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T-cell depletion	Role in disease	In arthritis A preliminary study of the effect on TCD in arthritis in mice models has shown that regulatory T cells play an important role in delayed-type hypersensitivity arthritis (DTHA) inflammation. This occurs by TCD inducing increased neutrofils and activity of IL-17 and RANKL.
T-cell depletion	Treatment use	Haploidentical stem cell transplantation TCD is heavily used in haploidentical stem cell transplantation (HSCT), a process in which cancer patients receive an infusion of healthy stem cells from a compatible donor to replenish their blood-forming elements.In patients with Acute Myeloid Leukemia (AML) and in their first remission, ex vivo TCD greatly reduced the incidence rate of GVHD, though survival was comparable to conventional transplants.
T-cell depletion	Treatment use	Bone marrow transplantation In allogeneic bone marrow transplants (BMT), the transplanted stem cells derive from the bone marrow. In cases where the donors are genetically similar, but not identical, risk of GVHD is increased. The first ex vivo TCD trials used monoclonal antibodies, but still had high incidence rates of GVHD. Additional treatment using complement or immunotoxins (along with anti-T-cell antibody) improved the depletion, thus increasing the prevention of GVHD. Depleting αβ T cells from the infused graft spares γδ T cells and NK cells promotes their homeostatic reconstitution, thus reducing the risk of GVHD.In vitro TCD selectively with an anti-T12 monoclonal antibody lowers the rate of acute and chronic GVHD post allogeneic BMT. Further, immune suppressive medications are usually unnecessary if CD6+ T cells are removed from the donor marrow.Patients can relapse even after a TCD allogeneic bone marrow transplant, though patients with chronic myelogenous leukemia (CML) who receive a donor lymphocyte infusion (DLI) can restore complete remission.
University of California, San Diego Performance-Based Skills Assessment	University of California, San Diego Performance-Based Skills Assessment	The University of California, San Diego Performance-Based Skills Assessment (UPSA) was created by Dr. Thomas L. Patterson to provide a more reliable measure of every day functioning in patients with schizophrenia than the previously utilized methods such as self-report, clinician ratings or direct observation.
University of California, San Diego Performance-Based Skills Assessment	History	While everyday functioning has long been known to be affected in those with schizophrenia, the focus of testing and treatment had traditionally been on the symptoms of psychosis. As everyday functioning is fundamental for patients with cognitive impairment, the focal point has shifted towards accurate assessment of everyday functional capabilities.Self-reporting or observations by a clinician have been the most common instruments used to assess everyday functioning, but these methods have weaknesses. For example, when using the self-report method, interference by the subject's psychopathy in the perception of their abilities can cause results to be distorted, and in the case of clinicians’ ratings, patients are typically only observed for a short duration, so clinicians may not be capable of comprehensively evaluating the patient's ability to perform daily tasks.Dr. Thomas L. Patterson created the University of California, San Diego (UCSD) Performance-Based Skills Assessment (UPSA) to provide clinicians with a standardized set of tasks to assess a participant's real-world abilities. During an UPSA evaluation, participants perform every day activities under a clinician's direction. As a performance-based assessment, the UPSA has been found to be less vulnerable to error than self-report by the participant as it doesn't rely on the participant's level of awareness of their own abilities. The UPSA has been shown to be predictive of outcomes such as employment status, independence, and social skills, and shows a strong correlation with neuropsychological deficits.
University of California, San Diego Performance-Based Skills Assessment	Description	The UPSA is a role-play test in which participants are asked to utilize props to demonstrate how well they perform every day activities. Depending on the version, the UPSA is a paper-and-pen or electronic cognitive assessment that evaluates up to 6 domains of every day functioning: Household Management Communication Financial Skills Transportation Comprehension/Planning Medication Management
University of California, San Diego Performance-Based Skills Assessment	Administration	The Household Management, Communication, Transportation, Comprehension and Planning and Medication Management domains consist of one task each. The Financial Skills domain consists of two tasks. Depending on the version used, the assessment will encompass all or some of the following sub tests:
University of California, San Diego Performance-Based Skills Assessment	Versions	UPSA-2 A general version that allows for nationwide use in the United States. It uses all subscales, including Medication Management, and is intended for use in both small studies, and large multi-site clinical trials.
University of California, San Diego Performance-Based Skills Assessment	Versions	UPSA-B (Brief) A shorter version of the UPSA-2 that uses only the financial skills and communication skills subscales (i.e. counting change, telephone calls, and paying bills). This version of the UPSA takes approximately 15 minutes to complete and has been shown to be an accurate predictor of patient ability to live independently, as compared to the full version of the UPSA. When used outside of the United States, the check-writing portion of the UPSA -B is replaced with a verbal response portion for populations with little to no familiarity with check writing.
University of California, San Diego Performance-Based Skills Assessment	Versions	UPSA-2-VIM (Validation of Intermediate Measures) A full version of the UPSA-2, excluding the medication management task. UPSA-2-ER (Extended Range) A full version of the UPSA-2, containing additional questions to increase the level of difficulty for each subscale.
University of California, San Diego Performance-Based Skills Assessment	Versions	C-UPSA (Computerized) A computer-based version of the UPSA that requires either a laptop or a desktop computer for test administration. It was created to meet the demand of a more portable and less material-heavy everyday functioning assessment. Validation studies found that the UPSA and C-UPSA scores were significantly correlated and that the C-UPSA provided increased benefits to the users, including a decreased administration time and minimization of examiner impact on performance.
University of California, San Diego Performance-Based Skills Assessment	Versions	UPSA-M (Mobile) An iOS tablet-based mobile application version of the UPSA, successive of the C-UPSA. Advantages of the UPSA-M include standardized instructions, audio recording of the subject's responses, easier administration, and the option to administer the entire UPSA or the UPSA-B through the same program. Additionally, the tablet touch-screen design mimics real-life.
University of California, San Diego Performance-Based Skills Assessment	Use	Various versions of the UPSA have been used in multiple phase 2 and 3 clinical trials, as well as academic studies in populations with schizophrenia, bipolar disorder, Alzheimer's disease, mild cognitive impairment (MCI), psychosis, and others. Translated and localized versions of the UPSA-2, UPSA-2-VIM, UPSA-2ER and UPSA-B are available for international use.
University of California, San Diego Performance-Based Skills Assessment	Other Cognitive Assessment Tools	SCoRS - Schizophrenia Cognition Rating Scale VRFCAT - Virtual Reality Functional Capacity Assessment Tool
Restylane	Restylane	Restylane is the trade name for a range of injectable fillers with a specific formulation of non-animal sourced hyaluronic acid (HA). In the United States, Restylane was the first hyaluronic acid filler to be approved by the U.S. Food and Drug Administration (FDA) for cosmetic injection into subdermal facial tissues.Restylane is produced by Galderma.
