Gholam A. Peyman

Gholam A. Peyman (born 1 January 1937) is an ophthalmologist, retina surgeon, and inventor. He is best known for his invention of LASIK eye surgery, a vision correction procedure designed to allow people to see clearly without glasses. He was awarded the first US patent for the procedure in 1989.
Life and career.
Peyman was born in Shiraz, Iran. At the age of 19, he moved to Germany to begin his medical studies. He received his MD at the University of Freiburg in 1962. He completed his internship at St. Johannes Hospital in Duisburg, Germany in 1964 and at Passaic General Hospital in Passaic, New Jersey in 1965. Peyman completed his residency in ophthalmology and a retina fellowship at the University of Essen, Essen Germany, in 1969 and an additional postdoctoral fellowship in retina at the Jules Stein Eye Institute, UCLA School of Medicine in Los Angeles in 1971. Peyman held the position of assistant professor of ophthalmology at the UCLA School of Medicine from 1971 and served as associate professor and then professor of ophthalmology and ocular oncology at the Illinois Eye and Ear Infirmary, University of Illinois at Chicago during 1971-1987.
Peyman held a joint appointment at the School of Medicine and also at the Neuroscience Center of Excellence at the Louisiana State University Medical University Medical Center in New Orleans during 1987-2000. During 1998-2000 Peyman held the Prince Abdul Aziz Bin Ahmed Bin Abdul Aziz Al Saud Chair in Retinal Diseases. During 2000-2006, Peyman served as professor of ophthalmology, ocular oncology and co-director, Vitreo-Retinal Service, Tulane University School of Medicine in New Orleans.
During 2006-2007 he was professor of ophthalmology at the University of Arizona, Tucson, with a cross appointment at University of Arizona College of Optical Sciences. He has been emeritus professor of ophthalmology at Tulane University since 2009.
Peyman is currently professor of basic medical sciences at the University of Arizona College of Medicine - Phoenix & Optical engineering at the University of Arizona in Tucson.
Peyman was awarded in 2013 an honoree doctorate degree from the National University of Cordoba in Argentina.
The Invention of LASIK surgery and its improvements.
At the Illinois Eye and Ear Infirmary, Peyman, because of his interest in the effects of lasers on tissues in the eye, began evaluating the potential use of a laser to modify corneal refraction in rabbits. No prior study had existed on this concept. The laser was applied to the surface of the cornea using different patterns. This laser created significant scarring. His conclusions at that time were: 1) one has to wait for the development of an ablative laser and 2) one should not ablate the surface of the cornea but, instead, the ablation should take place under a flap in order to prevent scarring, pain and other undesirable sequelae. Peyman published the first article on this subject in 1980.
In late 1982, he read an article from IBM Laboratories, published in "Laser Focus", describing the photo-ablative properties of an excimer laser on organic material. This was very exciting information, but, unfortunately, Peyman did not have access to this laser, which at the time was new and very expensive. By 1985 and beyond, many investigators were interested in ablating the corneal surface. However, because of his previous experience with the laser, Peyman wanted to avoid surface ablation in order to prevent potential corneal scarring and the pain associated with the removal of the corneal epithelium, necessary to expose the surface of the cornea. Therefore, in July 1985, he applied for a patent that described a method of modifying corneal refractive errors using laser ablation under a corneal flap. This US patent was accepted after two revisions and issued in June, 1989. Peyman performed a number of experimental studies evaluating the effect of various excimer lasers in collaboration with Physics Department of the University of Helsinki, Finland. Since he had purchased an Erb-Yag laser in the U.S., he evaluated the concept using this laser "in vivo" in rabbit and primate eyes and described the creation of a hinged corneal flap to enable the ablation to be performed on the exposed corneal bed, thus reducing the potential for postoperative scarring and pain.
Always aware of the potential limitations of his invention, Peyman devoted considerable time and effort in subsequent years to ameliorating them. In order to improve the risk/benefit considerations of the LASIK procedure, he invented in 2004 and patented a broad range of ablative and non-ablative inlays to be placed under the surgically
created corneal flap (US Patent 6,702,807). These inlays offered many potential advantages over the standard LASIK technique, the most significant of which is that the inlay procedure is reversible.
However their ablation was not predictable. In October 2009 Peyman invented and applied for a patent on a method of preventing corneal implant rejection, which was approved in 2017 (US Patent 9,681,942). It consisted of forming a Lasik flap in the cornea, raising the flap, inserting a lamellar cornea under the flap so as to overlie the exposed stromal tissue. The inlay is ablated with wavefront guided excimer laser, to correct the refractive errors of the eye, applying a cross linking solution to the inlay and stromal tissue of the cornea, replacing the corneal flap and cross linking the inlay with UV radiation, killing the cellular elements in the inlay and its surrounding cornea, preventing cellular migration in the inlay and its rejection or encapsulation by the host corneal cells. This new procedure is now called “Mesoick” (Meso means Inside, Implant, Crosslinking Keratomileusis (US Patent 9,037,033). This creates an immune privileged cell free space that does not initiate an immune response to an implant. A synthetic, crosslinked organic or polymeric lens can be implanted in the corneal pocket to compensate for the patient's refractive error. The implant can be exchanged as the eye grows or refractive need dictates.
Laser in ophthalmology.
Peyman has been granted 200 US Patents covering a broad range of novel medical devices, intra-ocular drug delivery, surgical techniques, as well as new methods of diagnosis and treatment.
Development of direct intraocular drug delivery and Vitrectomy
Surgical removal of intraocular tumors
Remote controlled system for Laser Surgery.
This technology enables an ophthalmologist to treat a patient located in another location e.g. another city by a laser system controlled remotely, via the internet, using a sophisticated secure system in a non-contact fashion.
Development of precision thermotherapy in oncology
Therapy of malignant tumors in early-stage along with imaging and immune therapy and precision localized drug delivery:
Tele-laser system and tele- medicine with a novel Dynamic Identity recognition
Macular degeneration
Intravitreal slow-release Rock inhibitors alone or in combination with Anti-VEGF
Artificial Retina Stimulation
Quantum dots and Optogenetic for artificial retinal and brain stimulation and gene therapy
Gene therapy with non-viral nanoparticles and CRISPR
Adaptic optic phoropter for automated vision correction and Tunable light field camera in use for VR and AR technology
Honors and awards.
Among other awards and honors, Peyman has received the National Medal of Technology and Innovation (2012), the Waring Medal of the "Journal of Refractive Surgery" (2008), and the American Academy of Ophthalmology's Lifetime Achievement Award (2008) He was named a fellow of the National Academy of Inventors in 2013.


Proavis

Proavis refers to a hypothetical extinct species or hypothetical extinct taxon and was coined in the early 20th century in an attempt to support and explain the hypothetical evolutionary steps and anatomical adaptations leading from non-avian theropod dinosaurs to birds. The term has also been used by defenders of the thecodontian origin of birds. The concept should not be confused with the genus "Protoavis".
History.
The term "Proavis" was first coined, although under the form "Pro-Aves", by English osteologist and zoologist William Plane Pycraft in "The Origin of Birds", a 1906 article published in the magazine "Knowledge and Scientific News". Pycraft added to his article his own drawn depiction of the hypothetical animal, a restoration entitled "One of the Pro-Aves". Pycraft's "Pro-Avis" (singular of "Pro-Aves") was arboreal, as suggested Professor Osborn six years before, in 1900, in an article dealing with the hypothetical common ancestors of dinosaurs and birds. Pycraft assumed that birds had developed as tree-dwelling dinosaurs, gliding on membranes between the limbs and the trunk. These membranes would gradually have been covered by increasingly more elongated scales, which eventually would have evolved into feathers.
A year after Pycraft's article, the Hungarian aristocrat and paleontologist Franz Nopcsa, who, while residing at London, had seen Pycraft's restoration, drew his own vision of the animal, a picture and article published in a 1907 issue of the "Proceedings of the Zoological Society of London" (an English science publication nowadays known as "Journal of Zoology"). But this time, for his own "Pro-Avis" restoration, Nopcsa suggested a cursorial origin, not arboreal. The "Pro-Avis" would thus have been a running animal, accelerating and prolonging its jumps by flapping with feathered forelimbs. There is a model of Nopcsa's restoration, still preserved, and recently restored, in the Grant Museum of Zoology, the only remaining university zoological museum in London.
When Pycraft published his book "A History of Birds", in 1910, he reinserted his 1906 restoration "One of the Pro-Aves" (in page 39). In the following years, as of 1913, Danish artist and amateur zoologist Gerhard Heilmann also used and popularised the term "Proavis", this time presenting the public with more accurate and anatomically probable drawings. Heilmann favoured a scientific model in which the assumed "Proavis" was arboreal and of thecodontian descent, thus not a dinosaur.
In 1961, Czech paleontologist Josef Augusta included "Proavis" in his book "Prehistoric Birds and Reptiles". The animal illustration, as were all illustrations in the book, was painted by Zdeněk Burian.
During the 1970s the work of John Ostrom, breathing new life into the hypothesis that birds were dinosaurs, revived the interest in the direct ancestors of birds. Ostrom assumed these were cursorial. An illustration of a running dinosaur explicitly indicated as a "Proavis" was in 1976 published by Dieter Stefan Peters.
In 1991 and 1996 "proavis" or "protoavis" models were proposed by respectively Samuel Tarsitano and Alan Feduccia, both adherents of the "thecodont" hypothesis about the origins of birds. These "proaves" were supposed to be arboreal, with short necks, long trunks, sprawling legs, non-elongated hindlimbs, small hands and feet, small general size, and gliding on membranes. Feduccia's "protoavis" had membranes on the forelimbs only and was fashioned on the model of "Megalancosaurus".
The term "Proavis" was used again in 1999, when Joseph Garner, Graham Taylor, and Adrian Thomas proposed their "pouncing proavis model", an hypothesis entailing that the origin of avian flight rested in a predatory behaviour, the "proavis" jumping on its prey from trees (see "pouncing proavis model" in Origin of avian flight).
In his 2002 book "Dinosaurs of the Air", Gregory S. Paul tried to conceptually model a "pro-avian". In his view the direct ancestors of birds cannot have been completely arboreal, because in that case they would probably have used membranes to fly. He thought they must have represented an intermediate ecological stage, in which the hindlimbs still had largely cursorial adaptations whereas the arms had been elongated in order to climb. Feathers, originally serving the insulation of an already warm-blooded animal, would by elongation have turned the arms into wings in order to fly. More generally, the proavians would, in view of their basal theropod forebears and bird descendants, have been typified by long necks, a short trunk, long fingers with opposable digits, a decoupling of the locomotor functions of the forelimbs and hindlimbs, a lack of a propatagium, a shallow tail, and a weight of about one kilogramme. Paul illustrated his analysis with a skeletal diagram, accompanied by a life illustration of a "proavis". When in 2013 "Aurornis" was described, at the time the most basal known member of the Avialae, the group consisting of birds and their closest relatives, the Italian paleontologist Andrea Cau remarked it bore an uncanny resemblance to Paul's "proavis".


