recruited to the Cascade, and the target DNA from the phage is cleaved. But, for instance, when AcrF1 and AcrF2 are found (anti-CRISPR proteins), these interact with Cas7f and Cas8f-Cas5f, respectively, not allowing the binding to the phage DNA. Moreover, the cleaving of the target is prevented by the union between AcrF3 and Cas3.
Anti-CRISPR	Function	The majority of Acr genes are located next to anti-CRISPR-associated (Aca) genes, which encode proteins with a helix-turn-helix DNA-binding motif. Aca genes are preserved, and researchers are using them to identify Acr genes, but the function of the proteins they encode is not totally clear. The Acr-associated promoter produces high levels of Acr transcription just after the phage DNA injection into the bacteria takes place and, afterward, Aca proteins repress the transcription. If this wasn't repressed, the constant transcription of the gene would be lethal to the phage. Therefore, Aca activity is essential to ensure its survival.
Anti-CRISPR	Function	Phage-phage cooperation Moreover, it has been verified that bacteria with CRISPR-Cas systems are still partially immune to Acr. Consequently, initial abortive phage infections may be unable to hamper CRISPR immunity, but phage-phage cooperation can increasingly boost Acr production and promote immunosuppression, which might produce an increase on the vulnerability of the host cell to reinfection, and finally allow a successful infection and spreading of a second phage. This cooperation creates an epidemiological tipping point, in which, depending on the initial density of Acr-phages and the strength of CRISPR/Acr binding, phages can either be eliminated or originate a phage epidemic (the number of bacteriophages is amplified).If the starting levels of phages are high enough, the density of immunosuppressed hosts reaches a critical point where there are more successful infections than unsuccessful ones. Then, an epidemic begins. If this point is not reached, phage extinction occurs, and immunosuppressed hosts recover their initial state.
Anti-CRISPR	Function	Phage immune evasion It has become clear that Acr proteins play an important role in allowing phage immune evasion, though it is still unclear how anti-CRISPR proteins synthesis can overcome the host’s CRISPR-Cas system, which can shatter the phage genome within minutes after the infection.
Anti-CRISPR	Mechanisms	Within all the Anti-CRISPR proteins that have been discovered so far, mechanisms have been described for only 15 of among them. These mechanisms can be divided into three different types: crRNA loading interference, DNA binding blockage and DNA cleavage prevention. CrRNA loading interference CrRNA (CRISPR RNA) loading interference mechanism has been mainly associated with the AcrIIC2 protein family. In order to block Cas9 activity, it prevents the correct assembly of the crRNA‐Cas9 complex.
Anti-CRISPR	Mechanisms	DNA binding blockage AcrIIC2 has been shown not to be the only one capable of blocking DNA binding. There are 11 other Acr family proteins that can also carry it out. Some among those are AcrIF1, AcrIF2, and AcrIF10, which act on different subunits of the Cascade effector complex of the type I‐F CRISPR‐Cas system, preventing the DNA to bind to the complex.Furthermore, AcrIIC3 prevents DNA binding by promoting dimerization of Cas9 and AcrIIA2 mimics DNA, thereby blocking the PAM recognition residues and consequently preventing dsDNA (double-stranded DNA) recognition and binding.
Anti-CRISPR	Mechanisms	DNA cleavage prevention AcrE1, AcrIF3 and AcrIIC1 can prevent target DNA cleavage. Using X-ray crystallography, AcrE1 was discovered to bind to the CRISPR associated Cas3. Likewise, biochemical and structural analysis of AcrIF3 showed its capacity of binding to Cas3 as a dimer so as to prevent the recruitment of Cas3 to the Cascade complex. Finally, thanks to biochemical and structural AcrIIC1 studies, it was found that it binds to the active site of the HNH endonuclease domain in Cas9, which prevents DNA from cleaving. Thus, it turns Cas9 into an inactive but DNA bound state.
Anti-CRISPR	Applications	Reducing CRISPR-Cas9 off-target cuts AcrIIA4 is one of the proteins responsible for the CRISPR-Cas9 system inhibition, the mechanism used in mammalian cells edition. Addition of AcrIIA4 in human cells avoids Cas9 interaction with the CRISPR system, reducing its ability to cut DNA. However, diverse studies have reached the conclusion that adding it in small proportions after the genome editing has been done, reduces the number of off-target cuts at the concrete sites in which Cas9 interacts, a thing that makes the whole system much more precise.
Anti-CRISPR	Applications	Avoiding ecological consequences One of the main objectives of using CRISPR-Cas9 technology is eradicating diseases, some of which are found in disease vectors, such as mosquitoes. Anti-CRISPR proteins can impede gene drive, which could create uncertain and catastrophic consequences in ecosystems. Detect presence of Cas9 in a sample In order to know whether a certain bacterium synthesises Cas9, and therefore uses CRISPR-Cas9, or to detect accidental or not allowed use of this system, AcrIIC1 can be used. As the aforementioned protein binds to Cas9, a centrifugal microfluidic platform has been designed to detect it and determine its catalytic activity.
Anti-CRISPR	Applications	Phage therapy Antibiotic resistance is a public health problem that is constantly increasing, because of the bad use of antibiotics. Phage therapy consists of the infection of bacteria using phages, which are much more specific and cause less side effects than antibiotics. Acrs could inhibit the CRISPR-Cas9 system of some bacteria and allow these phages to infect bacterial cells without being attacked by its immune system.
Godzilla Generations	Godzilla Generations	Godzilla Generations is an action game developed by General Entertainment and published by Sega for the Dreamcast in 1998. It was exclusively released in Japan as one of the system's four launch titles. The game is based on the Godzilla franchise and involves the player controlling various giant monsters in an attempt to destroy real-life Japanese cities. A sequel, Godzilla Generations: Maximum Impact, was released in Japan in 1999.
Godzilla Generations	Gameplay	Godzilla Generations is an action game where the player must control one of five monsters from the Godzilla universe. Initially, only Godzilla and Mechagodzilla can be selected, while the other characters are unlocked by progressing through the game. The game world is composed of five cities, each comprising two stages, except the final city which has three. The object of the game is to proceed to the next stage by destroying everything on the stage within a set time limit, such as buildings and trees. Each character has projectile attacks, the ability to block incoming attacks and the ability to heal themselves.