Restylane	Medical uses	Restylane is most commonly used for lip enhancement (volume and contouring). It is used to diminish wrinkles and aging lines of the face such as the nasolabial folds (nose to mouth lines) and melomental folds (sad mouth corners). It may also be used for filling aging-related facial hollows and "orbital troughs" (under and around the eyes), as well as for cheek volume and contouring of the chin, lips and nose.
Restylane	Side effects	A treatment with a dermal filler like Restylane can cause some temporary bruising in addition to swelling and numbness for a few days. In rare cases there has been reports of lumps or granulomas. These side effects can be easily reversed with a treatment of hyaluronidase, which is an enzyme that speeds up the natural degradation of the injected hyaluronic acid filler.Several studies have been done to understand the long-term side effects of restylane and other hyaluronic acid fillers. In certain cases, the filler results in a granulomatous foreign body reaction.Even though side effects are rare Restylane should not be used in or near areas where there is or has been skin disease, inflammation or related conditions. Restylane has not been tested in pregnant or breast-feeding women.
Restylane	Contraindications	Restylane dermal fillers are generally considered safe, there are certain contraindications and safety rules that online licensed providers should be aware of before buying and injecting Restylane fillers.
Restylane	Contraindications	Contraindications for Restylane Dermal Fillers: Patients with a history of severe allergies or anaphylaxis should not receive Restylane fillers; Restylane fillers should not be used in patients who are allergic to hyaluronic acid or any of the other ingredients in the product; Patients with active infections or inflammation at the injection site should not receive Restylane fillers until the infection or inflammation has cleared up; Restylane fillers should not be used in patients who are pregnant or breastfeeding, as the safety of these products has not been established in these populations; Patients with bleeding disorders or taking blood-thinning medications should be closely monitored when receiving Restylane fillers.
Restylane	Treatment techniques	Most injectors inject the filler with a small needle under the skin. Numbing creams or injections decrease pain. A new way to use Restylane was described in the August 2007 issue of the Journal of Drugs in Dermatology by Dutch cosmetic doctor Tom van Eijk, whose "fern pattern" injection technique aims to restore dermal elasticity rather than to fill underneath the wrinkles.
Restylane	Advantages of this procedure	It is worth noting that mimic wrinkles are inextricably linked to the skin and affect the formation of fine wrinkles. Muscles woven into the dermis, contracting, tighten the skin, which provides mimic facial mobility. Their constant movement stretches the skin and leads to its sagging. This drug helps to restore weakened tissue and increase its volume without external damage.
Chinese whispers	Chinese whispers	Chinese whispers (some Commonwealth English), or telephone (American English and Canadian English), is an internationally popular children's game in which messages are whispered from person to person and then the original and final messages are compared. This sequential modification of information is called transmission chaining in the context of cultural evolution research, and is primarily used to identify the type of information that is more easily passed on from one person to another.Players form a line or circle, and the first player comes up with a message and whispers it to the ear of the second person in the line. The second player repeats the message to the third player, and so on. When the last player is reached, they announce the message they just heard, to the entire group. The first person then compares the original message with the final version. Although the objective is to pass around the message without it becoming garbled along the way, part of the enjoyment is that, regardless, this usually ends up happening. Errors typically accumulate in the retellings, so the statement announced by the last player differs significantly from that of the first player, usually with amusing or humorous effect. Reasons for changes include anxiousness or impatience, erroneous corrections, or the difficult-to-understand mechanism of whispering.
Chinese whispers	Chinese whispers	The game is often played by children as a party game or on the playground. It is often invoked as a metaphor for cumulative error, especially the inaccuracies as rumours or gossip spread, or, more generally, for the unreliability of typical human recollection.
Chinese whispers	Etymology	United Kingdom, Australian, and New Zealand usage In the UK, Australia and New Zealand, the game is typically called "Chinese whispers"; in the UK, this is documented from 1964.Various reasons have been suggested for naming the game after the Chinese, but there is no concrete explanation. One suggested reason is a widespread British fascination with Chinese culture in the 18th and 19th centuries during the Enlightenment. Another theory posits that the game's name stems from the supposed confused messages created when a message was passed verbally from tower to tower along the Great Wall of China.Critics who focus on Western use of the word Chinese as denoting "confusion" and "incomprehensibility" look to the earliest contacts between Europeans and Chinese people in the 17th century, attributing it to a supposed inability on the part of Europeans to understand China's culture and worldview. In this view, using the phrase "Chinese whispers" is taken as evidence of a belief that the Chinese language itself is not understandable. Yunte Huang, a professor of English at the University of California, Santa Barbara, has said that: "Indicating inaccurately transmitted information, the expression 'Chinese Whispers' carries with it a sense of paranoia caused by espionage, counterespionage, Red Scare, and other war games, real or imaginary, cold or hot." Usage of the term has been defended as being similar to other expressions such as "It's all Greek to me" and "Double Dutch".
Chinese whispers	Etymology	Alternative names As the game is popular among children worldwide, it is also known under various other names depending on locality, such as Russian scandal, whisper down the lane, broken telephone, operator, grapevine, gossip, secret message, the messenger game, and pass the message, among others. In Turkey, this game is called kulaktan kulağa, which means "from (one) ear to (another) ear". In France, it is called téléphone arabe ("Arabic telephone") or téléphone sans fil ("wireless telephone"). In Germany the game is known as Stille Post ("quiet mail"). In Poland it is called głuchy telefon, meaning "deaf telephone". In Medici-era Florence it was called the "game of the ear".The game has also been known in English as Russian Scandal, Russian Gossip and Russian Telephone.In North America, the game is known under the name telephone. Alternative names used in the United States include Broken Telephone, Gossip, and Rumors. This North American name is followed in a number of languages where the game is known by the local language's equivalent of "broken telephone", such in Malaysia as telefon rosak, in Israel as telefon shavur (טלפון שבור), in Finland as rikkinäinen puhelin, and in Greece as halasmeno tilefono (χαλασμένο τηλέφωνο).
Chinese whispers	Game	The game has no winner: the entertainment comes from comparing the original and final messages. Intermediate messages may also be compared; some messages will become unrecognizable after only a few steps.
Chinese whispers	Game	As well as providing amusement, the game can have educational value. It shows how easily information can become corrupted by indirect communication. The game has been used in schools to simulate the spread of gossip and its possible harmful effects. It can also be used to teach young children to moderate the volume of their voice, and how to listen attentively; in this case, a game is a success if the message is transmitted accurately with each child whispering rather than shouting. It can also be used for older or adult learners of a foreign language, where the challenge of speaking comprehensibly, and understanding, is more difficult because of the low volume, and hence a greater mastery of the fine points of pronunciation is required.