Robert Fischell

Robert Fischell (born 1929) is a physicist, prolific inventor, and holder of more than 200 U.S. and foreign medical patents. His inventions have led to the creation of several biotechnology companies. He worked at the Johns Hopkins University Applied Physics Laboratory full-time for 25 years, and part-time for an additional 13 years. He contributed to APL's satellite navigation work, and later developed a rechargeable implantable pacemaker that could be programmed with radiowaves, (Pacesetter Systems purchased by Siemens, now the CRM division of St. Jude Medical). He and his team at Hopkins also helped miniaturize the implantable cardiac defibrillator. Mr. Fischell went on to invent the implantable insulin pump (MiniMed, spun off from Pacesetter Systems in 1985), numerous coronary stents used to open clogged arteries (IsoStent merged with Cordis, in turn purchased by Johnson & Johnson), and two feedback systems that provide early warning of epileptic seizures (NeuroPace) and heart attacks (Angel Medical Systems). Fischell recently donated $30 million to the University of Maryland College Park Foundation to establish a bioengineering department and an institute for biomedical devices at the A. James Clark School of Engineering.
In 2005, he was awarded the TED Prize, receiving $100,000 and three wishes, including a braintrust on medical liability and the successful design of a device to cure migraines.
Fischell received his B.S. in Mechanical Engineering from Duke University in 1951. He received his M.S. from the University of Maryland in 1953 in Physics, which is part of the University of Maryland College of Computer, Mathematical, and Natural Sciences. Fischell was awarded an honorary doctorate from the University of Maryland in 1996.
He has three sons (from oldest to youngest), David, Tim, and Scott Fischell. He is married to Susan R. Fischell and they live in Maryland.
He was awarded the National Medal of Technology and Innovation in 2016.


Class II PI 3-kinases

Class II PI 3-kinases are a subgroup of the enzyme family, phosphoinositide 3-kinase that share a common protein domain structure, substrate specificity and method of activation.
Class II PI 3-kinases were the most recently identified class of PI 3-kinases.
There are three class II PI 3-kinase isoforms expressed in mammalian cells;


SR 59230A

SR 59230A is a selective antagonist of the beta-3 adrenergic receptor, but was subsequently shown to also act at α1 adrenoceptors at high doses. It has been shown to block the hyperthermia produced by MDMA in animal studies.


DicF RNA

DicF RNA is a non-coding RNA that is an antisense inhibitor of cell division gene ftsZ. DicF is bound by the Hfq protein which enhances its interaction with its targets. Pathogenic "E. coli" strains possess multiple copies of sRNA DicF in their genomes, while non-pathogenic strains do not. DicF and Hfq are both necessary to reduce FtsZ protein levels, leading to cell filamentation under anaerobic conditions.


L-Ribonucleic acid aptamer

An -ribonucleic acid aptamer (-RNA aptamer, trade name Spiegelmer) is an RNA-like molecule built from -ribose units. It is an artificial oligonucleotide named for being a mirror image of natural oligonucleotides. -RNA aptamers are a form of aptamers. Due to their -nucleotides, they are highly resistant to degradation by nucleases. -RNA aptamers are considered potential drugs and are currently being tested in clinical trials.
Features.
Chemical properties.
-RNA aptamers, built using -ribose, are the enantiomers of natural oligonucleotides, which are made with -ribose. Nucleic acid aptamers, including -RNA aptamers, contain adenosine monophosphate, guanosine monophosphate, cytidine monophosphate, uridine monophosphate, a phosphate group, a nucleobase and a ribose sugar.
Biological characteristics.
Like other aptamers, -RNA aptamers are able to bind molecules such as peptides, proteins, and substances of low molecular weight. The affinity of -RNA aptamers to their target molecules often lies in the pico to nanomolar range and is thus comparable to antibodies.
-RNA aptamers themselves have low antigenicity. In contrast to other aptamers, -RNA aptamers have high stability in blood serum, since they are less susceptible to be cleaved hydrolytically by enzymes. They are excreted by the kidneys in a short time due to their low molar mass (which is below the renal threshold).
-RNA aptamers modified with a higher molar mass, such as PEGylated -RNA aptamers, show a prolonged plasma half-life.
Production.
Unlike other aptamers, -RNA aptamers are not directly made using systematic evolution of ligands by exponential enrichment (SELEX), as -nucleic acids are not amenable to enzymatic methods, such as polymerase chain reaction (PCR), used in SELEX. Therefore, the selection is done with mirrored target molecules.
Reflection of the target molecule.
The first step is the production of the target's enantiomer. In the case of peptides and small proteins that are produced synthetically, an enantiomer is made using synthetic -amino acids. If the target is a larger protein molecule, beyond synthetic abilities, the enantiomer of an epitope is produced.
SELEX.
Conventional (up to 1016 different oligonucleotides) existing molecule library serves as a starting point for the subsequent SELEX process. Selection, separation, and amplification using the mirror image of the target molecule is performed.
Sequencing and synthesis.
The sequence of the oligonucleotide selected using SELEX is determined with the help of DNA sequencing. This information is used for the synthesis of the oligonucleotide's enantiomer, the -RNA aptamer, using -nucleotides.
Use.
-RNA aptamers have been obtained for the chemokines CCL2 and CXCL12, the complement components C5a and ghrelin. They are currently in preclinical or clinical development. Proof-of-concept for an anti-CCL2/MCP-1 -RNA aptamers has recently been demonstrated in diabetic nephropathy patients. They can also be used as diagnostic agents.


Rebecca M. Bergman

Rebecca M. Bergman is an American chemical engineer and the President of Gustavus Adolphus College in St. Peter, Minnesota. She began her term in July 2014, and is the first woman to serve as President at the college, which was founded in 1862. Before her presidency, she was a senior executive at Medtronic, and served on the college's Board of Trustees from 2007 to 2014.
Medtronic career.
Bergman received a B.S. in chemical engineering from Princeton University, followed by a Ph.D. in chemical engineering and material science from the University of Minnesota.
Bergman spent 26 years at Medtronic, Inc., from 1988 to 2014, including 14 as a senior executive. Her most recent position was Vice President of Research, Technology, and Therapy Delivery Systems for the company’s Cardiac Rhythm Disease Management (CRDM) business, where she led a research and development team of scientists and engineers. She previously served as Vice President, CRDM New Therapies & Diagnostics as well as Vice President, Corporate Science and Technology, where she directed biomaterials and biosciences R&D, new therapy development, and information management initiatives.
Honors and Distinctions.
Bergman was elected as a Fellow of the American Institute for Medical and Biological Engineering in 2001. She was also elected as a member into the National Academy of Engineering in 2010 for technical leadership in the development of interventional vascular devices and drug delivery systems.
She serves as a member of the Board of Directors of Sigma-Aldrich, on the Board of Directors of The Bakken Museum, and on a number of academic advisory boards. She previously served on the National Advisory Council of the National Institute of Biomedical Imaging and Bioengineering of the National Institute of Health and the St. Catherine University Board of Trustees.


D-glutamate(D-aspartate) oxidase

In enzymology, a D-glutamate(D-aspartate) oxidase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are D-glutamate, H2O, and O2, whereas its 3 products are 2-oxoglutarate, NH3, and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with oxygen as acceptor. The systematic name of this enzyme class is D-glutamate(D-aspartate):oxygen oxidoreductase (deaminating). Other names in common use include D-glutamic-aspartic oxidase, and D-monoaminodicarboxylic acid oxidase. This enzyme participates in alanine and aspartate metabolism. It employs one cofactor, FAD.


BRL-54443

BRL-54443 is a drug which acts as a selective agonist for the 5-HT1E and 5-HT1F serotonin receptor subtypes.


C0465 RNA

The C0465 RNA is a bacterial non-coding RNA of 78 nucleotides in length that is found between the "tar" and "cheW" genes in the genomes of "Escherichia coli" and "Shigella flexneri". This ncRNA was originally identified in E.coli using high-density oligonucleotide probe arrays (microarray). The function of this ncRNA is unknown.


Flagellin

Flagellin is a globular protein that arranges itself in a hollow cylinder to form the filament in a bacterial flagellum. It has a mass of about 30,000 to 60,000 daltons. Flagellin is the principal component of bacterial flagellum, and is present in large amounts on nearly all flagellated bacteria.
Structure.
The structure of flagellin is responsible for the helical shape of the flagellar filament, which is important for its proper function. It is transported through the center of the filament to the tip where it polymerases spontaneously into a part of the filament. It is unfolded by the FliS () flagellar secretion chaperone during transport. The filament is made up of eleven smaller "protofilaments", nine of which contains flagellin in the L-type shape and the other two in the R-type shape.
The helical N- and C-termini of flagellin form the inner core of the flagellin protein, and is responsible for flagellin's ability to polymerize into a filament. The middle residues make up the outer surface of the flagellar filament. While the termini of the protein are quite similar among all bacterial flagellins, the middle portion is wildly variable and can be absent in some species. The flagellin domains are numbered from the helical core (D0/D1) to the outside (D2, ...); when viewed from the amino-acid sequence, D0/D1 appears on the two termini. Flagellin-like structural proteins are found in other portions of the flagellum, such as the hook (flgE; ), the rod at the base, and the cap at the top.
The middle part of  "E. coli" (and related) flagellin, D3, displays a beta-folium fold and appears to maintain flagellar stability.
Immune response.
In mammals.
Mammals often have acquired immune responses (T-cell and antibody responses) to flagellated bacterium, which occur frequently to flagellar antigens. Flagellin has also been shown to directly interact with TLR5 on T cells. Some bacteria are able to switch between multiple flagellin genes in order to evade this response.
The propensity of the immune response to flagellin may be explained by two facts:
In plants.
In addition, a 22-amino acid sequence (flg22) of the conserved N-terminal part of flagellin is known to activate plant defence mechanisms. Flagellin perception in "Arabidopsis thaliana" functions via the receptor-like-kinase FLS2 (FLAGELLIN SENSING 2). Upon flg22 detection, FLS2 quickly binds to BAK1 (BRI1-associated kinase 1) to initiate signalling by reciprocal transphosphorylation of their kinase domains. Mitogen-activated-protein-kinases (MAPK) acts as downstream signalling compounds, leading ultimately to PAMP-triggered immunity in which more than 900 genes are up-/down-regulated upon flg22 treatment.
Pre-stimulation with a synthetic flg22-peptide led to enhanced resistance against bacterial invaders.