Godzilla Generations	Development and release	Godzilla Generations was developed by General Entertainment and published by Sega as a launch title for the Dreamcast. It was originally known as simply Godzilla, before its name was changed in July 1998. The game was exclusively released in Japan on November 27, 1998.
Godzilla Generations	Reception	Godzilla Generations received lukewarm reviews from Japanese gaming magazine Famitsu and a very negative response from Western journalists, despite fans showing interest in the game at the 1998 Tokyo Game Show. Computer and Video Games reviewer Kim Randell described the game as dull and cited issues such as poor controls, a constantly shifting camera and the player character blocking the player's view. Peter Bartholow of GameSpot derided the game as "terrible" and one of the worst games of 1998. Bartholow found it impossible to block incoming attacks due to the creatures' slow gait. He stated that because of this the developers added a healing ability to each creature, allowing players to continue through the game without fear of their character dying, "There's no strategy, no technique. Just the extreme tedium of tromping through cities." Edge criticized the graphics quality, clumsy controls, and confusing camera system, which was said to make in-game objects difficult for players to locate.Despite showing interest in a preview, describing the game as looking like "a riot", Jaz Rignall of IGN and his colleagues were less enthusiastic when their first Dreamcast console arrived three months later with three Japanese launch games. He found "while it brought many smiles and jeers, it didn't impress", the gathered journalists quickly lost interest and moved onto another game. In a November 2002 review of Godzilla: Destroy All Monsters Melee, GameSpy's David Hodgson described himself as "still wincing from Godzilla: Generations". He went on to say the game "seemed to adhere to the loony premise that bizarre camera angles, a monster trudging in extreme slow motion, and the knuckle-gnawingly slow chipping away of scenery was the new high watermark in monstrous fighting action. It wasn't. It was crap".Japan-GameCharts reported that the game sold approximately 22,870 copies.
Godzilla Generations	Sequel	Godzilla Generations: Maximum Impact was developed by General Entertainment and published by Sega for the Dreamcast on December 23, 1999, exclusively in Japan. The game is split into levels in which Godzilla is stomping forward through a city while he has to shoot enemies. The player can also make Godzilla duck attacks, by holding or tapping the analog pad. In other levels, Godzilla can walk freely and has to fight in one-on-one against Biollante, King Ghidorah, Mothra, the new robot bosses SMG-IInd and MGR-IInd, SpaceGodzilla, the Super X-III which is the game's smallest boss and the last boss, Destoroyah. Godzilla is the only playable character in the game. He can shoot heat rays at his enemies. IGN gave the game 2.5 out of 10 in their review.
Urushi-e	Urushi-e	Urushi-e (漆絵 "lacquer picture[s]") refers to three different techniques in Japanese art. Though urushi-e is most associated with woodblock, the term urushi-e is not exclusive to that medium. It can also refer to pictures using lacquer as a paint on three-dimensional lacquered objects; and paintings using actual lacquer on paper or occasionally silk.
Urushi-e	Technique	In Japanese woodblock printing, urushi-e generally refers to a hand-painted technique. Instead of printing with urushi (natural lacquer) it was painted on by hand. This meant that urushi-e pictures could be more colorful than most block prints of the time. Five colors were available when the technique was first developed; brown, yellow, green, red, and black. Urushi-e was sometimes used as a term to describe all hand-painted woodblock prints in Japan, not only those painted with lacquer, however, only urushi-e used iro-urushi, meaning colored lacquer, made from mixing clear lacquer and one of the five pigments. Artists such as Nishimura Shigenaga c.1680s-1750 were also known to use black ink thickened with hide glue to attain a lacquer-like effect on some on his prints. In addition to colored lacquer, gold was sometimes applied to urushi-e works in the form of gold leaf and powders.
Urushi-e	Prints	Urushi-e woodblock prints were made using thick, dark black lines, and were sometimes hand-colored. The ink was mixed with an animal-based glue called nikawa, which thickened it and gave it a lustrous shine, said to resemble lacquer. Most often, this was used not in creating the entire print, but only in enhancing a particular element, such as an obi or a figure's hair, to give it shine and make the image more luxurious overall.Prints which include urushi-e elements are likely to also feature the use of mica, metal dusts, and other elements which enhanced the appearance, quality and value of the works. The technique was most popular in the early 18th century Japan during the Edo era and can be seen in works by many artists of the time.
Urushi-e	Paintings	In painting, the term refers to the use of colored lacquers, produced by mixing pigments with clear lacquer. The use of colored lacquer for painting goes back to the prehistoric Jōmon period, and became especially popular in the Nara period (8th century), when a great many works were made using red lacquer against a black background. Until the 19th century, however, the use of natural pigments restricted the colors accessible to artists to red, black, yellow, green, and light brown.
Urushi-e	Artists	Artist Shibata Zeshin (1807-1891) is known for his innovations in this regard, and is believed by some to be the first to use lacquer not just as a decorative element (in painting boxes, furniture, and pottery) but as a medium for painted scrolls. Zeshin experimented extensively with various substances, which he mixed with lacquer to create a variety of effects, including simulating the appearance of various metals (iron, gold, bronze, copper), and imitating the appearance and texture of Western oil painting.Other artists who used the technique include: Torii Kiyonobu I (1664-1729) a member of the Torii ukiyo-e school used urushi-e.
Urushi-e	Artists	Torii Kiyomasu another member of the Torii school also made five pigment urushi-e. Another artist Nishimura Shigenaga, used it in brass powder in some of his urushi-e works. Okumura Masanobu was another who used this technique in the Edo era.
Ten Little Fingers and Ten Little Toes	Ten Little Fingers and Ten Little Toes	Ten Little Fingers and Ten Little Toes is a 2008 children's picture book by Mem Fox and Helen Oxenbury. It is about babies, who, although they are from around the world, all share the common trait of having the same number of digits.
