Antibody-drug conjugates are designed to deliver a toxic chemotherapy directly to tumors.
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Occasionally, he will pause, midsentence, determined to make sure he conjugates a conditional verb correctly (he does).
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The second is cultural: the idea that car travel conjugates American life in its healthiest and most distinctive forms.
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FRANKFURT (Reuters) - A class of treatments known as antibody-drug conjugates (ADC) combine cancer-tracking proteins with powerful cell toxins.
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The interim result gives further credence to a class of molecules known as antibody drug conjugates (ADC) that belantamab mafodotin belongs to.
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At Daiichi Sankyo, the Japanese drugmaker earlier this year said it would spend 15 billion yen ($136 million) to raise production of antibody drug conjugates.
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Daiichi Sankyo also has an interest in cancer, given its expertise in antibody drug conjugates, a new kind of "armed antibody" that can carry a cancer-killing payload to tumour cells, which could complement AstraZeneca's work in the field.
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The FDA has approved several antibody-drug conjugates, including Kadcyla for the treatment of some breast cancers, Adcetris for Hodgkin lymphoma and a type of non-Hodgkin T-cell lymphoma, and Zevalin for a type of non-Hodgkin B-cell lymphoma.
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Allylestrenol is eliminated mainly in urine, 44% by 24 hours and 67% within 4 days. It is excreted almost completely as conjugates, with 75% of these being sulfate conjugates and 24% being glucuronide conjugates.
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Known substrates of OAT1 include para-aminohippurate (PAH), dicarboxylates, prostaglandins, cyclic nucleotides, urate, folate, diuretics, ACE inhibitors, antiviral agents, beta- lactam antibiotics, antineoplastics, mycotoxins, sulfate conjugates, glucuronide conjugates, cysteine conjugates, ochratoxin A, NSAIDs, mercapturic acids and uremic toxins.
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Immunoconjugates are antibodies conjugated (joined) to a second molecule, usually a toxin, radioisotope or label. These conjugates are used in immunotherapy and to develop monoclonal antibody therapy as a targeted form of chemotherapy when they are often known as antibody-drug conjugates. When the conjugates include a radioisotope see radioimmunotherapy. When the conjugates include a toxin see immunotoxin.
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After phase II reactions, the xenobiotic conjugates may be further metabolized. A common example is the processing of glutathione conjugates to acetylcysteine (mercapturic acid) conjugates. Here, the γ-glutamate and glycine residues in the glutathione molecule are removed by Gamma-glutamyl transpeptidase and dipeptidases. In the final step, the cystine residue in the conjugate is acetylated.
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In mathematics, in particular field theory, the conjugate elements of an algebraic element α, over a field extension L/K, are the roots of the minimal polynomial pK,α(x) of α over K. Conjugate elements are also called Galois conjugates or simply conjugates. Normally α itself is included in the set of conjugates of α.
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Glutathione conjugates to NAPQI, and the resulting ensemble is excreted.
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Consequently, estrogen conjugates have estrogenic activity via conversion into unconjugated estrogens.
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Hydrocodone is excreted in urine, mainly in the form of conjugates.
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Similar reasoning proves both pairs, W & Y, X & Z, are conjugates.
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Polymer-drug conjugates are nano-medicine products under development for cancer diagnosis and treatment. There are more than 10 anticancer conjugates in clinical development. Polymer-drug conjugates are drug molecules held in polymer molecules, which act as the delivery system for the drug. Polymer drugs have passed multidrug resistance (MDR) testing and hence may become a viable treatment for endocrine-related cancers.
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OHPC is eliminated 50% in feces and 30% in urine when given by intramuscular injection to pregnant women. Both the free steroid and conjugates are excreted by these routes, with the conjugates more prominent in feces.
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Estrogens are excreted primarily by the kidneys as conjugates via the urine.
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Conjugates that were formed were predominated by sulfate conjugates over glucuronide conjugates by a ratio of 6:1. The metabolism of o-toluidine involves many competing activating and deactivating pathways, including N-acetylation, N-oxidation and N-hydroxylation, and ring oxidation. 4-Hydroxylation and N-acetylation of toluidine are the major metabolic pathways in rats. The primary metabolism of o-toluidine takes place in the endoplasmic reticulum.
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Fluidigm sells a variety of commonly used metal-antibody conjugates, and an antibody conjugation kit.
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Studies also showed CHPs and their fluorophore conjugates have superior stability in contact with serum.
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Figure 2. Examples of nanoparticle superlattices that can be synthesized based on SNA- nanoparticle conjugates.
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Methyltestosterone is excreted 90% in the urine as conjugates and other metabolites, and 6% in feces.
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ST1C3 sulfates large benzylic alcohols such as 1-hydroxymethyl-pyrene to chemically reactive mutagenic sulpho conjugates.
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DHT is excreted in the urine as metabolites, such as conjugates of 3α-androstanediol and androsterone.
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Using anti-PLAC1/drug conjugates they have shown that PLAC1-based immunotherapy is highly promising[50, 51].
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Generally, Polymer-Protein hybrids can be synthesized by interfacial self-assembly of protein–polymer conjugates in emulsions.
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Acetaminophen is metabolized in the liver via glucuronide conjugation, sulfate conjugation or oxidation. The CYP450 dependent (CYP1A2, CYP2E1, and CYP3A4) oxidation pathway produces a reactive metabolite that conjugates with glutathione. The glutathione conjugate is then metabolized to cysteine and mercapturic acid conjugates. Hydrocodone is mainly excreted in the urine.
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An Immune stimulating antibody conjugate (ISAC) is a mAb that conjugates an antibody to an immune-stimulatory agent. They have been used in targeting tumors in mouse models, particularly to turn "cold tumors into hot ones". Immune stimulating antibody conjugates work by activating dendritic cells within the tumor, and are capable of being delivered systemically. With some patients being resistant to checkpoint inhibitors, immune stimulating antibody conjugates may be able to harness an immune response generated through the stimulation of toll-like receptors.
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Diameters and their conjugates are defined in Book I (Definitions 4-6). Not every diameter has a conjugate.
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BODIPY conjugates are widely studied as potential sensors and for labelling by exploiting its highly tunable optoelectronic properties.
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Androsterone is sulfated into androsterone sulfate and glucuronidated into androsterone glucuronide and these conjugates are excreted in urine.
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This will enable selective delivery of anticancer conjugates. A natural polymer dextrin and pendant chain polyacetals, have shown ability of pH-dependent degradation after incorporation into cell compartments. Also diethylstilboestrol (DES) conjugates can undergo pH-dependent degradation. Polymer-Directed Enzyme Prodrug Therapy (PDEPT) is an example of two-step anticancer treatment.
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Tibolone is metabolized in the liver and intestines. It is a prodrug and is rapidly transformed into several metabolites, including δ4-tibolone, 3α-hydroxytibolone, and 3β-hydroxytibolone, as well as sulfate conjugates of these metabolites. 3α-Hydroxytibolone is formed by 3α-hydroxysteroid dehydrogenase, 3β-hydroxytibolone is formed by 3β-hydroxysteroid dehydrogenase, δ4-tibolone is formed by Δ5-4-isomerase, and the sulfate conjugates of tibolone and its metabolites are formed by sulfotransferases, mainly SULT2A1. The sulfate conjugates can be transformed back into free steroids by steroid sulfatase.
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The fields and conjugates form an infinite dimensional phase space, because fields have an infinite number of degrees of freedom.
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Thermoresponsive conjugates have been exploited for the subsequent separation of proteins from a complex mixture. This method has been utilized to purify polyclonal antibodies in serum samples. This method of purification is rapid, sensitive, inexpensive and could be used to purify various types of antibodies. Thermoresponsive conjugates can also be exploited to mediate bioactivity.
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By now only traditional chemotherapeutic agents like doxorubicin, paclitaxel, camptothecins and platinates have been clinically tested in drug conjugates. Due to successful clinical proof-of-concept, second-generation conjugates are now being developed. Experimental chemotherapy and novel polymer-based combinations are currently under investigation. Instead of passive targeting developed so far, new approaches will provide receptor-mediated delivery.
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At least one of their conjugates, IT-101, has been investigated in a clinical trial at City of Hope National Medical Center.
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Specificity of folate conjugates for the FR has been shown by competition tests with free folate. When this ligand, known to bind the FR, is added in excess of the folate conjugate, it outcompetes the conjugate, indicating that the folate conjugate specifically binds the FR, and not other receptors, in the process of receptor-mediated endocytosis. Addition of an enzyme that frees the folate receptor from the cell membrane and addition of antibodies to the FR also reverse the internalization of folate conjugates, providing further evidence that folate conjugates bind the FR with specificity. While some drugs and radioimaging agents are delivered to cells as folate conjugates in a one-to-one folate-to-conjugate ratio, folate- targeted liposomes allow for the delivery of larger amounts of chemotherapeutic agents.
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During phase II metabolism, phase I metabolites undergo glucuronidation and sulfation to form multiple glucuronide and sulfate conjugates, that are eliminated via urine.
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In the face of challenges in producing ubiquitin conjugates using traditional molecular biology and enzymatic approaches, the Brik lab has developed a number of novel chemical methods for the preparation of large quantities of highly homogeneous and pure ubiquitin conjugates which have shed light on the mechanisms of ubiquitin signaling and enabled the discovery of novel modulators for the enzymes involved these processes.
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Hudak et al. explored the strategy of producing protein-protein conjugates with the help of the aldehyde tag. Their aim was to connect full length human IgG (hIgG) to the human growth hormone (hGH). These protein- protein conjugates can be superior to monomeric proteins in terms of serum half life in protein therapeutics and, additionally, have appealing dual binding properties.
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For many PAHs it has been proven that they are conjugated, in phase II, with either glucuronide, sulfate or glutathione. More research on this topic is necessary for benzo[c]fluorene. Glucuronide and sulfate conjugates of PAH metabolites are generally excreted in the bile and urine. Glutathione conjugates are further metabolized to mercapturic acids in the kidney and are excreted in the urine.
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Giljohann DA, Seferos DS, Prigodich AE, Patel PC, Mirkin CA. Gene regulation with polyvalent siRNA-nanoparticle conjugates. J Am Chem Soc 2009;131:2072–2073.
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PDEPT uses polymer-drug conjugates, drugs contained within a polymer 'shell' such as pHPMA and designed to be released only by a specific enzyme.
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Many dyes undergo self-quenching, which can decrease the brightness of protein-dye conjugates for fluorescence microscopy, or can be harnessed in sensors of proteolysis.
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The class of locally finite groups is closed under subgroups, quotients, and extensions . Locally finite groups satisfy a weaker form of Sylow's theorems. If a locally finite group has a finite p-subgroup contained in no other p-subgroups, then all maximal p-subgroups are finite and conjugate. If there are finitely many conjugates, then the number of conjugates is congruent to 1 modulo p.
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Most commonly, the weak antigen is a polysaccharide that is attached to strong protein antigen. However, peptide/protein and protein/protein conjugates have also been developed.
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Sulfate conjugates are a heterogeneous class of polar, anionic organosulfate compounds containing an ester of sulfuric acid. Sulfate conjugates commonly result from the metabolic conjugation of endogenous and exogenous compounds with sulfate (-OSO3−). Biosynthesis of sulfate esters requires an activated sulfate donor, usually adenosine 5'-phosphosulfate (APS) or 3'-phosphoadenosine-5'-phosphosulfate (PAPS).M. T. Madigan, J. M. Martinko, J. Parker "Brock Biology of Microorganisms" Prentice Hall, 1997. .
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Consider the 2D isometry point group Dn. The conjugates of a rotation are the same and the inverse rotation. The conjugates of a reflection are the reflections rotated by any multiple of the full rotation unit. For odd n these are all reflections, for even n half of them. This group, and more generally, abstract group Dihn, has the normal subgroup Zm for all divisors m of n, including n itself.
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Estriol is an end-product of phase I estrogen metabolism and cannot be converted into estradiol or estrone. The main metabolites of estriol are estrogen conjugates, including estriol sulfates, estriol glucuronides, and mixed estriol sulfate/glucuronide conjugates. 16α-Hydroxyestrone is known to occur as a metabolite of estriol as well. The biological half-life of oral estriol has been reported to be in the range of 5 to 10 hours.
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Doxepin is eliminated primarily in the urine and predominantly in the form of glucuronide conjugates, with less than 3% of a dose excreted unchanged as doxepin or nordoxepin.
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Halsted, p. 25 Alternatively, the polar line of P is the set of projective harmonic conjugates of P on a variable secant line passing through P and C.
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Also under development are site-specific conjugation (TDCs) and novel conjugation techniques to further improve stability and therapeutic index, α emitting immunoconjugates, antibody-conjugated nanoparticles and antibody-oligonucleotide conjugates.
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The conjugates of a reflection are reflections with a translated, rotated, and reflected mirror plane. The conjugate closure of a singleton containing a reflection is the whole E(n).
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E1S, also known as estrone 3-sulfate or as estra-1,3,5(10)-trien-17-one 3-sulfate, is a naturally occurring estrane steroid and a derivative of estrone. It is an estrogen conjugate or ester, and is specifically the C3 sulfate ester of estrone. Related estrogen conjugates include estradiol sulfate, estriol sulfate, estrone glucuronide, estradiol glucuronide, and estriol glucuronide, while related steroid conjugates include dehydroepiandrosterone sulfate and pregnenolone sulfate. The logP of E1S is 1.4.
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This is difficult on clinical grounds alone. It may be suspected by examination of the urine for conjugates of methacrylic acid. The diagnosis is made by sequencing the mutated gene.
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Pentarins are nanoparticle drugs, similar to antibody-drug conjugates but smaller, that have been described as "mini-smart bombs". They are believed to be capable of penetrating dense tumor-based cancers.
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Tannins are astringent, bitter polyphenolic compounds that bind to and precipitate organic compounds. Gallic acid conjugates all of the catechins, such as EGCG (Epigallocatechin gallate), which are tannins with astringent qualities.
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Mannan oligosaccharides-protein conjugates are involved in interactions with the animal's immune system and as result enhance immune system activity. They also play a role in animal antioxidant and antimutagenic defense.
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The interconversion between estradiol and estrone is mediated by 17β-hydroxysteroid dehydrogenases (17β-HSDs), whereas the conversion of estrone into estrone sulfate is mediated by estrogen sulfotransferases (ESTs) and the transformation of estrone sulfate into estrone by steroid sulfatase (STS). The metabolic clearance rates and hence blood half-lives of estrogen conjugates like estrone sulfate are much longer than those of estradiol and estrone. Estrogen conjugates, primarily estrone sulfate, serve as a large circulating reservoir for estradiol, and because of this, they function to greatly extend the biological half-life of oral estradiol. As such, the biological half-life of oral estradiol is a composite parameter that is dependent on interconversion between estradiol and estrogen conjugates, as well as on enterohepatic recirculation.
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His lab designed and developed N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates as a lysosomal delivery vehicle to cancer cells. The concept of using poly(HPMA) as polymeric drug carriers has opened a new perspective in modern pharmaceutical science, and developed into the first polymer-drug conjugates entering clinical trials.Clinical Cancer Research Vol. 5, 83–94, January 1999 For these contributions, he was elected as a member of the United States National Academy of Engineering in 2011.
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Whereas free steroids like estradiol are lipophilic and can enter cells via passive diffusion, steroid conjugates like E1S are hydrophilic and are unable to do so. Instead, steroid conjugates require active transport via membrane transport proteins to enter cells. Studies in animals and humans have had mixed findings on uptake of exogenously administered E1S in normal and tumorous mammary gland tissue. This is in contrast to substantial uptake of exogenously administered estradiol and estrone by the mammary glands.
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Gairaigo are generally nouns, which can be subsequently used as verbs by adding auxiliary verb . For example, "play soccer" is translated as サッカーをする (sakkā o suru). Some exceptions exist, such as , which conjugates as a normal Japanese verb – note the unusual use of katakana () followed by hiragana (). Another example is gugu-ru (ググる, "to google"), which conjugates as a normal Japanese verb, in which the final syllable is converted into okurigana to enable conjugation.
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Cyclodextrin "half-channels". Top: postulated "gramicidin-like" mechanism . Bottom: chemical structures of these cyclodextrin-conjugates. The first synthetic ion channel was constructed by partial substitution on the primary rim of β-cyclodextrin.
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Consider the element . By construction, is fixed by , and only has three conjugates over : : , : , : . Using the identity: :, one finds that : , : , : . Therefore is a root of the polynomial :, which consequently has Galois group over .
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The conjugates consist of a cyclodextrin- containing polymer (Cyclosert) that acts as a drug delivery system, and a linked medication, such as a chemotherapeutic drug of already proven efficacy.IT-101 trial The size of the polymer is designed to “fit” the specific target, as vessels in a neoplasm allow for leakage of different sizes of polymers, as in healthy tissue. The leaked conjugates are concentrated in the target area. As a result, chemotherapeutic activity is locally enhanced, while general side effects are decreased.
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Some types of polymers being tested now are poly(ethylene glycol) (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), and poly(lactide-co-glycolide) (PLGA) copolymers have been successful in medical research. Recently there has been a growing interest in polymer conjugation with biologically active components. Such conjugates usually accumulate in tumors and can reduce toxicity in the body. Depending on the desired location, polymer conjugates can be synthesized to either have degradable or non-degradable chemical bonds with their associated drug.
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A cocktail of pendant drugs could be delivered by water-soluble polymer platforms. The physical and chemical properties of the polymers used in polymer-drug conjugates are specially synthesized to flow through the kidneys and liver without being filtered out, allowing the drugs to be used more effectively. Traditional polymers used in polymer-drug conjugates can be degraded through enzymatic activity and acidity. Polymers are now being synthesized to be sensitive to specific enzymes that are apparent in diseased tissue.
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A single administered dose of estradiol is absorbed 15% as estrone, 25% as E1S, 25% as estradiol glucuronide, and 25% as estrone glucuronide. Formation of estrogen glucuronide conjugates is particularly important with oral estradiol as the percentage of estrogen glucuronide conjugates in circulation is much higher with oral ingestion than with parenteral estradiol. Estrone glucuronide can be reconverted back into estradiol, and a large circulating pool of estrogen glucuronide and sulfate conjugates serves as a long-lasting reservoir of estradiol that effectively extends its terminal half-life of oral estradiol. To demonstrate the importance of first-pass metabolism and the estrogen conjugate reservoir in the pharmacokinetics of estradiol, the terminal half-life of oral estradiol is 13 to 20 hours whereas with intravenous injection its terminal half-life is only about 1 to 2 hours.
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Independent of this activity, USP18 is also a member of the deubiquitinating protease family of enzymes. It is known to remove ISG15 conjugates from a broad range of protein substrates, a process known as deISGylation.
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Apart from the biosimilars noted above, trastuzumab is also a component of some antibody-drug conjugates, such as trastuzumab emtansine. Another ADC, trastuzumab deruxtecan was approved for use in the United States in December 2019.
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So for example, the first Brocard point of triangle ABC is the same as the second Brocard point of triangle ACB. The two Brocard points of a triangle ABC are isogonal conjugates of each other.
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Equilin is converted into 17β-dihydroequilin in the liver and in other tissues. Equilin and 17β-dihydroequilin can also be transformed into equilenin and 17β-dihydroequilenin. Equilin is excreted in the form of glucuronide conjugates.
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Higher powers give correspondingly better rational approximations. This property stems from the fact that for each n, the sum of nth powers of an algebraic integer x and its conjugates is exactly an integer; this follows from an application of Newton's identities. When x is a Pisot number, the nth powers of the other conjugates tend to 0 as n tends to infinity. Since the sum is an integer, the distance from xn to the nearest integer tends to 0 at an exponential rate.
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Because microbes recognize and utilize only certain siderophores, such conjugates are anticipated to have selective antimicrobial activity. Microbial iron transport (siderophore)-mediated drug delivery makes use of the recognition of siderophores as iron delivery agents in order to have the microbe assimilate siderophore conjugates with attached drugs. These drugs are lethal to the microbe and cause the microbe to apoptosise when it assimilates the siderophore conjugate. Through the addition of the iron-binding functional groups of siderophores into antibiotics, their potency has been greatly increased.
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Her research considers polymer materials, including arrays, films for patterning, bioactive proteins and new ways to develop protein- polymer conjugates. These conjugates are used in medical therapeutics to treat a range of diseases, and are synthesised by polymerising from proteins and amino acid-reactive initiators. Maynard has considered the mechanisms that underpin the function of known therapeutics. This includes the development of new synthetic pathways, such as controlled radical polymerization and click chemistry, to make polymers with narrow molecular weight distributions and anchoring sites for particular surfaces.
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One major drawback of siRNA-based therapies is that they lack sufficient in-vivo delivery of siRNA into the target cells because of the large size and negative charge density of siRNA. Efficient transfer of siRNA to the liver has been achieved by lipid nanoparticles, polymer conjugates, and peptide conjugates. One of the major challenges of current methods of transfer is the nonbiodegradability of the vessel once it is inside the body. This challenge is solved by using biodegradable poly(amide) polymers derived from polymerization of NCAs.
