Metabotropic glutamate receptor 3

Metabotropic glutamate receptor 3 (mGluR3) is an inhibitory Gi/G0-coupled G-protein coupled receptor (GPCR) generally localized to presynaptic sites of neurons in classical circuits. However, in higher cortical circuits in primates, mGluR3 are localized post-synaptically, where they strengthen rather than weaken synaptic connectivity. In humans, mGluR3 is encoded by the "GRM3" gene. Deficits in mGluR3 signaling have been linked to impaired cognition in humans, and to increased risk of schizophrenia, consistent with their expanding role in cortical evolution.
Structure.
In humans, mGluR3 is encoded by the GRM3 gene on chromosome 7. At least five protein-coding isoforms are predicted based on genomic information. The mGluR3 protein is a seven-pass transmembrane protein.
Function.
L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities.
Clinical significance.
The mGluR3 receptor encoded by the GRM3 gene has been found to be associated with a range of psychiatric disorders, including bipolar affective disorder as well as schizophrenia.
A mutation in the Kozak sequence in the 1st exon of the GRM3 gene was shown to change translation and transcription of cloned GRM3 gene constructs and was significantly associated with bipolar disorder with an odds ratio of 4.4. Subsequently, a marker in GRM3 was implicated in a large genome-wide association study of schizophrenia with statistical significance of p<10−9. A follow-up study of the Kozak sequence variant showed that it was associated with increased risk of bipolar disorder, schizophrenia and alcoholism. The mGluR3 receptor encoded by GRM3 is targetable by several drugs that have been used in previous trials of schizophrenia and anxiety disorder. The agonist, antagonist and allosteric modulator drugs of mGluR3 can now be explored as new treatments for mental illness. Other scientific evidence has been published which shows that the well established anti-manic drug lithium carbonate also changes GRM3 gene expression in the mouse brain after treatment with lithium carbonate.
Ligands.
mGluR3 modulators that are significantly selective over the isoform mGluR2 are known since 2013.
Interactions.
Metabotropic glutamate receptor 3 has been shown to interact with:


Sincalide

Sincalide (INN) is a cholecystokinetic drug administered by injection to aid in diagnosing disorders of the gallbladder and pancreas. It is the 8-amino acid C-terminal fragment of cholecystokinin, and also known as CCK-8.
Common adverse effects following administration include abdominal discomfort and nausea. These effects are more pronounced following rapid infusion.
Clinical Use.
Indications.
Sincalide may be used to stimulate gallbladder contraction, as may be assessed by contrast agent cholecystography or ultrasonography, or to obtain by duodenal aspiration a sample of concentrated bile for analysis of cholesterol, bile salts, phospholipids, and crystals. It can also be used to stimulate pancreatic secretion (especially in conjunction with secretin) prior to obtaining a duodenal aspirate for analysis of enzyme activity, composition, and cytology. In some instances it is used to accelerate the transit of a barium meal through the small bowel, thereby decreasing the time and-extent of radiation associated with fluoroscopy and x-ray examination of the intestinal tract.


French flag model

The French flag model is a conceptual definition of a morphogen, described by Lewis Wolpert in the 1960s. A morphogen is defined as a signaling molecule that acts directly on cells (not through serial induction) to produce specific cellular responses dependent on morphogen concentration. During early development, morphogen gradients generate different cell types in distinct spatial order. French flag patterning is often found in combination with others: vertebrate limb development is one of the many phenotypes exhibiting Turing overlapped with a complementary pattern (in this case Turing pattern).
Overview.
In the French flag model, the French flag is used to represent the effect of a morphogen on cell differentiation: a morphogen affects cell states based on concentration, these states are represented by the different colors of the French flag: high concentrations activate a "blue" gene, lower concentrations activate a "white" gene, with "red" serving as the default state in cells below the necessary concentration threshold.
The French flag model was championed by the leading "Drosophila" biologist, Peter Lawrence. Christiane Nüsslein-Volhard identified the first morphogen, Bicoid, one of the transcription factors present in a gradient in the "Drosophila" syncytial embryo. Two labs, that of Gary Struhl and that of Stephen Cohen, then demonstrated that a secreted signaling protein, Decapentaplegic (the "Drosophila" homologue of transforming growth factor beta), acted as a morphogen during later stages of "Drosophila" development. The substance governs the pattern of tissue development and, in particular, the positions of the various specialized cell types within a tissue. It spreads from a localized source and forms a concentration gradient across a developing tissue.
Well-known morphogens include: decapentaplegic/transforming growth factor beta, Hedgehog/Sonic hedgehog, Wingless/Wnt, epidermal growth factor, and fibroblast growth factor.
Some of the earliest and best-studied morphogens are transcription factors that diffuse within early "Drosophila melanogaster" (fruit fly) embryos. However, most morphogens are secreted proteins that signal between cells.
Morphogens are defined conceptually, not chemically, so simple chemicals such as retinoic acid may also act as morphogens.
Difficulties with the French flag model.
The basis of the French flag model is the idea that a morphogen autonomously forms a gradient with individual cells reading the concentration of the gradient. Cells then respond to a specific level of gradient with a specific differentiation to match the position the gradient indicates they are in. While widely accepted as an important model for understanding morphogenesis, it is not universally accepted by all developmental biologists. The difficulties with all gradient based models of morphogenesis were extensively reviewed by Richard Gordon and include seven specific points:
External links.
NCBI resources.
From the National Center for Biotechnology Information:


Apraclonidine

Apraclonidine (INN), also known under the brand name Iopidine, is a sympathomimetic used in glaucoma therapy. It is an α2 adrenergic receptor agonist and a weak α1 adrenergic receptor agonist.
Topical apraclonidine is administered at a concentration of 1% for the prevention and treatment of post-surgical intraocular pressure (IOP) elevation and 0.5% for short-term adjunctive therapy in patients on maximally tolerated medical therapy who require additional reduction of IOP. One drop is usually added one hour prior to laser eye surgery and another drop is given after the procedure is complete.
Clinical uses.
Apraclonidine is indicated for the short-term adjunctive treatment of glaucoma for patients on maximally tolerated medical therapy who require additional reduction of IOP. These patients, who are treated with apraclonidine to delay surgery, should have frequent follow-up examinations and treatment should be discontinued if the intraocular pressure rises significantly.
Apraclonidine may be useful in the diagnosis of Horner's syndrome. In Horner's syndrome, the sympathetic innervation to the pupillary dilator muscle is lost. The affected pupil is thus miotic and the pupillary dilator responds to denervation by increasing α1 receptors. Apraclonidine is useful in this case due to its weak α1-adrenergic properties. When applied to the denervated (and thus hyper-sensitive) pupillary dilator muscle, a super-normal dilatory response is generated in which the pupil dilates to a degree greater than that which would be seen in a non-denervated muscle. This causes the reversal of anisocoria that is characteristic of Horner's.
Topical apraclonidine can also decrease IOP in glaucoma patients by increasing trabecular outflow, in a similar way to clonidine, but without the cardiovascular side effects. Apraclonidine has been compared with other treatments such as brimonidine and pilocarpine in preventing IOP spikes after laser trabeculoplasty. The results did not show significant differences in the reduction of IOP for apraclonidine, when compared to brimonidine or pilocarpine.