Chinese whispers	Notable games	In 2008 1,330 children and celebrities set a world record for the game of Chinese Whispers involving the most people. The game was held at the Emirates Stadium in London and lasted two hours and four minutes. Starting with "together we will make a world of difference", the phrase morphed into "we're setting a record" part way down the chain, and by the end had become simply "haaaaa". The previous record, set in 2006 by the Cycling Club of Chengdu, China, had involved 1,083 people.In 2017 a new world record was set for the largest game of Chinese Whispers in terms of the number of participants by school-children in Tauranga, New Zealand. The chain involved 1,763 school children and other individuals and was held as part of Hearing Week 2017. The starting phrase was "Turn it down". As of 2022 this remained the world record for the largest game of Chinese Whispers by number of participants according to the Guinness Book of Records.In 2012 a global game of Chinese Whispers was played spanning 237 individuals speaking seven different languages. Beginning in St Kilda Library in Melbourne, Australia, the starting phrase "Life must be lived as play" (a paraphrase of Plato) had become "He bites snails" by the time the game reached its end in Alaska 26 hours later. In 2013, the Global Gossip Game had 840 participants and travelled to all 7 continents.
Chinese whispers	Variants	A variant of Chinese Whispers is called Rumors. In this version of the game, when players transfer the message, they deliberately change one or two words of the phrase (often to something more humorous than the previous message). Intermediate messages can be compared. There is a second derivative variant, no less popular than Rumors, known as Mahjong Secrets (UK), or Broken Telephone (US), where the objective is to receive the message from the whisperer and whisper to the next participant the first word or phrase that comes to mind in association with what was heard. At the end, the final phrase is compared to the first in front of all participants.
Chinese whispers	Variants	The pen-and-paper game Telephone Pictionary (also known as Eat Poop You Cat) is played by alternately writing and illustrating captions, the paper being folded so that each player can only see the previous participant's contribution. The game was first implemented online by Broken Picture Telephone in early 2007. Following the success of Broken Picture Telephone, commercial boardgame versions Telestrations and Cranium Scribblish were released two years later in 2009. Drawception, and other websites, also arrived in 2009.
Chinese whispers	Variants	A translation relay is a variant in which the first player produces a text in a given language, together with a basic guide to understanding, which includes a lexicon, an interlinear gloss, possibly a list of grammatical morphemes, comments on the meaning of difficult words, etc. (everything except an actual translation). The text is passed on to the following player, who tries to make sense of it and casts it into their language of choice, then repeating the procedure, and so on. Each player only knows the translation done by his immediate predecessor, but customarily the relay master or mistress collects all of them. The relay ends when the last player returns the translation to the beginning player.
Chinese whispers	Variants	Another variant of Chinese whispers is shown on Ellen's Game of Games under the name of Say Whaaat?. However, the difference is that the four players will be wearing earmuffs; therefore the players have to read their lips. A party game variant of telephone known as "wordpass" involves saying words out loud and saying a related word, until a word is repeated.
Chinese whispers	As a metaphor	Chinese whispers is used in a number of fields as a metaphor for imperfect data transmission over multiple iterations. For example the British zoologist Mark Ridley in his book Mendel's demon used Chinese Whispers as an analogy for the imperfect transmission of genetic information across multiple generations. In another example, Richard Dawkins used Chinese Whispers as a metaphor for infidelity in memetic replication, referring specifically to children trying to reproduce drawing of a Chinese junk in his essay Chinese Junk and Chinese Whispers. It was used in the movie Tár to represent gossip circling within an orchestra.
Huntington's disease in popular culture	Huntington's disease in popular culture	Huntington's disease has been shown in numerous formats, more so as awareness of the condition has increased. Here is a list of references to it in popular culture;
Huntington's disease in popular culture	Books	Ann Brashares's 2011 novel Sisterhood Everlasting (later found one of the four "sisters", Tibby Rollins, had HD) James S. A. Corey's 2015 novella The Vital Abyss, part of The Expanse book series (reveals the backstory of the former Protogen researcher Paolo Cortázar, whose mother was diagnosed with "Type C Huntington's" in his adolescence, which was the primary impetus for his becoming a research scientist).
Huntington's disease in popular culture	Books	Kathy Reichs' 2020 novel A Conspiracy of Bones Lisa Genova's 2015 novel Inside the O'Briens (relates the slow development of HD in the main character, a Boston police officer, and its effects on his identity, work, and family) Pål Johan Karlsen's 2002 novel Daimler (main character Daniel Grimsgaard is affected). Joe Klein's Woody Guthrie: A Life: The book discloses the effects of the disorder in both Woody Guthrie and his mother. Ian McEwan's 2005 novel Saturday. The character of Baxter is negatively portrayed in his affliction. Nick O'Donohoe's Crossroads books (BJ Vaughan has HD). Ruth Rendell, writing as Barbara Vine, 1989 British novel The House of Stairs (main character Elizabeth Vetch is at risk). Robert J. Sawyer's 1997 novel Frameshift (main character Pierre Tardivel). Steven T. Seagle's autobiographical 2004 graphic novel It's a Bird... features the author coming to grips with the presence of HD in his family. Dorothy Norvell Snyder's semi-autobiographical 1980 novel Heirloom: A Novel, How One Family Lived with One of Life's Cruelest Diseases—Huntington's. Mary Helen Specht's 2015 novel Migratory Animals. Jacqueline Susann's 1966 novel Valley of the Dolls (night club singer Tony Polar). Diane Tullson's 2001 novel Saving Jasey (Trist, Jasey and their grandfather). Kurt Vonnegut's 1985 novel Galapagos. Nancy Werlin's 2004 novel Double Helix (Ava Samuels (mother of the protagonist), Kayla Matheson and others). Walter Jon Williams' 1986 cyberpunk novel Hardwired features a genetically engineered, virally-transmitted version of Huntington's. Charlotte Raven's 2021 memoir ‘’Patient 1’’ which describes her becoming affected by Huntington's and participating in a clinical trial of the drug tominersen.
Huntington's disease in popular culture	Films	In the 1967 film Valley of the Dolls, Tony Polar, the singer married to Jennifer North, has Huntington's Chorea. Arlo Guthrie's 1969 film Alice's Restaurant, which depicts Guthrie's father Woody suffering from what was then called "Huntington's Chorea", and features numerous mentions of the condition by the younger Guthrie to his peers and the draft board's medical staff.
Huntington's disease in popular culture	Films	Broken Elf, a 2010 documentary by Robert Ciesla featuring Jukka, an alcoholic man with advanced Huntington's disease. Screened at Reikäreuna Film Festival, September 7, 2013 Do You Really Want to Know?, a 2013 documentary by John Zaritsky featuring Huntington's disease researcher Jeff Carroll Huntington's Dance a 2014 release by Chris Furbee an 18-year-long journey with a family affected by Huntington's Disease. World Premiere at Slamdance, January 19, 2014 The Lion's Mouth Opens, a 2014 documentary by Lucy Walker (director) featuring filmmaker Marianna Palka The Inheritance, a 2014 documentary film The Faith of Anna Waters, a 2016 horror movie released in the U.S. as The Offering, depicts a crime reporter whose sister dies of Huntington's and whose niece inherits it ... as does, eventually, she as well.
