ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online.
SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses
Cambridge Antibody Technology
Cambridge Antibody Technology was a biotechnology company headquartered in Cambridge, United Kingdom. Its core focus was on antibody therapeutics, primarily using phage display, Technology developed by CAT was used to create adalimumab, the first fully human antibody blockbuster drug. Humira, the name of adalimumab, is an anti-TNF antibody discovered by CAT as D2E7, developed in the clinic. The company was behind belimumab, the antibody drug marketed as Benlysta. Founded in 1989, CAT was acquired by AstraZeneca for £702m in 2006, AstraZeneca subsequently acquired MedImmune LLC, which it combined with CAT to form a global biologics division called MedImmune. CAT was often described as the jewel in the crown of the British biotechnology industry, CAT was founded in 1989 by, amongst others, Dr. David Chiswell, Dr. Greg Winter and the Medical Research Council. Subsequently, in January 1990 operations began at the MRC laboratories in Cambridge, in May of that year, operations moved to the Daly Research Laboratories at Babraham Institute, Cambridge.
In 1992, CAT moved to Beech House on the Melbourn Science Park to occupy units B1, in 1993 the company expanded into unit B3, into B4 into 1995, and in 1998 into units B5, B6, B8 and B9. CAT completed the occupation of Beech House by finally occupying B7 by the late 1990s, CAT listed on the London Stock Exchange in 1997, raising £43 million, and went through a second round of funding in 2000, raising over £90 million. In 1999, CAT expanded into a location in Melbourn called Cambridge House. After leaving Melbourn, CAT sold this location on to housing developers in early 2006, in 2000, after a succession of deals that focussed on harnessing the exploitation of the human genome, CATs share price peaked at over £50 per share. Also in 2000, CAT decided to out of Melbourn to a science park called Granta Park. Of the buildings on the park, the first to be occupied was the Franklin Building followed, in late 2002, the Franklin Building, named after Rosalind Franklin, was formally opened in 2001 by David Sainsbury, Baron Sainsbury of Turville.
The Milstein Building was named after César Milstein, and had a design with separate laboratory. In the same year, CAT listed on the NASDAQ, on the 15 July 1998, CAT completed the acquisition of Aptein Inc. This acquisition. further strengthened its leading position in antibody display technology. giving CAT controlling patents in the field of polysome display. Aptein was founded by Glenn Kawasaki, who is currently, amongst other positions, according to an article published in Nature in 2002, that focused on the automation of proteomics. In Apteins technology, stop codons are eliminated so that the completed antibody, the system, which CAT is now optimizing, is entirely cell-free and so is more amenable to automation
Modern humans are the only extant members of Hominina tribe, a branch of the tribe Hominini belonging to the family of great apes. Several of these hominins used fire, occupied much of Eurasia and they began to exhibit evidence of behavioral modernity around 50,000 years ago. In several waves of migration, anatomically modern humans ventured out of Africa, the spread of humans and their large and increasing population has had a profound impact on large areas of the environment and millions of native species worldwide. Humans are uniquely adept at utilizing systems of communication for self-expression and the exchange of ideas. Humans create complex structures composed of many cooperating and competing groups, from families. Social interactions between humans have established a wide variety of values, social norms, and rituals. These human societies subsequently expanded in size, establishing various forms of government, today the global human population is estimated by the United Nations to be near 7.5 billion.
In common usage, the word generally refers to the only extant species of the genus Homo—anatomically and behaviorally modern Homo sapiens. In scientific terms, the meanings of hominid and hominin have changed during the recent decades with advances in the discovery, there is a distinction between anatomically modern humans and Archaic Homo sapiens, the earliest fossil members of the species. The English adjective human is a Middle English loanword from Old French humain, ultimately from Latin hūmānus, the words use as a noun dates to the 16th century. The native English term man can refer to the species generally, the species binomial Homo sapiens was coined by Carl Linnaeus in his 18th century work Systema Naturae. The generic name Homo is a learned 18th century derivation from Latin homō man, the species-name sapiens means wise or sapient. Note that the Latin word homo refers to humans of either gender, the genus Homo evolved and diverged from other hominins in Africa, after the human clade split from the chimpanzee lineage of the hominids branch of the primates.