ATyr Pharma

aTyr Pharma is a public biotherapeutics company () that is focused on researching the extracellular functionality and signalling pathways of tRNA synthetases.
The company's lead product candidate, ATYR1923, is a selective modulator of Neuropilin-2 (NRP2) that downregulates both the innate and adaptive immune responses in inflammatory disease states. aTyr is developing ATYR1923 as a potential disease-modifying therapy for patients with interstitial lung disease (ILD), a group of rare immune-mediated disorders that cause progressive fibrosis of the lung interstitium and remain a high unmet medical need. ATYR1923 is currently being investigated in a clinical trial in pulmonary sarcoidosis patients.
The company was founded in 2005 and is headquartered in San Diego, CA, and led by CEO Sanjay S. Shukla, M.D., M.S.
History.
In 2005, aTyr was founded by Paul Schimmel, Ph.D., and Xiang-Lei Yang, Ph.D., two aminoacyl tRNA synthetase scientists at The Scripps Research Institute. In 2009, Bruce Beutler, M.D., recipient of the 2011 Nobel Prize in Physiology or Medicine, joined aTyr as a member of the scientific advisory board.
In April 2007, Polaris Partners and Alta Partners co-led a $10.5 million Series B financing. In October 2010, Series C financing totaled $23 million and was led by Domain Associates. This round was followed by a $49 million Series D in August 2013.
aTyr was a winner of the 2011 Red Herring 100 North America Award for discovering and developing innovative medicines based on Physiocrine biology.
In January 2015, aTyr announced its first FSHD patient enrolled in a Phase 1b/2 clinical trial of Resolaris. In February and April of that same year, Resolaris received EMA Orphan Drug Designation and U.S. FDA Orphan Designation for treatment of FSHD.
In April 2015, aTyr raised $76 million in a Series E, led by Sofinnova Ventures, and filed for an IPO. The company began trading as LIFE on the Nasdaq stock exchange.
In October 2015, aTyr initiated a Phase 1b/2 clinical trial on Resolaris for patients with LGMD2B and the following month initiated a Phase 1b/2 clinical trial in patients with early onset FSHD. aTyr's second IND candidate, ATYR 1923, was selected in November 2015. ATYR 1923 is an engineered fusion protein. ATYR 1923 was developed for the potential treatment of severe pulmonary diseases with an immune and fibrotic component, including interstitial lung disease.
Throughout 2016 and into the first half of 2017 aTyr released data on three Phase 1b/2 trials for Resolaris in adults with FSHD or LGMD2B, and early onset FSHD patients (ages 16–20). Data from these trials showed encouraging results for safety, tolerability, immunogenicity and pharmacokinetic profile, and signals of clinical activity in regards to muscle strength (Manual Muscle Testing) and disease burden (Individualized Neuromuscular Quality of Life score – INQoL).
ATyr's primary focus is on ATYR1923, a clinical stage product candidate which binds to the NRP2 receptor and is designed to down regulate immune engagement in interstitial lung diseases (ILDs). ATYR1923 is currently being investigated in a clinical trial in patients with pulmonary sarcoidosis. In January 2020, ATyr entered into a license with Kyorin Pharmaceutical Co., Ltd. for the development and commercialization of ATYR1923 for ILDs in Japan. Under the license agreement, Kyorin received an exclusive right to develop and commercialize ATYR1923 in Japan for all forms of ILDs including, sarcoidosis, chronic hypersensitivity pneumonitis (CHP) and connective tissue disease ILD (CTD-ILD). aTyr recently initiated a clinical trial for ATYR1923 in patients with severe respiratory complications related to COVID-19.
Therapeutic concept.
Homeostasis, or the coordinated regulation of tissues within the body, is fundamental to the maintenance of the overall health of an organism. Lack of homeostasis can lead to disease and death. The process of homeostasis was first described in 1865 by the French physiologist Claude Bernard and Walter Cannon later coined the term. In the 150 years since this discovery, many proteins associated with homeostatic pathways have been discovered, ranging from insulin to erythropoietin.
aTyr was founded after Dr. Schimmel discovered several nontranslational functions of aminoacyl tRNA synthetases, which are primarily responsible for the production of a vital component of protein synthesis, aminoacyl-tRNAs. [23] These nontranslational functions have since been shown to play an important role in maintaining homeostasis. [23] One of these nontranslational functions is modulation and regulation of the immune response. [23] This modulatory activity is a result of Physiocrines, a novel class of proteins that are present as biologically active signaling regions of the tRNA synthetases. aTyr's research is based on the premise that Physiocrines are involved in orchestrating homeostatic activities to help the body restore diseased or damaged tissue to a healthier state.
By researching and understanding the role of Physiocrines in immune modulation, aTyr has developed two IND candidates.