Huntington's disease in popular culture	Television	Sammy Davis Jr. in the 1970 episode "Song of Willie" from the series The Mod Squad Dr Ethan Hardy in BBC drama series Casualty. Joseph Campanella in the 1970 episode "Dance to No Music" from the series Marcus Welby, M.D. Edward Dunglass, the goth teen from the Australian soap opera Home and Away (1999–2000) The 2018 thriller series "Philharmonia" has the mother and grandmother of the central protagonist, Helene Barizet, being victims of Huntington's disease. Thus questions about her sanity play a part in the plot. Dr. Samantha O'Hara from the Australian medical drama All Saints Hannah's father from the American drama Everwood, as revealed in the episode "Need to Know" (3x10) Characters in the episodes "Pad'ar" (3x08) and "the Sins of the Father" (4x03) of Gene Roddenberry's Earth: Final Conflict. Angie Padgett from the episode "In Which Charlotte Goes Down the Rabbit Hole" (1x06) of Private Practice. Dr. Remy "Thirteen" Hadley, one of the doctors who joins House's second team on House. Her mother died of Huntington's disease when she was a child. During the season 4 finale, Hadley discovers she also has the disease. In season 7 it is revealed she assisted her brother in killing himself when his Huntington's symptoms got too bad. An episode of the BBC drama Waterloo Road In the season 8 finale of Scrubs, a woman is diagnosed with Huntington's disease, and her son has to make the decision to find out whether or not he also has the condition. In The Bold Ones: The New Doctors, Dr. Paul Hunter counsels a pregnant woman whose irritable husband is found to have the disease. After explaining the 50-50 odds, he advises her to have the baby, trusting in the advance of medical science.
Huntington's disease in popular culture	Television	The episode "Second Sight" of the third season of Without a Trace ends with the revelation that the disappearance and kidnapping of the girl Malone's team was searching for, was in truth an elaborate set-up so that she could return to her estranged gypsy family – a decision she took after discovering she had the disease, inherited from her grandmother. Knowing she just wants to live the time she has left with her parents, Malone lets her and her father go.
Huntington's disease in popular culture	Television	In a season 4 episode of Breaking Bad, Walter White shares a childhood memory of his father who was diagnosed with Huntington's disease with his son. In the season 3 premiere episode "Fear" (aired September 29, 2013) of the ABC series Revenge, the character of Conrad Grayson, played by Henry Czerny, is seen passing out during a political speech. In the very next scene, a doctor informs him that he has Huntington's disease. "Fighting Huntington's Disease", a 2010 episode of the CBC News Network documentary series Connect with Mark Kelley, depicted the life and work of Huntington's disease researcher and advocate Dr Jeff Carroll, himself a carrier of the genetic mutation that causes Huntington's disease. The episode was nominated for a Gemini award for 'Best Lifestyle/Practical Information Segment.
Huntington's disease in popular culture	Television	David Collins was a fictional character in the BBC soap opera EastEnders in 2004. He was played by Dan Milne. David was the husband of Jane Collins. He had Huntington's disease and lived in a hospice. Jane kept David a secret from her new boss Ian, but one day Ian demanded to know why she was infrequent with her work, and Jane took him to meet David. Ian regularly visited him until David died shortly after Christmas 2004, leaving Jane heartbroken.
Huntington's disease in popular culture	Television	In the second episode of the second season of BBC's Ripper Street, HD (referred to as Huntington's Chorea) and the possibility of it being passed on in a prominent family are the cause of the death of a woman and the stealing of her child by the patriarch of the family. His son had been diagnosed with HD and is the father of the stolen child. The patriarch took the child to make sure that HD ended with his son, his intention being to kill the child if signs of the disorder manifested themselves.
Huntington's disease in popular culture	Television	Season 2, Episode 3 "Drop Dead Diva", Gloria Rubens plays a professor that petitions the court to be cryogenically frozen before the disease causes too much irreversible damage. Season 7, Episode 3 Call the Midwife, An expectant mother is diagnosed with the degenerative neurological disorder Huntington's disease, and quickly deteriorates to the point where she is unable to look after her children. Her eldest daughter too is diagnosed, and placed in a hospice. Season 2, Episode 15 The Rookie, Colin has Huntington's disease and Rachel may have it too but she's refused to get tested because she doesn't want to know. Colin thinks that because Bradford is committed to the job, he'll never be able to take care of Rachel the way she may need one day. In the Amazon Prime series ZeroZeroZero Chris Lynwood has Huntington's disease. The show reveals that Chris and his older sister Emma (played by Andrea Riseborough) lost their mother to the disease, which the now-30-year-old Chris inherited from her. The 2020 Ken Burns documentary The Gene: An Intimate History discussed Huntington's disease, including the discovery of the gene and interviews with Nancy Wexler and other prominent scientists involved in Huntington's disease research and drug development. In the Australian soap opera Neighbours Chloe Brennan and her mother Fay Brennan both have Huntington's. Fay died due to complications caused by the disease in episode 8573 in 2021. Season 1, Episode 8 Pooch Perfect Contestant Corina reveals she has Huntington's disease. In Season 58, Episode 163 of the soap opera General Hospital, Britt Westbourne finds out she may have Huntington's disease. In Season 2, Episode 3 of the science fiction show The Expanse, it is revealed that Paolo Cortázar's mother died from Huntington's disease.
Huntington's disease in popular culture	Television	In Season 3 (1995), Episode 7 (Family Ties) of the British TV show Peak Practice, Jack becomes involved in the plight of Nancy who has Huntington's disease. He is concerned about her when she tries to take her life. Jack tracks down her sister who hasn't visited Nancy for years because she is scared she too may have the illness. Jack is alarmed when Nancy's sister reveals that Nancy has a son who doesn't even know he's at risk from having Huntington's disease.
Huntington's disease in popular culture	Television	In Season 6 (1988), Episode 129 (Curtains) of the TV show St. Elsewhere, Dr. Morrison counsels a family about genetic testing and Huntington's disease. In Season 8 (1997), Episode 7 (Out of the Blue) of the TV show Baywatch, Mitch tries to get Jordan to meet her real biological mother on a fishing outing, who's dying from a brain disorder and thinks the problem is hereditary. It turns out to be Huntington's Disease. In Season 3 (2002), Episode 6 (Old Wounds) of the TV show The District, Nancy is diagnosed with Huntington's disease after falling from a fire escape and having a concussion while chasing a criminal.
Huntington's disease in popular culture	Television	In Season 2 (2009), Episode 1 (Gilted Lily) of the TV show In Plain Sight, Lily is laid out serenely on the bed. Her note says she found her birth father years ago, and discovered he died of Huntington's Disease, that she started showing symptoms a few months ago and that she wants her kids to remember her as she was.