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627x627px The applications of antibody-oligonucleotide conjugates have expanded beyond CITE-seq, and can be adapted for sample multiplexing as well as CRISPR screens. Cell Hashing: New York Genome Center further adapted the use of their antibody- oligonucleotide conjugates to enable sample multiplexing for scRNA-seq. This technique called, Cell Hashing, uses oligonucleotide-labelled antibodies against ubiquitously expressed cell surface proteins from a particular tissue sample. In this case, an oligonucleotide sequence contains a unique barcode which would be specific to cells from distinct samples.
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Antibody-drug conjugates are examples of bioconjugates and immunoconjugates. ADCs combine the targeting capabilities of monoclonal antibodies with the cancer-killing ability of cytotoxic drugs. They can be designed to discriminate between healthy and diseased tissue.
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Raloxifene is mainly excreted in bile and is eliminated in feces. Less than 0.2% of a dose is excreted unchanged in urine and less than 6% of a dose is excreted in urine as glucuronide conjugates.
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If K is given inside an algebraically closed field C, then the conjugates can be taken inside C. If no such C is specified, one can take the conjugates in some relatively small field L. The smallest possible choice for L is to take a splitting field over K of pK,α, containing α. If L is any normal extension of K containing α, then by definition it already contains such a splitting field. Given then a normal extension L of K, with automorphism group Aut(L/K) = G, and containing α, any element g(α) for g in G will be a conjugate of α, since the automorphism g sends roots of p to roots of p. Conversely any conjugate β of α is of this form: in other words, G acts transitively on the conjugates.
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Once unconjugated bilirubin arrives in the liver, a liver enzyme UDP-glucuronyl transferase conjugates bilirubin + glucuronic acid → bilirubin diglucuronide (conjugated bilirubin). Bilirubin that has been conjugated by the liver is water-soluble and excreted into the gallbladder.
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Bicalutamide is eliminated in similar proportions in feces (43%) and urine (34%), while its metabolites are eliminated roughly equally in urine and bile. The drug is excreted to a substantial extent in unmetabolized form, and both bicalutamide and its metabolites are eliminated mainly as glucuronide conjugates. The glucuronide conjugates of bicalutamide and its metabolites are eliminated from the circulation rapidly, unlike unconjugated bicalutamide. The pharmacokinetics of bicalutamide are not affected by consumption of food, a person's age or body weight, renal impairment, or mild-to-moderate hepatic impairment.
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In the case where the conic is a circle, on the extended diameters of the circle, harmonic conjugates with respect to the circle are inverses in a circle. This fact follows from one of Smogorzhevsky's theorems:A.S. Smogorzhevsky (1982) Lobachevskian Geometry, Mir Publishers, Moscow :If circles k and q are mutually orthogonal, then a straight line passing through the center of k and intersecting q, does so at points symmetrical with respect to k. That is, if the line is an extended diameter of k, then the intersections with q are harmonic conjugates.
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Giljohann, D. A.; Seferos, D. S.; Prigodich, A. E.; Patel, P. C.; Mirkin, C. A. "Gene Regulation with Polyvalent siRNA-Nanoparticle Conjugates," J. Am. Chem. Soc., 2009,131, 2072–2073, doi: 10.1021/ja808719p. The proposed mechanism is that, unlike their linear counterparts, SNAs have the ability to complex scavenger receptor proteins to facilitate endocytosis.Choi, C. H. J.; Hao, L.; Narayan, S. P.; Auyeung, E.; Mirkin, C. A. “Mechanism for the Endocytosis of Spherical Nucleic Acid Nanoparticle Conjugates,” Proc. Natl. Aca. Sci. USA, 2013, 110, 7625-7630, doi: 10.1073/pnas.1305804110.
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Whereas oral estriol results in high levels of estriol conjugates which greatly exceed those of unconjugated estriol, vaginal estriol has been found to produce levels of unconjugated estriol and estriol conjugates that are similar. The absorption of estrogens by the skin is described as low for estriol, moderate for estradiol, and high for estrone. This is related to the number of hydroxyl groups in the molecules; the more hydroxyl groups, the lower the skin permeability. This may account for the relative lack of use of transdermal or topical estriol.
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The first-pass effect that occurs with oral estradiol results in unusually high levels of estrone and estrogen conjugates in the circulation as well as of estradiol in the liver. These unique properties of oral estradiol result in a number of pharmacological differences relative to the other routes of administration of estradiol. The high levels of estrone and estrogen conjugates that occur with oral estradiol raise the question of the pharmacodynamic significance of these metabolites. In contrast to estradiol however, estrone has very low activity as an estrogen.
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Antibody-drug conjugates (ADCs) are antibodies linked to one or more drug molecules. Typically when the ADC meets the target cell (e.g. a cancerous cell) the drug is released to kill it. Many ADCs are in clinical development.
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Anthramycin contains pyrrolobenzodiazepine core Pyrrolobenzodiazepines (PBD) are a class of compound that may have antibiotic or anti-tumor properties. Some dimeric pyrrolobenzodiazepines are used as the cytotoxic drug payloads in antibody-drug conjugates, for example in SGN-CD33A.
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Ume Sámi, like Finnish, the other Sámi languages, and Estonian, has a negative verb. In Ume Sámi, the negative verb conjugates according to mood (indicative and imperative), person (1st, 2nd and 3rd) and number (singular, dual and plural).
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The regular Moroccan Arabic verb conjugates with a series of prefixes and suffixes. The stem of the conjugated verb may change a bit, depending on the conjugation: The stem of the Moroccan Arabic verb for "to write" is kteb.
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Using the same notation as above; If a variable line through the point is a secant of the conic , the harmonic conjugates of with respect to the two points of on the secant all lie on the polar of .
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Most individuals with SBCADD are identified through newborn screening, where they present with an elevation of a five carbon acylcarnitine species. Confirmatory testing includes plasma and urine analysis to identify the carnitine and glycine conjugates of 2-methylbutyryl-CoA.
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The indicative mood has four tenses: present, future and two past tenses. In addition, there are four past tense structures which include auxiliary verbs. Verbs are negated by use of an auxiliary negative verb that conjugates with personal endings.
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109 (1934), pp. 647–660. Informally, the theorem says that every subgroup of a free product is itself a free product of a free group and of its intersections with the conjugates of the factors of the original free product.
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The algebra of throws by Karl von Staudt (1847) is an approach to geometry that is independent of metric. The idea was to use the relation of projective harmonic conjugates and cross-ratios as fundamental to the measure on a line.
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15-lipoxygenase acts by binding to phospholipids and yields hydroperoxy and epoxy metabolites. One such metabolite, 15-hydroxyeicosatetranoic acid (15-HETE), is released intracellularly, where it conjugates to phosphatidylethanolamine, a phospholipid component. 15-HETE-PE induces expression of the mucin MUC5AC.
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The first two pathways occur more than pathway three. The most common metabolite is the 4-OH-3-MeO metabolite. The metabolites containing a hydroxyl-group would be excreted as their conjugates in urine. The three metabolic pathways of butylone.
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It is mostly excreted in the urine (around 30–50%) as metabolites either free or as glucuronide and sulfate conjugates within 24 hours. 2% of the unchanged drug is excreted in the urine. Small amounts are also excreted in feces.
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Due to this reaction, glycidamide becomes critical to the genotoxicity of acrylamide.Luo, Y. S., Long, T. Y., Shen, L. C., Huang, S. L., Chiang, S. Y., & Wu, K. Y. (2015). Synthesis, characterization and analysis of the acrylamide-and glycidamide-glutathione conjugates.
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The map taking w to BwB is an isomorphism from the set of elements of W to the set of double cosets of B; this is the Bruhat decomposition G = BWB. If T is a subset of S then let W(T) be the subgroup of W generated by T: we define and G(T) = BW(T)B to be the standard parabolic subgroup for T. The subgroups of G containing conjugates of B are the parabolic subgroups; conjugates of B are called Borel subgroups (or minimal parabolic subgroups). These are precisely the standard parabolic subgroups.
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Antibody conjugates of glucose oxidase and to lactoperoxidase have been found to effective in killing tumor cells in vitro. In addition, macrophages exposed to lactoperoxidase are stimulated to kill cancer cells. Peroxidase-generated hypothiocyanite inhibits herpes simplex virus and human immunodeficiency virus.
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Inari Sami, like Finnish and the other Sami languages, has a negative verb. In Inari Sami, the negative verb conjugates according to mood (indicative, imperative and optative), person (1st, 2nd, 3rd) and number (singular, dual and plural). Ind. pres. Imperative Optative sg.
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The pharmaceuticals pass sewage treatment plants. They like estrogen conjugates may cause problems. Drugs of the research were common, present in the aquatic environment and inability to be adequately removed by sewage treatment plants.WHELEHAN, M., VON STOCKAR, U. and MARISON, I.W., 2010.
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These conjugates can be reversed by UBL- specific isopeptidases that have similar mechanisms to that of the deubiquitinating enzymes. Within some species, the recognition and destruction of sperm mitochondria through a mechanism involving ubiquitin is responsible for sperm mitochondria's disposal after fertilization occurs.
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When the speaker conjugates in intransitive, the sentence has no concrete object (in this case, the object is nothing or something like something, anything). In the transitive conjugation, there is a concrete object. This feature also exists in the other Ugric languages.
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The half-lives of DHEA metabolites range up to 3.6 days. Within 30 days, 91% of a dose of prasterone enanthate is eliminated. Approximately 94% is excreted in urine and 6% in feces. Prasterone enanthate is eliminated mainly in the form of metabolites and conjugates.
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An octa-guanidinium dendrimer attached to the end of a Morpholino can deliver the modified oligo (called a Vivo-Morpholino) from the blood to the cytosol. Delivery-enabled Morpholinos, such as peptide conjugates and Vivo-Morpholinos, show promise as therapeutics for viral and genetic diseases.
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Bicalutamide is eliminated in feces (43%) and urine (34%), whereas its metabolites are eliminated in approximately equal proportions in urine and bile. It is excreted to a substantial extent in its unmetabolized form, with both bicalutamide and its metabolites excreted mainly as glucuronide conjugates.
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Metabolism of acrylamide to glycidamide and their cytotoxicity in isolated rat hepatocytes: protective effects of GSH precursors. Archives of toxicology, 80(12), 820-828. Whether this is the case for glycidamide remains unclear. Glycidamide can be detoxified through different pathways to glycidamide-glutathione conjugates.
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Emmenin and Progynon were estriol products marketed in the 1930s which were manufactured from the urine of pregnant women and contained estriol conjugates, primarily estriol glucuronide. Estriol for multiple sclerosis had the tentative brand name Trimesta but did not complete development and was never marketed.
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The basic algebraic operations for real interval numbers (real closed intervals) can be extended to complex numbers. It is therefore not surprising that complex interval arithmetic is similar to, but not the same as, ordinary complex arithmetic. It can be shown that, as it is the case with real interval arithmetic, there is no distributivity between addition and multiplication of complex interval numbers except for certain special cases, and inverse elements do not always exist for complex interval numbers. Two other useful properties of ordinary complex arithmetic fail to hold in complex interval arithmetic: the additive and multiplicative properties, of ordinary complex conjugates, do not hold for complex interval conjugates.
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Each such product equivalence can be expressed as an equality to the identity, such as :, :, or :. Informally, we can consider these products on the left hand side as being elements of the free group , and can consider the subgroup R of F which is generated by these strings; each of which would also be equivalent to 1 when considered as products in D8. If we then let N be the subgroup of F generated by all conjugates x−1Rx of R, then it follows by definition that every element of N is a finite product x1−1r1x1 ... xm−1rm xm of members of such conjugates.
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Unlike residuals, conjugacy is an equivalence relation between operations: if f is the conjugate of g then g is also the conjugate of f, i.e. the conjugate of the conjugate of f is f. Another advantage of conjugacy is that it becomes unnecessary to speak of right and left conjugates, that distinction now being inherited from the difference between x• and •x, which have as their respective conjugates x▷ and ◁x. (But this advantage accrues also to residuals when x\ is taken to be the residual operation to x•.) All this yields (along with the Boolean algebra and monoid axioms) the following equivalent axiomatization of a residuated Boolean algebra.
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The modification of proteins with Ufm1 is also reversible. Two novel cysteine proteases have been identified to date (UFSP1 and UFSP2) which cleave Ufm1-peptide C-terminal fusions and also removes Ufm1 from native intracellular conjugates. These proteases have no obvious homology to ubiquitin deconjugating enzymes.
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Estrogen esters also occur naturally in the body, for instance estrogen conjugates like estrone sulfate and estrone glucuronide and the very long-lived lipoidal estradiol, which is constituted by ultra-long-chain esters like estradiol palmitate (ester of 16 carbons) and estradiol stearate (ester of 18 carbons).
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Estrone is excreted in urine in the form of estrogen conjugates such as estrone sulfate. Following an intravenous injection of labeled estrone in women, almost 90% is excreted in urine and feces within 4 to 5 days. Enterohepatic recirculation causes a delay in excretion of estrone.
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She is also the President of the Indian Society of Developmental Biologists Prof. Swapan Kumar Pati is the Chair of TSU. He received the Shanti Swarup Bhatnagar Prize for Science and Technology in 2010. His work related to the preparation of julolidine conjugates has been patented. Prof.
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Tigecycline is metabolized through glucuronidation into glucuronide conjugates and N-acetyl-9-aminominocycline metabolite. Therefore, dose adjustments are needed for patients with severe hepatic impairment. More so, it is primarily eliminated unchanged in the feces and secondarily eliminated by the kidneys. No renal adjustments are necessary.
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Cantuzumab ravtansine (huC242-SPDB-DM4) is an antibody-drug conjugate designed for the treatment of cancers. The humanized monoclonal antibody cantuzumab (huC242) is linked to a cytotoxic agent, ravtansine (DM4). It uses a more hindered disulfide linkage than cantuzumab mertansine.Antibody-Drug Conjugates and Immunotoxins: From Pre-Clinical Development to ...
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Inversely, reactions that form a positive charge on said carbon (i.g. Cytochrome-P450 oxidation of the double bond), are faster with MeAN as the reactant. As a result, in metabolism, MeAN conjugates less with glutathione (GSH) than AN, and is activated more easily. El Hadri, L., et al. (2005).
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Nanoparticle delivery through the BBB can be increased by introducing peptide conjugates to improve permeability to the central nervous system. For instance, recent studies have shown an improvement in gold nanoparticle delivery efficiency by conjugating a peptide that binds to the transferrin receptors expressed in brain endothelial cells.
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Hebrew Verbs: Qal Perfect, Hebrew4christians.com. Retrieved August 27, 2020. The Classical Hebrew verb conjugates according to person and number in two finite tenses, the perfect and the imperfect. Both of these can then be modified by means of prefixes and suffixes to create other "actions" of the verb.
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There are several different proteases which can remove NEDD8 from protein conjugates. UCHL1, UCHL3 and USP21 proteases have dual specificity for NEDD8 and ubiquitin. Proteases specific for NEDD8 removal are the COP9 signalosome which removes NEDD8 from the CUL1 subunit of SCF ubiquitin ligases, and NEDP1 (or DEN1, SENP8).
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A different (unrelated) configuration is an impedance matching connection in which the source and load impedances are either equal or complex conjugates. Such a configuration serves to either prevent reflections when transmission lines are involved, or to maximize power delivered to the load given an unchangeable source impedance.
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Total exposures to both doxepin and nordoxepin differ by almost 10-fold in CYP2D6 ultra-rapid versus poor metabolizers. Both doxepin and nordoxepin are also transformed into glucuronide conjugates. The elimination half-life of nordoxepin is approximately 31 hours, which is almost twice that of doxepin (mean 17 hours).
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Heather D. Maynard is the Dr Myung Ki Hong Professor in Polymer Science at the University of California, Los Angeles. She works on protein-polymer conjugates and polymeric drugs. Maynard is a Fellow of the Royal Society of Chemistry and the American Association for the Advancement of Science.
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Estrone is excreted in urine in the form of estrogen conjugates such as estrone sulfate and estrone glucuronide. Following an intravenous injection of labeled estrone in women, almost 90% is excreted in urine and feces within 4 to 5 days. Enterohepatic recirculation causes a delay in excretion of estrone.
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Let X0 be the countable subset given by the finitely many Fn-orbits of the fixed points hi ±∞, the fixed points of the hi and all their conjugates. Since X is uncountable, there is an element of g with fixed points outside X0 and a point w outside X0 different from these fixed points. Then for some subsequence (gm) of (gn) :gm = h1n(m,1) ··· hkn(m,k), with each n(m,i) constant or strictly monotone. On the one hand, by successive use of the rules for computing limits of the form hn·wn, the limit of the right hand side applied to x is necessarily a fixed point of one of the conjugates of the hi's.
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As long as the rotation angle \alpha is nonzero (i.e., the rotation is not the identity tensor), there is one and only one such direction. Because A has only real components, there is at least one real eigenvalue, and the remaining two eigenvalues must be complex conjugates of each other (see Eigenvalues and eigenvectors#Eigenvalues and the characteristic polynomial). Knowing that 1 is an eigenvalue, it follows that the remaining two eigenvalues are complex conjugates of each other, but this does not imply that they are complex—they could be real with double multiplicity. In the degenerate case of a rotation angle \alpha=180^\circ, the remaining two eigenvalues are both equal to -1.
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The duocarmycin have shown activity in a variety of multi-drug resistant (MDR) models. Agents that are part of this class of duocarmycins have the potency in the low picomolar range. This makes them suitable for maximizing the cell-killing potency of antibody-drug conjugates to which they are attached.
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Noratropine (24%), atropine-N-oxide (15%), tropine (2%) and tropic acid (3%) appear to be the major metabolites, while 50% of the administered dose is excreted as apparently unchanged atropine. No conjugates were detectable. Evidence that atropine is present as (+)-hyoscyamine was found, suggesting that stereoselective metabolism of atropine probably occurs.
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However, PhIP may also undergo a detoxification pathway through Phase II conjugation reaction via UDP-glucuronosyltransferases (UGTs) to form N-glucuronide conjugates. PhIP's nitrenium ion intermediate is a powerful electrophile that has propensity to form C-8 guanine adducts with the DNA.Felton, J., et al. (1997). Health Risks of Heterocyclic Amines.
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Zeatin is a cytokinin derived from adenine, which occurs in the form of a cis- and a trans-isomer and conjugates. Zeatin was discovered in immature corn kernels from the genus Zea. It promotes growth of lateral buds and when sprayed on meristems stimulates cell division to produce bushier plants.
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GSH / S-transferase activity can abrogate E2-3,4-Q levels via formation of glutathione conjugates. E2-3,4-Q is a potent nucleophile, and will readily react with electrophilic DNA. This yields the formation of the DNA adducts 4-OHE2-1-N7Gua and 4-OHE2-1-N3Ade via a Michael addition.
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The Hilbert transform is an anti-self adjoint operator relative to the duality pairing between Lp(R) and the dual space Lq(R), where p and q are Hölder conjugates and 1 < p,q < ∞. Symbolically, :\langle Hu, v \rangle = \langle u, -Hv \rangle for u ∈ Lp(R) and v ∈ Lq(R) .
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These give the first non-trivial cases of the Weil conjectures (proved by Hasse). If is an elliptic curve over a finite field with elements, then the number of points of defined over the field with elements is , where and are complex conjugates with absolute value . The zeta function is : .
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An ideal oscillator would generate a pure sine wave. In the frequency domain, this would be represented as a single pair of Dirac delta functions (positive and negative conjugates) at the oscillator's frequency; i.e., all the signal's power is at a single frequency. All real oscillators have phase modulated noise components.
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STRO-002 is an ADC targeting folate receptor alpha, a cell-surface protein highly expressed in gynecological cancers. To date, Sutro's drug discovery efforts have focused on antibody-drug conjugates, cytokine-based immuno-oncology therapies, and bispecific antibodies primarily directed at clinically-validated targets for which the current standard of care is suboptimal.
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Any involution in Co0 can be shown to be conjugate to an element of the Golay code. Co0 has 4 conjugacy classes of involutions. A permutation matrix of shape 212 can be shown to be conjugate to a dodecad. Its centralizer has the form 212:M12 and has conjugates inside the monomial subgroup.
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Left and right division are examples of forming a quasigroup by permuting the variables in the defining equation. From the original operation ∗ (i.e., ) we can form five new operations: (the opposite operation), / and \, and their opposites. That makes a total of six quasigroup operations, which are called the conjugates or parastrophes of ∗.
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One of the utilities of the method is demonstrated temperature control of biotin binding and release. Biotin binding was observed below the LCST, while above the LCST the conjugates aggregated, and the biotin binding affinity was reduced by ~20%. By changing the temperature, the recovery of the biotinylated molecules can be achieved.
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This fourth song has a duration of 2 minutes. If the cantata conjugates the emotions, regret, pain, violence, sadness, it is tenderness that emerges from Toi ma patiente for the first solo chorus. There is a harmonious resemblance of this song with Une barque sur l'océan from the Miroirs by Maurice Ravel.
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Some phosphate-acetylcholinesterase conjugates continue to react after the phosphate docks to the site, evolving into a more recalcitrant state. This process is known as aging. Aged phosphate-acetylcholinesterase conjugate are resistant to antidotes such as pralidoxime. Pralidoxime is often used with atropine (a muscarinic antagonist) to help reduce the parasympathetic effects of organophosphate poisoning.
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The short half-life of dienogest relative to other 19-nortestosterone progestins is in part due to its lack of binding to SHBG and hence prolongation in the circulation. The clearance of dienogest is 3 L/h. It is eliminated mainly in the urine, both as sulfate and glucuronide conjugates and as free steroid.