Ten Little Fingers and Ten Little Toes	Reception	Ten Little Fingers has been commended for its positive treatment of racial diversity.A review by The New York Times stated that "two beloved picture-book creators — the storyteller Mem Fox and the artist Helen Oxenbury — merge their talents in a winsome look at babies around the world". Booklist called it "a standout for its beautiful simplicity" and "a gentle, joyous offering" School Library Journal described it as a "nearly perfect picture book" and concluded: "Whether shared one-on-one or in storytimes, where the large trim size and big, clear images will carry perfectly, this selection is sure to be a hit". Publishers Weekly, in a starred review, wrote: "Put two titans of kids' books together for the first time, and what do you get (besides the urge to shout, "What took you so long?")? The answer: an instant classic". New York Journal of Books, in a review of a bilingual edition, wrote: "This is a sturdy, toddler-sized board book that has something for everybody. Ms. Fox's text, soft and pure, offers sweet innocence, the joy of lives beginning, and the unique beauty of the mother-child love. Artist Helen Oxenbury's exquisite illustrations are the perfect complement to the text".The Horn Book Magazine referred to it as a "love song": "Snuggle up with your favorite baby and kiss those fingers and toes to both your hearts' content". BookPage Reviews called it "a jewel of a picture book" and wrote: "With minimal text, and sweet illustrations by beloved British artist Helen Oxenbury, it's truly an international treat. .. Ten Little Fingers and Ten Little Toes gently presents—but never preaches—a satisfying lesson about humanity and international harmony".Ten Little Fingers has also been reviewed by the Journal of Children's Literature, The Christian Century, First Opinions -- Second Reactions, YC: Young Children, Library Sparks, Reading Time, and the New England Reading Association Journal.It won the 2009 Australian Book Industry Book of the Year for Younger Children Award
Chasles–Cayley–Brill formula	Chasles–Cayley–Brill formula	In algebraic geometry, the Chasles–Cayley–Brill formula, also known as the Cayley–Brill formula, states that a correspondence T of valence k from an algebraic curve C of genus g to itself has d + e + 2kg united points, where d and e are the degrees of T and its inverse. Michel Chasles introduced the formula for genus g = 0, Arthur Cayley stated the general formula without proof, and Alexander von Brill gave the first proof. The number of united points of the correspondence is the intersection number of the correspondence with the diagonal Δ of C×C. The correspondence has valence k if and only if it is homologous to a linear combination a(C×1) + b(1×C) – kΔ where Δ is the diagonal of C×C. The Chasles–Cayley–Brill formula follows easily from this together with the fact that the self-intersection number of the diagonal is 2 – 2g.
Rafoxanide	Rafoxanide	Rafoxanide is a salicylanilide used as an anthelmintic. It is most commonly used in ruminant animals to treat adult liver flukes of the species Fasciola hepatica and Fasciola gigantica.
Threaded pipe	Threaded pipe	A threaded pipe is a pipe with screw-threaded ends for assembly.
Threaded pipe	Tapered threads	The threaded pipes used in some plumbing installations for the delivery of gases or liquids under pressure have a tapered thread that is slightly conical (in contrast to the parallel sided cylindrical section commonly found on bolts and leadscrews). The seal provided by a threaded pipe joint depends upon multiple factors: the labyrinth seal created by the threads; a positive seal between the threads created by thread deformation when they are tightened to the proper torque; and sometimes on the presence of a sealing coating, such as thread seal tape or a liquid or paste pipe sealant such as pipe dope. Tapered thread joints typically do not include a gasket.
Threaded pipe	Tapered threads	Especially precise threads are known as "dry fit" or "dry seal" and require no sealant for a gas-tight seal. Such threads are needed where the sealant would contaminate or react with the media inside the piping, e.g., oxygen service. Tapered threaded fittings are sometimes used on plastic piping. Due to the wedging effect of the tapered thread, extreme care must be used to avoid overtightening the joint. The overstressed female fitting may split days, weeks, or even years after initial installation. Therefore many municipal plumbing codes restrict the use of threaded plastic pipe fittings. Both British standard and National pipe thread standards specify a thread taper of 1:16; the change in diameter is one sixteenth the distance travelled along the thread. The nominal diameter is achieved some small distance (the "gauge length") from the end of the pipe.
Threaded pipe	Straight threads	Pipes may also be threaded with cylindrical threaded sections, in which case the threads do not themselves provide any sealing function other than some labyrinth seal effect, which may not be enough to satisfy either functional or code requirements. Instead, an O-ring seated between the shoulder of the male pipe section and an interior surface on the female, provides the seal.
Alphanumeric brand name	Alphanumeric brand name	An alphanumeric brand name is a brand name composed only of letters and numbers (alphanumericals). Examples include 7 Up, Saks Fifth Avenue, Audi A4, Canon A75. They may serve as abbreviations (e.g. 3M, formerly known as the Minnesota Mining and Manufacturing Company), indicate model extensions (iPhone 3G, iPhone 4, etc.), symbolize physical product attributes (the V-shaped V8 engine), incorporate technical attributes (AMD32 chips use 32-bit processors), refer to inventory codes or internal design numbers (e.g., Levi's 501).Kunter Gunasti and William T. Ross (2010) define two dimensions of alphanumeric brand names: "link", or the connection between the brand name and a specific product feature or the product as a whole; and "alignability", or whether the preferences for a product can be aligned with the numbers included in the brand names in an ascending or descending trend.Selcan Kara, Gunasti and Ross (2015) delineated the number and letter components of alphanumeric brands and observed that for new brand extensions firms can either change the letters or numbers of their parent brand names. Altering the number components of brand names (e.g. Audi A3 vs. A4 vs. A6 vs. A8) led to more favorable consumer reactions compared to changing the letter components (e.g. Mercedes C350 vs. E350 vs. S350).Gunasti and Timucin Ozcan (2016) further categorized alphanumeric brand names as either "round" or "non-round". They showed that use of "round numbers" in brand names is pervasive because this practice increases the tendency of consumers to perceive products as more complete (including all necessary attributes). For example, labeling an identical product with an "S200" brand (round number) as opposed to an "S198" or "S203" brand can make consumers believe that the product is superior and more well-rounded. They also found that the presence of competitor alphanumeric brand name (e.g. Garmin 370) can affect consumer choices among the focal brand (e.g. TomTom 350 vs. TomTom 360). Gunasti and Berna Devezer (2016) observed that this effect occurs only for competing firms' products.
IBM Information Management System	IBM Information Management System	The IBM Information Management System (IMS) is a joint hierarchical database and information management system that supports transaction processing.
IBM Information Management System	History	IBM designed the IMS with Rockwell and Caterpillar starting in 1966 for the Apollo program, where it was used to inventory the very large bill of materials (BOM) for the Saturn V moon rocket and Apollo space vehicle.The first "IMS READY" message appeared on an IBM 2740 terminal in Downey, California, on August 14, 1968.