Baccatin III

Baccatin III is an isolate from the yew tree (Genera "Taxus"). Baccatin III is a precursor to the anti-cancer drug paclitaxel (Taxol).
In 2014, researchers reported introduction and expression of the endophytic fungal gene responsible for synthesizing baccatin III (10-deacetylbaccatin III 10-O-acetyltransferase), to the mushroom "Flammulina velutipes". Researchers achieved the same accomplishment with" Escherichia coli" in 2000.


Giant golden mole

The giant golden mole "(Chrysospalax trevelyani)" is a small mammal found in Africa. At in length, it is the largest of the golden mole species. The mole has dark, glossy brown fur; the name "golden" comes from the Greek word for green-gold, the family Chrysochloridae name.
Characteristics.
The giant golden mole has a subterranean lifestyle. It has large claws, powerful fore limbs, no external tail or ears, wedge-shaped head, leather pad, and skin covering the eyes. It is approximately 208-235 millimetres in length and 410-500 grams in weight. With dark and brown skin on the upper parts and faded on the underparts, the hair is longer and coarser than any other species of golden mole: thick, with dense, woolly underfur.
Biology.
The largest, rarest, and most endangered of all 17 species of golden moles, the giant golden mole spends most of its time underground and is blind and deaf. It is nocturnal, hunting mostly at night, but also in some cool and cloudy daytime conditions. It is solitary; it does not form groups, despite some social behavior such as hibernating in others' burrows among the roots of trees in winter, only moving slightly to keep its body temperature in range and twitching to maintain body temperature while sleeping. Female Giant Golden moles give birth to one or two offspring at a time while it has stocks of food supply.
Diet.
The giant golden mole digs semi-permanent tunnels for hunting food and may feed on the surface hiding in the leaf litter. It eats mainly millipedes and giant earthworms, but also crickets, cockroaches, grasshoppers, worms, and snails.
Habitat.
The giant golden mole is a subterranean small mammal, living in chambers and passages underneath a very specific habitat, forests with soft soil, deep leaf litter layers, and well-developed undergrowth. The giant golden mole is endemic to South Africa, mostly in a restricted area in the Eastern Cape.
Population.
Status.
The giant golden mole was classified as Endangered (EN) in 2010 on IUCN Red List of Threatened Species. The population is decreasing due to habitat loss resulting mainly from human activities affecting its habitat such as firewood collection, bark stripping, cutting for construction, overgrazing of livestock, and clearance of forest. Moreover, the giant golden mole is preyed on by domestic dogs in that area.
Conservation.
The giant golden mole currently receives little protection, and is not a main conservation target. Research is needed to protect this species and to assess the status and viability of the remaining populations.


Chlorobium

Chlorobium (also known as "Chlorochromatium") is a genus of green sulfur bacteria. They are photolithotrophic oxidizers of sulfur and most notably utilise a noncyclic electron transport chain to reduce NAD+. Photosynthesis is achieved using a Type 1 Reaction Centre using bacteriochlorophyll (BChl) "a". Two photosynthetic antenna complexes aid in light absorption: the Fenna-Matthews-Olson complex ("FMO", also containing BChl "a"), and the chlorosomes which employ mostly BChl "c", "d", or "e". Hydrogen sulfide is used as an electron source and carbon dioxide its carbon source.
"Chlorobium" species exhibit a dark green color; in a Winogradsky column, the green layer often observed is composed of "Chlorobium". This genus lives in strictly anaerobic conditions below the surface of a body of water, commonly the anaerobic zone of a eutrophic lake.
"Chlorobium aggregatum" is a species which exists in a symbiotic relationship with a colorless, nonphotosynthetic bacteria. This species looks like a bundle of green bacteria, attached to a central rod-like cell which can move around with a flagellum. The green, outer bacteria use light to oxidize sulfide into sulfate. The inner cell, which is not able to perform photosynthesis, reduces the sulfate into sulfide. These bacteria divide in unison, giving the structure a multicellular appearance which is highly unusual in bacteria.
"Chlorobium" species are thought to have played an important part in mass extinction events on Earth. If the oceans turn anoxic (due to the shutdown of ocean circulation) then "Chlorobium" would be able to out compete other photosynthetic life. They would produce huge quantities of methane and hydrogen sulfide which would cause global warming and acid rain. This would have huge consequences for other oceanic organisms and also for terrestrial organisms. Evidence for abundant "Chlorobium" populations is provided by chemical fossils found in sediments deposited at the Cretaceous mass extinction.
The complete "C. tepidum" genome, which consists of 2.15 megabases (Mb), was sequenced and published in 2002. It synthesizes chlorophyll "a" and bacteriochlorophylls (BChls) "a" and "c", of which the model organism has been used to elucidate the biosynthesis of BChl "c". Several of its carotenoid metabolic pathways (including a novel lycopene cyclase) have similar counterparts in cyanobacteria.
Molecular signatures for "Chlorobi".
Comparative genomic analysis has led to the identification of 2 conserved signature indels which are uniquely found in members of the phylum "Chlorobi" and are thus characteristic of the phylum. The first indel is a 28-amino-acid insertion in DNA polymerase III and the second is a 12 to 14 amino acid insertion in alanyl-tRNA synthetase. These indels are not found in any other bacteria and thus serve as molecular markers for the phylum. In addition to the conserved signature indels, 51 proteins which are uniquely found in members of the phylum "Chlorobi". 65 other proteins have been identified which are unique to the "Chlorobi" phylum, however these proteins are missing in several "Chlorobi" species and are not distributed throughout the phylum with any clear pattern. This means that significant gene loss may have occurred, or the presence of these proteins may be a result of horizontal gene transfer. Of these 65 proteins, 8 are found only in "Chlorobium luteolum" and "Chlorobium phaeovibrioides". These two species form a strongly supported clade in phylogenetic trees and a close relationship between these species is further supported by the unique sharing of these 8 proteins.
Relatedness of "Chlorobi" to "Bacteroidetes" and "Fibrobacteres" phyla.
Species from the "Bacteroidetes" and "Chlorobi" phyla branch very closely together in phylogenetic trees, indicating a close relationship. Through the use of comparative genomic analysis, 3 proteins have been identified which are uniquely shared by virtually all members of the "Bacteroidetes" and "Chlorobi" phyla. The sharing of these 3 proteins is significant because other than these 3 proteins, no proteins from either the" Bacteroidetes" or "Chlorobi" phyla are shared by any other groups of bacteria. Several conserved signature indels have also been identified which are uniquely shared by members of the "Bacteroidetes" and "Chlorobi" phyla. The presence of these molecular signatures supports the close relationship of the "Bacteroidetes" and "Chlorobi" phyla. Additionally, the phylum "Fibrobacteres" is indicated to be specifically related to these two phyla. A clade consisting of these three phyla is strongly supported by phylogenetic analyses based upon a number of different proteins These phyla also branch in the same position based upon conserved signature indels in a number of important proteins. Lastly and most importantly, two conserved signature indels (in the RpoC protein and in serine hydroxymethyltransferase) and one signature protein PG00081 have been identified that are uniquely shared by all of the species from these three phyla. All of these results provide compelling evidence that the species from these three phyla shared a common ancestor exclusive of all other bacteria and it has been proposed that they should all recognized as part of a single “FCB”superphylum.


Aliasger K. Salem

Aliasger K. Salem is the Bighley Chair and Professor of Pharmaceutical Sciences at the University of Iowa College of Pharmacy. Salem's primary appointment at the University of Iowa is based in the College of Pharmacy, with additional secondary appointments in the College of Dentistry, Department of Chemical and Biochemical Engineering, Department of Biomedical Engineering, Department of Chemistry, and the Holden Comprehensive Cancer Center.
Salem was an American Cancer Society Research Scholar from 2009 to 2013. Salem is currently the leader of the Experimental Therapeutics (ET) program at the Holden Comprehensive Cancer Center and co-director of the Nanotoxicology Core at the Environmental Health Sciences Research Center. Aliasger Salem is the Associate Editor for The AAPS Journal - The official journal of the American Association for Pharmaceutical Scientists (Springer-Nature) and an editorial board member for a number of other journals including the International Journal of Pharmaceutics (Elsevier). Aliasger Salem has been or is a member of a number of grant review study sections including panels for the American Cancer Society, the National Institutes of Health, the National Science Foundation, and the Department of Defense (DoD): Congressionally Directed Medical Research Programs (CDMRP) Prostate and Breast Cancer Research Programs.
Salem has received a number of teaching awards including a Council of Teaching Instructional Improvement Award in 2008 and a Collegiate Teacher of the Year award in 2012. He serves as a faculty adviser in the National Organization for the Professional Advancement of Black Chemists and Chemical Engineers. Prior to joining the University of Iowa in 2004, he was a postdoctoral fellow at the Johns Hopkins School of Medicine and completed his PhD at the School of Pharmacy and Pharmaceutical Sciences at the University of Nottingham in the UK.
Salem's research interests include nanotechnology, microfabrication, particle and drug delivery systems, implantable chips, the design of gene delivery systems, regenerative medicine, and the development of vaccines.


Emulate

Emulate, Inc. (Emulate) is a startup company that is commercializing Organs-on-Chips technology—a human cell-based technology that recreates organ-level function to model organs in healthy and diseased states. The technology has applications in pharmaceutical research, product development, testing how different medicines, chemicals, and foods affect human health. Emulate has also worked with Cedars-Sinai Medical Center on a precision medicine initiative that uses Organs-on-Chips technology in the clinical setting. This initiative is designed to provide clinicians with better data about how an individual patient may respond to treatment. The company also signed a Cooperative Research and Development Agreement (CRADA) with the U.S. Food and Drug Administration to advance and qualify its Human Emulation System to meet regulatory evaluation for product testing.
Technology.
Emulate's Organs-on-Chips technology has been used to recreate the function of a variety of different organs, including the liver, intestine, brain, kidney, and lung. The company's Organ-Chips are about the size of a AA battery and feature two fluidic channels that create the flow of blood and other fluids. The chips are made of a flexible polymer and can be stretched to recreate similar motions to those of breathing or peristalsis. The company has developed a Human Emulation System that combines its Organ-Chips along with hardware and software apps. The system is designed to reduce some of the complexities of working with Organs-on-Chips technology and is built around the Organ-Chip, which recreates the microenvironment of an organ that is found within the body. An instrument called Zoë Culture Module provides pressure driven flow and recreates perfusion pressure and shear forces like those experienced in the human body.
History.
Emulate was spun out from the Wyss Institute for Biologically Inspired Engineering at Harvard University, where the technology was initially invented and then extensively developed. Scientific Founder Donald Ingber founded the company around 2013. James Coon is a co-founder and been the CEO since the company was incorporated. Geraldine Hamilton is the company's President and Chief Science Officer and Daniel Levner is the Chief Technology Officer.
In July 2014, the founders raised $12 million in a first round of financing. In March 2016, the company raised a Series B round of investment of $28 million from repeat and new investors, including NanoDimension, ALS Finding a Cure, Atel Ventures and Laboratory Corp. of America Holdings. In February 2018, Emulate formed strategic partnerships with Roche, a Swiss-based pharmaceutical company, and Takeda, a pharmaceutical company based in Japan. The company raised its most recent round of funding in June 2018 when they announced that they had raised a Series C round of funding led by Silicon Valley-based capital firm Founders Fund.