CareCloud

CareCloud, Inc. (formerly MTBC) is a publicly traded American healthcare information technology company that provides a full suite of proprietary cloud-based solutions, together with related business services, to healthcare providers and hospitals throughout the United States. The Company maintains its headquarters in Somerset, New Jersey and employs approximately 3,500 team members worldwide.
CareCloud’s common stock trades on the Nasdaq Global Market under the ticker symbol “MTBC,” and its Series A Preferred Stock trades on the Nasdaq Global Market under the ticker symbol “MTBCP.”
History.
CareCloud was founded in 1999 (as MTBC) by American entrepreneur and businessperson, Mahmud Haq as Medical Transcription Billing, Corp in the United States. The earliest days of the Company were focused on providing transcription and manual medical billing to healthcare providers primarily located in New Jersey.
In 2004 , the company developed a fully integrated suite of services that includes a proprietary practice management platform, ONC-ACB, meaningful use stage 2 certified complete electronic health records software and a revenue cycle management service.
On June 6, 2013, former ambassador to Pakistan, Cameron Munter joined MTBC's Board of Directors.
On July 23, 2014, the company went public on NASDAQ Capital Market under the ticker symbol "MTBC." The preferred stock trades under “MTBCP.”
In 2017, the company launched talkEHR, the industry’s first voice-enabled electronic health record, to provide doctors with a more natural means of charting and documenting encounters.
In 2019, they changed the corporation name from Medical Billing Transcription, Corp to MTBC, Inc.
In 2021, they changed the corporation name to CareCloud, Inc.
The company also has operations in Pakistan and Sri Lanka.
Acquisitions.
Post-IPO, the company (as MTBC) made 16 acquisitions including revenue cycle management and healthcare IT companies in the United States. Some of the key acquisitions include Gulf Coast Billing (2016), Renaissance Physician Services (2016), MediGain (2016), Orion (2018).
In 2020, CareCloud (formerly MTBC) made two major acquisitions of healthcare technology companies; CareCloud Corporation and Meridian Medical Management for reportedly up to $40M and $24.8M, respectively.
Products and Services.
CareCloud offers Software-as-a-Service (or SaaS) platform that includes revenue cycle management (RCM), business intelligence, telehealth, practice management (PM) electronic health record (EHR), patient experience management (PXM), Robotic Process Automation (RPA), and solutions for high-performance medical groups.
Awards.
In 2020, CareCloud (as MTBC) was awarded public company of the year by TechUnited New Jersey. In years 2009-2012 and 2016, the company was included in the Deloitte Technology Fast 500 list as a fastest growing US tech company. In years 2010-2013, they were included in the Inc. 5000 as a fastest growing US company. In 2012, CareCloud was nominated for the US Secretary of State's Award for Corporate Excellence. In 2015, they were ranked as a Top 50 EHR software company by Medical Economics.


Nadezhda Rimskaya-Korsakova

Nadezhda Nikolayevna Rimskaya-Korsakova ( née Purgold (October 19 (N.S. October 31), 1848May 24, 1919) was a Russian pianist and composer as well as the wife of composer Nikolai Rimsky-Korsakov. She was also the mother of Russian musicologist Andrey Rimsky-Korsakov.
Life.
Early years.
Born Nadezhda Nikolayevna Purgold in St. Petersburg, she was the youngest of three daughters and the great-granddaughter of the 18th century jurist Johann Purgold. She started playing the piano at age nine, continuing her piano studies at the St. Petersburg Conservatory with Anton Gerke. She also studied music theory at the conservatory with Nikolai Zaremba and, later, composition and orchestration with Rimsky-Korsakov but did not graduate. During the 1860s and '70s she played piano at musical soirees at the home of Alexander Dargomyzhsky, becoming friends with Dargomyzhsky, Modest Mussorgsky and Alexander Borodin. Mussorgsky, who was fond of both Nadezhda and her sister Alexandra and would become close to both, called Nadezhda "our darling orchestra." She also played at gatherings in her home works of Mily Balakirev and of other members of "The Five." Among the works she played with the "kuchka" were Mussorgsky's operas "Zhenitba" ("Marriage") and "Boris Godunov", plus Nikolai Rimsky-Korsakov's "The Maid of Pskov".
Marriage.
She met Rimsky-Korsakov at Dargomyzhsky's home in the spring of 1868. Not long after their first meeting he wrote a song which he dedicated to her. He also started visiting her frequently, both at the Purgold home in St. Petersburg and at the family's summer residence in Lyesnov. She found in him an abundance of warmth and gentleness. He proposed to her in December 1871, and they married in July 1872. Mussorgsky was Rimsky-Korsakov's best man. The Rimsky-Korsakovs would eventually have seven children. Nadezhda was to become a musical as well as domestic partner with her husband, much as Clara Schumann had been with her own husband Robert. Beautiful, capable, strong-willed and far better trained musically than her husband at the time they married, she proved a good and most demanding critic of his work; her influence over him in musical matters was strong enough for Balakirev and Stasov to wonder sometimes whether she was leading him astray from their musical preferences. Although she gradually gave up composition after her marriage, she had a considerable influence on the creation of his first three operas. She travelled with her husband, attended rehearsals and proofread and arranged compositions by him and others. Years later, Nikolai Rimsky-Korsakov wrote: "The overture [from "The Maid of Pskov"], from the first note to the last one, belongs to a no-good girl whom I love very, very much."
Her enthusiasm for Nikolai Gogol's work became reflected in both her husband's compositions and those of his friends. On the day of their betrothal, she and Rimsky-Korsakov read Gogol's short story "May Night" together. Afterwards, she told him that he should write an opera based on it. A week or two later she wrote him, "I've been reading yet another of Gogol's stories today, "The Fair at Sorochyntsi." This is good, too, and would even be suitable for an opera, but not for "you"; in any case, it's not like 'May Night.' As for "that", it's so stuck in my head that nothing will drive it out." Either she or her sister Alexandra then suggested "The Fair at Sorochyntsi" to Mussorgsky. He did not act on it at the time, but a couple of years later, he reconsidered.
Nadezhda was also very prominent in the Rimsky-Korsakovs' social life, active in gatherings at the Rimsky-Korsakov household as both accompanist and performer. At one of these soirees, Pyotr Ilyich Tchaikovsky played the finale of his "Little Russian" Symphony. After hearing it, she begged the composer in tears to let her arrange it for piano duet. However, illness intervened and Tchaikovsky made the arrangement himself.
Outspokenness.
Like her husband in his later years, Nadezhda's musical tastes became less progressive; she rated her son-in-law Maximilian Steinberg a greater composer than Igor Stravinsky. She could also be noticeably tactless about such matters. Stravinsky later wrote about one such incident that occurred at Rimsky-Korsakov's funeral:
This was not the only time she was not afraid to speak her mind. In matters regarding her husband she was fiercely loyal. When Anton Rubinstein reassumed the directorship of the St. Petersburg Conservatory in 1887 and started replacing Russian professors with foreign ones, Stasov was outraged at the thought of Rimsky-Korsakov kowtowing to "the Great Ruler." Stasov told Balakirev that he had written to Rimsky-Korsakov "that their relations with the Conservatory and Rubinstein is Unitarianism (and, on the part of Cui, unadulterated apostasy)..."
When Stasov's letter arrived, Rimsky-Korsakov was hard at work completing Borodin's opera "Prince Igor". Nadezhda took it upon herself to answer Stasov:
Upon Rimsky-Korsakov's death in 1908, Nadezhda became the executrix of his literary and musical estates. This included the considerable job of editing and publishing his posthumous literary and musical works. These included his autobiography, "My Musical Life", collections of articles and notes on music plus a part of his correspondence with friends. She spent the rest of her life preserving his legacy, among other things, protesting Sergei Diaghilev's use of music from "Scheherazade" and "The Golden Cockerel" for ballets. She died of smallpox in St. Petersburg (by then renamed Petrograd) at age 70. After her death, her son Andrei continued her efforts, writing a multi-volume study of his father's life and work.
Music.
Arrangements.
Dargomyzhsky taught Rimskaya-Korsakova how to reduce orchestral scores, a task for which she was especially talented and adept and which she would put to good use. Her transcriptions (for piano four-hands) include works by Dargomyzhsky, Rimsky-Korsakov, Tchaikovsky, Borodin and Glazunov. She also arranged the vocal scores for Rimsky-Korsakov's "The Maid of Pskov" and "The Noblewoman Vera Sheloga", along with Borodin's "Prince Igor" in conjunction with Glazunov and her husband.
Original works.
Autograph manuscripts survive of a symphonic tableau after Gogol, "The Bewitched Place" ("Zakoldovannoye mesto"), an opera "Midsummer Night" in piano-vocal score, piano pieces and songs. She completed "The Bewitched Place" a week or two before her marriage, orchestrating it the following year. She stopped composing after her marriage to Rimsky-Korsakov. This may have been partly from unfavorable comparison of her works to her husband's, but likely also due to family responsibilities.
Bibliography.
She published two recollections of Dargomyzhsky, wrote a memoir of Mussorgsky and edited her husband's autobiography, "My Musical Life".