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Nanocarriers discovered thus far include polymer conjugates, polymeric nanoparticles, lipid-based carriers, dendrimers, carbon nanotubes, and gold nanoparticles. Lipid-based carriers include both liposomes and micelles. Examples of gold nanoparticles are gold nanoshells and nanocages. Different types of nanomaterial being used in nanocarriers allows for hydrophobic and hydrophilic drugs to be delivered throughout the body.
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Complex, nonlinear pharmacokinetics arise via autoinhibition of CYP2D6 and CYP2D8, resulting in zeroth order kinetics at higher doses. It is thought that this can result in sustained and higher concentrations of MDMA if the user takes consecutive doses of the drug. MDMA and metabolites are primarily excreted as conjugates, such as sulfates and glucuronides.
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This protein functions as a multispecific organic anion transporter, with oxidized glutathione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternative splicing by exon deletion results in several splice variants but maintains the original open reading frame in all forms.
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A bug blog Young spiders have a yellow- brown cephalothorax, with dark marginal and median stripes. Only after the last molting in the following spring the juveniles assume the typical coloration of the adults. The green coloration is due to the bilin micromatabilin and its conjugates in haemolymph, interstitial tissues and the yolk of oocytes.
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By taking conjugates, the number of partitions of into exactly k parts is equal to the number of partitions of in which the largest part has size . The function satisfies the recurrence : with initial values and if and and are not both zero.Richard Stanley, Enumerative Combinatorics, volume 1, second edition. Cambridge University Press, 2012. Chapter 1, section 1.7.
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Every word is conjugate to a cyclically reduced word, and a cyclically reduced conjugate of a cyclically reduced word is a cyclic permutation of the letters in the word. For instance b−1abcb is not cyclically reduced, but is conjugate to abc, which is cyclically reduced. The only cyclically reduced conjugates of abc are abc, bca, and cab.
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Most of the compound and its metabolites were excreted through feces and urine. There was no evidence of accumulation in the body of the rodents. The metabolites excreted out differed from male to female in rodents. While males excreted the carboxylic derivatives of the parent compound, the female rats excreted the sulfate conjugates of carboxylic acid.
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Testosterone and its metabolites are eliminated in urine. It is excreted mainly as androsterone glucuronide and etiocholanolone glucuronide. It is also excreted to a small extent as other conjugates such as testosterone glucuronide (1%), testosterone sulfate (0.03%), and androstanediol glucuronides. Only a very small amount of testosterone (less than 0.01%) is found unchanged in the urine.
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Hilbert's generalization was to consider the problem of attempting to find M+ and M− analytic, respectively, on the inside and outside of the curve Σ, such that on \Sigma one has :\alpha(z) M_+(z) + \beta(z) M_-(z) = c(z) where α, β, and c are arbitrary given complex-valued functions (no longer just complex conjugates).
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Tauroursodeoxycholic acid (TUDCA) is an ambiphilic bile acid. It is the taurine conjugate form of ursodeoxycholic acid (UDCA). Humans are found to have trace amounts of TUDCA. However, bears contain large amounts of TUDCA in their bile; UDCA and conjugates comprise about 47% of the bile in American black bears and up to 76% in Asiatic bears.
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Determination of urinary steroids and of steroid conjugates in blood. Ethyl glucuronide and ethyl sulfate are excreted in urine as metabolites of ethanol and are used to monitor alcohol use or dependence. Glucuronic acid and gluconic acid are fermentation products in Kombucha tea. Glucuronic acid is a precursor of ascorbic acid (vitamin C, formerly called as L-hexuronic acid).
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To obtain many of many of these bonds the use of peptides or amino acids. There is a strong desire to synthesize polymeric conjugates with bioactive components and other drugs. The tendency of polymer drug conjugate to react with the proper type cell(s) needs to still be worked on, despite many current advances.Khandare, Jayant, and Tamara Minko.
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Protacs achieve degradation through "hijacking" the cell's Ubiquitin–Proteosome system (UPS). The UPS consists of an E1 activating enzyme which conjugates to an E2 enzyme transferring a ubiquitin molecule to the E2. E2 then binds to the E3 ligase in a complex which can then recognize target proteins for subsequent ubiquitin tagging and degradation by the 26S proteosome.
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The ethylhexanol portion is a fatty alcohol, adding emollient and oil-like (water resistant) properties. This organic compound can penetrate into the skin where it acts as a photosensitizer. This results in an increased production of free radicals under illumination. In coral, octocrylene has been shown to accumulate in the form of fatty acid conjugates and trigger mitochondrial dysfunction.
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Whereas the biological half-life of estradiol given by intravenous injection is about 0.5 to 2 hours, the biological half-life of oral estradiol has a range of 13 to 20 hours due to the large and long-lasting pool of estrogen conjugates that is formed during first-pass metabolism and that serves to continuously replenish circulating estradiol levels.
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Polymer-protein conjugates can also form a higher ordered supramolecular structure via self-assembly of amphiphilic polymers into micelles and microcapsules, which is one of the most promising strategies to generate drug delivery systems. Such systems have the innate advantage of rapid preparation, a high drug loading capacity, ease of surface decoration, and the potential to be stimuli responsive.
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Pregnenolone has low bioavailability and is subject to high metabolism. Oral administration of 50 or 100 mg pregnenolone has been found to have minimal or negligible effect on urinary levels of testosterone and testosterone metabolites, including of androsterone, etiocholanolone, 5β-androstanediol, androstadienol, and androstenol (and/or their conjugates), and this suggests that only a small amount of pregnenolone is converted into testosterone. This is in accordance with findings on the conversion of DHEA into testosterone, in which only 1.5% of an oral dose of DHEA was found to be converted into testosterone. In contrast to the androstanes, 50 or 100 mg oral pregnenolone has been found to significantly and in fact "strongly" increase urinary levels of the progesterone metabolites pregnanediol and pregnanolone (and/or their conjugates), whereas pregnanetriol was unaffected.
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A projectivity is said to act from one range to another, though the two ranges may coincide as sets. A projective range expresses projective invariance of the relation of projective harmonic conjugates. Indeed, three points on a projective line determine a fourth by this relation. Application of a projectivity to this quadruple results in four points likewise in the harmonic relation.
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Applying g−1 to both sides of this equality yields ; that is, . An opposite inclusion follows similarly by taking and supposing . The above says that the stabilizers of elements in the same orbit are conjugate to each other. Thus, to each orbit, we can associate a conjugacy class of a subgroup of G (that is, the set of all conjugates of the subgroup).
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The algebraic field extension L/K is normal (we also say that L is normal over K) if every irreducible polynomial over K that has at least one root in L splits over L. In other words, if α ∈ L, then all conjugates of α over K (i.e., all roots of the minimal polynomial of α over K) belong to L.
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For example, 99mTc-EC20 was reported to concentrate in the livers, spleens and arthritic extremities of adjuvant-induced arthritic rats via a folate-dependent mechanism. Development of folate-drug conjugates for inflammation therapy is underway. It is expected that ailments which harbor activated macrophages (such as arthritis, psoriasis and inflammatory bowel disease) may someday be treatable with folate-targeted medicines.
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Sometimes the normal plural of a noun and the intensive plural are the same. For example behem, 'beast' singular, conjugates with the common feminine plural -oth, and behemoth + plural verb in, for example, the Genesis account of Noah's Ark indicates 'beasts' plural. But in the Book of Job behemoth + singular verb indicates 'giant beast', i.e. the sense of behemoth in English.
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Kynurenine—oxoglutarate transaminase 1 is an enzyme that in humans is encoded by the CCBL1 gene. It is one of the Kynurenine—oxoglutarate transaminases. This gene encodes a cytosolic enzyme which is responsible for the metabolism of cysteine conjugates of certain halogenated alkenes and alkanes. This metabolism leads to the formation of reactive metabolites which can lead to nephrotoxicity and neurotoxicity.
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That same year, Sutro Biopharma entered into an agreement with Celgene Corporation to discover and develop multispecific antibodies and antibody drug conjugates (ADCs). This followed the December 2012 collaboration between the two companies and focused on the field of immuno-oncology. In April 2015, Celgene announced a collaboration with AstraZeneca, worth $450 million, to study their Phase III immuno-oncology drug candidate MEDI4736.
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Detailed analysis of protein expression in Dictyostelium has been hampered by large shifts in the protein expression profile between different developmental stages and a general lack of commercially available antibodies for Dictyostelium antigens. In 2013, a group at the Beatson West of Scotland Cancer Centre reported an antibody-free protein visualization standard for immunoblotting based on detection of MCCC1 using streptavidin conjugates.
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This protein is a member of the MDR/TAP subfamily. Some members of the MDR/TAP subfamily are involved in multidrug resistance. This particular protein is responsible for the transport of taurocholate and other cholate conjugates from hepatocytes (liver cells) to the bile. In humans, the activity of this transporter is the major determinant of bile formation and bile flow.
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Manufacturing processes take place in clean rooms. :The GMP BioManufacturing BU is a full-service Contract Manufacturing Organization (CMO) and offers significant know-how in process development, technology transfer, formulation, scale-up and manufacturing of GMP proteins, protein conjugates, plasmids and bacterial vaccines for pre-clinical, clinical and commercial uses, all according to U.S. Food and Drug Administration (FDA) and EMA requirements.
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145-152 and indirectly controls plant branching. Finally, after studying pesticide systems in relation to industry, he programmed the synthesis of conjugates, which was carried out within a team of chemists.C Delétage-Grandon, JF Chollet, M Faucher, et JL Bonnemain, « Carrier-mediated uptake and phloem systemy of a 350-Dalton chlorinated xenobiotic with an α-amino acid function », Plant Physiol., (2001) 125, p.
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The basic mode of the sexual phase of reproduction appears to be conserved among Pseudo-nitzschia species. Upon mixing two strains of compatible mating type and of appropriate cell size for sexualization, cells align side by side and differentiate into gametangia. One active (+) and one passive (-) gamete are then produced within each gametangium. The active gamete migrates toward the passive partner and conjugates.
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Schematic structure of an antibody-oligonucleotide conjugate (AOC) Antibody- oligonucleotide conjugates or AOCs belong to a class of chimeric molecules combining in their structure two important families of biomolecules: monoclonal antibodies and oligonucleotides. Combination of exceptional targeting capabilities of monoclonal antibodies with numerous functional modalities of oligonucleotides has been fruitful for a variety of applications with AOC including imaging, detection and targeted therapeutics.
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Swedish is descended from Old Norse. Compared to its progenitor, Swedish grammar is much less characterized by inflection. Modern Swedish has two genders and no longer conjugates verbs based on person or number. Its nouns have lost the morphological distinction between nominative and accusative cases that denoted grammatical subject and object in Old Norse in favor of marking by word order.
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This was the first representative of the ABCC class of transporters. Later Ouellette showed in his own lab that LtpgpA is an arsenite-GSH transporter involved in antimony resistance in patients. # J, a new base in the DNA of trypanosomes and related parasites (30) (31). # Variation in the transferrin receptor allows African trypanosomes to efficiently take up transferrin in a range of mammals, notwithstanding the rapid evolution of mammalian transferrins (32) (33). # Biosynthesis of base J (34) and identification of J as an essential termination signal in RNA synthesis in Leishmania (35). # The MRP (ABCC) family of drug transporters has multiple members (36) (37) (38). Identification of new endogenous substrates for MRP3 (ABCC3) and BCRP (ABCG2): phyto-estrogen conjugates (39) (40); MRP4 (ABCC4): prostaglandins (41); and MRP5 (ABCC5): N-lactoyl-amino acids, a novel metabolites of mammals (42), and glutamate-conjugates (43).
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Once soaked, the fluid flows to the second conjugate pad in which the manufacturer has stored freeze dried bio-active particles called conjugates (see below) in a salt-sugar matrix. The conjugate pad contains all the reagents required for an optimized chemical reaction between the target molecule (e.g., an antigen) and its chemical partner (e.g., antibody) that has been immobilized on the particle's surface.
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Antisense therapy, siRNA, and other oligonucleotide and nucleic acid based biotherapeutics can be quantified with hybridization assays. Signalling of hybridization methods can be performed using oligonucleotide probes modified in-synthesis with haptens and small molecule ligands which act homologous to the capture and detection antibodies. As with traditional ELISA, conjugates to horse radish peroxidase (HRP) or alkaline phosphatase (AP) can be used as secondary antibodies.
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It is obvious that any conjugate pair of a circle are perpendicular to each other, but in an ellipse, only the major and minor axes are, the elongation destroying the perpendicularity in all other cases. Conjugates are defined for the two branches of a hyperbola resulting from the cutting of a double cone by a single plane. They are called conjugate branches. They have the same diameter.
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If these points are real, the curve is a hyperbola; if they are imaginary conjugates, it is an ellipse; if there is only one double point, it is a parabola. If the points at infinity are the cyclic points and , the conic section is a circle. If the coefficients of a conic section are real, the points at infinity are either real or complex conjugate.
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Australian journal of biological sciences, 32(1), 15-26.. Fluoride can be removed from fluoroacetate or fluorocitrate. It is involved in detoxifying the aryl and alkyl groups by converting them into glutathione conjugates. The C-F bond is cleaved because of a nucleophilic attack of carbon resulting in the formation of S-carboxymethyl glutathione. This can be afterward excreted in the form of S-carboxymethylcysteine.
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Macrophages become activated in chronic diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, atherosclerosis, diabetes, and most other inflammatory diseases. From a mechanistic perspective, the FR functions to concentrate exogenous ligands (e.g. folates and folate-drug conjugates) into the cell cytosol by endocytosis. The term endocytosis refers to the process whereby the plasma membrane invaginates and eventually forms a distinct intracellular compartment.
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Hepatic; the primary metabolite is 4-carboxypyrazole (about 80 to 85% of an administered dose). Other metabolites include the pyrazoles 4-hydroxymethylpyrazole and the N -glucuronide conjugates of 4-carboxypyrazole and 4-hydroxymethylpyrazole. Following multiple doses, fomepizole rapidly induces its own metabolism via the cytochrome P450 mixed-function oxidase system. In healthy volunteers, 1.0 to 3.5% of an administered dose was excreted unchanged in the urine.
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Bile acid-CoA:amino acid N-acyltransferase is an enzyme that in humans is encoded by the BAAT gene. The protein encoded by this gene is a liver enzyme that catalyzes the transfer of the bile acid moiety from the acyl-CoA thioester to either glycine or taurine, the second step in the formation of bile acid-amino acid conjugates which serve as detergents in the gastrointestinal tract.
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Note that when , then t(x) is negative, and that it is positive outside of the interval. The cross-ratio is a ratio of division ratios, or a double ratio. Setting the double ratio to minus one means that when , then c and d are harmonic conjugates with respect to a and b. So the division ratio criterion is that they be additive inverses.
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However, it is less sensitive than phosphatidylethanol (PEth) in detecting current regular alcohol consumption. The ethanol conjugates ethyl glucuronide and ethyl sulfate remain positive for up to three days after ethanol consumption and are quite useful for detection of occult/denied alcoholism. Both these substances are detectable clinically through urine drug testing by commercial toxicology labs. CDT is measured by taking a sample of a patient's blood.
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The conjugated hyperbilirubinemia is a result of defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into bile.Suzanne M Carter, MS Impaired biliary excretion of bilirubin glucuronides is due to a mutation in the canalicular multiple drug-resistance protein 2 (MRP2). A darkly pigmented liver is due to polymerized epinephrine metabolites, not bilirubin. Dubin–Johnson syndrome has an autosomal recessive pattern of inheritance.
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Two distinct secant lines to the conic, say and determine four points on the conic () that form a quadrangle. The point is a vertex of the diagonal triangle of this quadrangle. The polar of with respect to is the side of the diagonal triangle opposite . The theory of projective harmonic conjugates of points on a line can also be used to define this relationship.
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Also, no evidence indicates that CYP2D6 inhibition is useful in treating codeine dependence, though the metabolism of codeine to morphine (and hence further metabolism to glucuronide morphine conjugates) does have an effect on the abuse potential of codeine. However, CYP2D6 has been implicated in the toxicity and death of neonates when codeine is administered to lactating mothers, particularly those with increased enzyme activity ("ultra-rapid" metabolizers).
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The 10 inner automorphisms provide rotation of the mirrors by multiples of 36°, and reflections. As isometry group there are 10 more automorphisms; they are conjugates by isometries outside the group, rotating the mirrors 18° with respect to the inner automorphisms. As abstract group there are in addition to these 10 inner and 10 outer automorphisms, 20 more outer automorphisms; e.g., multiplying rotations by 3.
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The E2 protein subsequently transfers the ISG15 to specific E3 ligases (Herc5) and relevant intracellular substrates. Only one deconjugating protease with specificity to ISG15 has been identified to date: USP18 (a member of the USP family) cleaves ISG15-peptide fusions and also removes ISG15 (deISGylation) from native conjugates. The effects of ISGylation are incompletely understood and involve both activation and inhibition of antiviral immunity.
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The most common phosphoantigens from animal and human cells (including cancer cells) are isopentenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate (DMPP). Many microbes produce the highly active compound hydroxy-DMAPP (HMB- PP) and corresponding mononucleotide conjugates, in addition to IPP and DMAPP. Plant cells produce both types of phosphoantigens. Drugs activating human Vγ9/Vδ2 T cells comprise synthetic phosphoantigens and aminobisphosphonates, which upregulate endogenous IPP/DMAPP.
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The mono- and di- hydroxylated metabolites of FICZ are subject to further metabolic changes to glucuronide- and sulfate-conjugates. Sulfotransferase (SULT) catalyzed reactions resulted in a more pronounced reduction of the hydroxylated FICZ metabolites than the glucuronidation. Further studies using human recombinant SULTs showed that SULT1A1, -1A2, -1B1 and -1E1 exhibited high catalytic efficiencies and 2-hydroxylated FICZ was more efficiently conjugated than the 8-hydroxylated FICZ.
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The presence of the isopropyl radical was indicated by another observed product of the metabolism of iproniazid: the gas propane. Alkylating agents have the capability to bind to chemical groups such as amino, phosphate hydroxyl, imidazole and sulfhydryl groups. The formed isopropyl radical is able to form S-isopropyl conjugates in vitro. This diminishes covalent binding to other proteins, however it was only observed in vitro.
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The primary function of DPEP1 is to hydrolyze various dipeptides in renal metabolism. Specifically, it has been found to hydrolyze glutathione and its conjugates such as leukotriene D (Kozak and Tate, 1982). Several pieces of evidence suggest that DPEP1 is also responsible for the hydrolysis of the beta-lactam ring of various THM-class antibiotics, such as penem and carbapenem (Campbell et al., 1984).
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Schematic structure of an antibody-drug conjugate (ADC) Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 pharmaceutical companies were developing ADCs. ADCs are complex molecules composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug.
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It can be used as a marker of proteins, with which it easily forms conjugates via the sulfonyl chloride (SO2Cl) group. In water, the sulfonyl chloride group of unreacted Texas Red molecules hydrolyses to sulfonate and the molecule becomes the very water-soluble sulforhodamine 101 which is easy to wash out selectively. This is one of the advantages of conjugating with Texas Red vs. using a rhodamine-isothiocyanate for conjugation.
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This primary antibody could also be in the serum of a donor to be tested for reactivity towards the antigen. # Enzyme- linked secondary antibodies are applied as detection antibodies that also bind specifically to the antibody's Fc region (nonspecific). # The plate is washed to remove the unbound antibody-enzyme conjugates. # A chemical is added to be converted by the enzyme into a color or fluorescent or electrochemical signal.
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'Ga,' one of Old English forms of 'go' The principal parts of go are go, went, gone. In other respects, the modern English verb conjugates regularly. The irregularity of the principal parts is due to their disparate origin in definitely two and possibly three distinct Indo-European roots. Unlike every other English verb except be, the preterite (simple past tense) of go is not etymologically related to its infinitive.
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Nitrogen elimination by phenylbutyrate metabolites Phenylbutyrate is a prodrug. In the human body it is first converted to phenylbutyryl-CoA and then metabolized by mitochondrial beta-oxidation, mainly in the liver and kidneys, to the active form, phenylacetate. Phenylacetate conjugates with glutamine to phenylacetylglutamine, which is eliminated with the urine. It contains the same amount of nitrogen as urea, which makes it an alternative to urea for excreting nitrogen.
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In mathematics, Mautner's lemma in representation theory states that if G is a topological group and π a unitary representation of G on a Hilbert space H, then for any x in G, which has conjugates :yxy−1 converging to the identity element e, for a net of elements y, then any vector v of H invariant under all the π(y) is also invariant under π(x).
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CellSearch is the only FDA-approved platform for CTC isolation. This method is based on the use of iron nanoparticles coated with a polymer layer carrying biotin analogues and conjugated with antibodies against EpCAM for the capture of CTCs. Isolation is coupled to an analyzer to take images of isolated cells upon their staining with specific fluorescent antibody conjugates. Blood is sampled in an EDTA tube with an added preservative.
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Aesculetin (also known as esculetin, 6,7-dihydroxycoumarin and cichorigenin) is a derivative of coumarin. It is a natural lactone that derives from the intramolecular cyclization of a cinnamic acid derivative. It is present in chicory and in many toxic and medicinal plants, in form of glycosides and caffeic acid conjugates. This compound is used in some sunscreens, but there is evidence that it acts as a photosensitizer for DNA damage.