IBM Information Management System	History	In the interim period, IMS has undergone many developments as IBM System/360 technology evolved into the current z/OS and IBM zEnterprise System technologies. For example, IMS now supports the Java programming language, JDBC, XML, and, since late 2005, web services.Vern Watts was IMS's chief architect for many years. Watts joined IBM in 1956 and worked at IBM's Silicon Valley development labs until his death on April 4, 2009. He had continuously worked on IMS since the 1960s.
IBM Information Management System	Database	The IMS Database component stores data using a hierarchical model, which is quite different from IBM's later released relational database, IBM Db2. In IMS, the hierarchical model is implemented using blocks of data known as segments. Each segment can contain several pieces of data, which are called fields. For example, a customer database may have a root segment (or the segment at the top of the hierarchy) with fields such as phone, name, and age. Child segments may be added underneath another segment, for instance, one order segment under each customer segment represents each order a customer has placed with a company. Likewise, each order segment may have many children segments for each item on the order. Unlike other databases, you do not need to define all of the data in a segment to IMS. A segment may be defined with a size of 40 bytes but only define one field that is six bytes long as a key field that you can use to find the segment when performing queries. IMS will retrieve and save all 40 bytes as directed by a program but may not understand (or care) what the other bytes represent. In practice, often all the data in a segment may map to a COBOL copybook. Besides DL/I query usage, a field may be defined in IMS so that the data can be hidden from certain applications for security reasons. The database component of IMS can be purchased standalone, without the transaction manager component, and used by systems such as CICS.There are three basic forms of IMS hierarchical databases: "Full Function" databases Directly descended from the Data Language Interface (DL/I) databases originally developed for Apollo, full function databases can have primary and secondary indexes, accessed using DL/I calls from an application program, like SQL calls to IBM Db2 or Oracle.
IBM Information Management System	Database	Full function databases can be accessed by a variety of methods, although Hierarchical Direct (HDAM) and Hierarchical Indexed Direct (HIDAM) dominate. The other formats are Simple Hierarchical Indexed Sequential (SHISAM), Hierarchical Sequential (HSAM), and Hierarchical Indexed Sequential (HISAM). Full function databases store data using VSAM, a native z/OS access method, or Overflow Sequential (OSAM), an IMS-specific access method that optimizes the I/O channel program for IMS access patterns. In particular, OSAM performance benefits from sequential access of IMS databases (OSAM Sequential Buffering).
IBM Information Management System	Database	"Fast Path" databases Fast Path databases are optimized for extremely high transaction rates. Data Entry Databases (DEDBs) and Main Storage Databases (MSDBs) are the two types of Fast Path databases. DEDBs use a direct (randomizer) access technique similar to Full Function HDAM and IMS V12 provided a DEDB Secondary Index function. MSDBs do not support secondary indexing. Virtual Storage Option (VSO) DEDBs can replace MSDBs in modern IMS releases, so MSDBs are gradually disappearing.DEDB performance comes from use of high performance (Media Manager) access methods, asynchronous write after commit, and optimized code paths. Logging is minimized because no data is updated on disk until commit, so UNDO (before image) logging is not needed, nor is a backout function. Uncommitted changes can simply be discarded. Starting with IMS Version 11, DEDBs can use z/OS 64-bit storage for database buffers. DEDBs architecture includes a Unit of Work (UOW) concept which made an effective online reorganization utility simple to implement. This function is included in the base product.
IBM Information Management System	Database	High Availability Large Databases (HALDBs) IMS V7 introduced HALDBs, an extension of IMS full function databases to provide better availability, better handling of extremely large data volumes, and, with IMS V9, online reorganization to support continuous availability. (Third party tools exclusively provided online reorganization prior to IMS V9.) A HALDB can store in excess of 40 terabytes of data.Fast path DEDBs can only be built atop VSAM. DL/I databases can be built atop either VSAM or OSAM, with some restrictions depending on database organization. Although the maximum size of a z/OS VSAM dataset increased to 128 TB a few years ago, IMS still limits a VSAM dataset to 4 GB (and OSAM to 8 GB). This "limitation" simply means that IMS customers will use multiple datasets for large amounts of data. VSAM and OSAM are usually referred to as the access methods, and the IMS "logical" view of the database is referred to as the database "organization" (HDAM, HIDAM, HISAM, etc.) Internally the data are linked using 4-byte pointers or addresses. In the database datasets (DBDSs) the pointers are referred to as RBAs (relative byte addresses).Collectively the database-related IMS capabilities are often called IMS DB. IMS DB has grown and evolved over nearly four decades to support myriad business needs. IMS, with assistance from z/OS hardware – the Coupling Facility – supports N-way inter-IMS sharing of databases. Many large configurations involve multiple IMS systems managing common databases, a technique providing for scalable growth and system redundancy in the event of hardware or software failures.
IBM Information Management System	Transaction Manager	IMS is also a robust transaction manager (IMS TM, also known as IMS DC) – one of the "big three" classic transaction managers along with CICS and BEA (now Oracle) Tuxedo. A transaction manager interacts with an end user (connected through VTAM or TCP/IP, including 3270 and Web user interfaces) or another application, processes a business function (such as a banking account withdrawal), and maintains state throughout the process, making sure that the system records the business function correctly to a data store. Thus IMS TM is quite like a Web application, operating through a CGI program (for example), to provide an interface to query or update a database. IMS TM typically uses either IMS DB or Db2 as its backend database. When used alone with Db2 the IMS TM component can be purchased without the IMS DB component.IMS TM uses a messaging and queuing paradigm. An IMS control program receives a transaction entered from a terminal (or Web browser or other application) and then stores the transaction on a message queue (in memory or in a dataset). IMS then invokes its scheduler on the queued transaction to start the business application program in a message processing region. The message processing region retrieves the transaction from the IMS message queue and processes it, reading and updating IMS and/or Db2 databases, assuring proper recording of the transaction. Then, if required, IMS enqueues a response message back onto the IMS message queue. Once the output message is complete and available the IMS control program sends it back to the originating terminal. IMS TM can handle this whole process thousands (or even tens of thousands) of times per second. In 2013 IBM completed a benchmark on IMS Version 13 demonstrating the ability to process 100,000 transactions per second on a single IMS system.