ATP adenylyltransferase

In enzymology, an ATP adenylyltransferase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are ADP and ATP, whereas its two products are phosphate and P1,P4-bis(5'-adenosyl) tetraphosphate.
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is ADP:ATP adenylyltransferase. Other names in common use include bis(5'-nucleosyl)-tetraphosphate phosphorylase (NDP-forming), diadenosinetetraphosphate alphabeta-phosphorylase, adenine triphosphate adenylyltransferase, diadenosine 5',5'"-P1,P4-tetraphosphate alphabeta-phosphorylase, (ADP-forming), and dinucleoside oligophosphate alphabeta-phosphorylase. This enzyme participates in purine metabolism.


Proteinase K

In molecular biology Proteinase K (, "protease K", "endopeptidase K", "Tritirachium alkaline proteinase", "Tritirachium album serine proteinase", "Tritirachium album proteinase K") is a broad-spectrum serine protease. The enzyme was discovered in 1974 in extracts of the fungus "Engyodontium album" (formerly "Tritirachium album"). Proteinase K is able to digest hair (keratin), hence, the name "Proteinase K". The predominant site of cleavage is the peptide bond adjacent to the carboxyl group of aliphatic and aromatic amino acids with blocked alpha amino groups. It is commonly used for its broad specificity. This enzyme belongs to Peptidase family S8 (subtilisin). The molecular weight of Proteinase K is 28,900 daltons (28.9 kDa).
Enzyme activity.
Activated by calcium, the enzyme digests proteins preferentially after hydrophobic amino acids (aliphatic, aromatic and other hydrophobic amino acids). Although calcium ions do not affect the enzyme activity, they do contribute to its stability.
Proteins will be completely digested if the incubation time is long and the protease concentration high enough. Upon removal of the calcium ions, the stability of the enzyme is reduced, but the proteolytic activity remains. Proteinase K has two binding sites for Ca2+, which are located close to the active center, but are not directly involved in the catalytic mechanism. The residual activity is sufficient to digest proteins, which usually contaminate nucleic acid preparations. Therefore, the digestion with Proteinase K for the purification of nucleic acids is usually performed in the presence of EDTA (inhibition of metal-ion dependent enzymes such as nucleases).
Proteinase K is also stable over a wide pH range (4–12), with a pH optimum of pH 8.0.
An elevation of the reaction temperature from 37 °C to 50–60 °C may increase the activity several times, like the addition of 0.5–1% sodium dodecyl sulfate (SDS) or Guanidinium chloride (3 M), Guanidinium thiocyanate (1 M) and urea (4 M) . The above-mentioned conditions enhance proteinase K activity by making its substrate cleavage sites more accessible. Temperatures above 65 °C, trichloroacetic acid (TCA) or the serine protease-inhibitors AEBSF, PMSF or DFP inhibit the activity.
Proteinase K will not be inhibited by Guanidinium chloride, Guanidinium thiocyanate, urea, Sarkosyl, Triton X-100, Tween 20, SDS, citrate, iodoacetic acid, EDTA or by other serine protease inhibitors like Nα-Tosyl-Lys Chloromethyl Ketone (TLCK) and Nα-Tosyl-Phe Chloromethyl Ketone (TPCK).
Protease K activity in commonly used buffers
Applications.
Proteinase K is commonly used in molecular biology to digest protein and remove contamination from preparations of nucleic acid. Addition of Proteinase K to nucleic acid preparations rapidly inactivates nucleases that might otherwise degrade the DNA or RNA during purification. It is highly suited to this application since the enzyme is active in the presence of chemicals that denature proteins, such as SDS and urea, chelating agents such as EDTA, sulfhydryl reagents, as well as trypsin or chymotrypsin inhibitors.
Proteinase K is used for the destruction of proteins in cell lysates (tissue, cell culture cells) and for the release of nucleic acids, since it very effectively inactivates DNases and RNases. Some examples for applications:
Proteinase K is very useful in the isolation of highly native, undamaged DNAs or RNAs, since most microbial or mammalian DNases and RNases are rapidly inactivated by the enzyme, particularly in the presence of 0.5–1% SDS.
Purification of genomic DNA from bacteria (miniprep):
bacteria from a saturated liquid culture are lysed and proteins are removed by a digest with 100 μg/ml Proteinase K for 1 h at 37 °C;
The enzyme's activity towards native proteins is stimulated by denaturants such as SDS. In contrast, when measured using peptide substrates, denaturants inhibit the enzyme. The reason for this result is that the denaturing agents unfold the protein substrates and make them more accessible to the protease.
Inhibitors.
Proteinase K has two disulfide bonds, but it exhibits higher proteolytic activity in the presence of reducing agents (e.g. 5 mM DTT), suggesting that the presumed reduction of its own disulfide bonds does not lead to its irreversible inactivation. Proteinase K is inhibited by serine protease inhibitors such as phenylmethylsulfonyl fluoride (PMSF), diisopropylfluorophosphate (DFP), or 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF). Proteinase K activity is unaffected by the sulfhydryl modifying reagents: para-chloromercuribenzoic acid (PCMB), N-alpha-tosyl-L-lysyl-chloromethyl-ketone (TLCK), or N-alpha-Tosyl-l-phenylalanine Chloromethyl Ketone (TPCK), although presumably if these reagents were included alongside disulfide reducing reagents which exposed the typically-unavailable Proteinase K thiols, it may then become inhibited.


Arthrobacter russicus

Arthrobacter russicus is a species of Gram-positive bacteria, with type strain A1-3(T) (=GTC 863(T) =JCM 11414(T) =DSM 14555(T)).