The closest living relatives of humans are chimpanzees and gorillas, with the sequencing of both the human and chimpanzee genome, current estimates of similarity between human and chimpanzee DNA sequences range between 95% and 99%. The gibbons and orangutans were the first groups to split from the leading to the humans. The splitting date between human and chimpanzee lineages is placed around 4–8 million years ago during the late Miocene epoch, during this split, chromosome 2 was formed from two other chromosomes, leaving humans with only 23 pairs of chromosomes, compared to 24 for the other apes. There is little evidence for the divergence of the gorilla, chimpanzee. Each of these species has been argued to be an ancestor of hominins
In immunology, an antigen is a molecule capable of inducing an immune response on the part of the host organism, though sometimes antigens can be part of the host itself. In other words, an antigen is any substance that causes a system to produce antibodies against it. In most cases, an antibody can bind one specific antigen, in some instances, however. An antigen is a molecule that binds to Ag-specific receptors, Antigens are usually peptides, polysaccharides or lipids. In general, molecules other than peptides qualify as antigens but not as immunogens since they cannot elicit a response on their own. Furthermore, for a peptide to induce a response it must be a large enough size. The term antigen originally described a structural molecule that specifically to an antibody. It expanded to refer to any molecule or a molecular fragment that can be recognized by highly variable antigen receptors of the adaptive immune system. The antigen may originate from within the body or from the external environment, antigen presenting cells present antigens in the form of peptides on histocompatibility molecules.
The T cells of the immune system recognize the antigens. Depending on the antigen and the type of the histocompatibility molecule, for T-Cell Receptor recognition, the peptide must be processed into small fragments inside the cell and presented by a major histocompatibility complex. The antigen cannot elicit the immune response without the help of an immunologic adjuvant, the adjuvant component of vaccines plays an essential role in the activation of the innate immune system. An immunogen is a substance that is able to trigger a humoral and/or cell-mediated immune response and it first initiates an innate immune response, which causes the activation of the adaptive immune response. An antigen binds the highly variable immunoreceptor products once these have been generated, all immunogen molecules are antigens, although the reverse is not true. At the molecular level, an antigen can be characterized by its ability to bind to an antibodys variable Fab region, different antibodies have the potential to discriminate among specific epitopes present on the antigen surface. A hapten is a molecule that changes the structure of an antigenic epitope.
In order to induce a response, it needs to be attached to a large carrier molecule such as a protein. Antigens are usually proteins and polysaccharides, and less frequently and this includes parts of bacteria and other microorganisms
Sanofi S. A. is a French multinational pharmaceutical company headquartered in Gentilly, France, as of 2013 the worlds fifth-largest by prescription sales. The company was formed as Sanofi-Aventis in 2004 by the merger of Aventis and Sanofi-Synthélabo and it changed its name to Sanofi in May 2011. The company is a component of the Euro Stoxx 50 stock market index, Sanofi engages in the research and development and marketing of pharmaceutical drugs principally in the prescription market, but the firm develops over-the-counter medication. The company covers seven major areas, central nervous system, internal medicine, thrombosis. Sanofi was founded in 1973 as subsidiary of Elf Aquitaine, when Elf Aquitaine took control of the Labaz group, a pharmaceutical company. In 1993 Sanofi made a move into the Eastern Europe market by acquiring a controlling interest in Chinoin, Sanofi was incorporated under the laws of France in 1994 as a société anonyme, a form of limited liability company. Synthélabo was founded in 1970 through the merger of two French pharmaceutical laboratories, Laboratoires Dausse and Laboratoires Robert & Carrière, in 1973, the French cosmetics group L’Oréal acquired the majority of its share capital.