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Once absorbed, triclosan is metabolized by humans primarily through conjugation reactions into glucuronide and sulfate conjugates that are excreted in feces and urine. Pharmacokinetic studies demonstrate that triclosan sulfate and glucuronide may be formed in the liver at approximately equal rates at the environmentally relevant concentration of 1 to 5 microMolar. When concentrations of triclosan are below 1 microMolar, sulfonation is expected to be the major metabolic pathway for elimination.
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The medication has a very long biological half-life of 6 days with a single dose and 7 to 10 days with repeated administration. Bicalutamide and its metabolites are eliminated in urine, feces, and bile, mainly in the form of conjugates. The pharmacokinetics of bicalutamide are not influenced by food, age, body weight, renal impairment, or mild-to-moderate hepatic impairment, but ethnicity may influence its pharmacokinetics in some cases.
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Pite Sámi, like Finnish, the other Sámi languages and Estonian, has a negative verb. In Pite Sámi, the negative verb conjugates according to mood (indicative, imperative and optative), person (1st, 2nd and 3rd) and number (singular, dual and plural). This differs from some of the other Sámi languages, e.g. from Northern Sámi, which do not conjugate according to tense and other Sámi languages, that do not use the optative.
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They characterize combinatorial depth n as a condition on the number of conjugates of H intersecting in G thereby showing that combinatorial depth is finite. In more detail, one defines an ascending chain of sets of subgroups of H starting with the zero'th stage singleton set of H, the first stage intersecting H by all its conjugate subgroups, and the n'th stage is to intersect all subgroups of H in the (n-1)'st stage by all conjugates of H. Then the combinatorial depth of H in G is 2n if the n'th stage subset is equal to the (n-1)'st stage subset. For example, H is a normal subgroup of G if and only if H has combinatorial depth two in G. The minimum combinatorial depth follows from taking n to be minimum, and a technical definition of odd combinatorial depth. For example, d_c(H,G)=1 if and only if G=H C_G(H) (i.e.
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Common techniques for delivery into cultured cells include the Endo-Porter peptide (which causes the Morpholino to be released from endosomes), the Special Delivery system (no longer commercially available, used a Morpholino-DNA heteroduplex and an ethoxylated polyethylenimine delivery reagent), electroporation, or scrape loading. Delivery into adult tissues is usually difficult, though there are a few systems allowing useful uptake of unmodified Morpholino oligos (including uptake into muscle cells with Duchenne muscular dystrophy or the vascular endothelial cells stressed during balloon angioplasty). Though they permeate through intercellular spaces in tissues effectively, unconjugated PMOs have limited distribution into the cytosol and nuclear spaces within healthy tissues following IV administration. Systemic delivery into many cells in adult organisms can be accomplished by using covalent conjugates of Morpholino oligos with cell-penetrating peptides, and, while toxicity has been associated with moderate doses of the peptide conjugates, they have been used in vivo for effective oligo delivery at doses below those causing observed toxicity.
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Brentuximab vedotinADC Review / Journal of Antibody-drug Conjugates: Brentuximab Vedotin, February 18, 2014 consists of the chimeric monoclonal antibody brentuximab (cAC10, which targets the cell-membrane protein CD30) linked with maleimide attachment groups, cathepsin cleavable linkers (valine-citrulline), and para- aminobenzylcarbamate spacers to three to five units of the antimitotic agent monomethyl auristatin E (MMAE, reflected by the 'vedotin' in the drug's name).ADC Review / Journal of Antibody-drug Conjugates: Monomethyl auristatin E (MMAE), May 23, 2013 The peptide-based linker bonds the antibody to the cytotoxic compound in a stable manner so the drug is not easily released from the antibody under physiologic conditions to help prevent toxicity to healthy cells and ensure dosage efficiency. The peptide antibody-drug bond facilitates rapid and efficient drug cleavage inside target tumor cell. The antibody cAC10 part of the drug binds to CD30 which often occurs on diseased cells but rarely on normal tissues.
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The real projective line is a complete projective range that is found in the real projective plane and in the complex projective line. Its structure is thus inherited from these superstructures. Primary among these structures is the relation of projective harmonic conjugates among the points of the projective range. The real projective line has a cyclic order which is an important mathematical structure in showing that the real line is totally ordered and complete.
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Chemical structure of cholesterol. Sterols, such as cholesterol and its derivatives, are an important component of membrane lipids, along with the glycerophospholipids and sphingomyelins. Other examples of sterols are the bile acids and their conjugates, which in mammals are oxidized derivatives of cholesterol and are synthesized in the liver. The plant equivalents are the phytosterols, such as β-sitosterol, stigmasterol, and brassicasterol; the latter compound is also used as a biomarker for algal growth.
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This can be shown using Euler's formula. The product of a complex number and its conjugate is a real number: a^2 + b^2 (or r^2 in polar coordinates). Complex conjugates are important for finding roots of polynomials. According to the complex conjugate root theorem, if a complex number is a root to a polynomial in one variable with real coefficients (such as a quadratic or a cubic equation), then so is its conjugate.
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Example for 1st case of equidivisibility: m="UNCLE", n="ANLY", p="UN", q="CLEANLY", and s="CLE" We define a pair of words in A∗ of the form uv and vu as conjugate: the conjugates of a word are thus its circular shifts.Sakarovitch (2009) p.27 Two words are conjugate in this sense if they are conjugate in the sense of group theory as elements of the free group generated by A.
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Plant cytochrome P450s are involved in a wide range of biosynthetic reactions and target a diverse range of biomolecules. These reactions lead to various fatty acid conjugates, plant hormones, secondary metabolites, lignins, and a variety of defensive compounds. Plant genome annotations suggest that cytochrome P450 genes make up as much as 1% of the plant genes. The number and diversity of P450 genes is responsible, in part, for the multitude of bioactive compounds.
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His research has high impact in areas of bioconjugate chemistry, biorecognition of macromolecules, developments of drug delivery systems and self-assembled biomaterials. He has authored more than 440 scientific publications cited over 25,000 times. Many of his research has over the years advanced from concept to clinic and applied to a variety of different fields. Hydrogels from his laboratory have been in clinical use, and HPMA copolymer-anticancer drug conjugates in clinical trials.
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Carbon monoxide releasing materials (CORMAs) are essentially novel drug formulations and drug delivery platforms which have emerged to overcome the pharmaceutical limitations of most CORM species. An exemplary CORMA developed by Hubbell consists of a formulation of micelles prepared from triblock copolymers with a CORM entity, which is triggered for release via addition of cysteine. Other CO-releasing scaffolds include polymers, peptides, silica nanoparticles, nanodiamond, magnetic nanoparticles, nanofiber gel, metallodendrimers, and CORM-protein (macromolecule) conjugates.
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She began publishing articles in the newspaper ABC in 1997, and for the digital media outlet ' in 2010. In 2007, she created her own Internet portal on which, with the sponsorship of the Aquae Foundation and the collaboration of readers, the Diccionario Aceytuno de la Naturaleza began. In 2015, she began to make a series of videos and micro-documentaries for various media. In her works, Fernández-Aceytuno habitually conjugates and combines nature and poetry.
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With time, the mechanical complexity of TSP was simplified, and this interface became popular as the first ideal LC-MS interface for pharmaceutical applications comprising the analysis of drugs, metabolites, conjugates, nucleosides, peptides, natural products, and pesticides. The introduction of TSP marked a significant improvement for LC-MS systems and was the most widely applied interface until the beginning of the 1990s, when it began to be replaced by interfaces involving atmospheric pressure ionization (API).
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In 1857, in the second Beiträge, von Staudt contributed a route to number through geometry called the algebra of throws (). It is based on projective range and the relation of projective harmonic conjugates. Through operations of addition of points and multiplication of points, one obtains an "algebra of points", as in chapter 6 of Veblen & Young's textbook on projective geometry. The usual presentation relies on cross ratio (CA,BD) of four collinear points.
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Apigenin and chrysin are also transformed by C. elegans and produce apigenin 7-sulfate, apigenin 7,4′-disulfate, chrysin 7-sulfate. Sulfation also occurs on naringenin and produces naringenin-7-sulfate. Glucosylation may nevertheless occur but in 3'- position, as happens during the microbial transformation of psiadiarabin and its 6-desmethoxy analogue, 5,3′ dihydroxy-7,2′,4′,5′-tetramethoxyflavone, by Cunninghamella elegans NRRL 1392 that gives the 3′-glucoside conjugates of the two flavones.
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The nucleic acid shell imparts chemical and biological recognition abilities that include a greater binding strength,Lytton-Jean, A. K. R.; Mirkin, C. A., A thermodynamic investigation into the binding properties of DNA functionalized gold nanoparticle probes and molecular fluorophore probes. J. Am. Chem. Soc. 2005, 127, 12754-12755. cooperative melting behavior,Hurst, S. J.; Hill, H. D.; Mirkin, C. A. ““Three- Dimensional Hybridization” with Polyvalent DNA-Gold Nanoparticle Conjugates,” J. Am. Chem. Soc.
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Glutathione S-transferase, C-terminal domain is a structural domain of glutathione S-transferase (GST). GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain.
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Adhesion of cells on a surface coated with a thermoresponsive polymer. Displayed is a polymer with LCST Thermoresponsive polymers can be functionalized with moieties that bind to specific biomolecules. The polymer-biomolecule conjugate can be precipitated from solution by a small change of temperature.Jing Ping Chen, Allan S. Hoffman, Polymer-Protein Conjugates II. Affinity precipitation separation of human immunogammaglobulin by a poly(N-isopropylacrylamide)-protein A conjugate, Biomaterials, 1990, Volume 11, pp 631-634.
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Agglutination-PCR (ADAP) is an ultrasensitive solution-phase method for detecting antibodies. Antibodies bind to and agglutinate synthetic antigen–DNA conjugates, enabling ligation of the DNA strands and subsequent quantification by qPCR. Like other Immuno-PCR (IPCR) detection methods ADAP combines the specificity of antibody-antigen recognition and the sensitivity of PCR. ADAP detects zepto- to attomoles of antibodies in 2 μL of sample with a dynamic range spanning 5–6 orders of magnitude.
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Micromatabilin, the green pigment of the spider species Micrommata virescens, is characterized as a mixture of biliverdin conjugates. The two isolated fractions have identical absorption bands (free base: 620–630 μm, hydrochloride: 690 μm, zinc complex: 685–690 μm). Chromic acid degradation yields imides I, II, IIIa, and IIIb. Differences in the non-hydrolytic degradation and in polarity lead to the conclusion that fraction 1 is a monoconjugate and fraction 2a diconjugate of biliverdin.
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Polymer-protein hybrids are a class of nanostructure composed of protein- polymer conjugates (i.e. complexes composed of one protein attached to one or more polymer chains). The protein component generally gives the advantages of biocompatibility and biodegradability, as many proteins are produced naturally by the body and are therefore well tolerated and metabolized. Although proteins are used as targeted therapy drugs, the main limitations—the lack of stability and insufficient circulation times still remain.
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The first step involves preparation of the antibody-oligo conjugates also known as _A_ ntibody- _D_ erived _T_ ags (ADTs). ADT preparation involves labeling an antibody directed against a cell surface protein of interest with oligonucleotides for barcoding the antibody. Once you have the ADTs, the next step is to bind the cells with the desired ADT pool. The scRNA-seq libraries can be prepared using Drop-seq, 10X Genomics or ddSeq methods.
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When both the 2-wire and the 4-wire circuits must be balanced, double transformer hybrids are used, as shown at right. Signal into port W splits between X and Z, but due to reversed connection to the windings, cancel at port Y. Signal into port X goes to W and Y. But due to reversed connection to ports W and Y, Z gets no signal. Thus the pairs, W & Y, X & Z, are conjugates.
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A modern synthesis of hippuric acid involves the acylation of glycine with benzoyl chloride: :400px Biochemically, hippuric acid is produced from benzoic acid by direct glycine acylation. It is one of the two conjugates of benzoic acid produced metabolically, the other being the glucuronide. Both are eliminated from the body in urine. Benzoic acid is introduced into the body by ingestion (sodium benzoate is used as a preservative) and by hydrolysis of pharmaceutical agents such as benzyl benzoate.
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AZ01 is currently undergoing Phase I clinical trials in the US. Preclinical data indicates that AZ01 has the potential to be dosed once monthly compared to the current standard of care dosed anywhere from once daily to once per week. Allozyne's technology also enables the development of next generation antibody-drug conjugates (ADCs). This approach results in homogenous ADC products that are stably conjugated. In 2014, Allozyne was acquired by MedImmune, based on its ADC technology.
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Estrone is conjugated into estrogen conjugates such as estrone sulfate and estrone glucuronide by sulfotransferases and glucuronidases, and can also be hydroxylated by cytochrome P450 enzymes into catechol estrogens such as 2-hydroxyestrone and 4-hydroxyestrone or into estriol. Both of these transformations take place predominantly in the liver. Estrone can also be reversibly converted into estradiol by 17β-HSD. The blood half-life of estrone is about 10 to 70 minutes and is similar to that of estradiol.
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Phenylbutyrate, which is the product of phenylacetate, conjugates with glutamine to form phenylacetylglutamine, which is excreted by the kidneys. Similarly, sodium benzoate reduces ammonia content in the blood by conjugating with glycine to form hippuric acid, which is rapidly excreted by the kidneys. A preparation containing sodium phenylacetate and sodium benzoate is available under the trade name Ammonul. Acidification of the intestinal lumen using lactulose can decrease ammonia levels by protonating ammonia and trapping it in the stool.
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Because it has a root of absolute value 1, the minimal polynomial for a Salem number must be reciprocal. This implies that 1/α is also a root, and that all other roots have absolute value exactly one. As a consequence α must be a unit in the ring of algebraic integers, being of norm 1\. Every Salem number is a Perron number (a real algebraic number greater than one all of whose conjugates have smaller absolute value).
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Cats metabolize aspirin slowly because they lack the glucuronide conjugates that aid in the excretion of aspirin, making it potentially toxic if dosing is not spaced out properly. No clinical signs of toxicosis occurred when cats were given 25mg/kg of aspirin every 48 hours for 4 weeks, but the recommended dose for relief of pain and fever and for treating blood clotting diseases in cats is 10mg/kg every 48 hours to allow for metabolization.
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In transcendental number theory, the Lindemann–Weierstrass theorem is a result that is very useful in establishing the transcendence of numbers. It states the following. In other words the extension field has transcendence degree over An equivalent formulation , is the following. This equivalence transforms a linear relation over the algebraic numbers into an algebraic relation over by using the fact that a symmetric polynomial whose arguments are all conjugates of one another gives a rational number.
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Atomoxetine is excreted unchanged in urine at <3% in both extensive and poor CYP2D6 metabolizers, with >96% and 80% of a total dose being excreted in urine, respectively. The fractions excreted in urine as 4-hydroxyatomoxetine and its glucuronide account for 86% of a given dose in extensive metabolizers, but only 40% in poor metabolizers. CYP2D6 poor metabolizers excrete greater amounts of minor metabolites, namely N-desmethylatomoxetine and 2-hydroxymethylatomoxetine and their conjugates. Major metabolites of atomoxetine in humans.
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There is an enzymatic pathway via glutathione-S-transferase and a non- enzymatic pathway. These glycidamide-glutathione conjugates are further metabolized to mercapturic acids by different peptidases and transferases, such as gamma-glutamyl-transpeptidase, dipeptidase and N-acetyltransferase. The mercapturic acids that can be formed are N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA), N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-cysteine (GAMA2), and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA3) (Huang et al., 2011).
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A single dose of oral estradiol valerate is eliminated 54% in urine and 6% in feces. A substantial amount of estradiol is also excreted in bile. The urinary metabolites of estradiol are predominantly present in the form of estrogen conjugates, including glucuronides and, to a lesser extent, sulfates. The main metabolites of estradiol in urine are estrone glucuronide (13–30%), 2-hydroxyestrone (2.6–10.1%), unchanged estradiol (5.2–7.5%), estriol (2.0–5.9%), and 16α-hydroxyestrone (1.0–2.9%).
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The three- dimensional structure of the DNA shell imparts upon these conjugates novel chemical, physical, and biological properties that are not associated with the same sequences of linear DNA free in solution. For example, SNA-gold nanoparticle conjugates have been shown to exhibit increased uptake into cells compared to their linear counterparts.Rosi, N. L.; Giljohann, D. A.; Thaxton, C. S.; Lytton-Jean, A. K. R.; Han, M. S.; Mirkin, C. A. “Oligonucleotide- Modified Gold Nanoparticles for Intracellular Gene Regulation,” Science, 2006, 312, 1027-1030. doi: 10.1126/science.1125559. Furthermore, when hybridized to a nucleic acid “reporter” strand containing a fluorophore probe, these polyvalent nanoparticles can be used as intracellular probes to detect specific mRNA sequences within single living cells.305\. Seferos, D. S.; Giljohann, D. A.; Hill, H. D.; Prigodich, A. E.; Mirkin, C. A. “Nano-flares: Probes for Transfection and mRNA Detection in Living Cells,” Journal of the American Chemical Society, 2007, 129, 15477-15479. doi: 10.1021/ja0776529. Polyvalent DNA gold nanoparticles have also spurred significant advances in the field of materials science and engineering.
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Repeated additions of salt counterions were used to reduce the electrostatic repulsion between DNA strands and enable more efficient DNA packing on the nanoparticle surface. Since then, silver,Lee, J.-S.; Lytton- Jean, A. K. R.; Hurst, S. J.; Mirkin, C. A. “Silver Nanoparticle- Oligonucleotide Conjugates Based on DNA with Triple Cyclic Disulfide Moieties,” Nano Lett., 2007, 7, 2112-2115, doi: 10.1021/nl071108g iron oxide,Cutler, J. I.; Zheng, D.; Xu, X.; Giljohann, D. A.; Mirkin, C. A. “Polyvalent Oligonucleotide Iron Oxide Nanoparticle “Click” Conjugates,” Nano Lett., 2010, 10, 1477–1480, doi: 10.1021/nl100477m. silica,Young, K. L; Scott, A. W.; Hao, L.; Mirkin, S. E.; Liu, G.; Mirkin, C. A. “Hollow Spherical Nucleic Acids for Intracellular Gene Regulation Based Upon Biocompatible Silica Shells,” Nano Lett., 2012, 12, 3867–3871, doi: 10.1021/nl3020846. and semiconductorZhang, C.; Macfarlane, R. J.; Young, K. L.; Choi, C. H. J.; Hao, L.; Auyeung, E.; Liu, G. Zhou, X.; Mirkin, C. A. “A General Approach to DNA- Programmable Atom Equivalents,” Nature Materials, 2013, 12, 741-746, doi: 10.1038/nmat3647.
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Soorasamharam is the final and the most important day of the six days festivities. It is believed that Lord Murugan defeated Demon Surapadman on the very same day and the festival of Soorasamharam is observed every year to mark the victory of good over evil. It is important to note that the day when Shasti Tithi conjugates with panchami tithi is chosen for Soorasamharam vratam. Hence most temples observe Kanda Sashti on panchami tithi if Shasti Tithi starts before sunset on panchami Tithi.
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Due to its favorable characteristics, HPMA polymers and copolymers are also commonly used to produce synthetic biocompatible medical materials such as hydrogels. The development of pHPMA as anti-cancer drug delivery vehicles is initiated by Dr. Jindřich Kopeček and colleagues at the Czech (-oslovak) Academy of Sciences in Prague in the mid-1970s. Prior to this, it was used as a plasma expander. The Kopeček Laboratory designed and developed HPMA copolymer-drug conjugates as a lysosomal delivery vehicle to cancer cells.
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Soorasamharam is the final and the most important day of the six days festivities. It is believed that Lord Murugan defeated Demon Surapadman on the very same day and the festival of Soorasamharam is observed every year to mark the victory of good over evil. It is important to note that the day when Shasti Tithi conjugates with panchami tithi is chosen for Soorasamharam vratam. Hence most temples observe Kanda Sashti on panchami tithi if Shasti Tithi starts before sunset on panchami Tithi.
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Conjugates and their metabolites can be excreted from cells in phase III of their metabolism, with the anionic groups acting as affinity tags for a variety of membrane transporters of the multidrug resistance protein (MRP) family. These proteins are members of the family of ATP-binding cassette transporters and can catalyse the ATP-dependent transport of a huge variety of hydrophobic anions, and thus act to remove phase II products to the extracellular medium, where they may be further metabolized or excreted.
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Macrophages are the human body's first line of defense against invading pathogens. Normally, they circulate in the bloodstream in a dormant state, but at a site of inflammation due to injury or autoimmune disease, they become activated, changing shape and expressing different cell surface markers. The upregulated expression of the FR makes activated macrophages a useful tool in folate-targeted therapy. Activated, TNF-alpha producing macrophages express the beta isoform of the FR, and they are targetable with folate conjugates in vivo.
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The internal, coincident short edge of the medium rectangle and long edge of the small rectangle divides one of the square's other, two edges into two segments that stand to one another in the ratio ρ4. The fact that a rectangle of aspect ratio ρ2 can be used for dissections of a square into similar rectangles is equivalent to an algebraic property of the number ρ2 related to the Routh–Hurwitz theorem: all of its conjugates have positive real part.