Huntington's disease in popular culture	Television	In the Barbara Walter's ABC News Special (1990) A Perfect Baby, Walters shows the ravages of Huntington's disease, which does not appear until middle age and then destroys its victims both physically and mentally. In Season 7 (2010), Episode 4 (Can't Fight Biology) of the TV show Grey's Anatomy, Meredith is treating a woman, Lila, who eventually reveals that she has Huntington's Disease. In Season 1 (2022), Episode 1 of the FX Cable TV series The Old Man, Dan Chase played by Jeff Bridges is a widower whose wife died from Huntington's Disease. In Season 4 (2022), Episode 12 (The Long Goodbye) of the Netflix series Virgin River, Denny reveals to Lizzie that he is suffering from Huntington's disease which is the true reason he needs the medication Klonopin — which helps to ease muscle tremors, rigidity and anxiety in Huntington's patients. In Season 2 (2022), Episode 16 (Champagne Problems) of the CW TV series Walker, Cassie tells Ben that after they learned Lucas had Huntington's (disease), she couldn’t handle it. In Season 3 (2018), Episode 3 (Snakeskin) of the Australian TV series Wanted, Lola and Chelsea take refuge with an eccentric loner. Lola struggles with her past, while Chelsea hides her Huntington's symptoms. Unbeknown to them, both Brady and Maxine close in. In Season 14 (2017), Episode 12 (Off the Grid) of the CBS TV series NCIS, Bodie is revealed to have been suffering from Huntington's disease. Given the hereditary nature of the disease, it is likely that Ramsay also suffers from it. The team uses that, along with cell phone data, to track down Ramsay.
Huntington's disease in popular culture	Television	In Season 6 (2000), Episode 16 (Viable Options) of the NBC TV series ER, Dr. Mark Greene tells a patient that he has Huntington’s disease and that it’s genetic and that there is no cure. He also says that that might be why his father committed suicide. The patient worries that he might have passed on this trait to his daughter.
Huntington's disease in popular culture	Television	In Season 9 (2002), Episode 3 (Insurrection) of the NBC TV series ER, a late-stage Huntington's disease patient is rushed into the Emergency Room of a hospital. During the chaos caused when Dr. John Carter leads a walk-out to protest unsafe working conditions, the man's mother disconnects his ventilator so that he can die in peace. Dr. Susan Lewis figures out what the mother did but protects her.
Huntington's disease in popular culture	Television	In Season 4 (2018), Episode 5 (What You Don't Know) of the NBC TV series Chicago Med, Dr. Charles identifies Keith's illness as Huntington's. Keith admits the diagnosis, telling Daniel that there is no cure and that he wants to die before his Huntington's progresses further. In Season 7 (1993), Episode 11 (Bare Witness) of the NBC TV series L.A. Law, Gwen tells Daniel that she had a blood test for Huntington's chorea. That it's hereditary, hidden in midlife, causing lack of coordination, then mental deterioration and finally death. And that there's a 50/50 chance, she doesn't have it. In Season 4 (2023), Episode 15 (Donors) of the Fox TV series 9-1-1: Lone Star, Robert reveals that he was diagnosed with Huntington's Disease.
Huntington's disease in popular culture	Video games	In the "Cold, Cold Heart" DLC for Batman: Arkham Origins, it establishes the cause of Nora Fries' terminal illness to be Huntington's chorea.
Huntington's disease in popular culture	Radio	Mind Matters: RTÉ Radio 1 programme on Huntington's Disease, featuring a family affected from Ireland. Huntington's disease - two part ABC Radio National "The Health Report" program on the disorder examines the effects on families and the challenges it presents for the health system and society. (part 2) Dr. Gilmer and Mr. Hyde - This American Life report on a man imprisoned for life for a murder committed while undiagnosed with Huntington's disease. "What Are You Doing For The Test of Your Life" [2] - This American Life segment from the episode titled "It Says So Right Here": a report on a woman who has several family members who either have had or have been tested positive for Huntington's Disease and is going through the process of being tested.
Zebra (pen manufacturer)	Zebra (pen manufacturer)	Zebra Co., Ltd. (ゼブラ株式会社, Zebura Kabushiki gaisha) is a Japanese manufacturer of writing instruments, established in 1914 by Tokumatsu Ishikawa.The company sells a wide range of writing implements through retail stores, wholesalers and mail order. Zebra offers a line of writing instruments that include fountain, ballpoint, brush and gel pens, markers, highlighters and mechanical pencils.
Zebra (pen manufacturer)	History	Tokumatsu Ishikawa had begun to produce home-made nibs in 1897, until he established its own business in 1914, registering the name "Zebra" as a trademark. Ishikawa thought Zebra was an appropriate name because his goal was to build a business culture that resembled a family and zebras have a strong herding instinct. Zebra stripes resembling calligraphic pen strokes may also have been a reason for the name.In 1945, the Zebra facilities were destroyed during a bomb attack in World War II, but those would be reconstructed during the 1950s. In 1959 Zebra launched its first ballpoint pen manufactured. Four years later, the company renamed "Zebra Co., Ltd", with Hideaki Ishikawa becoming president of the firm.During the 1970s, Zebra marketed its first lines of markers, including brush-tip models, opening a new factory in Tokyo (1979). Zebra opened a subsidiary in the United States (1982). The 1990s and 2000s decade came with new subsidiaries in Canada, Indonesia, China, Mexico, and the United Kingdom.
Zebra (pen manufacturer)	Products	Zebra's line of pens and pencils include "The Original" F-301 and the M-301, which have stainless steel barrels and textured grips. Other product lines include Blen, Surari, Filare (emulsion ink ballpoint pens); Airfit, Z-Grip (ballpoint pen); Sarasa, Sarasa Dry (gel pens); Sharbo (multi-pens); CLiCKART (water-based coloring markers); DelGuard, Tect 2Way (mechanical pencils); Zensations (art products), Mildliner (double ended creative markers), Zebrite (double ended highlighters), and Zazzle (liquid highlighters). Zebra products are available across the US, Canada, Mexico, UK, Singapore, Korea, and Japan.
Zebra (pen manufacturer)	Products	Z-Grip In 2017, the Z-Grip line of retractable gel pens was transitioned to low viscosity ink, aka advanced ink. The benefits of the new formula, in addition to a smoother writing experience, was more vibrant colors and an option to create more nuanced hues.
Zebra (pen manufacturer)	Products	Steel The Steel line of pens follows a good, better, best hierarchy; 3-series, 4-series, and 7-series respectively. The 301 series is characterized by stainless steel shafts and hardened plastic grips. The 401 has the same stainless steel shaft with a rubber grip. Finally, the flagship pen, the 701 has a knurled grip and is completely stainless steel. A cross section of these barrel styles reflect different ink types. For example, the 3-series barrel is available in ballpoint, gel, mechanical pencil, fountain pen, highlighter, and rollerball pen. All Zebra stainless steel products are refillable, including leads and mechanical pencil erasers.
Zebra (pen manufacturer)	Products	Sarasa Dry The company transitioned all their plastic gel pens from different brands and consolidated under one name, Sarasa Dry. All the former products were reformulated to feature Zebra's award-winning Rapid Dry Ink technology, which was third party laboratory, tested and proven to be as fast or faster drying than the competition on a variety of surfaces and dries in less than a second on most surfaces. The assortment, X1, X10, X20, and X30, reflect different barrel styles to accommodate most consumer preferences.