Song Li (bioengineer)

Song Li (, born 1965) is a Chinese-American bioengineer and bioscientist. He is currently the Chancellor Professor and Department Chair at University of California, Los Angeles. His research is focused on cell and tissue engineering, mechanobiology and cardiovascular bioengineering. He edited 3 books, and served on the editorial boards of 5 scientific journals. He has co-authored over 200 papers, and is well recognized in the field of bioengineeirng. He is a Fellow of the International Academy of Medical and Biological Engineering, Biomedical Engineering Society and American Institute for Medical and Biological Engineering.
Education.
He received his Bachelor of Science in Mechanics and Engineering Science and also his Master of Science in Biomechanics from Peking University. He received his Ph.D. from University of California, San Diego in 1997, working with Professor Shu Chien.


Thiomargarita

Thiomargarita is a genus (family Thiotrichaceae) which includes the vacuolate sulfur bacteria species "Thiomargarita namibiensis", "Candidatus Thiomargarita nelsonii", and "Ca. Thiomargarita joergensii".
Representatives of this genus can be found in a variety of environments that are rich in hydrogen sulfide, including methane seeps, mud volcanoes, brine pools, and organic-rich sediments such as those found beneath the Benguela Current and Humboldt Current. These bacteria are generally considered to be chemolithotrophs that utilize reduced inorganic species of sulfur as metabolic electron donors to produce energy for the fixation of carbon into biomass. Carbon fixation occurs via the Calvin Benson Bassham cycle and possibly the reverse Krebs cycle.


C0299 RNA

The C0299 RNA family consists of a group of "Shigella flexneri" and "Escherichia coli" RNA genes which are 78 bases in length and are found between the "hlyE" and "umuD" genes. The function of this RNA is unknown.


Strombine dehydrogenase

In enzymology, a strombine dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are N-(carboxymethyl)-D-alanine, NAD+, and H2O, whereas its 4 products are glycine, pyruvate, NADH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is N-(carboxymethyl)-D-alanine:NAD+ oxidoreductase (glycine-forming). Other names in common use include strombine[N-(carboxymethyl)-D-alanine]dehydrogenase, and N-(carboxymethyl)-D-alanine: NAD+ oxidoreductase.


Lucas Timmins

Lucas Timmins is an American biomedical engineer. He is an Assistant Professor of Biomedical Engineering at the University of Utah, active in the fields of biomechanics and interventional cardiology.
Early life and education.
Timmins was born December 8, 1982 and grew up in Port Neches, Texas, a small refining town on coast of Texas near the Louisiana border. His father worked in refining, and his mother was a grade school teacher. He has one older sister. He attended Port Neches-Groves high school. He is married.
Timmins received a Bachelor of Science in Biomedical Engineering at Texas A&M University in 2005, He received the Whitaker International Fellowship in 2007, where he traveled to London and attended Queen Mary University of London. His Doctor of Philosophy in Biomedical Engineering was also received from Texas A&M University in 2010. His postdoctoral work was in Biomedical Engineering at Georgia Institute of Technology and Emory University School of Medicine from February 2010 - July 2015. As a postdoc he taught Problems in Biomedical Engineering and Biotransport at Georgia Tech.
Career and research.
Timmins worked at the Emory University school of medicine in the department of Radiology & Imaging Sciences as an Instructor August 2015- July 2016. He then moved to the University of Utah in August 2016 to be an Assistant Professor in the Department of Biomedical Engineering and an Affiliate Faculty Member in the Scientific Computing and Imaging Institute. He teaches Biomechanics Research and Biomechanics I at the University of Utah.
The scientific fields he is most actively involved in are biomechanics and interventional cardiology. His research has included work in determining how coronary hemodynamics drive the progression of coronary atherosclerosis1 and also understanding the mechanics dealing with failure of vascular stents.
Timmins was the primary author on a paper that looked at stented artery biomechanics to optimize device design2. This research aimed to validate an algorithm to optimizing stent design to minimize or maximize various blood vessel mechanical properties.
Timmins was a part of a team of researchers that investigated the correlation of plaque area, plaque composition, and vessel remodeling as a function of wall shear stress.
Timmins was a supporting author on a study exploring how device design effects the mechanics of the artery wall. The purpose of this study was to investigate the effects that different stent parameters have on the stresses in the artery wall after implantation and the resulting radial displacement that is achieved by the stent in the interest of preventing failures, such as restenosis or formation of a new blockage.


Louis Du Guernier

Louis Du Guernier (1677–1716) was an engraver.
Born in Paris in 1677, Louis was probably a descendant of the well-known French artists of the same name. He was a pupil of Louis de Chatillon, and came to England in 1708. He was a member of the academy in Great Queen Street and gained considerable skill as a designer, etcher, and engraver there. He was eventually chosen one of the directors, and remained so until he died. He was specially employed on small historical subjects, as illustrations to books and plays.
In 1714 he was associated with Claude du Bosc in engraving the battles of the Duke of Marlborough, as he was with the same partner in providing six plates for the expanded edition of The Rape of the Lock that year. Among others engraved by him were portraits of the Duke and Duchess of Queensberry after Godfrey Kneller, Dr. Isaac Barrow, Thomas Otway, and others; also an engraving of "Lot and his Daughters" after Caravaggio, done at the request of Charles Montagu, 1st Earl of Halifax, and some plates for John Baskett's large Bible.
He died of smallpox 19 September 1716, aged 39. Vertue says that ‘he was of stature rather low than middle size, very obliging, good temper, gentleman-like, and well beloved by all of his acquaintance.’ However, in the view of Edward Hodnett (English Book Illustration 1988, p. 75) he probably died around 1735.


Foundation Medicine

Foundation Medicine, Inc. is an American company based in Cambridge, Massachusetts which develops, manufactures, and sells genomic profiling assays based on next-generation sequencing technology for solid tumors, hematologic malignancies, and sarcomas.
History.
Foundation Medicine was founded in Cambridge, Massachusetts. The company was conceived after Broad Institute researchers Levi Garraway and Matthew Meyerson published a 2007 paper detailing a method for large-panel testing of 238 DNA mutations.
Foundation Medicine launched in 2010 with a $25 million Series A financing led by Third Rock Ventures. The company released its first commercial assay, or test, called FoundationOne in 2012. The company also began partnering with pharmaceutical companies to analyze patient samples. The first such program was piloted with Novartis in 2011, and by 2018, the company had more than 30 partnerships.
Foundation Medicine launched its second test, a hematological biomarker assay called FoundationOneHeme, in 2013. The company held its initial public offering in August 2013. The following year, Priority Health in Michigan became the first healthcare plan in the United States to cover the company’s tests.
In 2016, using FoundationCore data, Foundation Medicine released anonymized records detailing genomic data on cancers from 18,000 adult patients to the National Cancer Institute’s (NCI) Genomic Data Commons (GDC) portal.
In June, 2018, Roche announced it would acquire Foundation Medicine.
Foundation Medicine is now a subsidiary of Roche and It operates independently.
Products.
Foundation Medicine’s products include genomic tests used to test solid tumors and blood-based cancers and sarcomas, as well as data services.