IBM Information Management System	Application	Prior to IMS, businesses and governments had to write their own transaction processing environments. IMS TM provides a straightforward, easy-to-use, reliable, standard environment for high performance transaction execution. In fact, much of the world's banking industry relies on IMS, including the U.S. Federal Reserve. For example, chances are that withdrawing money from an automated teller machine (ATM) will trigger an IMS transaction. Several Chinese banks, by the late 2000s, have purchased IMS to support that country's burgeoning financial industry.Today IMS complements IBM Db2, IBM's relational database system, introduced in 1982. In general, IMS performs faster than Db2 for the common tasks but may require more programming effort to design and maintain for non-primary duties. Relational databases have generally proven superior in cases where the requirements, especially reporting requirements, change frequently or require a variety of viewpoint "angles" outside the primary or original function.A relational "data warehouse" may be used to supplement an IMS database. For example, IMS may provide primary ATM transactions because it performs well for such a specific task. However, nightly copies of the IMS data may be copied to relational systems such that a variety of reports and processing tasks may be performed on the data. This allows each kind of database to focus best on its relative strength.
Autoclave	Autoclave	An autoclave is a machine used to carry out industrial and scientific processes requiring elevated temperature and pressure in relation to ambient pressure and/or temperature. Autoclaves are used before surgical procedures to perform sterilization and in the chemical industry to cure coatings and vulcanize rubber and for hydrothermal synthesis. Industrial autoclaves are used in industrial applications, especially in the manufacturing of composites.
Autoclave	Autoclave	Many autoclaves are used to sterilize equipment and supplies by subjecting them to pressurized saturated steam at 121 °C (250 °F) for around 30-60 minutes at a pressure of 15 psi above atmospheric pressure (205 kPa or 2.02 atm) depending on the size of the load and the contents. The autoclave was invented by Charles Chamberland in 1879, although a precursor known as the steam digester was created by Denis Papin in 1679. The name comes from Greek auto-, ultimately meaning self, and Latin clavis meaning key, thus a self-locking device.
Autoclave	Uses	Sterilization autoclaves are widely used in microbiology and mycology, medicine and prosthetics fabrication, tattooing and body piercing, and funerary practice. They vary in size and function depending on the media to be sterilized and are sometimes called retort in the chemical and food industries.
Autoclave	Uses	Typical loads include laboratory glassware, other equipment and waste, surgical instruments, and medical waste.A notable recent and increasingly popular application of autoclaves is the pre-disposal treatment and sterilization of waste material, such as pathogenic hospital waste. Machines in this category largely operate under the same principles as conventional autoclaves in that they are able to neutralize potentially infectious agents by using pressurized steam and superheated water. A new generation of waste converters is capable of achieving the same effect without a pressure vessel to sterilize culture media, rubber material, gowns, dressings, gloves, etc. It is particularly useful for materials which cannot withstand the higher temperature of a hot air oven.Autoclaves are also widely used to cure composites, especially for melding multiple layers without any voids that would decrease material strength, and in the vulcanization of rubber. The high heat and pressure that autoclaves generate help to ensure that the best possible physical properties are repeatable. Manufacturers of spars for sailboats have autoclaves well over 50 feet (15 m) long and 10 feet (3 m) wide, and some autoclaves in the aerospace industry are large enough to hold whole airplane fuselages made of layered composites.Other types of autoclaves are used to grow crystals under high temperatures and pressures. Synthetic quartz crystals used in the electronics industry are grown in autoclaves. Packing of parachutes for specialist applications may be performed under vacuum in an autoclave, which allows the chutes to be warmed and inserted into their packs at the smallest volume.
Autoclave	Uses	A thermal effluent decontamination system functions as a single-purpose autoclave designed for the sterilization of liquid waste and effluent.
Autoclave	Air removal	It is very important to ensure that all of the trapped air is removed from the autoclave before activation, as trapped air is a very poor medium for achieving sterility. Steam at 134 °C (273 °F) can achieve a desired level of sterility in three minutes, while achieving the same level of sterility in hot air requires two hours at 160 °C (320 °F). Methods of air removal include: Downward displacement (or gravity-type): As steam enters the chamber, it fills the upper areas first as it is less dense than air. This process compresses the air to the bottom, forcing it out through a drain which often contains a temperature sensor. Only when air evacuation is complete does the discharge stop. Flow is usually controlled by a steam trap or a solenoid valve, but bleed holes are sometimes used. As the steam and air mix, it is also possible to force out the mixture from locations in the chamber other than the bottom.
Autoclave	Air removal	Steam pulsing: Air dilution by using a series of steam pulses, in which the chamber is alternately pressurized and then depressurized to near atmospheric pressure. Vacuum pumps: A vacuum pump sucks air or air/steam mixtures from the chamber. Superatmospheric cycles: Achieved with a vacuum pump. It starts with a vacuum followed by a steam pulse followed by a vacuum followed by a steam pulse. The number of pulses depends on the particular autoclave and cycle chosen. Subatmospheric cycles: Similar to the superatmospheric cycles, but chamber pressure never exceeds atmospheric pressure until they pressurize up to the sterilizing temperature.Stovetop autoclaves used in poorer or non-medical settings do not always have automatic air removal programs. The operator is required to manually perform steam pulsing at certain pressures as indicated by the gauge.
Autoclave	In medicine	A medical autoclave is a device that uses steam to sterilize equipment and other objects. This means that all bacteria, viruses, fungi, and spores are inactivated. However, prions, such as those associated with Creutzfeldt–Jakob disease, and some toxins released by certain bacteria, such as Cereulide, may not be destroyed by autoclaving at the typical 134 °C for three minutes or 121 °C for 15 minutes and instead should be immersed in sodium hydroxide (1N NaOH) and heated in a gravity displacement autoclave at 121 °C for 30 min, cleaned, rinsed in water and subjected to routine sterilization. Although a wide range of archaea species, including Geogemma barosii, can survive and even reproduce at temperatures found in autoclaves, their growth rate is so slow at the lower temperatures in the less extreme environments occupied by humans that it is unlikely they could compete with other organisms. None of them are known to be infectious or otherwise pose a health risk to humans; in fact, their biochemistry is so different from our own and their multiplication rate is so slow that microbiologists need not worry about them.Autoclaves are found in many medical settings, laboratories, and other places that need to ensure the sterility of an object. Many procedures today employ single-use items rather than sterilizable, reusable items. This first happened with hypodermic needles, but today many surgical instruments (such as forceps, needle holders, and scalpel handles) are commonly single-use rather than reusable items (see waste autoclave). Autoclaves are of particular importance in poorer countries due to the much greater amount of equipment that is re-used. Providing stove-top or solar autoclaves to rural medical centers has been the subject of several proposed medical aid missions.Because damp heat is used, heat-labile products (such as some plastics) cannot be sterilized this way or they will melt. Paper and other products that may be damaged by steam must also be sterilized another way. In all autoclaves, items should always be separated to allow the steam to penetrate the load evenly.