In 1991, Synthelabo acquired Laboratories Delalande and Laboratoires Delagrange, the merged company was based in Paris, France. The merged company was based in Schiltigheim, near Strasbourg, Hoechst had seven primary businesses, Hoechst Marion Roussel, AgrEvo, HR Vet, Dade Behring, Centeon and Messer. Aventis invested $45 million in Regeneron and made an upfront payment of $80 million in cash, Sanofi-Aventis was formed in 2004 when Sanofi-Synthélabo acquired Aventis. In early 2004, Sanofi-Synthélabo made a takeover bid worth €47.8 billion for Aventis. The three-month takeover battle concluded when Sanofi-Synthélabo launched a bid of €54.5 billion in place of the previously rejected hostile bid. In 2006, Iraqis infected with HIV sued Sanofi and Baxter due to HIV-contaminated haemophilia blood products sold by Merieux in the 1980s, when Apotex disclosed the oral agreement to the FTC, the FTC launched an investigation that led to Dolan being fired by BMS. Apotex sued BMS and Sanofi for $3.4 billion for allegedly breaching the settlement agreement, in 2009 the companies expanded the deal to $160 million per year and extended it through 2017.
As of 2009 the collaboration had four antibodies in clinical development and had filed an IND for a fifth, the dealmaking continued beyond 2010, and included, In 2008, for about €1. The deal was approved by Brazils antitrust authorities in May 2010, in 2010, for around $130 million, Nepentes Pharma, a Polish dermocosmetics company. In 2010, for around $520.6 million in cash, in 2014, 66% stake in Globalpharma, Dubai-based generics manufacture.7 billion in cash. The deal means Sanofi is now one of the consumer healthcare leaders by market share
Clinical trials are experiments or observations done in clinical research. Clinical trials generate data on safety and efficacy and they are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial – their approval does not mean that the therapy is safe or effective, only that the trial may be conducted. Clinical trials can vary in size and cost, and they can involve a research center or multiple centers. Clinical study design aims to ensure the validity and reproducibility of the results. Trials can be costly, depending on a number of factors. The sponsor may be an organization or a pharmaceutical, biotechnology or medical device company. Certain functions necessary to the trial, such as monitoring and lab work, may be managed by an outsourced partner, only 10 percent of all drugs started in human clinical trials become an approved drug.
Some clinical trials involve healthy subjects with no pre-existing medical conditions, other clinical trials pertain to patients with specific health conditions who are willing to try an experimental treatment. When participants are healthy volunteers who receive financial incentives, the goals are different than when the participants are sick, during dosing periods, study subjects typically remain under supervision for one to 40 nights. Usually pilot experiments are conducted to gain insights for design of the trial to follow. There are two goals to testing medical treatments, to whether they work well enough, called efficacy or effectiveness. The benefits must outweigh the risks, in the US, the elderly constitute only 14 percent of the population, while they consume over one-third of drugs. Women and people with unrelated medical conditions are frequently excluded. For women, a reason for exclusion is the possibility of pregnancy. If the sponsor cannot obtain enough test subjects at one location investigators at other locations are recruited to join the study, during the trial, investigators recruit subjects with the predetermined characteristics, administer the treatment and collect data on the subjects health for a defined time period.
The researchers send the data to the sponsor, who analyzes the pooled data using statistical tests. Except for small, single-location trials, the design and objectives are specified in a document called a clinical trial protocol
These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and assign numbers of atoms of the other elements in the compound, as ratios to the key element.
For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula.
For example, ethanol may be represented by the chemical formula CH3CH2OH
A placebo is a substance or treatment with no active therapeutic effect. A placebo may be given to a person in order to deceive the recipient into thinking that it is an active treatment. This phenomenon, in which the recipient perceives an improvement in condition due to personal expectations, research about the effect is ongoing. Placebos are an important methodological tool in medical research, common placebos include inert tablets, vehicle infusions, sham surgery, and other procedures based on false information. Placebo effects are the subject of research aiming to understand underlying neurobiological mechanisms of action in pain relief, immunosuppression, Parkinsons disease. Brain imaging techniques done by Emeran Mayer, Johanna Jarco and Matt Lieberman showed that placebo can have real, in other cases, like asthma, the effect is purely subjective, when the patient reports improvement despite no objective change in the underlying condition. The placebo effect is a phenomenon, in fact, it is part of the response to any active medical intervention.