Zebra (pen manufacturer)	Products	Surari Range of "emulsion-ink" hybrid ink oil-based ballpoint pens, similar to Uni's Jetstream, Pentel's Vicuna and Pilot's Acroball.
Zebra (pen manufacturer)	Products	Zensations Zebra entered the art and activity space with the launch of their Zensations brand of products, geared towards new and amateur artists looking for a slightly higher quality than products solely created for children. The brand encompasses technical pens and pencils, refillable colored mechanical pencils, fineliner markers, calligraphy pens, brush pens (black and colors), and more. Line extensions are developed periodically to refresh the line.
Zebra (pen manufacturer)	Products	DelGuard A mechanism employed in the DelGuard system developed by Zebra, causes the lead sleeve in a mechanical pencil to extend outward when excessive pressure is applied at an angle. When excess vertical pressure is applied on the lead, the lead is automatically retracted inwards. Thus, the lead is protected (within certain limits) in both cases. In Japan, 0.3 and 0.7 versions of the DelGuard is available alongside the 0.5 version, whereas in the US, only the 0.5 version is available.
Zebra (pen manufacturer)	Products	Sharbo Sharbo is a line of multifunction pens. A pen may contain one or more ink refills plus a mechanical pencil component. Examples are Sharbo X and SK-Sharbo+1.
Quadratic field	Quadratic field	In algebraic number theory, a quadratic field is an algebraic number field of degree two over Q , the rational numbers.
Quadratic field	Quadratic field	Every such quadratic field is some Q(d) where d is a (uniquely defined) square-free integer different from 0 and 1 . If d>0 , the corresponding quadratic field is called a real quadratic field, and, if d<0 , it is called an imaginary quadratic field or a complex quadratic field, corresponding to whether or not it is a subfield of the field of the real numbers.
Quadratic field	Quadratic field	Quadratic fields have been studied in great depth, initially as part of the theory of binary quadratic forms. There remain some unsolved problems. The class number problem is particularly important.
Quadratic field	Discriminant	For a nonzero square free integer d , the discriminant of the quadratic field K=Q(d) is d if d is congruent to 1 modulo 4 , and otherwise 4d . For example, if d is −1 , then K is the field of Gaussian rationals and the discriminant is −4 . The reason for such a distinction is that the ring of integers of K is generated by (1+d)/2 in the first case and by d in the second case.
Quadratic field	Discriminant	The set of discriminants of quadratic fields is exactly the set of fundamental discriminants.
Quadratic field	Prime factorization into ideals	Any prime number p gives rise to an ideal pOK in the ring of integers OK of a quadratic field K . In line with general theory of splitting of prime ideals in Galois extensions, this may be p is inert (p) is a prime ideal.
Quadratic field	Prime factorization into ideals	The quotient ring is the finite field with p2 elements: OK/pOK=Fp2 .p splits (p) is a product of two distinct prime ideals of OK The quotient ring is the product OK/pOK=Fp×Fp .p is ramified (p) is the square of a prime ideal of OK The quotient ring contains non-zero nilpotent elements.The third case happens if and only if p divides the discriminant D . The first and second cases occur when the Kronecker symbol (D/p) equals −1 and +1 , respectively. For example, if p is an odd prime not dividing D , then p splits if and only if D is congruent to a square modulo p . The first two cases are, in a certain sense, equally likely to occur as p runs through the primes—see Chebotarev density theorem.The law of quadratic reciprocity implies that the splitting behaviour of a prime p in a quadratic field depends only on p modulo D , where D is the field discriminant.
Quadratic field	Class group	Determining the class group of a quadratic field extension can be accomplished using Minkowski's bound and the Kronecker symbol because of the finiteness of the class group. A quadratic field K=Q(d) has discriminant so the Minkowski bound is Then, the ideal class group is generated by the prime ideals whose norm is less than MK . This can be done by looking at the decomposition of the ideals (p) for p∈Z prime where \|p\|<Mk.
Quadratic field	Class group	page 72 These decompositions can be found using the Dedekind–Kummer theorem.
Quadratic field	Quadratic subfields of cyclotomic fields	The quadratic subfield of the prime cyclotomic field A classical example of the construction of a quadratic field is to take the unique quadratic field inside the cyclotomic field generated by a primitive p th root of unity, with p an odd prime number. The uniqueness is a consequence of Galois theory, there being a unique subgroup of index 2 in the Galois group over Q . As explained at Gaussian period, the discriminant of the quadratic field is p for p=4n+1 and −p for p=4n+3 . This can also be predicted from enough ramification theory. In fact, p is the only prime that ramifies in the cyclotomic field, so p is the only prime that can divide the quadratic field discriminant. That rules out the 'other' discriminants −4p and 4p in the respective cases.
Quadratic field	Quadratic subfields of cyclotomic fields	Other cyclotomic fields If one takes the other cyclotomic fields, they have Galois groups with extra 2 -torsion, so contain at least three quadratic fields. In general a quadratic field of field discriminant D can be obtained as a subfield of a cyclotomic field of D th roots of unity. This expresses the fact that the conductor of a quadratic field is the absolute value of its discriminant, a special case of the conductor-discriminant formula.
Quadratic field	Orders of quadratic number fields of small discriminant	The following table shows some orders of small discriminant of quadratic fields. The maximal order of an algebraic number field is its ring of integers, and the discriminant of the maximal order is the discriminant of the field. The discriminant of a non-maximal order is the product of the discriminant of the corresponding maximal order by the square of the determinant of the matrix that expresses a basis of the non-maximal order over a basis of the maximal order. All these discriminants may be defined by the formula of Discriminant of an algebraic number field § Definition.
Quadratic field	Orders of quadratic number fields of small discriminant	For real quadratic integer rings, the ideal class number, which measures the failure of unique factorization, is given in OEIS A003649; for the imaginary case, they are given in OEIS A000924. Some of these examples are listed in Artin, Algebra (2nd ed.), §13.8.
Annex	Annex	Annex or annexe may refer to:
Annex	Places	The Annex, a neighbourhood in downtown Toronto, Ontario, Canada The Annex (New Haven), a neighborhood of New Haven, Connecticut, US Annex, Oregon, a census-designated place in the US
Annex	Other uses	Annex (comics), a Marvel Comics character Addendum or appendix at the end of a document The Annex, Grand Cayman, a football ground in George Town, Cayman Islands "Annex", B-side of the 1980 Orchestral Manoeuvres in the Dark single "Enola Gay" Annex, an early name for the Bangkok Adventist Hospital "Annex" is a place in oregon
Quantitative proteomics	Quantitative proteomics	Quantitative proteomics is an analytical chemistry technique for determining the amount of proteins in a sample. The methods for protein identification are identical to those used in general (i.e. qualitative) proteomics, but include quantification as an additional dimension. Rather than just providing lists of proteins identified in a certain sample, quantitative proteomics yields information about the physiological differences between two biological samples. For example, this approach can be used to compare samples from healthy and diseased patients. Quantitative proteomics is mainly performed by two-dimensional gel electrophoresis (2-DE), preparative one-dimensional gel electrophoresis, or mass spectrometry (MS). However, a recent developed method of quantitative dot blot (QDB) analysis is able to measure both the absolute and relative quantity of an individual proteins in the sample in high throughput format, thus open a new direction for proteomic research. In contrast to 2-DE, which requires MS for the downstream protein identification, MS technology can identify and quantify the changes.