Autoclave	In medicine	Autoclaving is often used to sterilize medical waste prior to disposal in the standard municipal solid waste stream. This application has become more common as an alternative to incineration due to environmental and health concerns raised because of the combustion by-products emitted by incinerators, especially from the small units which were commonly operated at individual hospitals. Incineration or a similar thermal oxidation process is still generally mandated for pathological waste and other very toxic or infectious medical waste. For liquid waste, an effluent decontamination system is the equivalent hardware.
Autoclave	In medicine	In dentistry, autoclaves provide sterilization of dental instruments.
Autoclave	In medicine	In most of the industrialized world medical-grade autoclaves are regulated medical devices. Many medical-grade autoclaves are therefore limited to running regulator-approved cycles. Because they are optimized for continuous hospital use, they favor rectangular designs, require demanding maintenance regimens, and are costly to operate. (A properly calibrated medical-grade autoclave uses thousands of gallons of water each day, independent of task, with correspondingly high electric power consumption.)
Autoclave	In research	Autoclaves used in education, research, biomedical research, pharmaceutical research and industrial settings (often called "research-grade" autoclaves) are used to sterilize lab instruments, glassware, culture media, and liquid media. Research-grade autoclaves are increasingly used in these settings where efficiency, ease-of-use, and flexibility are at a premium. Research-grade autoclaves may be configured for "pass-through" operation. This makes it possible to maintain absolute isolation between "clean" and potentially contaminated work areas. Pass-through research autoclaves are especially important in BSL-3 or BSL-4 facilities.
Autoclave	In research	Research-grade autoclaves—which are not approved for use in sterilizing instruments that will be directly used on humans—are primarily designed for efficiency, flexibility, and ease-of-use. They display a wide range of designs and sizes, and are frequently tailored to their use and load type. Common variations include either a cylindrical or square pressure chamber, air- or water-cooling systems, and vertically or horizontally opening chamber doors (which may be electrically or manually powered).
Autoclave	In research	In 2016, the Office of Sustainability at the University of California, Riverside (UCR) conducted a study of autoclave efficiency in their genomics and entomology research labs, tracking several units' power and water consumption. They found that, even when functioning within intended parameters, the medical-grade autoclaves used in their research labs were each consuming 700 gallons of water and 90 kWh of electricity per day (1,134MWh of electricity and 8.8 million gallons of water total), because they consumed energy and water continuously, even when not in use. UCR's research-grade autoclaves performed the same tasks with equal effectiveness, but used 83% less energy and 97% less water.
Autoclave	Quality assurance	In order to sterilize items effectively, it is important to use optimal parameters when running an autoclave cycle. A 2017 study performed by the Johns Hopkins Hospital biocontainment unit tested the ability of pass-through autoclaves to decontaminate loads of simulated biomedical waste when run on the factory default setting. The study found that 18 of 18 (100%) mock patient loads (6 PPE, 6 linen, and 6 liquid loads) passed sterilization tests with the optimized parameters compared to only 3 of 19 (16%) mock loads that passed with use of the factory default settings.There are physical, chemical, and biological indicators that can be used to ensure that an autoclave reaches the correct temperature for the correct amount of time. If a non-treated or improperly treated item can be confused for a treated item, then there is the risk that they will become mixed up, which, in some areas such as surgery, is critical.
Autoclave	Quality assurance	Chemical indicators on medical packaging and autoclave tape change color once the correct conditions have been met, indicating that the object inside the package, or under the tape, has been appropriately processed. Autoclave tape is only a marker that steam and heat have activated the dye. The marker on the tape does not indicate complete sterility. A more difficult challenge device, named the Bowie-Dick device after its inventors, is also used to verify a full cycle. This contains a full sheet of chemical indicator placed in the center of a stack of paper. It is designed specifically to prove that the process achieved full temperature and time required for a normal minimum cycle of 134 °C for 3.5–4 minutes.To prove sterility, biological indicators are used. Biological indicators contain spores of a heat-resistant bacterium, Geobacillus stearothermophilus. If the autoclave does not reach the right temperature, the spores will germinate when incubated and their metabolism will change the color of a pH-sensitive chemical. Some physical indicators consist of an alloy designed to melt only after being subjected to a given temperature for the relevant holding time. If the alloy melts, the change will be visible.Some computer-controlled autoclaves use an F0 (F-nought) value to control the sterilization cycle. F0 values are set for the number of minutes of sterilization equivalent to 121 °C (250 °F) at 103 kPa (14.9 psi) above atmospheric pressure for 15 minutes. Since exact temperature control is difficult, the temperature is monitored, and the sterilization time adjusted accordingly.
Genotyping by sequencing	Genotyping by sequencing	In the field of genetic sequencing, genotyping by sequencing, also called GBS, is a method to discover single nucleotide polymorphisms (SNP) in order to perform genotyping studies, such as genome-wide association studies (GWAS). GBS uses restriction enzymes to reduce genome complexity and genotype multiple DNA samples. After digestion, PCR is performed to increase fragments pool and then GBS libraries are sequenced using next generation sequencing technologies, usually resulting in about 100bp single-end reads. It is relatively inexpensive and has been used in plant breeding. Although GBS presents an approach similar to restriction-site-associated DNA sequencing (RAD-seq) method, they differ in some substantial ways.