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The same is true for any power of g: conjugates of g^n are roots of polynomial :x^3-Tr(g^n)\\!\ x^2 + Tr(g^n)^p x -1 and this polynomial is completely determined by Tr(g^n). The idea behind using traces is to replace g^n \in GF(p^6) in cryptographic protocols, e.g. the Diffie–Hellman key exchange by Tr(g^n) \in GF(p^2) and thus obtaining a factor of 3 reduction in representation size.
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Due to the cytokine pattern, which corresponds more closely to Th1, an immune deviation is seen in this direction in most experimental models, away from Th2 characteristics. Conjugates are being developed as vaccines or are already being used without a priori knowledge. A peculiarity first recognized in 2006 is the expression of TLR2 on Tregs (a type of T cell), which experience both TCR-controlled proliferation and functional inactivation. This leads to disinhibition of the early inflammation phase and of specific antibody formation.
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However, to achieve the best and most desirable results, many factors are needed to be taken into the design of hapten conjugates. These include the method of hapten conjugation, the type of carrier used and the hapten density. Variations in these factors could lead to different strengths of immune response toward the newly formed antigenic determinant. In general, these carrier proteins should be immmunogenic and contain enough amino acid residues in the reactive side chains to conjugate with the haptens.
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That is achieved with special features of the Japanese language, which conjugates verbs based on both tense and politeness. It may also include social concepts such as gift giving or serving. The uchi-soto relationship can lead to someone making great personal sacrifices to honor a visitor or other person in an out-group. One of the complexities of the uchi-soto relationship lies in the fact that groups are not static; they may overlap and change over time and according to situation.
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The A and B transferases are the foundation of the human ABO blood group system. Both A and B transferases are glycosyltransferases, meaning they transfer a sugar molecule onto an H-antigen. This allows H-antigen to synthesize the glycoprotein and glycolipid conjugates that are known as the A/B antigens. The full name of A transferase is alpha 1-3-N-acetylgalactosaminyltransferase and its function in the cell is to add N-acetylgalactosamine to H-antigen, creating A-antigen.
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The current CEO, William Newell, joined Sutro in January 2009. The company has raised over $201.7 million from venture investors, collaborators and the public markets. Sutro's cell-free protein synthesis and site-specific conjugation platform, XpressCF+, contributed to the discovery of STRO-001 and STRO-002, internally- developed antibody drug conjugates, or ADCs. STRO-001 is an ADC targeting CD74, a protein highly expressed in multiple myeloma and non-Hodgkin's lymphoma, and is currently in a Phase I clinical trial.
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Both doxepin and nordoxepin are hydroxylated mainly by CYP2D6, and both doxepin and nordoxepin are also transformed into glucuronide conjugates. The elimination half-life of doxepin is about 15–18 hours, whereas that of nordoxepin is around 28–31 hours. Up to 10% of Caucasian individuals show substantially reduced metabolism of doxepin that can result in up to 8-fold elevated plasma concentrations of the drug compared to normal. Nordoxepin is a mixture of (E) and (Z) stereoisomers similarly to doxepin.
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The conjugation of polyethylene glycol (PEG) chains to potential drug candidates extends the stability against proteases in body fluids and at the same time reduces renal clearance and immunogenicity. The first application described here, deals with the formation of protein-protein conjugates through bioorthogonal probes.Hudak, J. E., Barfield, R. M., de Hart, G. W., Grob, P., Nogales, E., Bertozzi, C. R. and Rabuka, D. (2012) Synthesis of Heterobifunctional Protein Fusions Using Copper-Free Click Chemistry and the Aldehyde Tag. Angew. Chem. Int.
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Nanobody conjugates recognizing antigen presenting cells have been successfully used for tumor detection or targeted antigen delivery to generate strong immune response. Orally available single-domain antibodies against E. coli-induced diarrhoea in piglets have been developed and successfully tested. Other diseases of the gastrointestinal tract, such as inflammatory bowel disease and colon cancer, are also possible targets for orally available single-domain antibodies. Detergent-stable species targeting a surface protein of Malassezia furfur have been engineered for use in anti- dandruff shampoos.
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In the same month the company announced it would co-commercialize Argenx's preclinical immunotherapy, ARGX-115. ARGX-115 is a first-in-class immunotherapy targeting GARP (glycoprotein A repetitions predominant), a membrane protein believed to enhance the immunosuppressive effects of T cells. The company also announced a deal to co-develop/commercialize at least one of CytomX Probody's conjugates against CD71 (transferrin receptor 1). In March 2020, AbbVie announced plans to evaluate the Kaletra/Aluvia HIV medicine as possible COVID-19 treatment.
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The conjugates of testosterone and its hepatic metabolites are released from the liver into circulation and excreted in the urine and bile. Only a small fraction (2%) of testosterone is excreted unchanged in the urine. In the hepatic 17-ketosteroid pathway of testosterone metabolism, testosterone is converted in the liver by 5α-reductase and 5β-reductase into 5α-DHT and the inactive 5β-DHT, respectively. Then, 5α-DHT and 5β-DHT are converted by 3α-HSD into 3α-androstanediol and 3α-etiocholanediol, respectively.
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A study was conducted to define the pharmacological response of humans to ractopamine. A single oral dose of 40 mg of ractopamine hydrochloride was given to human volunteers. The drug was rapidly absorbed; the mean blood plasma half-life was around 4 hrs and it was not detected in plasma 24 hrs after dosing. Less than 5% of total ractopamine excreted represented the parent drug, while the urinary metabolites were monoglucuronide and monosulfate conjugates, with ractopamine monosulfate being the major metabolite present.
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In mathematics, the Honda–Tate theorem classifies abelian varieties over finite fields up to isogeny. It states that the isogeny classes of simple abelian varieties over a finite field of order q correspond to algebraic integers all of whose conjugates (given by eigenvalues of the Frobenius endomorphism on the first cohomology group or Tate module) have absolute value . showed that the map taking an isogeny class to the eigenvalues of the Frobenius is injective, and showed that this map is surjective, and therefore a bijection.
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Fluparoxan has rat and human protein binding of 81-92% and 95% respectively. Fluparoxan shows high in vitro permeability in MCDK (Papp nm/s =2500) and Caco-2 (Papp nm/s =2000) cells which correlates well with the known high oral intestinal absorption (100%) in humans. Fluparoxan is well absorbed following oral dosing in all animals. Clearance was largely metabolic, with both oral and intravenous doses being excreted mainly via the urine (> 90%, of administered dose), chiefly as phase II metabolites (sulphamic acid and carbamoyI glucuronide conjugates).
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Folate targeting is a method utilized in biotechnology for drug delivery purposes. This Trojan Horse process, which was created by Drs. Christopher P. Leamon and Philip S. Low, involves the attachment of the vitamin, folate (folic acid), to a molecule/drug to form a "folate conjugate". Based on the natural high affinity of folate for the folate receptor protein (FR), which is commonly expressed on the surface of many human cancers, folate-drug conjugates also bind tightly to the FR and trigger cellular uptake via endocytosis.
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Dirk Struik (1953) Lectures in Analytic and Projective Geometry, page 19, Addison-Wesley In Cambridge, England, John J. Milne gave readers the benefit of his reading of Pappus. In 1985, Alexander Jones wrote his thesis at Brown University on the subject. A revised form of his translation and commentary was published by Springer-Verlag the following year. Jones succeeds in showing how Pappus manipulated the complete quadrangle, used the relation of projective harmonic conjugates, and displayed an awareness of cross-ratios of points and lines.
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In 1980, he was appointed a NATO Fellowship to work with Jean-Marie Lehn (Nobel Prize, 1987), and was appointed to a Lectureship in Chemistry at Durham University, beginning in January 1982. Parker's research investigates the design and synthesis of functional molecules, materials and conjugates and has straddled the traditional disciplines of Physical, Organic and Inorganic Chemistry. Often collaborating with European and UK industry, he has worked on diverse collaborative projects leading to the introduction of imaging and therapeutic agents, including the antibody conjugate MyloTargR (Celltech Ltd.).
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Illustration of the duality between points and lines, and the double meaning of "incidence". If two lines a and k pass through a single point Q, then the polar q of Q joins the poles A and K of the lines a and k, respectively. The concepts of a pole and its polar line were advanced in projective geometry. For instance, the polar line can be viewed as the set of projective harmonic conjugates of a given point, the pole, with respect to a conic.
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Heidelberg Pharma, GmbH, based in Ladenburg, Germany, a pharmaceutical company providing pre-clinical drug discovery and development services, has developed a new antibody-drug conjugate or ADC technology based on α-amanitin. Amanitin- based ADCs have shown outstanding activity in therapy-resistant tumor cells, e.g. cells expressing multi-drug resistant transporters, tumor-initiating cells and non-dividing cells at picomolar concentrations. The unique mode of action or MOA of α-amanitin seems to make the amanitin-based antibody-drug conjugates a suitable toxic payload.
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Some non-prime numbers n are such that every group of order n is cyclic. One can show that n = 15 is such a number using the Sylow theorems: Let G be a group of order 15 = 3 · 5 and n3 be the number of Sylow 3-subgroups. Then n3 \mid 5 and n3 ≡ 1 (mod 3). The only value satisfying these constraints is 1; therefore, there is only one subgroup of order 3, and it must be normal (since it has no distinct conjugates).
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Enterohepatic recirculation may occur with estetrol, similarly to other steroidal estrogens, although it has also been reported that estetrol does not seem to enter the enterohepatic circulation. Estetrol is excreted mostly or completely in urine, virtually entirely in the form of conjugates (unconjugated accounting for 0.2–0.7%). In one study, a median of 79.7% (range 61.1–99.0%) was recovered from urine; this was primarily as estetrol glucuronide (median 60.7%, range 47.6–77.2%), and, to a lesser extent, as estetrol sulfate (median 17.6%, range 13.2–22.1%).
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FAP expression is seen on activated stromal fibroblasts of more than 90% of all human carcinomas. Stromal fibroblasts play an important role in the development, growth and metastasis of carcinomas. Several approaches of FAP targeting mainly in cancer treatment are currently being tested including the use of low molecular weight inhibitors, prodrugs activated by FAP, various anti-FAP antibodies and their conjugates, FAP-CAR T cells, and FAP vaccines. By cleaving FGF-21, FAP is also thought to play a possible role in energy metabolism.
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Let w ∈ F(A) be such that w = 1 in G. Then the area of w, denoted Area(w), is defined as the minimum of the areas of all van Kampen diagrams with boundary labels w (van Kampen's lemma says that at least one such diagram exists). One can show that the area of w can be equivalently defined as the smallest n≥0 such that there exists a representation (♠) expressing w as a product in F(A) of n conjugates of the defining relators.
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The most common bioconjugations are coupling of a small molecule (such as biotin or a fluorescent dye) to a protein, or protein-protein conjugations, such as the coupling of an antibody to an enzyme. Other less common molecules used in bioconjugation are oligosaccharides, nucleic acids, synthetic polymers such as polyethylene glycol, and carbon nanotubes. Antibody-drug conjugates such as Brentuximab vedotin and Gemtuzumab ozogamicin are also examples of bioconjugation, and are an active area of research in the pharmaceutical industry. Recently, bioconjugation has also gained importance in nanotechnology applications such as bioconjugated quantum dots.
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Metabolism of acetaminophen (paracetamol), acetanilide and phenacetin Cytochromes and 3A4 convert approximately 5% of paracetamol to a highly reactive intermediary metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione to form cysteine and mercapturic acid conjugates. In cases of paracetamol overdose, the sulfate and glucuronide pathways become saturated, and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become depleted, as the demand for glutathione is higher than its regeneration.
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Proteins of the OAT family catalyze the Na+-independent facilitated transport of fairly large amphipathic organic anions (and less frequently neutral or cationic drugs), such as bromosulfobromophthalein, prostaglandins, conjugated and unconjugated bile acids (taurocholate and cholate), steroid conjugates, thyroid hormones, anionic oligopeptides, drugs, toxins and other xenobiotics. One family member, OATP2B1, has been shown to use cytoplasmic glutamate as the exchanging anion. Among the well characterized substrates are numerous drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives and anticancer drugs. Other substrates include luciferin, thyroid hormones and quinolones.
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Thus, isometry groups of e.g. type p4m and p4g are both mapped to point groups of type D4. For a given isometry group, the conjugates of a translation in the group by the elements of the group generate a translation group (a lattice)--that is a subgroup of the isometry group that only depends on the translation we started with, and the point group associated with the isometry group. This is because the conjugate of the translation by a glide reflection is the same as by the corresponding reflection: the translation vector is reflected.
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Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the sodium salts of estrogen conjugates found in horses, such as estrone sulfate and equilin sulfate. CEEs are available in the form of both natural preparations manufactured from the urine of pregnant mares and fully synthetic replications of the natural preparations. They are formulated both alone and in combination with progestins such as medroxyprogesterone acetate.
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As an MFS protein, SLC46A3 is a membrane transporter, mainly involved in the movement of substrates across the lipid bilayer. The protein works via secondary active transport, where the energy for transport is provided by an electrochemical gradient. A proposed function of SLC46A3 of rising importance is the direct transport of maytansine-based catabolites from the lysosome to the cytoplasm by binding the macrolide structure of maytansine. Among the different types of antibody-drug conjugates (ADCs), maytansine-based noncleavable linker ADC catabolites, such as lysine-MCC-DM1, are particularly responsive to SLC46A3 activity.
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A field lens optically conjugates the pupil of the main objective lens in the region of a bank of compensation lenses, and the final compensation lenses optically conjugate the mirror to the surface of a photodetector. For each frame formed on the film, one compensation lens is required, but some designs have used a series of flat mirrors. As such, these cameras typically do not record more than one hundred frames, but frame counts up to 2000 have been recorded. This means they record for only a very short time – typically less than a millisecond.
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Selenium may be measured in blood, plasma, serum or urine to monitor excessive environmental or occupational exposure, confirm a diagnosis of poisoning in hospitalized victims or to assist in a forensic investigation in a case of fatal overdosage. Some analytical techniques are capable of distinguishing organic from inorganic forms of the element. Both organic and inorganic forms of selenium are largely converted to monosaccharide conjugates (selenosugars) in the body prior to being eliminated in the urine. Cancer patients receiving daily oral doses of selenothionine may achieve very high plasma and urine selenium concentrations.
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Microarray CDs and DVDs have a protective film which must be stripped to reveal the gold reflective film or polycarbonate (PC) base. The surface of the disk can be activated to reveal the metal layer which allows compounds to bind to it. Compounds such as UV/ozone or an oxygen plasma treatment can be used to activate the disk to produce a hydrophilic surface with densely packed carboxylic acid groups. As one-off microassay can be printed onto the activated disks using a noncontact printer to dispel nanoliter quantities of coating conjugates onto the disk.
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Deleterious mutations in the ETFA and ETFB genes encoding ETF or the ETFDH gene encoding ETF:QO are associated with multiple acyl-CoA dehydrogenase deficiency (MADD; OMIM #231680; previously called glutaric aciduria type II). Biochemically, MADD is characterized by elevated levels of a series of carnitine conjugates of the substrates of the different partner dehydrogenases of the ETF/ETF:QO hub, e.g. glutaric, lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.[5] Accumulation of substrates and derivatives of the upstream dehydrogenases and energy deficiency upon fasting cause the clinical phenotype.
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Deleterious mutations in the ETFB and ETFA genes encoding ETF or the ETFDH gene encoding ETF:QO are associated with multiple acyl-CoA dehydrogenase deficiency (MADD; OMIM #231680; previously called glutaric aciduria type II). Biochemically, MADD is characterized by elevated levels of a series of carnitine conjugates of the substrates of the different partner dehydrogenases of the ETF/ETF:QO hub, e.g. glutaric, lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. Accumulation of substrates and derivatives of the upstream dehydrogenases and energy deficiency upon fasting cause the clinical phenotype.
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One of the mechanisms of antineoplastic resistance is over-expression of drug-metabolizing enzymes or carrier molecules. By increasing expression of metabolic enzymes, drugs are more rapidly converted to drug conjugates or inactive forms that can then be excreted. For example, increased expression of glutathione promotes drug resistance, as the electrophilic properties of glutathione allow it to react with cytotoxic agents, inactivating them. In some cases, decreased expression or loss of expression of drug-metabolising enzymes confers resistance, as the enzymes are needed to process a drug from an inactive form to an active form.
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RPN2 is a unique integral glycoprotein in rough ER membrane that is involved in translocation and the maintenance of the structural uniqueness of the rough ER. It is also an essential subunit of N-oligosaccharyl transferase complex that conjugates high mannose oligosaccharides to asparagine residues in the N-X-S/T consensus motif of nascent polypeptide chains. RPN2 regulates the glycosylation of multi-drug resistance, and thus its interference could decrease the membrane localization of P-glycoprotein by reducing its glycosylation status and restored the sensitivity to docetaxel.
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A conic in the projective plane is a curve C that has the following property: If P is a point not on C, and if a variable line through P meets C at points A and B, then the variable harmonic conjugate of P with respect to A and B traces out a line. The point P is called the pole of that line of harmonic conjugates, and this line is called the polar line of P with respect to the conic. See the article Pole and polar for more details.
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The isodynamic points are the isogonal conjugates of the two Fermat points of triangle ABC, and vice versa.; . The Neuberg cubic contains both of the isodynamic points.. If a circle is partitioned into three arcs, the first isodynamic point of the arc endpoints is the unique point inside the circle with the property that each of the three arcs is equally likely to be the first arc reached by a Brownian motion starting at that point. That is, the isodynamic point is the point for which the harmonic measure of the three arcs is equal..
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Yeast two hybrid experimentation has revealed that C8orf34 interacts with a number of proteins insular to the nucleus. The protein has been shown to interact with ubiquitin C, a precursor protein to polyubiquitin, which functions to lead various effects in the cell cycle depending on the residues it conjugates to. C8orf34 has also demonstrated interactions with MTUS2 (microtubule associated tumor suppressor candidate 2). There is not much information available about this protein candidate, but it is likely to be involved in tumor-suppression functions and cell cycle regulation.
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The glycine-N-acyltransferase protein conjugates glycine with acyl-CoA substrates in the mitochondria primarily in liver and kidney. The glycine N-acyltransferase enzyme is involved in the detoxification of a wide range of xenobiotic and endogenous metabolites. These include benzoic acid, a compound found in fruits and vegetables and used in medicine and foodstuffs as a preservative; salicylic acid, a metabolite of aspirin; and several endogenous metabolites. The diversity is demonstrated by the wide range of acylglycines excreted in the urines of patients with defects of organic acid metabolism.
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In mathematics, dianalytic manifolds are possibly non-orientable generalizations of complex analytic manifolds. A dianalytic structure on a manifold is given by an atlas of charts such that the transition maps are either complex analytic maps or complex conjugates of complex analytic maps. Every dianalytic manifold is given by the quotient of an analytic manifold (possibly non-connected) by a fixed-point-free involution changing the complex structure to its complex conjugate structure. Dianalytic manifolds were introduced by , and dianalytic manifolds of 1 complex dimension are sometimes called Klein surfaces.
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He also made discoveries about projective harmonic conjugates; relating these to the poles and polar lines associated with conic sections. He developed the concept of parallel lines meeting at a point at infinity and defined the circular points at infinity that are on every circle of the plane. These discoveries led to the principle of duality, and the principle of continuity and also aided in the development of complex numbers. As a military engineer, he served in Napoleon's campaign against the Russian Empire in 1812, in which he was captured and held prisoner until 1814.
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Furthermore, magnetic anomalies on the Malvinas Plate do not align with their conjugates on the African Plate if the spreading rates and directions of South America and Africa are used as a guide. They also noted that the Agulhas Fracture Zone do not lay perpendicular to traces of the South America-Africa spreading north of it and cannot, therefore, have been generate by this spreading.; The Agulhas Rift is the abandoned Malvinas-Africa ridge crest. 97 Ma the plate boundary in the Agulhas Basin was reorganised when the Mid-Atlantic Ridge made an eastward jump.
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Vaccines rely on immune modulation or augmentation. Vaccination either excites or reinforces the immune competence of a host to ward off infection, leading to the activation of macrophages, the production of antibodies, inflammation, and other classic immune reactions. Antibacterial vaccines have been responsible for a drastic reduction in global bacterial diseases. Vaccines made from attenuated whole cells or lysates have been replaced largely by less reactogenic, cell-free vaccines consisting of purified components, including capsular polysaccharides and their conjugates, to protein carriers, as well as inactivated toxins (toxoids) and proteins.
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Isorhamnetin is an O-methylated flavon-ol from the class of flavonoids. A common food source of this 3'-methoxylated derivative of quercetin and its glucoside conjugates are pungent yellow or red onions, in which it is a minor pigment, quercetin-3,4'-diglucoside and quercetin-4'-glucoside and the aglycone quercetin being the major pigments. Pears, olive oil, wine and tomato sauce are rich in isorhamnetin. Others sources include the spice, herbal medicinal and psychoactive Mexican tarragon (Tagetes lucida), which is described as accumulating isorhamnetin and its 7-O-glucoside derivate.