Biopanning

Biopanning is an affinity selection technique which selects for peptides that bind to a given target. All peptide sequences obtained from biopanning using combinatorial peptide libraries have been stored in a special freely available database named BDB. This technique is often used for the selection of antibodies too.
Biopanning involves 4 major steps for peptide selection. The first step is to have phage display libraries prepared. This involves inserting foreign desired gene segments into a region of the bacteriophage genome, so that the peptide product will be displayed on the surface of the bacteriophage virion. The most often used are genes pIII or pVIII of bacteriophage M13.
The next step is the capturing step. It involves conjugating the phage library to the desired target. This procedure is termed panning. It utilizes the binding interactions so that only specific peptides presented by bacteriophage are bound to the target. For example, selecting antibody presented by bacteriophage with coated antigen in microtiter plates.
The washing step comes after the capturing step to wash away the unbound phages from solid surface. Only the bound phages with strong affinity are kept. The final step involves the elution step where the bound phages are eluted through changing of pH or other environment conditions.
The end result is the peptides produced by bacteriophage are specific. The resulting filamentous phages can infect gram-negative bacteria once again to produce phage libraries. The cycle can occur many times resulting with strong affinity binding peptides to the target.


Hymenistatin

Hymenistatin is a cyclic peptide isolated from the sea sponge "Phakellia fusca". It is a cyclic octapeptide whose sequence is cyclo[Ile-Ile-Pro-Pro-Tyr-Val-Pro-Leu].


Mivazerol

Mivazerol is an alpha-adrenergic agonist.


Cyclobacterium qasimii

Cyclobacterium qasimii is a horseshoe-shaped, psychrotolerant and non-motile bacterium from the genus of Cyclobacterium which has been isolated from marine sediments from Kongsfjorden in Svalbard.


SKF-38,393

SKF-38,393 is a synthetic compound of the benzazepine chemical class which acts as a selective D1/D5 receptor partial agonist. It has stimulant and anorectic effects.


Guanoxabenz

Guanoxabenz is a metabolite of guanabenz.


Bivalent chromatin

Bivalent chromatin are segments of DNA, bound to histone proteins, that have both repressing and activating epigenetic regulators in the same region. These regulators work to enhance or silence the expression of genes. Since these regulators work in opposition to each other, they normally interact with chromatin at different times. However, in bivalent chromatin, both types of regulators are interacting with the same domain at the same time. Bivalent chromatin domains are normally associated with promoters of transcription factor genes that are expressed at low levels. Bivalent domains have also been found to play a role in developmental regulation in pluripotent embryonic stems cells, as well as gene imprinting.
Bivalent epigenetic regulators.
The most common antagonistic epigenetic regulators found together on bivalent chromatin domains are methylation marks on histone 3 lysine 4 (H3K4me3) and histone 3 lysine 27 (H3K27me3). The H3K27me3 mark silences the gene while the H3K4me3 mark allows the gene to not be permanently silenced, and activated when needed. Embryonic stem cells and imprinted genes are associated with both activating (H3K4me3) and repressive (H3K27me3) marks, as they allow a gene to be repressed until activation is needed. Although there is abundant evidence for co-localization of H3K4me3 and H3K27me3 at the same location in the genome, most evidence suggests that they do not occur on the same molecule but may occur on different copies of histone H3 within the same nucleosome.
Embryonic stem cells and development.
Bivalent chromatin domains are found in embryonic stem (ES) cells and play an important role in cell differentiation. When keeping an ES cell in its undifferentiated state, bivalent domains of DNA are used to silence developmental genes that would activate cell differentiation, while keeping the genes poised and ready to be activated. When an ES cell receives a signal to differentiate into a specified cell lineage, activation of the specific developmental genes are needed for differentiation. The developmental genes needed will be activated and the other genes that are not required for that cell lineage will be repressed through their bivalent domains.
H3K4me3 and H3K27me3 marks found on the bivalent domains regulate whether or not an embryonic stem cell differentiates or remains unspecified (pluripotent state). The epigenetic marks contribute to the expression of some genes, and silencing of others during pluripotency and differentiation. H3K27me3 marks repress developmental control genes and stop the cell from differentiating, to ensure that the cell maintains pluripotency. Although this mark represses the lineage control genes, it does keep them ready for activation upon differentiation. When the cell receives the signal to differentiate to a specific type of cell, H3K27me3 will be removed from the genes needed for differentiation, while H3K27me3 maintains repression of developmental control genes that are unnecessary for the chosen lineage. The developmentally regulated process of resolving bivalent chromatin is aided by the activity of ATP-chromatin remodelers such as SWI/SNF, which hydrolyze ATP to evict Polycomb-group proteins from bivalent chromatin.
Only a specific subset of regulators will be activated by H3K4me3 to give a certain cell lineage. This mark activates developmental regulators upon differentiation, and makes the genes needed for differentiation more efficient. Having the activating H3K4me3 mark protects genes from being silenced permanently by repelling transcription repressors and blocking repressive DNA methylation.
Once the cell has differentiated to a specific type of cell only one of the marks remain associated with the chromatin.
Imprinting.
Imprinting is the process by which one parental allele is silenced while the allele from the other parent is expressed. The human "GRB10" gene displays imprinted gene expression, and in mice, this imprinted Grb10 expression is enabled by the presence of bivalent chromatin. The Grb10 gene in mice has a bivalent domain that uses H3K4me3 and H3K27me3 modifications as a tool to express genes from one parent while the other is silenced. This allows the gene to be expressed by only one parent in a specific tissue. In most somatic tissues, the Grb10 gene is expressed from the maternal allele, except in the brain where it is expressed from the paternal allele. H3K4me3 and H3K27me3 marks are used on the paternal allele of the gene to keep it silenced in all tissues except the brain. The same methylation marks are used on the maternal allele of the gene in brain tissue. When the genes are being expressed the H3K27me3 repressive mark is removed from the bivalent domain.


GRIA3

Glutamate receptor 3 is a protein that in humans is encoded by the "GRIA3" gene.
Function.
Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. This gene belongs to a family of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Alternative splicing at this locus results in several different isoforms which may vary in their signal transduction properties.
Genome studies have uncovered a tentative link between defective GRIA3 variants and a highly elevated risk of schizophrenia.
Interactions.
GRIA3 has been shown to interact with GRIP1 and PICK1.
RNA editing.
Several ion channels and neurotransmitters receptors pre-mRNA as substrates for ADARs. This includes 5 subunits of the glutamate receptor: ionotropic AMPA glutamate receptor subunits (Glur2, Glur3, Glur4) and kainate receptor subunits (Glur5, Glur6). Glutamate gated ion channels are made up of four subunits per channel with each subunit contributing to the pore loop structure. The pore loop structure is related to that found in K+ channels (e.g., human Kv1.1 channel). The human Kv1.1 channel pre mRNA is also subject to A to I RNA editing. The function of the glutamate receptors is in the mediation of fast neurotransmission to the brain. The diversity of the subunits is determined, as well as rna splicing by RNA editing events of the individual subunits. This give rise to the necessarily high diversity of these receptors. GluR3 is a gene product of the GRIA3 gene and its pre-mRNA is subject to RNA editing.
Type.
A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3, with ADAR1 and ADAR2 being the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR2 are widely expressed in tissues while ADAR3 is restricted to the brain. The double-stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site with residues usually in a neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS)
Location.
The pre-mRNA of this subunit is edited at one position. The R/G editing site is located in exon 13 between the M3 and M4 regions. Editing results in a codon change from an arginine (AGA) to a glycine (GGA). The location of editing corresponds to a bipartite ligand interaction domain of the receptor. The R/G site is found at amino acid 769 immediately before the 38-amino-acid-long flip and flop modules introduced by alternative splicing. Flip and Flop forms are present in both edited and nonedited versions of this protein. The editing complementary sequence (ECS) is found in an intronic sequence close to the exon. The intronic sequence includes a 5' splice site. The predicted double stranded region is 30 base pairs in length. The adenosine residue is mismatched in genomically encoded transcript, however this is not the case following editing. Despite similar sequences to the Q/R site of GluR-B, editing at this site does not occur in GluR-3 pre-mRNA. Editing results in the targeted adenosine, which is mismatched prior to editing in the double-stranded RNA structure to become matched after editing. The intronic sequence involved contains a 5' donor splice site.
Conservation.
Editing also occurs in rat.
Regulation.
Editing of GluR-3 is regulated in rat brain from low levels in embryonic stage to a large increase in editing levels at birth. In humans, 80-90% of GRIA3 transcripts are edited. The absence of the Q/R site editing in this glutamate receptor subunit is due to the absence of necessary intronic sequence required to form a duplex.
Consequences.
Structure.
Editing results in a codon change from (AGA) to (GGA), an R to a G change at the editing site.
Function.
Editing at R/G site allows for faster recovery from desensitisation. Unedited Glu-R at this site have slower recovery rates. Editing, therefore, allow sustained response to rapid stimuli. A crosstalk between editing and splicing is likely to occur here. Editing takes place before splicing. All AMPA receptors occur in flip and flop alternatively spliced variants. AMPA receptors that occur in the Flop form desenstise faster than the flip form. Editing is also thought to affect splicing at this site.