Heliobacteria

Heliobacteria are a unique subset of prokaryotic bacteria that process light for energy. Distinguishable from other phototrophic bacteria, they utilize a unique photosynthetic pigment, bacteriochlorophyll "g" and are the only known Gram-positive phototroph. They are a key player in symbiotic nitrogen fixation alongside plants, and share a reaction center with green-sulfur bacteria.
RNA trees place the heliobacteria among the Firmicutes. They have no outer membrane and like certain other firmicutes (Clostridia), they form heat-resistant endospores, which contain high levels of calcium and dipicolinic acid. Heliobacteria are the only firmicutes known to be phototrophic.
Metabolism.
The heliobacteria are phototrophic: they convert light energy into chemical energy using a type I reaction center. The primary pigment involved is bacteriochlorophyll "g", which is unique to the group and has a unique absorption spectrum; this gives the heliobacteria their own environmental niche. Phototrophic processes take place at the cell membrane, which does not form folds or compartments as it does in purple bacteria. Though heliobacteria are phototrophic, they can create energy without light using pyruvate fermentation, which generates significantly less energy than it could with light.
Heliobacteria are photoheterotrophic, requiring organic carbon sources, and they are exclusively anaerobic. Bacteriochlorophyll "g" is inactivated by the presence of oxygen, making them obligate anaerobes (they cannot survive in aerobic conditions). Heliobacteria have been found in soils, hot springs, soda lakes and are common in the waterlogged soils of paddy fields. They are avid nitrogen fixers, so are probably important in the fertility of paddy fields. Heliobacteria are mainly terrestrial phototrophs, contrary to the multitudes of others that are aquatic, and often form mutualistic relationships with the plants near them.
Taxonomy.
Heliobacteria should not be confused with "Helicobacter", which is a genus of bacteria with quite different characteristics.
Family Heliobacteriaceae
Notes:
♠ Strain found at the National Center for Biotechnology Information (NCBI) but has no standing with the Bacteriological Code (1990 and subsequent Revision) as detailed by List of Prokaryotic names with Standing in Nomenclature (LPSN) as a result of the following reasons:
• No pure culture isolated or available for prokaryotes.
• Not validly published because the effective publication only documents deposit of the type strain in a single recognized culture collection.
• Not approved and published by the International Journal of Systematic Bacteriology or the International Journal of Systematic and Evolutionary Microbiology (IJSB/IJSEM).


Anthranilate adenylyltransferase

In enzymology, an anthranilate adenylyltransferase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are ATP and anthranilate, whereas its two products are diphosphate and N-adenylylanthranilate.
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is ATP:anthranilate N-adenylyltransferase. This enzyme is also called anthranilic acid adenylyltransferase.


American Joint Replacement Registry

The American Joint Replacement Registry (AJRR) is a non-profit organization established to foster the creation of a national center for data collection, and is dedicated to the improvement in arthroplasty patient care.
History.
In partnership with the American Academy of Orthopaedic Surgeons (AAOS), the AJRR was founded in 2009 with the goal to optimize patient outcomes through collection of data on all primary and revision total joint replacement procedures in the U.S., while enhancing patient safety, improving quality of care, and reducing the cost for patients. Since then, the AJRR has grown to over 620 participating hospitals with over 400,000 procedures in their database. Both figures are expected to increase by year's end, and will continue to do so as more participants join the registry.
In February 2010, The AAOS ratified the AJRR Board of Directors. In November 2010, AJRR received 501(c)(3) status, and in December 2010, their Business Plan was finalized and approved by the AJRR Board of Directors.
In March 2011, the Pilot Program was initiated, with successful Level I data transmission and collection from pilot sites completed in July of the same year.
In 2012, the national registry software was launched. In August 2012, Jeffrey P. Knezovich, CAE, was hired as AJRR's first Executive Director.
In November 2013, AJRR launched a pilot program of Level II, Level III, and Level IV data collection systems. That pilot study is expected to be concluded by the end of the third quarter 2014.
In February 2014, the AJRR was named to the National Quality Registry Network (NQRN) Council, an initiative of the American Medical Association; and, in May, 2014, the AJRR was named a Qualified Clinical Data Registry (QCDR) by the Centers for Medicare and Medicaid Services (CMS).
On January 1, 2015, the AJRR officially became a freestanding association. 2015 also marked the formation of the AJRR User Group Network, the merger of the California Joint Replacement Registry (CJRR) into AJRR, and the enrolling of the 600th hospital.
References.
(CMS)