Quantitative proteomics	Quantification using spectrophotometry	The concentration of a certain protein in a sample may be determined using spectrophotometric procedures. The concentration of a protein can be determined by measuring the OD at 280 nm on a spectrophotometer, which can be used with a standard curve assay to quantify the presence of tryptophan, tyrosine, and phenylalanine. However, this method is not the most accurate because the composition of proteins can vary greatly and this method would not be able to quantify proteins that do not contain the aforementioned amino acids. This method is also inaccurate due to the possibility of nucleic acid contamination. Other more accurate spectrophotometric procedures for protein quantification include the Biuret, Lowry, BCA, and Bradford methods. An alternative method for label free protein quantification in clear liquid is cuvette-based SPR technique, that simultaneously measures the refractive index ranging 1.0 to 1.6 nD and concentration of the protein ranging from 0.5 µL to 2 mL in volume. This system consists of the calibrated optical filter with very high angular resolution and the interaction of light with this crystal forms a resonance at a wavelength which correlates to concentration and refractive index near the crystal.
Quantitative proteomics	Quantification using two dimensional electrophoresis	Two-dimensional gel electrophoresis (2-DE) represents one of the main technologies for quantitative proteomics with advantages and disadvantages. 2-DE provides information about the protein quantity, charge, and mass of the intact protein. It has limitations for the analysis of proteins larger than 150 kDa or smaller than 5kDa and low solubility proteins. Quantitative MS has higher sensitivity but does not provide information about the intact protein.
Quantitative proteomics	Quantification using two dimensional electrophoresis	Classical 2-DE based on post-electrophoretic dye staining has limitations: at least three technical replicates are required to verify the reproducibility. Difference gel electrophoresis (DIGE) uses fluorescence-based labeling of the proteins prior to separation has increased the precision of quantification as well as the sensitivity in the protein detection. Therefore, DIGE represents the current main approach for the 2-DE based study of proteomes.
Quantitative proteomics	Quantification using mass spectrometry	Mass spectrometry (MS) represents one of the main technologies for quantitative proteomics with advantages and disadvantages. Quantitative MS has higher sensitivity but can provide only limited information about the intact protein. Quantitative MS has been used for both discovery and targeted proteomic analysis to understand global proteomic dynamics in populations of cells (bulk analysis) or in individual cells (single-cell analysis).Early approaches developed in the 1990s applied isotope-coded affinity tags (ICAT), which uses two reagents with heavy and light isotopes, respectively, and a biotin affinity tag to modify cysteine containing peptides. This technology has been used to label whole Saccharomyces cerevisiae cells, and, in conjunction with mass spectrometry, helped lay the foundation of quantitative proteomics. This approach has been superseded by isobaric mass tags, which are also used for single-cell protein analysis.
Quantitative proteomics	Quantification using mass spectrometry	Relative and absolute quantification Mass spectrometry is not inherently quantitative because of differences in the ionization efficiency and/or detectability of the many peptides in a given sample, which has sparked the development of methods to determine relative and absolute abundance of proteins in samples. The intensity of a peak in a mass spectrum is not a good indicator of the amount of the analyte in the sample, although differences in peak intensity of the same analyte between multiple samples accurately reflect relative differences in its abundance.
Quantitative proteomics	Quantification using mass spectrometry	Stable isotope labeling in mass spectrometry Stable isotope labels An approach for relative quantification that is more costly and time-consuming, though less sensitive to experimental bias than label-free quantification, entails labeling the samples with stable isotope labels that allow the mass spectrometer to distinguish between identical proteins in separate samples. One type of label, isotopic tags, consist of stable isotopes incorporated into protein crosslinkers that causes a known mass shift of the labeled protein or peptide in the mass spectrum. Differentially labeled samples are combined and analyzed together, and the differences in the peak intensities of the isotope pairs accurately reflect difference in the abundance of the corresponding proteins.
Quantitative proteomics	Quantification using mass spectrometry	Absolute proteomic quantification using isotopic peptides entails spiking known concentrations of synthetic, heavy isotopologues of target peptides into an experimental sample and then performing LC-MS/MS. As with relative quantification using isotopic labels, peptides of equal chemistry co-elute and are analyzed by MS simultaneously. Unlike relative quantification, though, the abundance of the target peptide in the experimental sample is compared to that of the heavy peptide and back-calculated to the initial concentration of the standard using a pre-determined standard curve to yield the absolute quantification of the target peptide.
Quantitative proteomics	Quantification using mass spectrometry	Relative quantification methods include isotope-coded affinity tags (ICAT), isobaric labeling (tandem mass tags (TMT) and isobaric tags for relative and absolute quantification (iTRAQ)), label-free quantification metal-coded tags (MeCAT), N-terminal labelling, stable isotope labeling with amino acids in cell culture (SILAC), and terminal amine isotopic labeling of substrates (TAILS). A mathematically rigorous approach that integrates peptide intensities and peptide-measurement agreement into confidence intervals for protein ratios has emerged.Absolute quantification is performed using selected reaction monitoring (SRM).
Quantitative proteomics	Quantification using mass spectrometry	Metal-coded tags Metal-coded tags (MeCAT) method is based on chemical labeling, but rather than using stable isotopes, different lanthanide ions in macrocyclic complexes are used. The quantitative information comes from inductively coupled plasma MS measurements of the labeled peptides. MeCAT can be used in combination with elemental mass spectrometry ICP-MS allowing first-time absolute quantification of the metal bound by MeCAT reagent to a protein or biomolecule. Thus it is possible to determine the absolute amount of protein down to attomole range using external calibration by metal standard solution. It is compatible to protein separation by 2D electrophoresis and chromatography in multiplex experiments. Protein identification and relative quantification can be performed by MALDI-MS/MS and ESI-MS/MS.
Quantitative proteomics	Quantification using mass spectrometry	Mass spectrometers have a limited capacity to detect low-abundance peptides in samples with a high dynamic range. The limited duty cycle of mass spectrometers also restricts the collision rate, resulting in an undersampling. Sample preparation protocols represent sources of experimental bias.