Zero ionic layer

Zero ionic layer is the main site of interaction in the core SNARE complex. Dipole-dipole interactions take place between 3 glutamine (Q) residues and 1 arginine (R) residue exposed in this layer. Despite that, the majority of the SNARE complex is hydrophobic because of the leucine zipper. Extensively studied layers within the SNARE alpha-helical bundle are designated from "-7" to "+8". Zero ionic layer is at the center of the bundle, and thus designated as "0" layer.
Structure.
SNARE complex is a bundle formed by 4 alpha-helical proteins, including vesicle-associated Synaptobrevin and cell-membrane-associated Syntaxin and SNAP. When the bundle is viewed on the side, for every alpha-helical turn, the alpha-carbons from each helix form a plane, which is thus designated as a "layer". Along the helical bundle from N-terminus to C-terminus, layers are designated from "-7" to "+8" respectively. "0" layer (i.e. zero ionic layer) is at the center of the helical bundle.
The zero ionic layer is an ionic domain within the otherwise largely hydrophobic alpha-helical complex (SNARE complex) . It is stabilized by attractive forces(dipole-dipole interactions) between three partially negatively charged carbonyl groups of glutamine residues and a positively charged arginine. Specifically, these interacting groups include Q226 on Syntaxin, Q53 on SNAP-25 (Sn1), Q174 on SNAP-25 (Sn2) and R56 on Synaptobrevin (v-SNARE).
The 4 amino acids are asymmetrically arranged in the layer, as shown in the picture. However, their intensive interactions ensure the layer's stability: the arginine side chain end lies in the center of the asymmetry and amino groups form hydrogen bonds with the three glutamine residues. Thus, steric and electrostatic fit is well established.
Function and research interest.
SNARE proteins are a family of a proteins that are located in cell membranes to mediate any secretory pathways. The complex is formed during exocytosis, a process where the vesicles inside the cell fuse with the cell membrane to secrete molecules into the extracellular space.
The zero ionic layer of the SNARE complex is at special interest to scientists studying SNARE because of its three characteristics. Firstly, it is the only hydrophilic region in the entire hydrophobic SNARE complex; secondly, unlike most of the other layers, it displays asymmetry; thirdly, the 3Q:1R arrangement is found in almost all of the SNARE superfamily among eukaryotic cells. These unique aspects imply its importance to eukaryotic organisms in general. However, the exact and functions of zero ionic layer is still under investigation.
Previous studies have focused on how mutations in this layer would affect the functionality of SNARE complex in secretory pathways. Even though the exact mechanism still awaits further investigation, these studies have revealed that the integrity of zero ionic layer is not essential to the proper alignment during complex formation, but it is essential to the disassociation of SNARE complex and the recycling of its 4 constituent alpha-helical proteins after exocytosis.
An ATPase (NSF) together with a cofactor (α-SNAP) facilitates the breakdown of the SNARE complex after the completion of exocytosis. Studies have suggested that, during the disassociation process, the NSF/α-SNAP complex acts specifically on the zero ionic layer, particularly, the glutamine residue (Q226) in Syntaxin. The glutamine residue transmits the conformational change of NSF/α-SNAP complex to the SNARE complex in order to disrupt and thus disassociate the SNARE complex at the zero ionic layer. More specifically, even though the ionic layer is buried within the hydrophobic complex for the most part, during disassociation, NSF/α-SNAP complex may disturb the hydrophobic shielding and thus let water molecules into the core. This exposure of other hydrophilic molecules disturb the original hydrogen bonding equilibrium and thus facilitate disassembly of the alpha-helical bundle.
Mutation and alternation.
In studies that use exocytotic SNAREs of yeast as models, a mutation from glutamine to arginine in the zero ionic layer leads to yeast cells that have deficient growth and protein secretion ability. However, a mutation from arginine to glutamine in this layer leads to yeast cells that are functionally wild-type. In the mutation where all four amino acids in the zero ionic layer are glutamine residues, the cells still exhibit normal secretory ability, but defects may become pronounced when there are other mutations.
Complementary mutations, where a glutamine to arginine mutation is paired with an arginine to glutamine mutation in the zero ionic layer, have resulted in functionally wild-type yeast cells too, according to their secretory ability.
These mutation studies have been done to study the role of the four amino acids in zero ionic layer. Underlying mechanisms of why these mutations would lead to certain results are not well discussed. In general, the glutamine residues in this layer are of critical importance to the functionality of mutated strains. As long as the glutamine is intact or compensated in someway during mutation, functionality of SNARE complex will be retained.


Thiobuscaline

Thiobuscaline, or 3,5-dimethoxy-4-butylthiophenethylamine, is a lesser-known psychedelic drug.
History.
It is an analog of buscaline. Thiobuscaline was first synthesized by Alexander Shulgin. In his book "PiHKAL (Phenethylamines i Have Known And Loved)", the dosage range is listed as 60–120 mg, and the duration is listed as 8 hours. Thiobuscaline is an entheogen, and it causes a threshold. Very little data exists about the pharmacological properties, metabolism, and toxicity of thiobuscaline.


Talinolol

Talinolol is a beta blocker.
Stereochemistry.
Talinolol contains a stereocenter and consists of two enantiomers. This is a racemate, i.e. a 1: 1 mixture of ("R")- and the ("S")-forms:


Daisy Yen Wu

Daisy Yen Wu (, 12 June 190227 May 1993) was the first Chinese woman engaged as an academic researcher in biochemistry and nutrition. Born into a wealthy industrial family in Shanghai, from a young age she was tutored in English and encouraged to study. She graduated from Nanjing Jinling Women's University in 1921 and then studied in the United States, graduating with a master's degree in biochemistry from Teachers College, Columbia University in 1923. Returning to China, she became an assistant professor at Peking Union Medical College between 1923 and her marriage at the end of 1924 to Hsien Wu. Collaborating with him, she conducted research on proteins and studied nutrition. After their marriage she continued to assist in the research conducted by Wu as an unpaid staff member until 1928. She and her husband collaborated in writing the first Chinese textbook on nutrition, which remained in print through the 1990s.
While raising their children, Yen Wu recognized that educational opportunities were limited and founded the Mingming School () in 1934 to provide a modern comprehensive education for Chinese children. She also raised funds in 1936 to build a school hospital for their alma mater, the Jinling Women's College, and earned a degree in French. In 1949, as her husband was in the United States and unable to return because of the Chinese Communist Revolution, she took the children abroad. Hired as a researcher for the Medical College of Alabama, she resumed collaboration with her husband, until his death in 1959. Moving to New York City in 1960, she conducted research for the United Nations Children's Fund to develop nutritional standards from 1960 to 1964. From 1964 to 1971 she worked as a lecturer and created a reference library for the Institute of Human Nutrition at Columbia University College of Physicians and Surgeons and from 1971 to 1987 she worked at St. Luke's Hospital Center, creating a library for the New York Obesity Research Center. Throughout her life, Yen Wu created numerous scholarships in China, Taiwan, and the United States which bear the name of family members and allow students to further their education. She died in 1993 in Ithaca, New York.
Early life.
Yan Caiyun was born on 12 June 1902 in Shanghai, China, to Yang Lifen () and (). Her mother was a Christian and raised the couple's twelve children. Her father was from the well-to-do () and was employed in the Ministry of Agriculture, Industry and Commerce. He eventually took over and managed the family businesses. Yan's paternal grandfather, () served as an advisor to Li Hongzhang, an official of the Qing dynasty, and was an industrialist. He founded China's salt industry, as well as banks, factories, pharmacies, and tea shops around the country. Both her grandfather and father were also talented painters and calligraphers. Convinced of the importance of education, Yan Zijun hired teachers from the university to tutor the children from a young age in English and Chinese before they attended primary school in Shanghai.
In 1908, Yan entered McTyeire School, a private girls' school. In 1913, the family moved to Tianjin, where Yan and two of her sisters, and Youyun prepared for the entrance exams of the Chinese and Western Girls' High School. She passed the examination and enrolled in the middle of 1914, completing her studies there in June 1917. She was admitted to Nanjing Jinling Women's University (later renamed Ginling College), earning a bachelor's degree with honours in 1921. As Yan was keen to continue her education, her father allowed her to go abroad to study in the United States. She enrolled in chemistry studies at Smith College in 1922, and began using the English name "Daisy Yen". Over the summer break, she took courses at the University of Chicago in chemistry, nutrition, and physics and the next fall enrolled in biochemistry courses at Teachers College, Columbia University. She studied nutrition, a field which at the time was in its infancy, under Henry Clapp Sherman and Mary Swartz Rose, taking particular interest in the analysis of vitamin content in food. She received her master's degree in May 1923.
Career.
Scientific work (1923–1928).
Yen was hired by the China Medical Board of the Rockefeller Foundation as an assistant professor in biochemistry at Peking Union Medical College and contracted for a year from September 1923. The biochemistry department had just been founded and Yen was its second employee. She lectured and worked as an assistant to Hsien Wu, whose research initially focused on blood chemistry. She assisted in his research on protein denaturation and published several papers with him: "关于稀酸、稀碱对蛋白质作用的一些新观察" (Some New Observations on the Effects of Dilute Acids and Bases on Proteins, 1924), "蛋白质变性的研究，I．稀酸和稀碱对蛋白质的影响" (Research on Protein Denaturation, I: The Effect of Dilute Acid and Alkali on Protein, 1924), "蛋白质的热变性" (Thermal Denaturation of Protein, 1925), and "乳胶体对有色溶液的作用" (The Effect of Latex on Colored Solution, 1926). These studies would later become the basis for Hsien Wu's theory on protein denaturation first presented in 1931.
Despite her contract being renewed for another year, when Yen and Wu decided to marry, she knew her position would be terminated, as there was a policy that spouses could not work together. The couple married on 20 December 1924 in Shanghai and Yen Wu resigned. They honeymooned in the United States and Yen Wu made plans to resume her studies and complete her doctoral work under Sherman at Columbia. She accompanied Hsien Wu to Europe and discovered she was pregnant, which put an end to her pursuit for further education, and she returned to China. Working as unpaid staff in Hsien Wu's lab, she continued to assist in research, but papers published rarely listed her name as the primary researcher. She also temporarily taught organic chemistry for students at the Xiehe Nursing School.
Yen Wu conducted her own research on nutrition for the biochemistry department, believed to be the first such studies carried out by a woman in China. She analyzed the chemical composition of many types of Chinese foods. Vitamin research was still in its infancy, but she determined the amount of carbohydrates, fat, fiber, protein, and water in various foods. Together with Hsien Wu, she began researching vegetarianism, the predominant Chinese diet at the time, using white mice as subjects, a technique Yen had learned from Sherman. By feeding one set of mice a typical diet based on grains such as corn, rice, sorghum, and wheat combined with peas, soybeans, and other vegetables; and another mouse group a diet of grain and meat, they discovered significant growth differentials and problems with rickets in the vegetarian group. Altering the vegetarian diet by adding bell peppers, cabbage, mustard greens, or rapeseed they found that growth rates were similar to the meat-eating mice and the animals had no signs of vitamin deficiencies.
Her next joint project with Hsien Wu was to conduct research on the diet of people in Beijing. The Department of Public Health and Sanitation collected materials from various groups throughout the country, including businesses, factories, farms, households, restaurants, and schools and presented their survey results to Yen and Hsien. They analyzed the survey, determining daily consumption rates of carbohydrates, fats, and proteins finding that the diet of people in Beijing was fairly representative of a typical diet throughout the country. They noted that compared to a Western diet, there were deficiencies in high-quality protein, calcium, phosphorus, and vitamins A and D. Their conclusions were that malnutrition was the cause of the high rates of disease and mortality, as well as intellectual disabilities and short stature, prevalent among Chinese children at the time. Their collaboration produced "营养概论" (Introduction to Nutrition, 1929) the first textbook on nutrition in China. Hsien Wu also published "中国食物之营养价值" (The Nutritional Value of Chinese Food, 1928) incorporating Yen's research.
Family and philanthropy (1929–1949).
In 1928, after the birth of her third child, Yen Wu withdrew from active work in the laboratory and focused on raising her children while compiling the research notes of her husband and assisting him in the development of his career. Within seven years of marrying, she had given birth to five children and was concerned about the level of educational opportunities available for them. She founded the Mingming School () in 1934 with the aim of providing a modern comprehensive education and hired Wang Suyi, an alumnus of Columbia, as principal and a full-time teacher. The private school was operated by a board of her friends upon which she served as treasurer. Yen Wu was a member of various civic improvement clubs and worked with her sisters to raise funds in 1936 to build a school hospital for their alma mater, the Jinling Women's College. She returned to school, studying French at the and graduating in 1944. In 1947, Hsien Wu went to the United States to work as a visiting professor at Columbia University, but was unable to return because of the Chinese Communist Revolution. When the communists took over their home in Beijing in 1949, Yen Wu decided to join him abroad.
Life abroad (1949–1992).
Yen Wu brought the children to Birmingham, Alabama, where Hsien Wu had become chair of the biochemistry department at the University of Alabama. In 1950, she was hired to work as a biochemical researcher for the Medical College of Alabama. As before, she conducted research jointly with her husband, until he suffered a heart attack in 1953 and retired. They moved to Boston, where Yen Wu cared for Hsien Wu and compiled their research. Between 1949 and 1959, they published four papers and wrote three abstracts for presentation at academic conferences, mostly about amino acid metabolism. After Hsien Wu died on 8 August 1959, Yen Wu published her husband's biography and in 1960, moved to New York City, to be near her children.
In the spring of 1960, Yen Wu was hired as a researcher by the Food Conservation Division of the United Nations Children's Fund. She was tasked with testing various foods and making recommendations to improve nutritional standards for children. In 1961, she established the Yen Tse-King Memorial Scholarship, in honor of her father, and the Wu Hsien Memorial Scholarship, in honor of her husband, at the Tunghai University in Taichung, Taiwan. The scholarships were intended to be awarded annually to assist women students in become physicians or any student of biological chemistry in completing their education. In August 1964, Yen Wu went to work at the Institute of Human Nutrition at Columbia University College of Physicians and Surgeons, where she built a reference library and organized finding aids for the materials for the staff and students of the college.
In 1971, she retired but began working three days a week as a consultant in nutrition and metabolism for St. Luke's Hospital Center. Her work there was to establish the library for the New York Obesity Research Center. She also lectured on public health and nutrition at Columbia University. In addition to her employment, Yen Wu began editing and updating the publication "营养概论" (Introduction to Nutrition). She wrote eight supplemental chapters and a new edition of the book was published in Taiwan in 1974, and remained in print until the 1990s.
After a thaw in the cold war relations between China and the US leading to normalization in the 1970s, Yen Wu returned to China. She visited relatives in 1980 and 1984. In 1983, she attended the celebration for the 70th anniversary of the founding of Jinling Women's University with family and former classmates. That year, she established a scholarship fund named after her husband to be awarded by the Chinese Academy of Medical Sciences to fund the research of professors who have contributed to the development of Chinese biochemistry and molecular biology. She retired in 1987 and lived alone until 1992, when she moved to the home of her eldest son in Ithaca, New York. In 1993, to honor her husband's 100th birthday, she donated funds to the Chinese Academy of Medical Sciences to establish a biochemical library and purchase books, and created a scholarship at Harvard Medical School, both bearing his name.
Death and legacy.
Yen Wu died on 27 May 1993 at Tompkins Community Hospital in Ithaca, after a heart attack, and was buried at Forest Hills Cemetery, in the Jamaica Plain neighborhood of Boston, Massachusetts. The Wus' research papers on metabolism, diet, and nutrition were foundational to the development of later ideas on modern Chinese health and nutrition. At the time their work was completed, it was one of the most influential in China and led the biochemical department at Peking Union Medical College to prioritize studying nutrition. The papers they produced have become a prerequisite to any discussion of the historical development of nutritional study in China.
The couple's son, Ray Wu, became a noted molecular biologist at Cornell University, having "developed the first method for sequencing DNA" and was "widely recognized as one of the fathers of plant genetic engineering." In addition to the scholarships she founded, the Hsien and Daisy Yen Wu Scholarship was founded at Cornell to assist graduate students in completing their education. Harvard has an endowed chair, the Hsien Wu and Daisy Yen Wu Professor of Biological Chemistry and Molecular Pharmacology, named in their honor.