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Horseradish peroxidase is a 44,173.9-dalton glycoprotein with 6 lysine residues which can be conjugated to a labeled molecule. It produces a coloured, fluorimetric, or luminescent derivative of the labeled molecule when incubated with a proper substrate, allowing it to be detected and quantified. HRP is often used in conjugates (molecules that have been joined genetically or chemically) to determine the presence of a molecular target. For example, an antibody conjugated to HRP may be used to detect a small amount of a specific protein in a western blot.
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The elimination half-life of nandrolone decanoate administered by intramuscular injection is approximately 6 to 12 days. Studies that have assessed the duration of nandrolone decanoate via its anabolic effects, for instance on nitrogen balance, have found that a single 50 to 100 mg intramuscular injection had a duration of about 18 to 25 days. The blood half-life for the combined process of hydrolysis into nandrolone and elimination of nandrolone is 4.3 hours. Nandrolone and its metabolites are excreted in the urine, mainly in the form of conjugates.
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Endocyte is advancing the first technology platform for the creation of small molecule drug conjugates (a.k.a. SMDCs), which consist of a small molecule linked to a potent drug, and is developing a pipeline of SMDCs together with non-invasive companion imaging agents for cancer, inflammatory diseases and kidney disease (autosomal-dominant polycystic kidney disease/ADPKDor PKD). Endocyte’s lead drug candidate is vintafolide, an investigational targeted cancer therapeutic in late-stage development. In 2012 marketing rights were acquired by Merck for $120 million in an upfront payment and up to $880 million in milestone payments.
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Typically, complex forms are considered because of some desirable decomposition that the forms admit. On a complex manifold, for instance, any complex k-form can be decomposed uniquely into a sum of so-called (p,q)-forms: roughly, wedges of p differentials of the holomorphic coordinates with q differentials of their complex conjugates. The ensemble of (p,q)-forms becomes the primitive object of study, and determines a finer geometrical structure on the manifold than the k-forms. Even finer structures exist, for example, in cases where Hodge theory applies.
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Stanozolol has high oral bioavailability, due to the presence of its C17α alkyl group and the resistance to gastrointestinal and liver metabolism that it results in. The medication has very low affinity for human serum sex hormone-binding globulin (SHBG), about 5% of that of testosterone and 1% of that of DHT. Stanozolol is metabolized in the liver, ultimately becoming glucuronide and sulfate conjugates. Its biological half- life is reported to be 9 hours when taken by mouth and 24 hours when given by intramuscular injection in the form of an aqueous suspension.
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C) The DIBAC-hIgG and azide-hGH conjugates are joined by Cu-free click chemistry to protein trimers; X and Y are PEG-based linkers of different length. The Western blots were first stained with Ponceau and then incubated with IgG antibodies against hGH and subsequently treated with α-mIgG HRP and α-hIgG 647 for visualisation. In the hIgG-hGH conjugate Western blot (nonreducing conditions), two separate bands with different molecular weights are visible after immunodetection. These can be contributed to the formation of mono- and bi-conjugated hGH to hIgG.
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If the discriminant is positive, the distance would be non-zero, and there will be two solutions. However, there is also the case where the discriminant is less than zero, and this indicates the distance will be imaginary or some multiple of the complex unit , where and the parabola's zeros will be complex numbers. The complex roots will be complex conjugates, where the real part of the complex roots will be the value of the axis of symmetry. There will be no real values of where the parabola crosses the -axis.
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The ATG12-ATG5:ATG16L complex is responsible for elongation of the phagophore in the autophagy pathway. ATG12 is first activated by ATG7, proceeded by the conjugation of ATG5 to the complex by ATG10 via a ubiquitination-like enzymatic process. The ATG12-ATG5 then forms a homo-oligomeric complex with ATG16L. With the help of ATG7 and ATG3, the ATG12-ATG5:ATG16L complex conjugates the C terminus of LC3-I to phosphatidylethanolamine in the phospholipid bilayer, allowing LC3 to associate with the membranes of the phagophore, becoming LC3-II.
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A narrower class that is a totally symmetric quasigroup (sometimes abbreviated TS-quasigroup) in which all conjugates coincide as one operation: . Another way to define (the same notion of) totally symmetric quasigroup is as a semisymmetric quasigroup which also is commutative, i.e. . Idempotent total symmetric quasigroups are precisely (i.e. in a bijection with) Steiner triples, so such a quasigroup is also called a Steiner quasigroup, and sometimes the latter is even abbreviated as squag; the term sloop is defined similarly for a Steiner quasigroup that is also a loop.
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As HPLC is a method of determining (and possibly increasing) purity, using HPLC alone in evaluating concentrations of drugs is somewhat insufficient. With this, HPLC in this context is often performed in conjunction with mass spectrometry. Using liquid chromatography instead of gas chromatography in conjunction with MS circumvents the necessity for derivitizing with acetylating or alkylation agents, which can be a burdensome extra step. This technique has been used to detect a variety of agents like doping agents, drug metabolites, glucuronide conjugates, amphetamines, opioids, cocaine, BZDs, ketamine, LSD, cannabis, and pesticides.
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Attachment of UBLs might, alter substrate conformation, affect the affinity for ligands or other interacting molecules, alter substrate localization, and influence protein stability. UBLs are structurally similar to ubiquitin and are processed, activated, conjugated, and released from conjugates by enzymatic steps that are similar to the corresponding mechanisms for ubiquitin. UBLs are also translated with C-terminal extensions that are processed to expose the invariant C-terminal LRGG. These modifiers have their own specific E1 (activating), E2 (conjugating) and E3 (ligating) enzymes that conjugate the UBLs to intracellular targets.
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However, those covalent linking methods are limited by the concern that the synthetic covalent bond between CPP and nucleic acid may alter the biological activity of the latter. Thus, a new non-covalent strategy requiring no chemical modification with short amphipathic CPPs, like MPG and Pep-1 as carriers has been successfully applied for delivery of cargoes. These non-covalent conjugates are formed through either electrostatic or hydrophobic interactions. With this method, cargoes such as nucleic acids and proteins could be efficiently delivered while maintaining full biological activity.
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The kinetics of airway smooth muscle relaxation, as long as the onset and duration of bronchodilation in asthmatic patients, are reflected by the difference in the mechanism of interaction of short- (SABAs) and longacting β2-agonists (LABAs) and the β2-receptor. There are many formulations of selective β2-agonists; inhalation is the route of choice because it is the most rapidly effective and is associated with minimum side effects. Sulfate conjugates are the main metabolites; protein binding is rather weak and only insignificant interactions have been found with other drugs. The main enzymes that regulate metabolism of the chatecholamines are COMT and MAO.
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Depending on the two cell types involved in conjugates, trogocytosis can be unidirectional or bidirectional. Proteins transferred by trogocytosis are many and mostly include proteins inserted in or closely associated to the plasma membrane (proteins spanning the lipid bilayer or inserted in the extracellular or intracellular leaflets). For instance, human lymphocytes were recently shown to acquire the inner-membrane protein H-Ras, a G-protein vital for common lymphocyte functions and a prominent participant in human cancer, from the cells they scan. The transfer was cell contact-dependent and occurred in the context of cell-conjugate formation.
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Antibody-drug conjugates (ADCs) comprise an antibody, drug and a linker between them. The antibody will be targeted at a preferentially expressed protein in the tumour cells (known as a tumor antigen) or on cells that the tumor can utilise, such as blood vessel endothelial cells. They bind to the tumor antigen and are internalised, where the linker releases the drug into the cell. These specially targeted delivery vehicles vary in their stability, selectivity, and choice of target, but, in essence, they all aim to increase the maximum effective dose that can be delivered to the tumor cells.
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The Brik lab has been developing novel synthetic methods to prepare site-specifically modified proteins for biochemical, biophysical and functional analyses. The Brik group is one of world leaders in devising new methods to prepare ubiquitin-based conjugates necessary for detailed studies on ubiquitin signaling. Ubiquitination is the cellular process where the 76 amino acid ubiquitin protein, or a polyubiquitin chain, is linked to a protein target, affecting a variety of biological processes such as protein degradation, trafficking, transcription and the DNA damage response. Not surprisingly, ubiquitination plays a key role in various diseases, such as neurological disorders, infectious diseases and cancer.
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NAPQI becomes toxic when GSH is depleted by an overdose of acetaminophen, Glutathione is an essential antidote to overdose. Glutathione conjugates to NAPQI and helps to detoxify it. In this capacity, it protects cellular protein thiol groups, which would otherwise become covalently modified; when all GSH has been spent, NAPQI begins to react with the cellular proteins, killing the cells in the process. The preferred treatment for an overdose of this painkiller is the administration of N-acetyl-L-cysteine (either via oral or IV administration)), which is processed by cells to L-cysteine and used in the de novo synthesis of GSH.
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Digitoxin and related cardenolides display potent anticancer activity against a range of human cancer cell lines in vitro but the clinical use of digitoxin to treat cancer has been restricted by its narrow therapeutic index. Digitoxin glycorandomization led to the discovery of novel digitoxigenin neoglycosides which displayed improved anticancer potency and reduced inotropic activity (the perceived mechanism of general toxicity). Steroidal glycosides based upon this latter discovery served as the basis for the development of a new class of antibody-drug conjugate known as extracellular drug conjugates (EDCs) as first in class agents to treat cancer by the biotechnology company Centrose.
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In de Rham cohomology terms, a cohomology class of degree k is represented by a k-form α on V(C). There is no unique representative; but by introducing the idea of harmonic form (Hodge still called them 'integrals'), which are solutions of Laplace's equation, one can get unique α. This has the important, immediate consequence of splitting up :Hk(V(C), C) into subspaces :Hp,q according to the number p of holomorphic differentials dzi wedged to make up α (the cotangent space being spanned by the dzi and their complex conjugates). The dimensions of the subspaces are the Hodge numbers.
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Conjugated estriol, sold under the brand names Progynon and Emmenin, is an estrogen medication which was previously used for estrogen-type indications such as the treatment of menopausal symptoms in women. The term specifically refers to formulations of estriol conjugates which were manufactured from the estrogen-rich urine of pregnant women and were used as medications in the 1920s and 1930s. Conjugated estriol is analogous to and was superseded by conjugated estrogens (brand name Premarin), which is manufactured from the urine of pregnant mares. Conjugated estriol was among the first forms of pharmaceutical estrogen to be used in medicine.
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Siderophores have applications in medicine for iron and aluminum overload therapy and antibiotics for improved targeting. Understanding the mechanistic pathways of siderophores has led to opportunities for designing small-molecule inhibitors that block siderophore biosynthesis and therefore bacterial growth and virulence in iron- limiting environments. Siderophores are useful as drugs in facilitating iron mobilization in humans, especially in the treatment of iron diseases, due to their high affinity for iron. One potentially powerful application is to use the iron transport abilities of siderophores to carry drugs into cells by preparation of conjugates between siderophores and antimicrobial agents.
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Lanthionine ketimine also binds the brain protein lanthionine synthase-like protein-1 (LANCL1), a glutathione-binding protein of uncertain function. It has been hypothesized, but not proved, that LANCL1 might catalyze formation of glutathione-lanthionine conjugates in a pathway leading to lanthionine ketimine. Lanthionine ketimine and a synthetic, cell-penetrating ester derivative called lanthionine ketimine-5-ethyl ester (LKE) potentiate growth factor-dependent extension of neuron processes (neurites) in cell culture. This neurotrophic activity may occur through interaction of lanthionine ketimine with a protein called collapsin response protein-2 (CRMP2, also known as dihydropyrimidinase-like protein-2 or DPYSL2).
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When an F+ cell conjugates/mates with an F− cell, the result is two F+ cells, both capable of transmitting the plasmid to other F− cells by conjugation. A pilus on the F+ cell interacts with the recipient cell allowing formation of a mating junction, the DNA is nicked on one strand, unwound and transferred to the recipient. The F-plasmid belongs to a class of conjugative plasmids that control sexual functions of bacteria with a fertility inhibition (Fin) system. In this system, a trans-acting factor, FinO, and antisense RNAs, FinP, combine to repress the expression of the activator gene TraJ.
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The tolerability and therapeutic window of amanitin-based ADCs has been determined in a variety of rodent and non- human primate models. Furthermore, amanitin has a water-soluble structure, resulting in antibody-drug conjugates with low tendency for aggregation, even using higher drug to antibody ratios or DAR. In preclinical mouse models of prostate cancer, α-(alpha)-amanitin conjugated to an antibody directed against prostate-specific membrane antigen (PSMA; FOLH1; GCPII) showed high antitumoral activity and caused complete remission at single i.v. doses of 150 μg/kg of toxin, with no more than marginal weight loss in treated animals.
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Also, amanitin-based antibody-drug conjugates using an anti-Her2 antibody such as trastuzumab showed high antitumor activity in a series of models of preclinical oncology designed to establish efficacy of the trial drug in the treatment of HER2+ breast cancer. Alpha-amanitin is highly active in drug- resistant cells, independent of the status of expression of multi-drug resistant transporters because of its hydrophilic structure. Inhibition of RNA polymerase II caused by amanitin binding not only leads to apoptosis of dividing cells, but also of slowly growing cells – which are often observed in prostate cancer.
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The metabolism of nandrolone occurs in the liver and is very similar to that of testosterone, including reduction by 5α-reductase and 5β-reductase, dehydrogenation by 3α-hydroxysteroid dehydrogenase, 3β-hydroxysteroid dehydrogenase, and 17β-hydroxysteroid dehydrogenase, and conjugation. The metabolites of nandrolone include 5α-dihydronandrolone, 19-norandrosterone, and 19-noretiocholanolone, with 19-norandrosterone being the major metabolite. Other metabolites include 19-norandrostenedione, 19-norandrostanediols, 19-norepiandrosterone, and conjugates. Nandrolone also undergoes aromatization into estradiol similarly to testosterone, though at a rate of only about 20% of that of testosterone or possibly even less; one study found virtually no aromatization of nandrolone in men.
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Ehrlich reasoned that if a compound could be made that selectively targeted a disease-causing organism, then a toxin for that organism could be delivered along with the agent of selectivity. Hence, a "magic bullet" (Zauberkugel, his term for an ideal therapeutic agent) would be created that killed only the organism targeted. The concept of a "magic bullet" has to some extent been realized by the development of antibody-drug conjugates (a monoclonal antibody linked to a cytotoxic biologically active drug), as they enable cytotoxic drugs to be selectively delivered to their designated targets (e.g. cancer cells).
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Due to its flexibility with respect to the choice of monomers and reaction conditions, the RAFT process competes favorably with other forms of living polymerization for the generation of bio-materials. New types of polymers are able to be constructed with unique properties, such as temperature and pH sensitivity. Specific materials and their applications include polymer-protein and polymer-drug conjugates, mediation of enzyme activity, molecular recognition processes and polymeric micelles which can deliver a drug to a specific site in the body. RAFT has also been used to graft polymer chains onto polymeric surfaces, for example, polymeric microspheres.
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I. Theory and experimental method and Polarization of the fluorescence of macromolecules. II. Fluorescent conjugates of ovalbumin and bovine serum albumin. The theory paper (which contains an acknowledgement to F. Perrin for his suggestions) includes an extension of Perrin’s theory of depolarization due to rotation of ellipsoidal molecules. Specifically, Weber showed that Perrin’s complex equations, which required a knowledge of the orientation of the fluorophore’s absorption and emission oscillators with respect to the axis of rotation of the ellipsoid, could be considerably simplified if the fluorophores carrying the oscillators were assumed to be randomly oriented on the macromolecule.
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A heat-stable polypeptide present in these extracts, ATP-dependent proteolysis factor 1 (APF-1), was found to become covalently attached to the model protein substrate lysozyme in an ATP- and Mg2+-dependent process. Multiple APF-1 molecules were linked to a single substrate molecule by an isopeptide linkage, and conjugates were found to be rapidly degraded with the release of free APF-1. Soon after APF-1-protein conjugation was characterised, APF-1 was identified as ubiquitin. The carboxyl group of the C-terminal glycine residue of ubiquitin (Gly76) was identified as the moiety conjugated to substrate lysine residues.
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The first subset is homeomorphic to Ω(f) via a homeomorphism h which conjugates the restriction of f to Ω(f) with the restriction of fε to Ω1: : f_\epsilon\circ h(x)=h\circ f(x), \quad \forall x\in \Omega(f). If Ω2 is empty then h is onto Ω(fε). If this is the case for every perturbation fε then f is called omega stable. A diffeomorphism f is omega stable if and only if it satisfies axiom A and the no-cycle condition (that an orbit, once having left an invariant subset, does not return).
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Similarly to the case of progesterone, taking oral estriol with food greatly enhances its absorption. In addition, due to enterohepatic recycling, consuming a meal 4 hours after taking oral estriol can produce a second peak in estriol levels. Dosages of oral estriol of 4 to 10 mg have been found to result in a fairly large range of maximal estriol levels of 80 to 340 pg/mL. After a single oral dose of 8 mg estriol in postmenopausal women, maximal levels of 65 pg/mL estriol and 60 ng/mL estriol conjugates were produced within an hour.
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With continued daily administration, this increased to peak levels of 130 pg/mL estriol, whereas maximal levels of estriol conjugates remained at 60 ng/mL. Levels of estriol rapidly decreased to low levels following occurrence of peak levels. Consumption of a meal 4 hours after taking an oral dose of 8 mg estriol during continuous daily administration resulted in a second estriol peak 2 hours later of 120 pg/mL, with estriol levels declining slowly thereafter to about 25 pg/mL after 24 hours. The bioavailability of estriol is markedly increased with vaginal administration compared to oral administration.
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Estriol is excreted more than 95% in urine. This is due to the fact that estriol conjugates in the colon are completely hydrolyzed via bacterial enzymes and in turn estriol in this part of the body is reabsorbed into the body. The main urinary metabolites of exogenous estriol administered via intravenous injection in baboons have been found to be estriol 16α-glucuronide (65.8%), estriol 3-glucuronide (14.2%), estriol 3-sulfate (13.4%), and estriol 3-sulfate 16α-glucuronide (5.1%). The metabolism and excretion of estriol in these animals closely resembled that which has been observed in humans.
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B. Zhang, R. Wepf, K. Fischer, M. Schmidt, S. Besse, P. Lindner, B. T. King, R. Siegel, P. Schurtenberger, Y. Talmon, Y. Ding, M. Kröger, A. Halperin, A. D. Schlüter, Angew. Chem. Int. Ed. 2011, 50, 737. Dendronized polymers have been investigated for/as bulk structure control, responsivity to external stimuli, single molecule chemistry, templates for nanoparticle formation, catalysis, electro-optical devices, and bio-related applications. Particularly attractive is the use of water-soluble dendronized polymers for the immobilization of enzymes on solid surfaces (inside glass tubes or microfluidic devices) and for the preparation of dendronized polymer-enzyme conjugates.
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An efficient way to synthesize protein-polymer hybrid nanoparticles is to take advantage of photoinitiated reversible addition−fragmentation chain transfer (RAFT) polymerization-induced self-assembly(PISA) by using multi-RAFT modified bovine serum albumin (BSA) as a macromolecular chain transfer agent. RAFT mediated growth of the PHPMA chains will graft from the BSA-RAFT, and increase the hydrophobicity of the star BSA−PHPMA conjugates. At the critical aggregation concentration, they form nanoparticles due to the hydrophobic interactions. The resulting nanoparticles show excellent encapsulation capability for both hydrophobic and hydrophilic molecules, such as cancer drugs and DNA.
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In an acid-base reaction, an acid plus a base reacts to form a conjugate base plus a conjugate acid: Conjugates are formed when an acid loses a hydrogen proton or a base gains a hydrogen proton. Refer to the following figure: File:Conjugate base reaction.jpg We say that the water molecule is the conjugate acid of the hydroxide ion after the latter received the hydrogen proton donated by ammonium. On the other hand, ammonia is the conjugate base for the acid ammonium after ammonium has donated a hydrogen ion towards the production of the water molecule.
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Synthesis of bioconjugates involves a variety of challenges, ranging from the simple and nonspecific use of a fluorescent dye marker to the complex design of antibody drug conjugates. As a result, various bioconjugation reactions – chemical reactions connecting two biomolecules together – have been developed to chemically modify proteins. Common types of bioconjugation reactions on proteins are coupling of lysine amino acid residues, coupling of cysteine residues, coupling of tyrosine residues, modification of tryptophan residues, and modification of the N- and C- terminus. However, these reactions often lack chemoselectivity and efficiency, because they depend on the presence of native amino acid residues, which are usually present in large quantities that hinder selectivity.
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Similar mechanical allydonia induced by partial ligation of the sciatic nerve was also reduced by NaGly. Other arachidonic acid-amino acid conjugates did not have the same effects and the actions of NaGly were not affected by cannabinoid receptor agonists in either study, suggesting a novel non-cannabinoid receptor mediated approach to alleviate inflammatory pain. NaGly was shown to be endogenous ligand for the G-protein couple receptor GPR92 along with farnesyl pyrophosphate. In the dorsal root ganglia (DRG), where GPR92 was found to be localized NaGly increased intracellular calcium levels in DRG neurons, indicating a role of NaGly in the sensory nervous system through the activation of GPR92.
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In the standard assignment, the contains the charge conjugates of the right-handed down-type quark color triplet and a left-handed lepton isospin doublet, while the contains the six up-type quark components, the left-handed down-type quark color triplet, and the right-handed electron. This scheme has to be replicated for each of the three known generations of matter. It is notable that the theory is anomaly free with this matter content. The hypothetical right-handed neutrinos are a singlet of , which means its mass is not forbidden by any symmetry; it doesn't need a spontaneous symmetry breaking which explains why its mass would be heavy.