Quantitative proteomics	Quantification using mass spectrometry	Stable isotope labeling with amino acids in cell culture Stable isotope labeling with amino acids in cell culture (SILAC) is a method that involves metabolic incorporation of “heavy” C- or N-labeled amino acids into proteins followed by MS analysis. SILAC requires growing cells in specialized media supplemented with light or heavy forms of essential amino acids, lysine or arginine. One cell population is grown in media containing light amino acids while the experimental condition is grown in the presence of heavy amino acids. The heavy and light amino acids are incorporated into proteins through cellular protein synthesis. Following cell lysis, equal amounts of protein from both conditions are combined and subjected to proteotypic digestion. Arginine and lysine amino acids were chosen, because trypsin, the predominant enzyme used to generate proteotypic peptides for MS analysis, cleaves at the C-terminus of lysine and arginine. Following digestion with trypsin, all the tryptic peptides from cells grown in SILAC media would have at least one labeled amino acid, resulting in a constant mass shift from the labeled sample over non-labeled. Because the peptides containing heavy and light amino acids are chemically identical, they co-elute during reverse-phase column fractionation and are detected simultaneously during MS analysis. The relative protein abundance is determined by the relative peak intensities of the isotopically distinct peptides.
Quantitative proteomics	Quantification using mass spectrometry	Traditionally the level of multiplexing in SILAC was limited due to the number of SILAC isotopes available. Recently, a new technique called NeuCode SILAC, has augmented the level of multiplexing achievable with metabolic labeling (up to 4). The NeuCode amino acid method is similar to SILAC but differs in that the labeling only utilizes heavy amino acids. The use of only heavy amino acids eliminates the need for 100% incorporation of amino acids needed for SILAC. The increased multiplexing capability of NeuCode amino acids is from the use of mass defects from extra neutrons in the stable isotopes. These small mass differences however need to be resolved on high resolution mass spectrometers.
Quantitative proteomics	Quantification using mass spectrometry	One of the main benefits of SILAC is the level of quantitation bias from processing errors is low because heavy and light samples are combined before sample preparation for MS analysis. SILAC and NeuCode SILAC are excellent techniques for detecting small changes in protein levels or post-translational modifications between experimental groups.
Quantitative proteomics	Quantification using mass spectrometry	Isobaric labeling Isobaric mass tags (tandem mass tags) are tags that have identical mass and chemical properties that allow heavy and light isotopologues to co-elute together. All mass tags consist of a mass reporter that has a unique number of 13C substitutions, a mass normalizer that has a unique mass that balances the mass of the tag to make all the tags equal in mass and a reactive moiety that crosslinks to the peptides. These tags are designed to cleave at a specific linker region upon high-energy CID, yielding different-sized tags that are then quantitated by LC-MS/MS. Protein or peptide samples prepared from cells, tissues or biological fluids are labeled in parallel with the isobaric mass tags and combined for analysis. Protein quantitation is accomplished by comparing the intensities of the reporter ions in the MS/MS spectra. Three types of tandem mass tags are available with different reactivity: (1) reactive NHS ester which provides high-efficiency, amine-specific labeling (TMTduplex, TMTsixplex, TMT10plex and TMT11plex), (2) reactive iodacetyl function group which labels sulfhydryl-(-SH) groups (iodoTMT) and (3) reactive alkoxyamine functional group which provides covalent labeling of carbonyl-containing compounds (aminoxyTMT).
Quantitative proteomics	Quantification using mass spectrometry	A key benefit of isobaric labeling over other quantification techniques (e.g. SILAC, ICAT, Label-free) is the increased multiplex capabilities and thus increased throughput potential. The ability to combine and analyze several samples simultaneously in one LC-MS run eliminates the need to analyze multiple data sets and eliminates run-to-run variation. Multiplexing reduces sample processing variability, improves specificity by quantifying the proteins from each condition simultaneously, and reduces turnaround time for multiple samples. The current available isobaric chemical tags facilitate the simultaneous analysis of up to 11 experimental samples.
Quantitative proteomics	Quantification using mass spectrometry	Label-free quantification in mass spectrometry One approach for relative quantification is to separately analyze samples by MS and compare the spectra to determine peptide abundance in one sample relative to another, as in label-free strategies. It is generally accepted, that while label-free quantification is the least accurate of the quantification paradigms, it is also inexpensive and reliable when put under heavy statistical validation. There are two different methods of quantification in label-free quantitative proteomics: AUC (area under the curve) and spectral counting.
Quantitative proteomics	Quantification using mass spectrometry	Methods of label-free quantification AUC is a method by which for a given peptide spectrum in an LC-MS run, the area under the spectral peak is calculated. AUC peak measurements are linearly proportional to the concentration of protein in a given analyte mixture. Quantification is achieved through ion counts, the measurement of the amount of an ion at a specific retention time. Discretion is required for the standardization of the raw data. High-resolution spectrometer can alleviate problems that arise when trying to make data reproducible, however much of the work regarding normalizing data can be done through software such as OpenMS, and MassView.Spectral counting involves counting the spectra of an identified protein and then standardizing using some form of normalization. Typically this is done with an abundant peptide mass selection (MS) that is then fragmented and then MS/MS spectra are counted. Multiple samplings of the protein peak is required for accurate estimation of the protein abundance because of the complex physiochemical nature of peptides. Thus, optimization for MS/MS experiments is a constant concern. One alternative to get around this problems is use a data independent technique that cycles between high and low collision energies. Thus a large survey of all possible precursor and product ions is collected. This is limited, however, by the mass spectrometry software's ability to recognize and match peptide patterns of associations between the precursor and product ions.
Quantitative proteomics	Applications	Biomedical applications Quantitative proteomics has distinct applications in the medical field. Especially in the fields of drug and biomarker discovery. LC-MS/MS techniques have started to over take more traditional methods like the western blot and ELISA due to the cumbersome nature of labeling different and separating proteins using these methods and the more global analysis of protein quantification. Mass spectrometry methods are more sensitive to difference in protein structure like post-translational modification and thus can quantify differing modifications to proteins. Quantitative proteomics can circumvent these issues, only needing sequence information to be performed. It can be applied on a global proteome level, or on specifically isolating binding partners in pull-down or affinity purification experiments. Disadvantages, however, in sensitivity and analysis time must be kept in consideration.
Quantitative proteomics	Applications	Drug discovery Quantitative proteomics has the largest applications in the protein target identification, protein target validation, and toxicity profiling of drug discovery. Drug discovery has been used to investigate protein-protein interaction and, more recently, drug-small molecule interactions, a field of study called chemoproteomics. Thus, it has shown great promise in monitoring side-effects of small drug-like molecules and understanding the efficacy and therapeutic effect of one drug target over another. One of the more typical methodologies for absolute protein quantification in drug discovery is the use of LC-MS/MS with multiple reaction monitoring (MRM). The mass spectrometry is typically done by a triple quadrupole MS.
Signal Transduction and Targeted Therapy	Signal Transduction and Targeted Therapy	Signal Transduction and Targeted Therapy is a multidisciplinary peer-reviewed open access scientific journal covering biomedical research with a particular focus on signal transduction and its application to the drug development process. It was established in 2016 and is published by Nature Research. The editors-in-chief are Carlo M. Croce (Ohio State University), Kang Zhang (Macau University of Science and Technology), and Yu-Quan Wei (West China Medical Center). According to the Journal Citation Reports, the journal has a 2020 impact factor of 18.187.

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