The placebo effect points to the importance of perception and the role in physical health. The use of placebos as treatment in clinical medicine is ethically problematic as it introduces deception, the United Kingdom Parliamentary Committee on Science and Technology has stated that. prescribing placebos. Usually relies on some degree of patient deception and prescribing pure placebos is bad medicine and their effect is unreliable and unpredictable and cannot form the sole basis of any treatment on the NHS. In 1955, Henry K. Beecher proposed that placebos could have important effects. The article received a flurry of criticism, but the published a Cochrane review with similar conclusions. A placebo has been defined as a substance or procedure and that is objectively without specific activity for the condition being treated. Under this definition, a variety of things can be placebos. Likewise, the effects of stimulation from implanted electrodes in the brains of those with advanced Parkinsons disease are greater when they are aware they are receiving this stimulation, sometimes administering or prescribing a placebo merges into fake medicine.
Common placebos include pills or saline injections, fake surgeries have seen some use. An example is the Finish Meniscal Legion Study Group’s trial published in The New England Journal of Medicine, while examples of placebo treatments can be found, defining the placebo concept remains elusive. A placebo electronic cigarette contains 0 mg of nicotine, instead they introduced the term meaning response for the meaning that the brain associates with the placebo, which causes a physiological placebo effect
Transforming growth factor beta
Activated TGF-β complexes with other factors to form a serine/threonine kinase complex that binds to TGF-β receptors, which is composed of both type 1 and type 2 receptor subunits. After the binding of TGF-β, the type 2 receptor kinase phosphorylates and activates the type 1 receptor kinase that activates a signaling cascade. TGF-β is secreted by many types, including macrophages, in a latent form in which it is complexed with two other polypeptides, latent TGF-beta binding protein and latency-associated peptide. Serum proteinases such as plasmin catalyze the release of active TGF-β from the complex and this often occurs on the surface of macrophages where the latent TGF-β complex is bound to CD36 via its ligand, thrombospondin-1. Inflammatory stimuli that activate macrophages enhance the release of active TGF-β by promoting the activation of plasmin, macrophages can endocytose IgG-bound latent TGF-β complexes that are secreted by plasma cells and release active TGF-β into the extracellular fluid.
Among its key functions is regulation of processes, particularly in the gut. TGF-β plays a role in stem cell differentiation as well as T-cell regulation and differentiation. As such, it is a highly researched cytokine in the fields of cancer, auto-immune diseases and its immunosuppressive functions come to dominate, contributing to oncogenesis. The disregulation of its functions is implicated in the pathogenesis of autoimmune diseases. The primary four types are, TGF beta 1 – TGFB1 TGF beta 2 – TGFB2 TGF beta 3 – TGFB3 TGF beta 4 - TGRB4 The peptide structures of the TGF-β isoforms are highly similar. They are all encoded as large precursors, TGF-β1 contains 390 amino acids and TGF-β2. The mature TGF-β protein dimerizes to produce a 25 KDa active protein with many conserved structural motifs, TGF-β has nine cysteine residues that are conserved among its family. Eight form disulfide bonds within the protein to create a knot structure characteristic of the TGF-β superfamily. The ninth cysteine forms a bond with the ninth cysteine of another TGF-β protein to produce a dimer.
Many other conserved residues in TGF-β are thought to form secondary structure through hydrophobic interactions, all three TGF-βs are synthesized as precursor molecules containing a propeptide region in addition to the TGF-β homodimer. This complex remains in the cell until it is bound by another protein called Latent TGF-β-Binding Protein and it is this LLC that gets secreted to the extracellular matrix. In most cases, before the LLC is secreted, the TGF-β precursor is cleaved from the propeptide but remains attached to it by noncovalent bonds. After its secretion, it remains in the matrix as an inactivated complex containing both the LTBP and the LAP which need to be further processed in order to release active TGF-β
The immune system is a host defense system comprising many biological structures and processes within an organism that protects against disease. To function properly, a system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms. In many species, the system can be classified into subsystems, such as the innate immune system versus the adaptive immune system. In humans, the barrier, blood–cerebrospinal fluid barrier, and similar fluid–brain barriers separate the peripheral immune system from the neuroimmune system. Even simple unicellular organisms such as bacteria possess a rudimentary immune system in the form of enzymes that protect against bacteriophage infections, other basic immune mechanisms evolved in ancient eukaryotes and remain in their modern descendants, such as plants and invertebrates. These mechanisms include phagocytosis, antimicrobial peptides called defensins, and the complement system, jawed vertebrates, including humans, have even more sophisticated defense mechanisms, including the ability to adapt over time to recognize specific pathogens more efficiently.