Genotyping by sequencing	Methods	GBS is a robust, simple, and affordable procedure for SNP discovery and mapping. Overall, this approach reduces genome complexity with restriction enzymes (REs) in high-diversity, large genomes species for efficient high-throughput, highly multiplexed sequencing. By using appropriate REs, repetitive regions of genomes can be avoided and lower copy regions can be targeted, which reduces alignments problems in genetically highly diverse species. The method was first described by Elshire et al. (2011). In summary, high molecular weight DNAs are extracted and digested using a specific RE previously defined by cutting frequently in the major repetitive fraction of the genome. ApeKI is the most used RE. Barcode adapters are then ligated to sticky ends and PCR amplification is performed. Next-generation sequencing technology is performed resulting in about 100 bp single-end reads. Raw sequence data are filtered and aligned to a reference genome using usually Burrows–Wheeler alignment tool (BWA) or Bowtie 2. The next step is to identify SNPs from aligned tags and score all discovered SNPs for various coverage, depth and genotypic statistics. Once a large-scale, species-wide SNP production has been run, it is possible to quickly call known SNPs in newly sequenced samples.When initially developed, the GBS approach was tested and validated in recombinant inbred lines (RILs) from a high-resolution maize mapping population (IBM) and doubled haploid (DH) barley lines from the Oregon Wolfe Barley (OWB) mapping population. Up to 96 RE (ApeKI)-digested DNA samples were pooled and processed simultaneously during the GBS library construction, which was checked on a Genome Analyzer II (Illumina, Inc.). Overall, 25,185 biallelic tags were mapped in maize, while 24,186 sequence tags were mapped in barley. Barley GBS marker validation using a single DH line (OWB003) showed 99% agreement between the reference markers and the mapped GBS reads. Although barley lacks a complete genome sequence, GBS does not require a reference genome for sequence tag mapping, the reference is developed during the process of sampling genotyping. Tags can also be treated as dominant markers for alternative genetic analysis in the absence of a reference genome. Other than the multiplex GBS skimming, imputation of missing SNPs has the potential to further reduce GBS costs. GBS is a versatile and cost-effective procedure that will allow mining genomes of any species without prior knowledge of its genome structure.
XOR swap algorithm	XOR swap algorithm	In computer programming, the exclusive or swap (sometimes shortened to XOR swap) is an algorithm that uses the exclusive or bitwise operation to swap the values of two variables without using the temporary variable which is normally required. The algorithm is primarily a novelty and a way of demonstrating properties of the exclusive or operation. It is sometimes discussed as a program optimization, but there are almost no cases where swapping via exclusive or provides benefit over the standard, obvious technique.
XOR swap algorithm	The algorithm	Conventional swapping requires the use of a temporary storage variable. Using the XOR swap algorithm, however, no temporary storage is needed. The algorithm is as follows: Since XOR is a commutative operation, either X XOR Y or Y XOR X can be used interchangeably in any of the foregoing three lines. Note that on some architectures the first operand of the XOR instruction specifies the target location at which the result of the operation is stored, preventing this interchangeability. The algorithm typically corresponds to three machine-code instructions, represented by corresponding pseudocode and assembly instructions in the three rows of the following table: In the above System/370 assembly code sample, R1 and R2 are distinct registers, and each XR operation leaves its result in the register named in the first argument. Using x86 assembly, values X and Y are in registers eax and ebx (respectively), and xor places the result of the operation in the first register.
XOR swap algorithm	The algorithm	However, in the pseudocode or high-level language version or implementation, the algorithm fails if x and y use the same storage location, since the value stored in that location will be zeroed out by the first XOR instruction, and then remain zero; it will not be "swapped with itself". This is not the same as if x and y have the same values. The trouble only comes when x and y use the same storage location, in which case their values must already be equal. That is, if x and y use the same storage location, then the line: sets x to zero (because x = y so X XOR Y is zero) and sets y to zero (since it uses the same storage location), causing x and y to lose their original values.
XOR swap algorithm	Proof of correctness	The binary operation XOR over bit strings of length N exhibits the following properties (where ⊕ denotes XOR): L1. Commutativity: A⊕B=B⊕A L2. Associativity: (A⊕B)⊕C=A⊕(B⊕C) L3. Identity exists: there is a bit string, 0, (of length N) such that A⊕0=A for any A L4. Each element is its own inverse: for each A , A⊕A=0 .Suppose that we have two distinct registers R1 and R2 as in the table below, with initial values A and B respectively. We perform the operations below in sequence, and reduce our results using the properties listed above.
XOR swap algorithm	Proof of correctness	Linear algebra interpretation As XOR can be interpreted as binary addition and a pair of bits can be interpreted as a vector in a two-dimensional vector space over the field with two elements, the steps in the algorithm can be interpreted as multiplication by 2×2 matrices over the field with two elements. For simplicity, assume initially that x and y are each single bits, not bit vectors.
XOR swap algorithm	Proof of correctness	For example, the step: which also has the implicit: corresponds to the matrix (1101) as (1101)(xy)=(x+yy). The sequence of operations is then expressed as: (1101)(1011)(1101)=(0110) (working with binary values, so 1+1=0 ), which expresses the elementary matrix of switching two rows (or columns) in terms of the transvections (shears) of adding one element to the other. To generalize to where X and Y are not single bits, but instead bit vectors of length n, these 2×2 matrices are replaced by 2n×2n block matrices such as (InIn0In). These matrices are operating on values, not on variables (with storage locations), hence this interpretation abstracts away from issues of storage location and the problem of both variables sharing the same storage location.
XOR swap algorithm	Code example	A C function that implements the XOR swap algorithm: The code first checks if the addresses are distinct. Otherwise, if they were equal, the algorithm would fold to a triple x ^= x resulting in zero. The XOR swap algorithm can also be defined with a macro:
XOR swap algorithm	Reasons for avoidance in practice	On modern CPU architectures, the XOR technique can be slower than using a temporary variable to do swapping. At least on recent x86 CPUs, both by AMD and Intel, moving between registers regularly incurs zero latency. (This is called MOV-elimination.) Even if there is not any architectural register available to use, the XCHG instruction will be at least as fast as the three XORs taken together. Another reason is that modern CPUs strive to execute instructions in parallel via instruction pipelines. In the XOR technique, the inputs to each operation depend on the results of the previous operation, so they must be executed in strictly sequential order, negating any benefits of instruction-level parallelism.
XOR swap algorithm	Reasons for avoidance in practice	Aliasing The XOR swap is also complicated in practice by aliasing. If an attempt is made to XOR-swap the contents of some location with itself, the result is that the location is zeroed out and its value lost. Therefore, XOR swapping must not be used blindly in a high-level language if aliasing is possible. This issue does not apply if the technique is used in assembly to swap the contents of two registers.
XOR swap algorithm	Reasons for avoidance in practice	Similar problems occur with call by name, as in Jensen's Device, where swapping i and A[i] via a temporary variable yields incorrect results due to the arguments being related: swapping via temp = i; i = A[i]; A[i] = temp changes the value for i in the second statement, which then results in the incorrect i value for A[i] in the third statement.