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Modified-release dosage is a mechanism that (in contrast to immediate-release dosage) delivers a drug with a delay after its administration (delayed-release dosage) or for a prolonged period of time (extended-release [ER, XR, XL] dosage) or to a specific target in the body (targeted-release dosage).Pharmaceutics: Drug Delivery and Targeting, p. 7-13 Sustained-release dosage forms are dosage forms designed to release (liberate) a drug at a predetermined rate in order to maintain a constant drug concentration for a specific period of time with minimum side effects. This can be achieved through a variety of formulations, including liposomes and drug-polymer conjugates (an example being hydrogels).
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In 1946-1947, while studying at Yale, he coauthored with Leon Greenberg a series of three papers on acetanilide, an analgesic that was still in use at the time, aiming to establish why it caused methemoglobinemia. Although more than half a century had passed since acetanilide was first used clinically, there was wide-ranging disagreement concerning its metabolism, and numerous theories had been postulated. The first of these three papers summarized these theories, and reexamined the proportion of various acetanilide metabolites in human urine. Finding that p-aminophenol conjugates were excreted, they refuted the earlier theories that the accumulation of this substance in the body was causing methemoglobinemia.
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It is not strictly necessary to use phenol or chloroform if extracting RNA for Northern blotting or DNA for Southern blot analysis because the gel electrophoresis followed by transfer to a membrane will separate the RNA/DNA from the proteins. Additionally, since these methods use probes to bind to their conjugates, peptides that get through the process don't generally matter unless a peptide is an RNase or DNase, and then only if the enzyme manages to renature, which should not occur if proper protocols are followed. A possible exception might be when working with temperature extremophiles because some enzymes of these organisms can remain stable under extraordinary circumstances.
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Host cell proteins (HCPs) are process-related impurities, expressed by the host cell used for production of biopharmaceutical proteins. During the purification process, the majority of the HCPs are removed (>99%), but residual HCP amounts remain in the distributed products, such as monoclonal antibodies (mAbs), antibody-drug-conjugates (ADCs), therapeutic proteins, vaccines, and other protein-based biopharmaceuticals. National regulatory authorizations, such as FDA and EMA, require that biopharmaceuticals must be analysed and purified to reduce HCPs to an acceptable level. The HCP acceptance level is evaluated case-by-case and depends on multiple factors including; dose, frequency of drug administration, type of drug and severity of disease.
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Celltech and Wyeth entered into a collaboration in 1991 to develop antibody- drug conjugates. The humanized antibody portion was generated at Celltech and the DNA encoding it was transfected into CHO cells, which were sent to Wyeth, where chemists expressed and purified the antibodies and conjugated them with the linker to the cytotoxin; the work was published in 2004. Celltech was acquired by UCB in 2004 and Wyeth was acquired by Pfizer in 2009. In May 2013 a phase III trial in patients with relapsed or refractory CD22+ aggressive non-Hodgkin lymphoma (NHL) who were not candidates for intensive high-dose chemotherapy was terminated for futility.
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Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy (and thus distinguished from chemotherapy, that is, cytotoxic therapy). However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy. Another form of targeted therapy involves the use of nanoengineered enzymes to bind to a tumor cell such that the body's natural cell degradation process can digest the cell, effectively eliminating it from the body. Targeted cancer therapies are expected to be more effective than older forms of treatments and less harmful to normal cells.
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Sargent's first publication was in 1929, On Young's criteria for the convergence of Fourier series and their conjugates, published in the Mathematical Proceedings of the Cambridge Philosophical Society. In 1931 she was appointed an Assistant Lecturer at Westfield College and became a member of the London Mathematical Society in January 1932.. in 1936 she moved to Royal Holloway, University of London, at the time both women's colleges. In 1939 she became a doctoral student of Lancelot Bosanquet, but World War II broke out, preventing his formal supervision from continuing. In 1941 Sargent was promoted to lecturer at Royal Holloway, moving to Bedford College in 1948.
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Acrylamide is easily absorbed by the skin and distributed throughout the organism; the highest levels of acrylamide post-exposure are found in the blood, non-exposed skin, kidneys, liver, testes, and spleen. Acrylamide can be metabolically-activated by cytochrome P450 to a genotoxic metabolite, glycidamide, which is considered to be a critical mode of action to the carcinogenesis of acrylamide. On the other hand, acrylamide and glycidamide can be detoxified via conjugation with glutathione to form acrylamide- and isomeric glycidamide-glutathione conjugates, subsequently metabolized to mercapturic acids and excreted in urine. Acrylamide has also been found to have neurotoxic effects in humans who have been exposed.
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The name derives from the German mathematicians Alfred Clebsch and Paul Gordan, who encountered an equivalent problem in invariant theory. From a vector calculus perspective, the CG coefficients associated with the SO(3) group can be defined simply in terms of integrals of products of spherical harmonics and their complex conjugates. The addition of spins in quantum-mechanical terms can be read directly from this approach as spherical harmonics are eigenfunctions of total angular momentum and projection thereof onto an axis, and the integrals correspond to the Hilbert space inner product. From the formal definition of angular momentum, recursion relations for the Clebsch–Gordan coefficients can be found.
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P1-185, a progesterone oxime that was never marketed. While not esters, C3 and C20 oxime conjugates of progesterone, such as progesterone carboxymethyloxime (progesterone 3-(O-carboxymethyl)oxime; P4-3-CMO), P1-185 (progesterone 3-O-(L-valine)-E-oxime), EIDD-1723 (progesterone (20E)-20-[O-[(phosphonooxy)methyl]oxime] sodium salt), EIDD-036 (progesterone 20-oxime), and VOLT-02 (chemical structure unreleased), have been developed as water-soluble progesterone and neurosteroid prodrugs, although none have completed clinical development or been marketed as of yet.Guthrie, D. B., Lockwood, M. A., Natchus, M. G., Liotta, D. C., Stein, D. G., & Sayeed, I. (2017). "Progesterone phosphate analogs and uses related thereto" .
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BN-pairs can be used to prove that many groups of Lie type are simple modulo their centers. More precisely, if G has a BN-pair such that B is a solvable group, the intersection of all conjugates of B is trivial, and the set of generators of W cannot be decomposed into two non-empty commuting sets, then G is simple whenever it is a perfect group. In practice all of these conditions except for G being perfect are easy to check. Checking that G is perfect needs some slightly messy calculations (and in fact there are a few small groups of Lie type which are not perfect).
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The zinc finger proteins (ZFPs) can target on the specific zones in DNA sequences which helps the researchers to identify the particular sites in any DNA sequence efficiently with ZF Tools. He created the first commercially catalytic antibodies in the world. Catalytic antibody are capable of accomplishing the tasks that have been designed by the researchers in the body, which helps the researchers to understand the mechanisms of the particular zone in human body in order to develop new drugs. Barbas and his co-workers at The Scripps Research Institute (TSRI) invented antibody-drug conjugates to help create new therapies which can target on specific cell types.
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Catholic Bishops in Kenya are among those who have spread a conspiracy theory asserting that HCG forms part of a covert sterilization program, forcing denials from the Kenyan government. In order to induce a stronger immune response, some versions of human chorionic gonadotropin-based anti-fertility vaccines were designed as conjugates of the β subunit of HCG covalently linked to tetanus toxoid. It has been alleged that a non-conjugated tetanus vaccine used in developing countries is laced with a human chorionic gonadotropin based anti- fertility drug and is distributed as a means of mass sterilization. This charge has been vigorously denied by the World Health Organization (WHO) and UNICEF.
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The elimination half-life of raloxifene after a single dose is 27.7 hours (1.2 days), whereas its half-life at steady state at a dosage of 60 mg/day is 15.8 to 86.6 hours (0.7–3.6 days), with an average of 32.5 hours (1.4 days). The extended half-life of raloxifene is attributed to enterohepatic recirculation and its high plasma protein binding. Raloxifene and its glucuronide conjugates are interconverted by reversible metabolism and enterohepatic recycling, which prolongs the elimination half-life of raloxifene with oral administration. The medication is deconjugated into its active form in a variety of tissues, including liver, lungs, spleen, bone, uterus, and kidneys.
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On a nuclear level, during conjugation the original macronuclei fragment and the micronuclei mature and divide three times, with only one derivative of the first two divisions continuing to divide, forming two pronuclei in the third division. A pronuclei from each cell is exchanged and the two that end up in each cell fuse to form the synkaryon. The synkaryon divides twice with one derivative from each of the second divisions degenerating and the remaining derivatives becoming the new micronucleus and the macronucleus analge. After synkaryon division is complete, conjugates separate, now generating two cells with genetics distinct from the parent cells and from each other.
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In 1953, while still a medical resident he published work supporting the association of asbestos exposure and cancer of the lung. While at the NIH, he discovered the enzymatic defect causing the hereditary disorder of galactosemia. This work led to the development of a test for this disorder which is now being used in routine screening of newborns. In addition, he elucidated the ennzymatic mechanism for the formation of glucuronide conjugates, important for the detoxification of many compounds by the liver. After returning from the NIH in 1956, at the age of 31 he was chosen to head the Gastrointestinal Unit at the MGH.
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Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent. Because of its toxicity, it cannot be used as a drug itself; instead, it is linked to a monoclonal antibody (MAB) which directs it to the cancer cells. In International Nonproprietary Names for MMAE-MAB-conjugates, the name vedotin refers to MMAE plus its linking structure to the antibody.Statement on a nonproprietary name adopted by the USAN Council: Vedotin It is a potent antimitotic drug derived from peptides occurring in marine shell-less mollusc Dolabella auricularia called dolastatins which show potent activity in preclinical studies, both in vitro and in vivo, against a range of lymphomas, leukemia and solid tumors.
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Since 2004 Barba has been publishing a series of printed editions parallel to her films as another form to express and dismantle the cinematic organism. She conjugates its repertoire while she disbands and defines the relationships and hierarchies between image and word and like between image and viewer anew. The series Printed Cinema which won the artist book award 2006 at the Ontario Association of Art Galleries is published for specific exhibition spaces and accompanies her films as secondary literature for a limited time. The printed editions present an extended and free form of the exhibited film which reveal the filming process including research material and unused filmic fragments.
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This is likely because MeAN exists in part bound to red blood cells, and is therefore unavailable for GSH conjugation. Studies using radiolabeled carbon point out that the primary route by which methacrylonitrile left the body is the urine, at 43% of the dose. An additional 18% is excreted in faeces (15%) and exhaled air (2.5%). This means that about 40% of MeAN does not leave the body immediately and is either bound to macromolecules or forms unexcretable conjugates. The red blood cells retained significant amounts of radioactivity: more than 50% of the radioactivity in erythrocytes was detected as covalently bound to hemoglobin and membrane proteins. Day, W. W., et al. (1988).
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To date, four distinct FA- drug conjugates have entered clinical trials for the treatment of cancer: Vintafolide (EC145) represents a novel water-soluble FA conjugate of the powerful microtubule destabilizing agent, desacetylvinblastine monohydrazide (DAVLBH; a derivative of the natural product, vinblastine). EC145 was found to produce marked anti-tumor effect against well-established, subcutaneous FR- positive tumor xenografts using well tolerated regimens. EC145 also represents the first FA-drug conjugate to be evaluated in clinical trials, and it is currently (2009) being tested in a multi-national randomized Phase 2b trial in combination with pegylated liposomal doxorubicin (Doxil). EC0225 represents the "first in class" multi-drug, FA-targeted agent to be reported.
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The density of the field is greatest at the mirror points, of which there are always two for a given explosion, the so-called magnetic conjugates. The explosion can take place at either of these two points, and the magnetic field will cause them to concentrate at the other point as well. Christofilos noted that the conjugate point for most of the continental United States is in the South Pacific, far west of Chile, where such explosions would not be noticed. Thus, if one were to explode a series of such bombs in these locations, a massive radiation belt would form over the US, which might disable the warheads of a Soviet attack.
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Jindřich (Henry) Kopeček (born January 27, 1940, in Strakonice, Czech Republic) is a polymer chemist and pharmaceutical scientist notable as one of the pioneers in drug delivery.CRSNews2010 (Interview with Dr. Jindrich Kopecek) He is a Distinguished Professor at the University of Utah in Pharmaceutics & Pharmaceutical Chemistry, and Bioengineering,Kopecek Honored for Contributions (The Daily Utah Chronicle)The University of Utah and has been an editorial board member of 16 international scientific journals, and a fellow of several scientific societies.www.learned.cz/eng/engbiohf/kopecek.pdf Dr. Kopeček has made significant contribution to the developments of biomedical applicable hydrogels and polymeric drug conjugates. He was a member of the research group at Czechoslovak Academy of Sciences where polymeric soft contact lenses were invented.
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In particular, the oral route is subject to a high first-pass effect, which results in high levels of testosterone in the liver and consequent hepatic androgenic effects, as well as low potency due to first-pass metabolism in the intestines and liver into metabolites like dihydrotestosterone and androgen conjugates. Conversely, this is not the case for non-oral routes, which bypass the first pass. Different testosterone routes and dosages can achieve widely varying circulating testosterone levels. For purposes of comparison with normal physiological circumstances, circulating levels of total testosterone in men range from about 250 to 1,100 ng/dL (mean 630 ng/dL) and in women range from about 2 to 50 ng/dL (mean 32 ng/dL).
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He is an honors graduate of Dartmouth College and Harvard Medical School. After medical internship at Beth Israel Hospital he completed pediatrics residency training at the Massachusetts General Hospital and the Boston Children's Hospital, followed by a research fellowship in virology and infectious diseases, and then became a staff member at Children's Hospital working with Nobel Laureate John F. Enders. He remained with Enders for 12 years during which time they developed the attenuated measles vaccine now used throughout the world. In addition to his work on measles, Katz has been involved in studies of many other pathogens and infectious diseases including vaccinia, polio, rubella, influenza, pertussis, HIV, and Haemophilus influenzae b conjugates.
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They are verbs whose infinitive forms end in vowel + a/ä, for example puhua = "to speak", tietää = "to know". The group contains a very large number of verbs. Here is how tietää conjugates in the present indicative: :minä tiedän = I know :sinä tiedät = you (singular) know :hän tietää = (s)he/it knows :se tietää = (s)he/it knows :me tiedämme = we know :te tiedätte = you (plural/formal) know :he tietävät = they know :ne tietää = they know The personal endings are -n, -t, -(doubled final vowel), -mme, -tte, -vat. The inflecting stem is formed by dropping the final -a/ä of the infinitive and has a strong-grade consonant in the third-person forms and weak-grade elsewhere.
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The difference of two squares is used to find the linear factors of the sum of two squares, using complex number coefficients. For example, the complex roots of z^2 + 4 can be found using difference of two squares: :z^2 + 4 : = z^2 - i^2 \cdot 4 (since i^2 = -1) : = z^2 - (2 i)^2 : = (z + 2 i)(z - 2 i) Therefore, the linear factors are (z + 2 i) and (z - 2 i). Since the two factors found by this method are complex conjugates, we can use this in reverse as a method of multiplying a complex number to get a real number. This is used to get real denominators in complex fractions.
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In particular, the oral route is subject to a high first-pass effect, which results in high levels of estradiol and consequent estrogenic effects in the liver and low potency due to first-pass hepatic and intestinal metabolism into metabolites like estrone and estrogen conjugates. Conversely, this is not the case for parenteral (non- oral) routes, which bypass the intestines and liver. Different estradiol routes and dosages can achieve widely varying circulating estradiol levels. For purposes of comparison with normal physiological circumstances, menstrual cycle circulating levels of estradiol in premenopausal women are 40 pg/mL in the early follicular phase, 250 pg/mL at the middle of the cycle, and 100 pg/mL during the mid-luteal phase.
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Her expertise in protein phosphorylation and biological mass spectrometry have resulted in a number of professional appointments. She is currently Chair of BBSRC Committee D. Alongside Professors Sabine Flitsch and Perdita Barran, Eyers is also Co- founder and Scientific Director of Bio-Shape Ltd, a company specialising in the analysis of proteins, carbohydrates and their conjugates using mass spectrometry-based methods. Eyers' work in biological mass spectrometry focuses on the global and targeted analysis of post-translational modification on proteins. She has published over 70 research articles, has edited two books ('Quantitative Proteomics' published by RSC Press and 'Histidine Phosphorylation: Methods and Protocols published by Springer Press ) and she currently holds two patents.
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SNAs are the basis for a pipeline of therapeutic treatments that are being developed by Exicure. SNAs were shown to be able to deliver small interfering RNA (siRNA) to treat glioblastoma multiforme in a proof-of-concept study using a mouse model, reported by a research team led by Mirkin.Jensen, S. A.; Day, E. S.; Ko, C. H.; Hurley, L. A.; Luciano, J. P.; Kouri, F. M.; Merkel, T. J.; Luthi, A. J.; Patel, P. C.; Cutler, J. I.; Daniel, W. L.; Scott, A. W.; Rotz, M. W.; Meade, T. J.; Giljohann, D. A.; Mirkin, C. A.; Stegh, A. H. “Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma,” Science Trans. Med.
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This is in contrast to hydrophilic estrogen conjugates such as estrone sulfate and estradiol glucuronide, which require active transport via specific membrane transport proteins to enter cells. The ERs are nuclear receptors that are mostly present in the cell nucleus. Upon binding of estradiol to an ER, the receptor dimerizes (combines) with another estradiol- bound ER. These ER dimers can be ERα–ERα or ERβ–ERβ homodimers or ERα–ERβ heterodimers. Once in the dimerized state, the estradiol-bound ER–ER complex binds to short estrogen response elements (EREs) (of the minimal nucleotide sequence 5'-GGTCANNNTGACC-3', where N is any nucleotide) in the promoter regions of estrogen-responsive genes on chromosomes, in turn modulating their expression.
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In addition, unlike oral estradiol, transdermal estradiol is not associated with supraphysiological concentrations of estrone or estrogen conjugates like estradiol sulfate, and transdermal estradiol does not have disproportionate effects on liver protein synthesis. In accordance, estradiol, at typical menopausal replacement dosages, has been found not to increase the risk of blood clots or insulin resistance, nor to affect hepatic SHBG, IGF-1, GHBP, IGFBP, and other protein production and by extension circulating hepatic protein levels. However, at higher doses, transdermal estradiol has been associated with a significantly higher incidence of stroke in postmenopausal women, probably due to blood clots. Another larger study did not find a significantly higher risk of blood clots with similar doses of transdermal estradiol however.
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Exposure to o-toluidine enhances the microsomal activity of aryl hydrocarbon hydroxylase (particularly in the kidney), NADPH- cytochrome c reductase and the content of cytochrome P-450. Cytochrome P450–mediated N-hydroxylation to N-hydroxy-o-toluidine, a carcinogenic metabolite, occurs in the liver. N-Hydroxy-o-toluidine can be either metabolized to o-nitrosotoluene or conjugated with glucuronic acid or sulfate and transported to the urinary bladder via the blood. Once in the bladder, N-hydroxy-o-toluidine can be released from the conjugates in an acidic urine environment to either react directly with DNA or be bio-activated via sulfation or acetylation by cytosolic sulfotransferases or N-acetyltransferases (presumably NAT1).
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Autophagin-1 (Atg4/Apg4) is a unique cysteine protease responsible for the cleavage of the carboxyl terminus of Atg8/Apg8/Aut7, a reaction essential for its lipidation during autophagy.Development by self-digestion: molecular mechanisms and biological functions of autophagy by Levine B, Klionsky DJ. in Dev Cell. 2004 Apr;6(4):463-77. Review. Human Atg4 homologues cleave the carboxyl termini of the three human Atg8 homologues, microtubule-associated protein light chain 3 (LC3), GABARAP, and GATE-16.HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates byTanida I, Sou YS, Ezaki J, Minematsu- Ikeguchi N, Ueno T, Kominami E. in J Biol Chem.
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They can only cause their response as part of a complete antigen, involving their association with epidermal proteins forming hapten-protein conjugates. This, in turn, requires them to be protein-reactive. The conjugate formed is then recognized as a foreign body by the Langerhans cells (LCs) (and in some cases other Dendritic cells (DCs)), which then internalize the protein; transport it via the lymphatic system to the regional lymph nodes; and present the antigen to T-lymphocytes. This process is controlled by cytokines and chemokines – with tumor necrosis factor alpha (TNF-α) and certain members of the interleukin family (1, 13 and 18) – and their action serves either to promote or to inhibit the mobilization and migration of these LCs.
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Fluorescent probes and labels are an important tool for optical imaging. Some researchers have applied NIR imaging in rat model of acute myocardial infarction (AMI), using a peptide probe that can binds to apoptotic and necrotic cells. A number of near-infrared (NIR) fluorophores have been employed for in vivo imaging, including Kodak X-SIGHT Dyes and Conjugates, Pz 247, DyLight 750 and 800 Fluors, Cy 5.5 and 7 Fluors, Alexa Fluor 680 and 750 Dyes, IRDye 680 and 800CW Fluors. Quantum dots, with their photostability and bright emissions, have generated a great deal of interest; however, their size precludes efficient clearance from the circulatory and renal systems while exhibiting long-term toxicity.. Several studies have demonstrated the use of infrared dye-labeled probes in optical imaging.