Cassie Mitchell

Cassie Mitchell (born June 8, 1981) is an American engineer and Paralympic cyclist and track and field athlete.
Early life.
Mitchell was born in Muskogee, Oklahoma, and graduated from high school in Warner in 1999 as valedictorian of her class; shortly thereafter, she developed neuromyelitis optica, which left her paralyzed from the chest down with limited movement of her arms and hands and with permanent double vision. In 2004, she graduated from Oklahoma State University with a BS degree in chemical engineering. She later earned a PhD in biomedical engineering from both Emory and Georgia Tech universities.
Academic career.
Currently, she is a research professor at Wallace H. Coulter Department of Biomedical Engineering at both universities.
Paralympic career.
Mitchell won a silver medal at the 2011 IPC World Championships and the same year won five gold medals at the UCI World Para-cycling Championships and National Para-cycling Championships. In 2010, she won the national Para-cycling Championships for H1 criterium. She holds American and world records in multiple track and field events and medaled in discus throw and club throw at the 2016 Rio Paralympics. She placed fourth in the 100 m, 200 m and discus throw at the 2012 Paralympics.


Putrescine oxidase

In enzymology, a putrescine oxidase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are putrescine, O2, and H2O, whereas its 3 products are 4-aminobutanal, NH3, and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with oxygen as acceptor. The systematic name of this enzyme class is putrescine:oxygen oxidoreductase (deaminating). This enzyme participates in urea cycle and metabolism of amino groups. It employs one cofactor, FAD.


Pardoprunox

Pardoprunox (INN) (code name SLV-308) is an antiparkinsonian drug developed by Solvay for the treatment of Parkinson's disease that reached phase III clinical trials before being discontinued. It was also being investigated for the treatment of depression and anxiety but these indications appear to have been abandoned as well.
Pardoprunox acts as a D2 (pKi = 8.1) and D3 receptor (pKi = 8.6) partial agonist (IA = 50% and 67%, respectively) and 5-HT1A receptor (pKi = 8.5) full agonist (IA = 100%). It also binds to D4 (pKi = 7.8), α1-adrenergic (pKi = 7.8), α2-adrenergic (pKi = 7.4), and 5-HT7 receptors (pKi = 7.2) with lower affinity. Relative to other dopaminergic antiparkinsonian agents, pardoprunox is thought to have significantly less of a propensity for inducing certain side effects like dyskinesia and psychosis.


Semiquinone

Semiquinone (or ubisemiquinone) is a free radical resulting from the removal of one hydrogen atom with its electron during the process of dehydrogenation of a hydroquinone, such as hydroquinone itself or catechol, to a quinone or alternatively the addition of a single H atom to a quinone. It is highly unstable.
It is the first of two stages in reducing the supplementary form of CoQ10 ubiquinone to the active form ubiquinol.


Molybdopterin adenylyltransferase

Molybdopterin adenylyltransferase (, "MogA", "Cnx1") is an enzyme with systematic name "ATP:molybdopterin adenylyltransferase". This enzyme catalyses the following chemical reaction
This enzyme catalyses the activation of molybdopterin for molybdenum insertion.


K10 transport/localisation element (TLS)

The K10 transport/localisation element (TLS) is a 44 nucleotide K10 TLS regulatory element from "Drosophila melanogaster". K10 TLS is responsible for the transport and anterior localisation of K10 mRNA and acts to establish dorsoventral polarity in the oocyte. It was discovered by Julia Serano.


Fermentas

Fermentas was a biotechnology company specializing in the discovery and production of molecular biology products for life science research and diagnostics. Since 2010, Fermentas has been part of Thermo Fisher Scientific.
Corporate profile.
In 2003, Fermentas consolidated its international business and set up a controlling enterprise, Fermentas International in Canada. Fermentas International became the shareholder of Fermentas in Vilnius, Lithuania, and its joint ventures in the United States, Canada and Germany (as well as Fermentas China established in 2009).
In 2010, Fermentas International was acquired by Thermo Fisher Scientific. Fermentas, and all of its enterprises, became part of the Analytical Technology segment of the Thermo Fisher.
Fermentas has principal manufacturing operations in Vilnius, Lithuania.
Products.
Fermentas is a producer of molecular biology products and is known for its restriction enzymes and DNA ladders and molecular weight markers.
Main products are FastDigest and conventional restriction enzymes, DNA/RNA modifying enzymes, transfection reagents, nucleotides and primers, products for PCR and RT-PCR, molecular cloning, nucleic acid purification, in vitro transcription, molecular labeling and detection, DNA, RNA, protein electrophoresis.
All Fermentas’ products are produced in Class D clean-room facilities, qualified and certified as per EU directives and International Society for Pharmaceutical Engineering (ISPE) guidelines, which are prerequisite for GMP manufacturing. The company is operating under ISO9001, ISO13485 quality and ISO14001 environmental management systems.