XOR swap algorithm	Variations	The underlying principle of the XOR swap algorithm can be applied to any operation meeting criteria L1 through L4 above. Replacing XOR by addition and subtraction gives various slightly different, but largely equivalent, formulations. For example: Unlike the XOR swap, this variation requires that the underlying processor or programming language uses a method such as modular arithmetic or bignums to guarantee that the computation of X + Y cannot cause an error due to integer overflow. Therefore, it is seen even more rarely in practice than the XOR swap.
XOR swap algorithm	Variations	However, the implementation of AddSwap above in the C programming language always works even in case of integer overflow, since, according to the C standard, addition and subtraction of unsigned integers follow the rules of modular arithmetic, i. e. are done in the cyclic group Z/2sZ where s is the number of bits of unsigned int. Indeed, the correctness of the algorithm follows from the fact that the formulas (x+y)−y=x and (x+y)−((x+y)−y)=y hold in any abelian group. This generalizes the proof for the XOR swap algorithm: XOR is both the addition and subtraction in the abelian group (Z/2Z)s (which is the direct sum of s copies of Z/2Z ).
XOR swap algorithm	Variations	This doesn't hold when dealing with the signed int type (the default for int). Signed integer overflow is an undefined behavior in C and thus modular arithmetic is not guaranteed by the standard, which may lead to incorrect results. The sequence of operations in AddSwap can be expressed via matrix multiplication as: (1−101)(101−1)(1101)=(0110)
XOR swap algorithm	Application to register allocation	On architectures lacking a dedicated swap instruction, because it avoids the extra temporary register, the XOR swap algorithm is required for optimal register allocation. This is particularly important for compilers using static single assignment form for register allocation; these compilers occasionally produce programs that need to swap two registers when no registers are free. The XOR swap algorithm avoids the need to reserve an extra register or to spill any registers to main memory. The addition/subtraction variant can also be used for the same purpose.This method of register allocation is particularly relevant to GPU shader compilers. On modern GPU architectures, spilling variables is expensive due to limited memory bandwidth and high memory latency, while limiting register usage can improve performance due to dynamic partitioning of the register file. The XOR swap algorithm is therefore required by some GPU compilers.
Acute hemorrhagic edema of infancy	Acute hemorrhagic edema of infancy	Acute hemorrhagic edema of infancy is a skin condition that affects children under the age of two with a recent history of upper respiratory illness, a course of antibiotics, or both.: 833 The disease was first described in 1938 by Finkelstein and later by Seidlmayer as "Seidlmayer cockade purpura".
Major second	Major second	In Western music theory, a major second (sometimes also called whole tone or a whole step) is a second spanning two semitones (Play ). A second is a musical interval encompassing two adjacent staff positions (see Interval number for more details). For example, the interval from C to D is a major second, as the note D lies two semitones above C, and the two notes are notated on adjacent staff positions. Diminished, minor and augmented seconds are notated on adjacent staff positions as well, but consist of a different number of semitones (zero, one, and three).
Major second	Major second	The intervals from the tonic (keynote) in an upward direction to the second, to the third, to the sixth, and to the seventh scale degrees (of a major scale are called major.
Major second	Major second	The major second is the interval that occurs between the first and second degrees of a major scale, the tonic and the supertonic. On a musical keyboard, a major second is the interval between two keys separated by one key, counting white and black keys alike. On a guitar string, it is the interval separated by two frets. In moveable-do solfège, it is the interval between do and re. It is considered a melodic step, as opposed to larger intervals called skips.
Major second	Major second	Intervals composed of two semitones, such as the major second and the diminished third, are also called tones, whole tones, or whole steps. In just intonation, major seconds can occur in at least two different frequency ratios: 9:8 (about 203.9 cents) and 10:9 (about 182.4 cents). The largest (9:8) ones are called major tones or greater tones, the smallest (10:9) are called minor tones or lesser tones. Their size differs by exactly one syntonic comma (81:80, or about 21.5 cents). Some equal temperaments, such as 15-ET and 22-ET, also distinguish between a greater and a lesser tone. The major second was historically considered one of the most dissonant intervals of the diatonic scale, although much 20th-century music saw it reimagined as a consonance. It is common in many different musical systems, including Arabic music, Turkish music and music of the Balkans, among others. It occurs in both diatonic and pentatonic scales. Listen to a major second in equal temperament . Here, middle C is followed by D, which is a tone 200 cents sharper than C, and then by both tones together.
Major second	Major and minor tones	In tuning systems using just intonation, such as 5-limit tuning, in which major seconds occur in two different sizes, the wider of them is called a major tone or greater tone, and the narrower a minor tone or, lesser tone. The difference in size between a major tone and a minor tone is equal to one syntonic comma (about 21.51 cents).
Major second	Major and minor tones	The major tone is the 9:8 interval play , and it is an approximation thereof in other tuning systems, while the minor tone is the 10:9 ratio play . The major tone may be derived from the harmonic series as the interval between the eighth and ninth harmonics. The minor tone may be derived from the harmonic series as the interval between the ninth and tenth harmonics. The 10:9 minor tone arises in the C major scale between D & E and G & A, and is "a sharper dissonance" than 9:8. The 9:8 major tone arises in the C major scale between C & D, F & G, and A & B. This 9:8 interval was named epogdoon (meaning 'one eighth in addition') by the Pythagoreans.
Major second	Major and minor tones	Notice that in these tuning systems, a third kind of whole tone, even wider than the major tone, exists. This interval of two semitones, with ratio 256:225, is simply called the diminished third (for further details, see Five-limit tuning § Size of intervals). Some equal temperaments also produce major seconds of two different sizes, called greater and lesser tones (or major and minor tones). For instance, this is true for 15-ET, 22-ET, 34-ET, 41-ET, 53-ET, and 72-ET. Conversely, in twelve-tone equal temperament, Pythagorean tuning, and meantone temperament (including 19-ET and 31-ET) all major seconds have the same size, so there cannot be a distinction between a greater and a lesser tone.
Major second	Major and minor tones	In any system where there is only one size of major second, the terms greater and lesser tone (or major and minor tone) are rarely used with a different meaning. Namely, they are used to indicate the two distinct kinds of whole tone, more commonly and more appropriately called major second (M2) and diminished third (d3). Similarly, major semitones and minor semitones are more often and more appropriately referred to as minor seconds (m2) and augmented unisons (A1), or diatonic and chromatic semitones.

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