Jennifer L. West

Jennifer L. West is an American bioengineer. She is the Fitzpatrick University Professor of Biomedical Engineering at Duke University. In 2000, West cofounded Nanospectra Biosciences in Houston to develop a cancer therapy based on gold nanoparticles that destroy tumor cells and has been listed by MIT Technology Review as one of the 100 most innovative young scientists and engineers world wide.
Early life and education.
West graduated from the Massachusetts Institute of Technology in 1992 and completed her PhD at the University of Texas at Austin.
Career.
Rice University.
West joined the faculty at Rice University after receiving her doctoral degree from the University of Texas–Austin in 1996. As an associate professor in bioengineering and chemical engineering, West was awarded the 2002 Julia Mile Chance Prize for Excellence in Teaching. The following year, she was again recognized for her academic achievement with the 2003 Charles W. Duncan Jr. Achievement Award for Outstanding Faculty and listed by the MIT Technology Review as one of the 100 most innovative young scientists and engineers world wide.
During her tenure at Rice, West worked in the areas of gene therapy, biomaterials and tissue engineering alongside Naomi Halas. In 2000, Halas and West co-founded Nanospectra Biosciences in Houston to develop a cancer therapy based on gold nanoparticles that destroy tumor cells. They were co-recipients of the Best Discovery of 2003 Award from Nanotechnology Now for their "groundbreaking work to develop a cancer therapy based on metallic nanoshells." West and Halas were later honored by the YMCA as 2005 Outstanding Women of Achievement in Science and Technology. They followed up their nanoshells research in 2005 by developing a new approach to fighting cancer through targeted nanoparticles. The pair then developed a small beacon that was programmed to light up only when activated by specific proteases.
As a result of her academic accomplishments, West earned a grant from the Howard Hughes Medical Institute to "develop national model programs that infuse undergraduate teaching with cutting-edge research." She was also appointed chair of the Department of Bioengineering while continuing to serve as the Isabel C. Cameron Professor of Bioengineering and director of Rice’s Institute of Biosciences and Bioengineering. In 2009, West and her colleagues at the Texas Medical Center were asked to create a putty-like material that can be packed around broken bones on the battlefield to reduce complications from compound fractures. David Leebron praised West as "a scholar and researcher, one who pushes the limits of knowledge and discovery in the lab while always remaining focused on the purpose and potential of her scientific discoveries to improve our lives." For her overall "pioneering research in biomaterials engineering and advancing the fields of tissue engineering and bionanotechnology," West was the recipient of an O’Donnell Award and State Bar Inventors of the Year.
Using a grant from the National Institutes of Health for an investigation into neurovascular tissue regeneration in 2011, West and researchers at the Baylor College of Medicine found they could regenerate tissue in parts of the brain when it dies and withers after a stroke. In 2012, West received numerous accolades for her work including the Frank Annunzio Award, Duncan Award for Outstanding Academic Achievement, Admiral of the Texas Navy, Hershel M. Rich Invention Award, and CAREER Award. She was also elected a Fellow of the American Institute for Medical and Biological Engineering and Biomedical Engineering Society.
Duke University.
In 2013, West left Rice University to accept a position as the Fitzpatrick Family University Professor of Engineering at the Duke University (Duke). Prior to accepting the appointment, Duke sent architects to Rice so they could design a facility that could properly house her and her research group. During her first year in this role, her research team discovered that they could destroy soft-tissue tumors by injecting gold-covered nanoshells. Following this, she improved on her design by adding an extremely thin layer of hydrogels to the surface that, when heated, lose their water content and release any molecules trapped within.
West and her colleagues created the Retroject RJT1125 in 2014, a device that stabilizes the eyeball and allows a glaucoma drug to be injected into the veins near the iris. Afterwards, she began using nanoparticles to make the injection last longer. Two years later, West was elected to the National Academy of Engineering for "developments in photothermal and theranostic therapies and bioabsorbed scaffolds for tissue regeneration." In December 2016, West was elected a Fellow of the National Academy of Inventors for "translating this scholarship in tangible ways to positively influence medicine."


LY-266,097

LY-266,097 is a research ligand which acts as a potent and selective antagonist for the 5-HT2B receptor, with more than 100x selectivity over the related 5-HT2A and 5-HT2C receptor subtypes. It has been used to study the role of the 5-HT2B receptor in modulating dopamine release in the brain, as well as its involvement in other processes such as allodynia.


Watt W. Webb

Watt Wetmore Webb (August 27, 1927 – October 29, 2020) was an American biophysicist, known for his co-invention (with Winfried Denk and Jim Strickler) of Multiphoton microscopy in 1990.
Biography.
Professor Watt W. Webb’s undergraduate studies at MIT in Business and Engineering Administration for his SB degree in 1947 led him to engineering research and development at Union Carbide Corporation Research Laboratories until 1952, then back to MIT for his ScD in Metallurgy awarded in 1955, then returning to Union Carbide for solid-state and chemical physics and as coordinator of fundamental research and then assistant director of research until he joined the Cornell University faculty of Engineering Physics in 1961, introducing experimental research in superconductivity and in continuous phase transitions. He served as director of the School of Applied and Engineering Physics from 1983 to 1988 and was a member of the graduate faculties of eight fields, which indicates his interdisciplinary research focus. He has directed the NIH Developmental Resource for Biophysical Imaging Opto-Electronics for the last 20 years. He was on the board of directors and executive committee of the Cornell Center for Technology, Enterprise, and Commercialization, is affiliated with the university's Biophysics Program, the Cornell Center for Materials Research, the Nanobiotechnology Center and serves on the Executive Committee of the Neuroscience Focus Area. He has been a visiting scholar at Stanford University, a Guggenheim fellow, and a scholar in residence at the NIH Fogarty International Center for Advanced Study.
He is a fellow of the American Physical Society (APS) and the American Association for the Advancement of Science, a founding fellow of the American Institute for Medical and Biological Engineering, and an elected member of the National Academy of Engineering, the National Academy of Science, and the American Academy of Arts and Sciences. He won the APS Biological Physics Prize in 1990, the Ernst Abbe Lecture Award of the Royal Microscopical Society (UK) and Carl Zeiss (Germany) in 1997, the Michelson-Morley Award in 1999, the Rank Prize for Opto-electronics in 2000, the Jablonski Award Lecturer in 2001, was the National Lecturer of the Biophysical Society in 2002, the MIT Lord Lecturer in 2004, the Rohm and Haas Lecturer in 2005, and the Leonardo Lecturer for the Universita Vita-Salute San Raffaele in Milano, Italy in 2006 and has been selected for the Ernst Abbe award of the New York Microscopy Society in 2007. He has served as chairman of the Division of Biological Physics of APS and associate editor of Physical Review Letters. He has published over 310 papers in solid state and chemical physics and in biological physics; with 22 U.S. patents plus many foreign patents. He is active as a consultant and in various national advisory committees and professional societies.
Webb died on October 29, 2020 in New York City at the age of 93.
FCS and MPM.
Professor Webb pioneered the techniques of Fluorescence Correlation Spectroscopy (FCS) in 1972 and Multiphoton microscopy (MPM) in 1990. FCS enables single-molecule detection in solutions at nanomolar concentrations and provides temporal resolution of the dynamic processes of individual molecules signaled by their fluorescence. FCS reveals molecular mobility, conformational fluctuations and chemical reactions in solutions and allows the detection of extremely sparse molecules and particles. In situ measurements of the dynamics of fluorescence flicker by FCS, photobleaching, phototoxicity, and induced fluorescence are being used to discern dynamics of biological processes and molecular mechanisms of disease. Multiphoton excitation in laser scanning fluorescence microscopy provides for high resolution, high signal-to-noise imaging in living cells and deep in turbid tissues in vivo and significantly reduces photodamage and minimizes image degradation due to scattering and autofluorescence. His laboratory at Cornell University continues to extend the frontiers of these technologies, now for example extending MPM and FCS to imaging molecular processes within the cellular nucleus for gene expression in vivo. Recently initiated is the development of technology for introduction of MPM into Medical Endoscopy for in vivo, in situ real time diagnostics.
Honors.
In 2010 Webb was awarded the Alexander Hollaender Award in Biophysics by the National Academy of Sciences.