Agenus

Agenus Inc. is a Lexington, Massachusetts-based biotechnology company focused on immunotherapy including immuno-oncology, a field that uses the immune system to control or cure cancer. The company is developing checkpoint modulators (CPMs), patient-specific anti-cancer vaccines, and adjuvants that can be used with a range of vaccines. CPM development is a particularly fast-moving field, since early products have produced unprecedented clinical benefits for patients.
History.
Agenus (formerly Antigenics Inc.) was founded in 1994 by Garo H. Armen and Pramod K. Srivastava. The company has pioneered immunotherapies, including heat shock protein-based cancer vaccines, a program that has developed into its Prophage Series of personalized anti-cancer vaccines. Antigenics became a public company in February 2000 on the NASDAQ exchange with the ticker symbol AGEN. In 2000 Agenus acquired Aquila Biopharmaceuticals and a year later it acquired Aronex Pharmaceuticals. In February 2014 the company acquired a European firm, 4-Antibody, along with their portfolio of checkpoint modulators (CPMs) and a platform (Retrocyte Display® technology) to rapidly and efficiently discover new antibodies.
In October 2013, Agenus CEO Garo Armen issued a press release revealing that after an 18-month follow up on the RTS,S Malaria vaccine using QS21-Stimulon® is working well enough to support a regulatory filing in 2014. This is the first proof of the efficacy of Agenus's patented "QS-21 Stimulon" adjuvant
In April 2014, Agenus inked a deal with Merck potentially worth $100 million. Under the terms of that deal, Agenus is using its proprietary Retrocyte Display technology to discover antibodies against a pair of undisclosed checkpoint targets for the treatment of cancer. Agenus has advanced two of its own CPM candidates into early drug development and the company is planning to advance several more antibodies in clinical trials.
Today, Agenus is focused on developing a range of immuno-oncology products, including the Prophage vaccines, multiple checkpoint modulators (also known as checkpoint inhibitors or checkpoint antibodies) and its QS21-Stimulon adjuvant. The company's personalized, heat shock protein-based vaccines are in Phase 2 studies. The QS-21 Stimulon adjuvant platform is partnered with GlaxoSmithKline and Janssen. Several of those collaborations involve Phase 3 trials. Altogether, the company and its partners are sponsoring approximately 20 clinical trials of Agenus products.
Key partners and deals.
Merck: April 2014, Agenus announced a deal worth potentially $100 million with Merck. The deal involves the discovery and development of therapeutic antibodies to two undisclosed Merck checkpoint targets, both thought to be relevant for cancer treatment. Agenus will use its proprietary Retrocyte Display® platform to discover and optimize antibodies against the targets.
4-Antibody: February 2014, Agenus acquired European biotechnology firm 4-Antibody, along with its Retrocyte Display technology and a portfolio of checkpoint modulator antibody candidates .
Ludwig Cancer Research: 4-Antibody had been working on the checkpoint targets for several years in collaboration with Ludwig Cancer Research, one of the world's most renowned institutions for research into cancer and the immune system. The leader of the Ludwig collaborative laboratory at Memorial Sloan Kettering Cancer Center, Jedd Wolchok, is recognized as one of immuno-oncology's leading pioneers.
GlaxoSmithKline (GSK): March 2012, GSK paid Agenus $9 million to include additional rights to the two firms’ agreement around Agenus’ QS-21 Stimulon® adjuvant. The deal amended license and manufacturing terms. It also included royalty payments to Agenus for an undisclosed indication upon commercialization of a vaccine.
Product descriptions.
Checkpoint modulators (CPMs) interfere with cancers’ ability to “hijack” natural immune defense systems. To protect the body against disease, but without attacking healthy cells, the immune system uses multiple “checkpoint” systems. Some checkpoints stimulate immune responses while others inhibit them. Cancer cells can evolve means to evade checkpoints, and CPMs can reverse that effect, helping the immune system better fight the cancer.
Agenus has programs targeting the checkpoint modulators GITR, OX40, CTLA-4, LAG-3, TIM-3 and PD-1. The company is expanding that portfolio by using a proprietary process to generate fully human therapeutic antibody drug candidates. The platform is a high-throughput approach incorporating IgG format human antibody libraries expressed in mammalian B-lineage cells.
The Prophage series of patient-specific cancer vaccine candidates can also enhance the immune system's response to tumors. Because each cancer is unique, the vaccine is derived from the patient's own tumor sample. To process these samples, Agenus has established a multi-product "good manufacturing practices" facility, which has already helped process over 1,000 tumor samples from across the globe.
The company's QS-21 Stimulon® adjuvant platform strengthens and broadens immune responses to antigens on cancers or foreign invaders’ surfaces. Agenus has multiple partnerships around this product to study its effects with vaccines for diseases including Alzheimer's, melanoma, and malaria. In October 2013, GlaxoSmithKline and Agenus announced positive data from an 18-month follow-up of GSK's RTS,S malaria vaccine with QS21-Stimulon. GSK stated that the treatment was working well enough to support a regulatory filing. RTS,S is the most advanced vaccine for malaria in development.
Agenus is the sole US-manufacturer of a patented and FDA-approved triterpene glycoside extract (QS-21, Matrix M), which is a key component in the manufacturing of the Oxford–AstraZeneca COVID-19 as well as the Novavax COVID-19 vaccines. Supplies are tightly controlled, and the US has invoked the US Defence Production Act to preserve vaccine raw materials for its own companies.


Dendreon

Dendreon is a biotechnology company. Its lead product, Provenge (known generically as sipuleucel-T), is an immunotherapy for prostate cancer. It consists of a mixture of the patient's own blood cells (autologous, with dendritic cells thought to be the most important) that have been incubated with the Dendreon PAP-GM-CSF fusion protein.
Phase III clinical trial results demonstrating a survival benefit for prostate cancer patients receiving the drug were presented at the AUA meeting on April 28, 2009. After going through the approval process, Provenge was given full approval by the FDA on April 29, 2010. Dendreon's stock value fell 66% on August 4, 2011, after abandoning its forecast for its debut drug Provenge.
In November 2014, Dendreon filed for Chapter 11 bankruptcy protection and shortly afterwards announced that it had reached agreements on the terms of a financial restructuring with certain bond holders.
On February 20, 2015, Valeant Pharmaceuticals received approval to purchase all Dendreon assets. On January 9, 2017 Sanpower Group agrees to acquire Dendreon from Valeant for $819.9 million In June 2017, Sanpower Group, a Chinese conglomerate, purchased Dendreon from Valeant for $820 million.
Technology overview and pipeline.
Antigen delivery cassette and antigen presenting cells.
Dendreon's name derives from the "Dendritic Cell" which forms a major component of the company's product candidates that use the "Dendreon Cassette Technology" to insert a disease-specific target protein into a general platform. Their lead product, Provenge, is an example of their "rationally designed therapeutic process" intended to break immune tolerance to certain disease specific proteins. It is hypothesized that receptor mediated uptake of antigen by dendritic cells occurs when they are exposed to the Dendreon fusion protein which links the disease specific protein to a recognition protein. This approach is in contrast to other dendritic cell vaccines that use methods such as electroporation to get the DC's to present antigen related epitopes. In the case of Provenge, this disease related protein is prostatic acid phosphatase and the signalling component is GM-CSF.
Antigen selection.
Dendreon believes its process can be optimized and generalized to other diseases by exchanging the PAP component of Provenge with better targets specific to different diseased cells. Antigen selection is a significant issue with cancer vaccines in general. Presumably, therapeutic effect can be obtained by provoking a selective response against the diseased cells only. Dendreon has explored approaches to obtaining tumour-specific antigen targets under the theory that the immune system may be able to mount a more effective response than is otherwise possible against tumor associated antigens. Unaltered human PAP is expressed by normal prostate cells but recent discoveries suggest that cancer cells produce many more unique targets as well as proteins that are more highly expressed than in normal tissue. It has also been recently discovered that other enzymes expressed in nerves are identical to PAP and there is ongoing work to examine post-translational modifications to PAP and its correlation to disease state by Dendreon collaborators. PAP also appears to be expressed in breast cysts.
Prior work in this area has also included that of A. Sette at Epimmune and the Altered Peptide Ligand approach typified by Neurocrine Biotech's failed MS drug.
Nuvelo and patents acquired from Corvas.
Dendreon acquired the nematode anticoagulant Nuvelo. Selected Corvas patents include technologies for peptide analog synthesis and drugs that target coagulation and immune processes.
Early history.
Dendreon was founded in 1992 by Edgar Engleman and Samuel Strober based on the research performed in their laboratories at the Stanford University School of Medicine.
Drs. Engleman and Strober established the company, initially named Activated Cell Therapy, in Mountain View, California, after securing funding from Health Care Ventures in Edison, New Jersey. After several years the company changed its name to Dendreon and moved to Seattle, Washington.
Provenge.
Initial clinical results for Provenge in 2000 showed immune responses supporting the expected mode-of-action, as well as a PSA reduction which was thought to relate to clinical improvement. In 2006, Dendreon built a manufacturing facility in Morris Plains, New Jersey to accommodate production for a Phase III trial and possible 2007 drug approval by the U.S. Food and Drug Administration (FDA). In January 2007, the FDA accepted Dendreon's Biologic License Application (BLA) filing for Provenge.
On March 29, 2007, the FDA Office of Cellular, Tissue and Gene Therapies Advisory Committee voted 17-0 that Provenge is reasonably safe and 13-4 that the trial data showed substantial evidence that it is effective. However, on May 9, 2007, Dendreon received a letter from the FDA demanding more results and information before approval.
On April 14, 2009, Dendreon announced that the results for the Phase III trial of Provenge were positive, saying there had been a reduction in the odds of death compared to the use of a placebo. On April 28, 2009, the full details of the study were released. The trial found that patients treated with Provenge lived an average of 4.1 months longer than patients treated with the control (autologous cells without the GM-CSF / PAP fusion protein).
On April 29, 2010, the FDA approved Provenge for use in the treatment of advanced prostate cancer.
On June 7, 2010, the head of Medicare's Coverage and Analysis Group, Dr. Louis Jacques, sent three colleagues an email telling them that they should be sure not to leak the fact that his Group was considering a cap on Medicare coverage of this treatment. News of that caution itself did inevitably leak, and the price of Dendreon's stock fell 10% later that day.
Dendreonites.
Some journalists have referred to Provenge supporters as "Dendreonites" and the name is in routine usage in colloquial forums. Concerns for personal safety were raised among some doctors who were thought responsible for the delay of Provenge approval.
Dendreonites have questioned these doctors' objectivity; one of them, Dr. Howard Scher, was the lead clinical trial investigator for a rival prostate cancer drug from the biotech company Novacea.
Their concerns motivated organized protests at the FDA and American Society of Clinical Oncology (ASCO) meeting by various patient and investor advocacy groups which also filed a lawsuit alleging that the FDA's decision was influenced by conflicts of interest.


Herpetosiphon

Herpetosiphon is a genus of bacteria in the family "Herpetosiphonaceae".