Adaptive immunity creates immunological memory after a response to a specific pathogen. This process of acquired immunity is the basis of vaccination, disorders of the immune system can result in autoimmune diseases, inflammatory diseases and cancer. Immunodeficiency occurs when the system is less active than normal. In humans, immunodeficiency can either be the result of a disease such as severe combined immunodeficiency, acquired conditions such as HIV/AIDS. In contrast, autoimmunity results from an immune system attacking normal tissues as if they were foreign organisms. Common autoimmune diseases include Hashimotos thyroiditis, rheumatoid arthritis, diabetes mellitus type 1, immunology covers the study of all aspects of the immune system. Immunology is a science that examines the structure and function of the immune system and it originates from medicine and early studies on the causes of immunity to disease. The earliest known reference to immunity was during the plague of Athens in 430 BC, thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time.
In the 18th century, Pierre-Louis Moreau de Maupertuis made experiments with scorpion venom and observed that certain dogs and this and other observations of acquired immunity were exploited by Louis Pasteur in his development of vaccination and his proposed germ theory of disease. Pasteurs theory was in opposition to contemporary theories of disease. It was not until Robert Kochs 1891 proofs, for which he was awarded a Nobel Prize in 1905, viruses were confirmed as human pathogens in 1901, with the discovery of the yellow fever virus by Walter Reed. Immunology made an advance towards the end of the 19th century, through rapid developments, in the study of humoral immunity
Monoclonal antibodies are antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies can have monovalent affinity, in that they bind to the same epitope, in contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different plasma cell lineages. Bispecific monoclonal antibodies can be engineered, by increasing the therapeutic targets of one single monoclonal antibody to two epitopes, given almost any substance, it is possible to produce monoclonal antibodies that specifically bind to that substance, they can serve to detect or purify that substance. This has become an important tool in biochemistry, molecular biology, when used as medications, non-proprietary drug names end in -mab and many immunotherapy specialists use the word mab anacronymically. He and Élie Metchnikoff received the 1908 Nobel Prize for Physiology or Medicine for this work, in the 1970s, the B-cell cancer multiple myeloma was known.
It was understood that these cancerous B-cells all produce a type of antibody. This was used to study the structure of antibodies, but it was not yet possible to produce antibodies specific to a given antigen. They shared the Nobel Prize in Physiology or Medicine in 1984 for the discovery, in 1988, Greg Winter and his team pioneered the techniques to humanize monoclonal antibodies, eliminating the reactions that many monoclonal antibodies caused in some patients. Monoclonal antibodies are made by cell culture that involves fusing myeloma cells with mouse spleen cells immunized with the desired antigen. Rabbit B-cells can be used to form a rabbit hybridoma, polyethylene glycol is used to fuse adjacent plasma membranes, but the success rate is low, so a selective medium in which only fused cells can grow is used. This is possible because myeloma cells have lost the ability to synthesize hypoxanthine-guanine-phosphoribosyl transferase, the absence of HGPRT is not a problem for these cells unless the de novo purine synthesis pathway is disrupted.
Exposing cells to aminopterin, makes them unable to use the de novo pathway and become fully auxotrophic for nucleic acids, the selective culture medium is called HAT medium because it contains hypoxanthine and thymidine. This medium is selective for fused cells, unfused myeloma cells cannot grow because they lack HGPRT and thus cannot replicate their DNA. Unfused spleen cells cannot grow indefinitely because of their life span. Only fused hybrid cells, referred to as hybridomas, are able to grow indefinitely in the media because the spleen cell partner supplies HGPRT and this mixture of cells is diluted and clones are grown from single parent cells on microtitre wells. The antibodies secreted by the different clones are assayed for their ability to bind to the antigen or immuno-dot blot, the most productive and stable clone is selected for future use. The hybridomas can be grown indefinitely in a cell culture medium. They can be injected into mice, they produce tumors secreting an antibody-rich fluid called ascites fluid