L-pipecolate oxidase

In enzymology, a L-pipecolate oxidase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are L-pipecolate and O2, whereas its two products are 2,3,4,5-tetrahydropyridine-2-carboxylate and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with oxygen as acceptor. The systematic name of this enzyme class is L-pipecolate:oxygen 1,6-oxidoreductase. Other names in common use include pipecolate oxidase, and L-pipecolic acid oxidase. This enzyme participates in lysine degradation.


Phasor approach to fluorescence lifetime and spectral imaging

Phasor approach refers to a method which is used for vectorial representation of sinusoidal waves like alternative currents and voltages or electromagnetic waves. The amplitude and the phase of the waveform is transformed into a vector where the phase is translated to the angle between the phasor vector and X axis and the amplitude is translated to vector length or magnitude.
In this concept the representation and the analysis becomes very simple and the addition of two wave forms is realized by their vectorial summation.
In Fluorescence lifetime and spectral imaging, phasor can be used to visualize the spectra and decay curves. In this method the Fourier transformation of the spectrum or decay curve is calculated and the resulted complex number is plotted on a 2D plot where the X axis represents the Real component and the Y axis represents the Imaginary component. This facilitate the analysis since each spectrum and decay is transformed into a unique position on the phasor plot which depends on its spectral width or emission maximum or to its average lifetime. The most important feature of this analysis is that it is fast and it provides a graphical representation of the measured curve.
Temporal phasor.
If we have decay curve which is represented by an exponential function with lifetime of τ:
formula_1
Then the Fourier transformation at frequency ω is represented by the Lorentz function:
formula_2
This is a complex function and drawing the Imaginary versus real part of this function for all possible lifetimes will be a semicircle where the zero lifetime is located at (1,0) and the infinite lifetime located at (0,0). By changing the lifetime from zero to infinity the phasor point moves along a semicircle from (1,0) to (0,0). This suggest that by taking the Fourier transformation of a measured decay curve and mapping the result on the phasor plot the lifetime can be estimated from the position of the phasor on the semicircle.
Explicitly, the lifetime can be measured from the magnitude of the phasor as follow:
formula_3
This is a very fast approach compared to methods where they use fitting to estimate the lifetime.
Multi-exponential cases.
The semicircle represents all possible single exponential fluorescent decays. When the measured decay curve consists of a superposition of different mono-exponential decays, the phasor falls inside the semicircle depending on the fractional contributions of the components. For a bi-exponential case with lifetimes τ1 and τ2, all phasor values fall on a line connecting the phasors of τ1 and τ2 on the semicircle, and the distance from the phasor to τ1 determines the fraction α. Therefore, the phasor values of the pixels of an image with two lifetime components are distributed on a line connecting the phasors of τ1 and τ2. Fitting a line through these phasor points with slope (v) and interception (u) , will give two intersections with the semicircle that determine the lifetimes τ1 and τ2:
formula_4
This is a blind solution for unmixing two components based on their lifetimes, provided that the fluorescence decays of the individual components show a single exponential behavior.
Compatibility to different gate configurations.
For a system with discrete number of gates and limited time window the phasor approach needs to be adopted. The equation for reference semicircle is changed to:
formula_5
Where K is the number of gates and T is the total measurement window. The average lifetimes are calculated by:
And for a binary case after fitting a line through the data set of phasors and finding the slope (v) and interception (u) the lifetimes are calculated by:
formula_6
Effect of instrument response.
In a non-ideal and real situations, the measured decay curve is the convolution of the instrument response (the laser pulse distorted by system) with an exponential function which makes the analysis more complicated. Large number of techniques have been developed to overcome to this problem but in phasor approach this is simply solved by the fact that the Fourier transformation of a convolution is the product of Fourier transforms. This allows to take into account the effect of instrument response by taking the Fourier transformation of instrument response function and dividing the total phasor to instrument response transformation.
Spectral phasor.
Similar to temporal phasor the Fourier transformation of spectra can be used to make phasor. Considering a Gaussian spectrum with zero spectral width and changing the emission maximum from channel zero to K the phasor rotates on a circle from small angles to larger angles. This corresponds to shift theorem of Fourier transformation. Changing the spectral width from zero to infinity moves the phasor toward center. This means that the phasor for background signal which can be considered as a spectrum with infinite spectral width is located at center of phasor with coordinate of (0,0).
Linear property of the phasor approach.
One of the interesting property of the phasor approach is the linearity where the superposition of different spectra or decay curves can be analyzed by vectorial superposition of individual phasors. This is demonstrated in the figure where adding two spectra with different emission maximum resulted in a phasor which falls on a line connecting the phasors of individual phasors. For a ternary system adding 3 spectra falls inside a triangle made by phasors of individual spectra or decays.
Unmixing of Three components.
For a system which has three different components and they show different spectra, the phasor of the pixeles with different fractional intensities fall inside a triangle where the verti are made up by phasor of pure components. The fractional intensities then can be estimated by measuring the area of the triangle that each phasor makes with the phasor of pure vertix.
Reciprocal property.
This another interesting feature, there is a one-to-one correlation between the pixels in the image and their phasors on the phasor plot depending on their spectrum or decay curve. The phasors for pixels with similar temporal-spectral properties fall on a similar regions and this provide a mean for sorting the image pixels according to their temporal-spectral properties. By making region of interest on phasor plot a reciprocal transformation can be performed and the phasors can be projected back to the image which allows a basic segmentation.


Ptolemaia

Ptolemaia is a genus of extinct Afrotherian mammals from the Oligocene of East Africa. The genus and type species, "P. lyonsi", was described by Henry Fairfield Osborn in 1908 from the Jebel Qatrani Formation of Egypts' Fayum Depression. The genus name alludes to the Ptolemaic dynasty of Ancient Greece which ruled over the Egyptian region where "Ptolemaia" was discovered, while the specific epithet "lyonsi" honors H. G. Lyons, then director of the Egyptian Geological Survey. A second species, "P. grangeri", was described in 1987, and named after the early 20th century paleontologist Walter W. Granger. Fossils of "P. grangeri" are also known from Kenya.


Transrepression

In the field of molecular biology, transrepression is a process whereby one protein represses (i.e., inhibits) the activity of a second protein through a protein-protein interaction. Since this repression occurs between two different protein molecules (intermolecular), it is referred to as a trans-acting process.
The protein that is repressed is usually a transcription factor whose function is to up-regulate (i.e., increase) the rate of gene transcription. Hence the net result of transrepression is down regulation of gene transcription.
An example of transrepression is the ability of the glucocorticoid receptor to inhibit the transcriptional promoting activity of the AP-1 and NF-κB transcription factors. In addition to transactivation, transrepression is an important pathway for the anti-inflammatory effects of glucocorticoids. Other nuclear receptors such as LXR and PPAR have been demonstrated to also have the ability to transrepress the activity of other proteins.