Butyryl-CoA

Butyryl-coenzyme A (or butyryl-CoA) is the coenzyme A-activated form of butyric acid.
It is acted upon by butyryl-CoA dehydrogenase.
It is an intermediary compound of ABE fermentation
Butyryl-CoA is also converted from Crotonyl-CoA. This occurs when FADH- transfers a hydride to crotonyl-CoA. It is essential in reducing ferredoxins in anaerobic bacteria and archaea so that electron transport phosphorylation and substrate level phosphorylation can occur with increased efficiency.
Butyryl-COA dehydrogenase Oxidation-Reduction reaction consists of 2 electron transfer with 1 proton exchange. Ideally, this will occur between pH 5.5 and 7 for optimal reaction. In this range is where the enzyme is most stable.
From Redox data, Butyryl-COA dehydrogenase shows little to no activity at pH higher than 7.0. This is important as Enzyme midpoint potential is at pH 7.0 and at 25 degrees C. Therefore, changes above from this value will denature the enzyme.


Jeffrey Weitz

Jeffrey Weitz is a Canadian bioscientist, currently the Canada Research Chair in Thrombosis and Endowed Chair in Cardiovascular Medicine at McMaster University.


Peter McManus

Peter McManus VC (March 1829 – 27 April 1859) was born in Tynan, County Armagh, was an Irish recipient of the Victoria Cross, the highest and most prestigious award for gallantry in the face of the enemy that can be awarded to British and Commonwealth forces.
Details.
McManus was approximately 28 years old, and a private in the 1st Battalion, 5th Regiment of Foot (later The Northumberland Fusiliers), British Army during the Indian Mutiny when the following deed took place on 26 September 1857 at Lucknow, India for which he and Private John Ryan was awarded the VC:
He later achieved the rank of sergeant. He died from smallpox in Allahabad, British India, on 27 April 1859.


Disuccinimidyl suberate

Disuccinimidyl suberate (DSS) is a biochemical tool used as protein cross-linking agent.


Western rock elephant shrew

The western rock elephant shrew or western rock sengi ("Elephantulus rupestris") is a species of elephant shrew in the family Macroscelididae. It is found in Namibia, South Africa, possibly Angola, and possibly Botswana. Its natural habitats are subtropical or tropical dry shrubland and rocky areas.
Smaller members of western rock elephant shrew possess functional brown adipose tissue, which changes in thermogenic capacity depending on the season.


Leonus


Bachem Holding

Bachem Holding AG is a Swiss technology company active in the fields of chemistry, biochemistry and pharmaceuticals. It develops products and services for the pharmaceutical and biotechnology industry and research. Bachem is specialized in the commercial production of peptides and complex organic compounds as active pharmaceutical ingredients, in the production of peptide-based biochemicals and in the development of manufacturing processes for these compounds. Founded in 1971, the company is headquartered in Bubendorf, Canton Basel-Landschaft, Switzerland. In addition to the Bubendorf site, Bachem has another large production site in Switzerland in Vionnaz in the canton of Valais. Further production sites are located in the USA in the Californian cities of Vista and Torrance and in Great Britain in St Helens near Liverpool. An additional sales and distribution site is located in Tokyo (Japan). At the end of 2018, Bachem Holding AG had 1140 employees worldwide, generated sales of CHF 282.5 million and a net profit of CHF 46.6 million.
History.
In 1971, Peter Grogg founded Bachem Feinchemikalien AG with two employees in Liestal near Basel with the focus on peptide synthesis. In 1977, Bachem moved with eight employees to nearby Bubendorf, and, in 1978, it manufactured, for the first time, peptides for use in medicine under cGMP guidelines. Between 1981 and 1991 Bachem tripled its production capacity and built an administration building, and in 1995, facilities were further expanded including the quality control department to a total of 168'000 sq. ft. (15'600 m2).
Expansion into markets outside Europe began with the establishment of Bachem Bioscience, Inc. in Philadelphia, USA in 1987. To strengthen its presence in Europe, Bachem opened sales and marketing centers in Germany in 1988 and in France in 1993. In 1996 it acquired its largest competitor, Bachem, Inc., together with its subsidiaries in Germany and the United Kingdom. In June 1998, following a very successful IPO, Bachem's shares began to be publicly traded on the Swiss Stock Exchange. In 1999 and 2000, a new administration building and a further production facility were respectively opened at the Bubendorf site.
With the acquisition of the San Carlos, California based Peninsula Laboratories, Inc. and its affiliate Peninsula Laboratories Ltd., United Kingdom in December 1999, Bachem extended its strong position in therapeutically active peptides into immunology, a domain with strong future promise. In August 2000, Peninsula Laboratories Europe Ltd. and Bachem (UK) Ltd. merged to a single Bachem group affiliated company in the United Kingdom.
The acquisition of Sochinaz SA, a Swiss-based specialized manufacturer of active pharmaceutical ingredients in 2001, strengthened Bachem's expertise and once again expanded its manufacturing capabilities.
Reorganization of distribution was carried out in Germany and France as a result of the positive experiences gained with the realignment of the sales and marketing organization in the USA. As a result, the subsidiary in France was closed at the end of 2002. The subsidiary in Germany was relocated from Heidelberg to Weil am Rhein, was renamed Bachem Distribution Services GmbH and is now responsible for all customers in the European Union.
In 2003, a holding structure was introduced to align the factual organization of the company with an appropriate legal structure and to support management structure adjustments, given by continued company growth requirements. In 2010, Bachem commenced the partnership with Atheris laboratories offering the Melusine® range of research products for lead generation of new pharmaceutical candidates. In 2011, Bachem celebrated its 40th year as a producer of research ingredients and active pharmaceutical ingredients (APIs) for the pharmaceutical industry.
In 2013, Bachem and GlyTech Inc. teamed up to offer glycosylated peptides in their product pipelines. Bachem and affiliate were conducting groundbreaking work on interferon beta-1a and to manufacture glycosylated somatostatin analogues by chemical synthesis.
In 2015, Bachem acquired American Peptide Company, a mid-sized biotech establishment in Sunnyvale CA, not far from Bachem's US facility in Torrance, expanding the firm's GMP manufacturing and R&D capabilities for the US and international markets.
Corporate Structure.
Bachem Holding AG.
The Bachem Group has a holding structure since 2003. The shares are listed on the SWX Swiss Exchange under the abbreviation BANB. A majority of the shares are held by company founder Peter Grogg.
Locations.
From its headquarters in Bubendorf and its subsidiaries in Europe, the USA and Asia, Bachem operates worldwide. Bachem Holding AG currently consists of the following six locations:
Bachem Holding AG consists of the following divisions:
Business Development.
No business development figures have been published for the period from the foundation of the company in 1971 to its IPO in 1998. In the year of the successful IPO in 1998, the Bachem Group's turnover was CHF 96 million. By 2001, sales had risen to CHF 141 million, also due to acquisitions. After a phase of stagnation until 2004 (sales of CHF 148 million), the Group has since gone through a rather stormy, non-acquisition-related growth phase. Between 2005 and 2007, well over 100 additional full-time positions and jobs were created. In Switzerland, the Bachem Group also trains 37 apprentices in various professions.
The share of sales generated in North America was 39.6 % (2007). The rapid growth is primarily due to the sales growth of the Active Pharmaceutical Ingredients business unit. Detailed figures on the business development of the Bachem Group are published in semi-annual and annual reports.
In 2018, the Bachem Group (SIX: BANB) achieved record sales of CHF 282.5 million with a net profit of CHF 46.6 million (+11.7 % net profit compared to the previous year; +79.6 % compared to 2012). The operating result (EBIT) rose in 2018 by +8.3 % compared with 2017 to CHF 54.8 million (+58.0 % compared with 2012). The EBITDA margin reached 27.6 % and the EBIT margin 19.4 %. Due to the good business situation and high capacity utilization, Bachem created a total of 39 new jobs by the end of 2018. As at 31 December 2018, the Bachem Group employed a total of 1140 people in 1097 full-time positions.
Business Divisions.
Bachem's business activities are divided into two divisions: Research Chemicals and Active Pharmaceutical Ingredients.
The range of research chemicals includes amino acid derivatives, resins and reagents for peptide production and organic synthesis, bioactive peptides, enzyme substrates and other biochemicals. Bachem manufactures most of the products itself and offers them in a web shop where several thousand products can be found. Custom research chemicals are produced by custom synthesis.
Customers for research chemicals are scientists at universities, hospitals and in the research laboratories of the biotech and pharmaceutical industries.
In its Active Pharmaceutical Ingredients division, Bachem offers a wide range of mostly peptidic active ingredients, which are used in clinical studies, in market-approved drugs or, with increasing importance, in cosmetics. A distinction is made between patent-free (generics) and patent-protected (New Chemical Entities, NCEs) peptide pharmaceutical active ingredients. Typical examples of generic peptides are Calcitonin, Glucagon, Gonadorelin, Goserelin, Leuprolid, Somatostatin, Octreotide, Aviptadil, Desmopressin, Secretin, Sincalid, Thymosin, Oxytocin, Vasopressin.
The Bachem site in Vionnaz in the Swiss canton of Valais produces various non-peptidic generic active ingredients, including the widely used short-term anesthetic Propofol. In addition to such generic active ingredients, Bachem also offers process development and pharmaceutical active ingredients that are patented and may only be manufactured and used by the originator or a partner commissioned by the originator. In most cases, the collaboration is subject to a non-disclosure agreement. Many of these patented products are still in clinical trials.
The active pharmaceutical ingredients produced by Bachem are used in various therapeutic and diagnostic areas of human and veterinary medicine. Typical areas of application include cancer, osteoporosis, diabetes mellitus, Alzheimer's disease, nocturnal enuresis, hypoglycaemia, erectile dysfunction, cardiovascular diseases and diseases of the gastrointestinal tract.
Customers for active pharmaceutical ingredients are biotechnology companies, pharmaceutical and veterinary companies. Active ingredients account for the largest share of company sales. Current figures can be found in the annual report.


Degradome sequencing

Degradome sequencing (Degradome-Seq), also referred to as parallel analysis of RNA ends (PARE), is a modified version of 5'-Rapid Amplification of cDNA Ends (RACE) using high-throughput, deep sequencing methods such as Illumina's SBS technology. Degradome sequencing provides a comprehensive means of analyzing patterns of RNA degradation.
Degradome sequencing has been used to identify microRNA (miRNA) cleavage sites, because miRNAs can cause endonucleolytic cleavage of mRNA by extensive and often perfect complementarity to mRNAs. Degradome sequencing revealed many known and novel plant miRNA (siRNA) targets. Recently, degradome sequencing also has been applied to identify animal (human and mouse) miRNA-derived cleavages.