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The conversion of codeine to morphine occurs in the liver and is catalyzed by the cytochrome P450 enzyme CYP2D6. CYP3A4 produces norcodeine and UGT2B7 conjugates codeine, norcodeine, and morphine to the corresponding 3- and 6- glucuronides. Srinivasan, Wielbo and Tebbett speculate that codeine-6-glucuronide is responsible for a large percentage of the analgesia of codeine, and, thus, these patients should experience some analgesia. Many of the adverse effects will still be experienced in poor metabolizers. Conversely, 0.5-2% of the population are "extensive metabolizers"; multiple copies of the gene for 2D6 produce high levels of CYP2D6 and will metabolize drugs through that pathway more quickly than others. Some medications are CYP2D6 inhibitors and reduce or even completely block the conversion of codeine to morphine.
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One of the traps in a deductive system is circular reasoning, a problem that seemed to befall projective geometry until it was resolved by Karl von Staudt. As explained by Russian historians:Laptev, B.L. & B.A. Rozenfel'd (1996) Mathematics of the 19th Century: Geometry, page 40, Birkhäuser The purely geometric approach of von Staudt was based on the complete quadrilateral to express the relation of projective harmonic conjugates. Then he created a means of expressing the familiar numeric properties with his Algebra of Throws. English language versions of this process of deducing the properties of a field can be found in either the book by Oswald Veblen and John Young, Projective Geometry (1938), or more recently in John Stillwell's Four Pillars of Geometry (2005).
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Examples include the production of multi-specific Affimer molecules to target and recruit specific cells, fusion to Fc fragments or albumin binders to tune their half-life in vivo and for use as the targeting moiety in chimeric receptors or modified to carry a toxin in Affimer-drug conjugates. Affimer therapeutics are in discovery and preclinical development to tackle blood clotting disorders, antibiotic resistance, phenotypic drug discovery models and cancer, both via CAR-T cell therapy and as immune checkpoint inhibitors. Early studies using ex vivo human samples showed low immunogenicity associated with the Affimer scaffold, at levels comparable to a marketed antibody therapeutic. Furthermore, initial preclinical studies showed good efficacy and tolerability of the anti-PDL1 immuno-oncology Affimer therapeutic in mice.
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Two isometry groups are said to be equal up to conjugacy with respect to affine transformations if there is an affine transformation such that all elements of one group are obtained by taking the conjugates by that affine transformation of all elements of the other group. This applies for example for the symmetry groups of two patterns which are both of a particular wallpaper group type. If we would just consider conjugacy with respect to isometries, we would not allow for scaling, and in the case of a parallelogrammetic lattice, change of shape of the parallelogram. Note however that the conjugate with respect to an affine transformation of an isometry is in general not an isometry, although volume (in 2D: area) and orientation are preserved.
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From its current range of applications in basic research as well as in drug target validation, drug discovery, and therapeutic development, the potential use of oligonucleotides is foreseen in gene therapy (antisense drugs), disease prevention and agriculture. Antibody-drug conjugates (ADC) constitute a combination between small and big molecules. The small molecule parts, up to four different APIs, are highly potent cytotoxic drugs. They are linked with a monoclonal antibody, a big molecule which is of little or no therapeutic value in itself, but extremely discriminating for its targets, the cancer cells. The first commercialized ADCs were Isis’s Formivirisen and, more recently, Pfizer’s (formerly Wyeth) Mylotarg (gemtuzumab ozogamicin). Examples of ADCs in phase III of development are Abbott’s / Isis’s Alicaforsen and Eli Lilly’s Aprinocarsen.
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Another reason may be to prevent inbreeding. The ABCC11 gene determines axillary body odor and the type of earwax. The loss of a functional ABCC11 gene is caused by a 538G>A single- nucleotide polymorphism, resulting in a loss of body odor in people who are specifically homozygous for it. Firstly, it affects apocrine sweat glands by reducing secretion of odorous molecules and its precursors. The lack of ABCC11 function results in a decrease of the odorant compounds 3M2H, HMHA, and 3M3SH via a strongly reduced secretion of the precursor amino-acid conjugates 3M2H–Gln, HMHA–Gln, and Cys–Gly–(S) 3M3SH; and a decrease of the odoriferous steroids androstenone and androstenol, possibly due to the reduced levels and secretion of DHEAS and DHEA (possibly bacterial substrates for odoriferous steroids).
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The first evidence that sets of uniqueness have complex structure came from the study of Cantor-like sets. Salem and Zygmund showed that a Cantor-like set with dissection ratio ξ is a set of uniqueness if and only if 1/ξ is a Pisot number, that is an algebraic integer with the property that all its conjugates (if any) are smaller than 1. This was the first demonstration that the property of being a set of uniqueness has to do with arithmetic properties and not just some concept of size (Nina Bari had proved the case of ξ rational -- the Cantor-like set is a set of uniqueness if and only if 1/ξ is an integer -- a few years earlier). Since the 50s, much work has gone into formalizing this complexity.
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The residues that form the binding site for a given antigen, are selected among the hypervariable residues. It is possible to transform any AgBP of these families into a RF biosensor, specific of the target antigen, simply by coupling a solvatochromic fluorophore to one of the hypervariable residues that have little or no importance for the interaction with the antigen, after changing this residue into cysteine by mutagenesis. More specifically, the strategy consists in individually changing the residues of the hypervariable positions into cysteine at the genetic level, in chemically coupling a solvatochromic fluorophore with the mutant cysteine, and then in keeping the resulting conjugates that have the highest sensitivity (a parameter that involves both affinity and variation of fluorescence signal). This approach is also valid for families of antibody fragments.
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Plasma half life is between 3 and 4 hours and oral/intramuscular analgesic potency ratio is approximately equal to 1:1.5. The most common conversion ratio, given on equianalgesia charts used in the United States, Canada, the UK, Republic of Ireland, the European Union, Russia and elsewhere as 130 mg IM equals 200 mg PO—both of which are equivalent to 10 mg of morphine sulphate IV and 60 mg of morphine sulphate PO. The salt:freebase ratio of the salts of both drugs in use are roughly equivalent, and do not generally make a clinical difference.The Merck Index, 13th Edition: Morphine Hydrochloride Codeine is metabolised by O- and N-demethylation in the liver to morphine and norcodeine. Codeine and its metabolites are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid.
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Acidic and basic fibroblast growth factor, neurotrophin 3, transforming growth factor beta 1, transforming growth factor beta 2, nerve growth factor, brain derived neurotrophic factor can be given as examples for such growth factors. For some tissues like cartilage, highly dense polymeric scaffolds such as polyethylene glycol (PEG) are essential due to mechanical stress and that can be achieved by combining them with natural biodegradable cell-adhesive scaffolds since cells can not attach to synthetic polymers and take proper signals for normal cell function. Various scaffold combinations with PEG-based hydrogels are studied to assess the chondrogenic response to dynamic strain stimulation in a recent study. PEG-Proteoglycan, PEG-Fibrinogen, PEG-Albumin conjugates and only PEG including hydrogels are used to evaluate the mechanical effect on bovine chondrocytes by using a pneumatic reactor system.
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Tha mi a' bruidhinn. – "I am speaking" or "I speak" (lit. "Am I at speaking") The perfective past in regular verbs is indicated by lenition of the initial consonant, and d'/dh' addition with verbs that start with a vowel or "f" (do is the underlying form in all cases): bruidhinn "speak" : bhruidhinn mi "I spoke" òl "drink" : dh'òl mi "I drank" fuirich "wait, stay" : dh'fhuirich mi "I waited/stayed" Gaelic conjugates verbs to indicate either the present imperfective or the future tense: bruidhnnidh mi – "I speak", "I will speak", "I speak (at times/occasionally/often)". The habitual continuous and future continuous is expressed by using the habitual verb bi: Bidh mi a' bruidhinn – "I speak (regularly)", "I will be speaking", "I am speaking as a normal habit", etc.
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Synaffix is a biotechnology company headquartered in the Netherlands that has developed a clinical-stage platform technology for antibody-drug conjugates (ADCs) which are used primarily in the treatment of cancer. ADCs utilize potent small molecule payloads, similar to those used for chemotherapy, but are designed to target only the cancer cells and spare normal, healthy tissues. The proprietary technology of Synaffix was developed to enable the treatment of a wide variety of cancer types and is designed to significantly enhance the effectiveness while also improving the safety and tolerability of these targeted cancer therapeutics. Benchmarking studies consistently demonstrate that, with a given antibody and ADC payload, ADCs produced using Synaffix technology display significantly enhanced effectiveness and significantly enhanced tolerability and safety versus all 3-major clinical- stage ADC technologies.
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2/ With two competing companies in Europe, Inotech, Basil, Switzerland and Boehringer Mannheim, Germany, Dr. Sutula pioneered the concept of "reagent sets"—matched, quality-controlled antibodies and antibody-enzyme conjugates that can be used to prepare and perform one's own test. He integrated these ideas into plant diagnostics, expanded the scope of diagnostic assays, and guided Agdia to a continuous company growth over the past 35 years. 3/ In response to many requests, he formed Agdia Testing Services in 1982, a unit of Agdia. Agdia currently offers more than 200 tests that use several technologies, such as ELISA, Recombinase Polymerase Amplification (RPA), Polymerase Chain Reaction (PCR), nucleic acid hybridization, immunochromatography, and Immunofluorescence assay (IFA), to detect viruses, viroids, bacteria, fungi, mycoplasma, insects, plant hormones, and proteins in conventional and genetically modified crops (GMO).
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When taken orally, about 95% of a dose of estradiol is metabolized in the intestines and liver into estrone and estrogen conjugates such as estrone sulfate, estrone glucuronide, and estradiol sulfate, among others, prior to entering the circulation. As a result, circulating estrone and estrogen conjugate levels are markedly elevated, in a highly unphysiological manner, with oral estradiol. Whereas the ratio of circulating estradiol to estrone is about 1:1 in premenopausal women and with transdermal estradiol, oral estradiol produces a ratio of about 1:5 on average and as high as 1:20 in some women. In addition, whereas levels of estradiol with menopausal replacement dosages of oral estradiol are in the range of the follicular phase of the normal menstrual cycle, levels of estrone resemble those during the first trimester of pregnancy.
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Moreover, whereas normal physiological estrone sulfate levels are 10 to 25 times higher than those of estradiol and estrone in premenopausal women, levels of estrone sulfate with oral estradiol are an additional 8 to 20 times higher than normal premenopausal or postmenopausal estrone sulfate levels. One study found that estrone sulfate levels were 200-fold higher than estradiol levels with 2 mg/day oral micronized estradiol or oral estradiol valerate, and estrone sulfate levels can reach up to nearly 1,000-fold higher concentrations than estradiol in some cases. In contrast to oral estradiol, due to the lack of the first pass, an excess in estrone and estrogen conjugate levels does not occur with transdermal estradiol or other parenteral estradiol routes. The transformation of estradiol into estrone and estrogen conjugates is reversible.
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If we systematically and consistently reorder the three items in each triple (that is, permute the three columns in the array form), another orthogonal array (and, thus, another Latin square) is obtained. For example, we can replace each triple (r,c,s) by (c,r,s) which corresponds to transposing the square (reflecting about its main diagonal), or we could replace each triple (r,c,s) by (c,s,r), which is a more complicated operation. Altogether there are 6 possibilities including "do nothing", giving us 6 Latin squares called the conjugates (also parastrophes) of the original square. Finally, we can combine these two equivalence operations: two Latin squares are said to be paratopic, also main class isotopic, if one of them is isotopic to a conjugate of the other.
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In the yeast cell wall, mannan oligosaccharides are present in complex molecules that are linked to the protein moiety. There are two main locations of mannan oligosaccharides in the surface area of Saccharomyces cerevisiae cell wall. They can be attached to the cell wall proteins as part of –O and –N glycosyl groups and also constitute elements of large α-D- mannanose polysaccharides (α-D-Mannans), which are built of α-(1,2)- and α-(1,3)- D-mannose branches (from 1 to 5 rings long), which are attached to long α-(1,6)-D-mannose chains. This specific combination of various functionalities involves mannan oligosaccharides-protein conjugates and highly hydrophilic and structurally variable 'brush-like' mannan oligosaccharides structures that can fit to various receptors of animal digestive tracts, and to the receptors on the surface of bacterial membranes, impacts these molecules bioactivity.
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A special, reversal form of drug delivery where modulation of active migratory behaviour of the target cells is used to achieve targeted effects. The general components of the conjugates are designed as follows: (i) carrier – regularly possessing promoter effect also on internalization into the cell; (ii) chemotactically active ligands acting on the target cells; (iii) drug to be delivered in a selective way and (iv) spacer sequence which joins drug molecule to the carrier and due to it enzyme labile moiety makes possible the intracellular compartment specific release of the drug. Chemotactic drug-targeting Careful selection of chemotactic component of the ligand not only the chemoattractant character could be expended, however, chemorepellent ligands are also valuable as they are useful to keep away cell populations degrading the conjugate containing the drug. This mechanism of drug delivery is currently being studied.
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Sutro's Xpress CF Platform is based on Stanford Professor James R. Swartz's patented Open Cell-Free Synthesis (OCFS) technology. XpressCF technology enables the parallel expression of hundreds of protein variants in less than 24 hours, providing a platform for the discovery and development of a wide variety of protein classes including cytokines, vaccine carrier-proteins, antibodies, and novel antibody-based proteins. The XpressCF+ platform allows for precise incorporation of non-natural amino acids into a protein sequence, and Sutro is using this technology to develop homogeneous site-specific antibody-drug conjugates (ADCs). Once identified, production of protein drug candidates can be scaled in Sutro's cGMP manufacturing facility located in San Carlos, CA. Sutro's technology has also contributed to the formation of SutroVax, a vaccine spin off founded in 2015 that has raised over $170 million in capital.
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This follows as K(α) is K-isomorphic to K(β) by irreducibility of the minimal polynomial, and any isomorphism of fields F and F that maps polynomial p to p can be extended to an isomorphism of the splitting fields of p over F and p over F, respectively. In summary, the conjugate elements of α are found, in any normal extension L of K that contains K(α), as the set of elements g(α) for g in Aut(L/K). The number of repeats in that list of each element is the separable degree [L:K(α)]sep. A theorem of Kronecker states that if α is a nonzero algebraic integer such that α and all of its conjugates in the complex numbers have absolute value at most 1, then α is a root of unity.
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This was followed by another phase I trial in 1977-1978 examining previously sterilized women at 5 institutions in India with a more potent vaccine that combined the beta subunit of hCG with the alpha subunit of ovine luteinizing hormone to form a heterospecies dimer conjugated with both tetanus toxoid and diphtheria toxoid. The multiple carriers were used because it was found that a small percentage of women acquired carrier-specific immunosuppression due to repeated injection of conjugates with the same carrier. This more potent version of the vaccine was used in a phase II (efficacy) trial during 1991-1993 conducted at 3 locations: the All India Institute of Medical Sciences, Safdarjung Hospital in New Delhi, and the Post Graduate Institute of Medical Education and Research in Chandigarh. Primary immunization consisted of 3 injections at 6 week intervals, and 148 women known to be previously fertile completed primary immunization.
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The geometric relation between a central line and its associated triangle center can be expressed using the concepts of trilinear polars and isogonal conjugates. Let X = ( u ( a, b, c ) : v ( a, b, c ) : w ( a, b, c ) ) be a triangle center. The line whose equation is : x / u ( a, b, c ) + y / v ( a, b, c ) y + z / w ( a, b, c ) = 0 is the trilinear polar of the triangle center X. Also the point Y = ( 1 / u ( a, b, c ) : 1 / v ( a, b, c ) : 1 / w ( a, b, c ) ) is the isogonal conjugate of the triangle center X. Thus the central line given by the equation : f ( a, b, c ) x + g ( a, b, c ) y + h ( a, b, c ) z = 0 is the trilinear polar of the isogonal conjugate of the triangle center ( f ( a, b, c ) : g ( a, b, c ) : h ( a, b, c ) ).
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As Freudenthal notes :...up to Hilbert, there is no other example for such a direct derivation of the algebraic laws from geometric axioms as found in von Staudt's Beiträge. Another affirmation of von Staudt's work with the harmonic conjugates comes in the form of a theorem: :The only one-to-one correspondence between the real points on a line which preserves the harmonic relation between four points is a non-singular projectivity.Dirk Struik (1953) Lectures on Analytic and Projective Geometry, p 22, "theorem of von Staudt" The algebra of throws was described as "projective arithmetic" in The Four Pillars of Geometry (2005).John Stillwell, Sheldon Axler, Ken A. Ribet (2005) The Four Pillars of Geometry, page 128, Springer: Undergraduate Texts in Mathematics In a section called "Projective arithmetic", he says :The real difficulty is that the construction of a + b , for example, is different from the construction of b + a, so it is a "coincidence" if a + b = b + a.
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As a result, sublingual estradiol has been found to result in estradiol levels and a ratio of estradiol to estrone that are substantially higher than oral estradiol. Maximal circulating levels of estradiol are as much as 10-fold higher with sublingual administration than with oral administration, and the absolute bioavailability of estradiol is approximately 5-fold higher. On the other hand, levels of estradiol fall rapidly with sublingual administration, whereas they remain elevated for a prolonged period of time with oral administration. This is due to the large circulating pool of hormonally inert estrogen conjugates with long half-lives that is reversibly generated with oral estradiol during first-pass metabolism, which serves as a metabolism-resistant and long-lasting reservoir for continuous reconversion back into estradiol. It is also responsible for the differences in ratios between sublingual estradiol and oral estradiol in terms of maximal estradiol levels (10:1) achieved and absolute bioavailability (5:1).
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Another approach to the harmonic conjugate is through the concept of a complete quadrangle such as KLMN in the above diagram. Based on four points, the complete quadrangle has pairs of opposite sides and diagonals. In the expression of harmonic conjugates by H. S. M. Coxeter, the diagonals are considered a pair of opposite sides: :D is the harmonic conjugate of C with respect to A and B, which means that there is a quadrangle IJKL such that one pair of opposite sides intersect at A, and a second pair at B, while the third pair meet AB at C and D.H. S. M. Coxeter (1942) Non-Euclidean Geometry, page 29, University of Toronto Press It was Karl von Staudt that first used the harmonic conjugate as the basis for projective geometry independent of metric considerations: :...Staudt succeeded in freeing projective geometry from elementary geometry. In his Geometrie der Lage Staudt introduced a harmonic quadruple of elements independently of the concept of the cross ratio following a purely projective route, using a complete quadrangle or quadrilateral.
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The focus of his research is on developing methods for controlling the architecture of molecules and materials on the 1 – 100 nm length scale and utilizing such structures in the development of analytical tools that can be used in the areas of chemical and biological sensing, lithography, catalysis, and optics. Mirkin has pioneered the use of DNA and nanoparticles as synthons in materials science and the development of nanoparticle-based biodiagnostics. A common strategy used by Mirkin's group is the use of the unique properties of spherical nucleic acids (SNAs), spherical arrangements of nucleic acids with or without organic or inorganic nanoparticle cores, to enable the synthesis of novel materials and colloidal crystals, the development of high sensitivity probes for chemical and medical diagnostic purposes, and single-entity structures capable of intracellular gene regulation. His 1996 work with SNA-gold nanoparticle conjugates introduced the concept of a nanoparticle as an atom and nucleic acids as bonds, and it laid the ground work for the fields of colloidal crystal engineering with DNA and molecular diagnostics based upon well-defined nanoparticle and nanocrystal bioconjugates.
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In addition, estradiol levels were found to correlate with these effects, while estrone levels did not. These findings suggest that estrone contributes very little or not at all to the estrogenic potency of estradiol, while also not antagonizing the estrogenic activity of estradiol. This contradicts some cell-free in-vitro research suggesting that high concentrations of estrone might be able to partially antagonize the actions of estradiol. On the other hand, it has been suggested by some authors that the high levels of estrone and/or estrone conjugates with oral estradiol may result in excessive estradiol levels in certain tissues such as the breasts and endometrium, due to high expression in these tissues of the requisite enzymes (17β-HSDs and STS) necessary to transform these metabolites back into estradiol. In accordance, circulating levels of estrone sulfate have been found to be positively associated with breast density in postmenopausal women treated with oral estradiol, with 1.3% higher breast density observed for every 1 ng/mL greater level of estrone sulfate.
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If M1 and M2 are the midpoints of the diagonals AC and BD respectively in a tangential quadrilateral ABCD with incenter I, and if the pairs of opposite sides meet at J and K with M3 being the midpoint of JK, then the points M3, M1, I, and M2 are collinear. The line containing them is the Newton line of the quadrilateral. If the extensions of opposite sides in a tangential quadrilateral intersect at J and K, and the extensions of opposite sides in its contact quadrilateral intersect at L and M, then the four points J, L, K and M are collinear.. If the incircle is tangent to the sides AB, BC, CD, DA at T1, T2, T3, T4 respectively, and if N1, N2, N3, N4 are the isotomic conjugates of these points with respect to the corresponding sides (that is, AT1 = BN1 and so on), then the Nagel point of the tangential quadrilateral is defined as the intersection of the lines N1N3 and N2N4. Both of these lines divide the perimeter of the quadrilateral into two equal parts.
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Suppose that g is a complex semisimple Lie algebra, with a Borel subalgebra b containing a Cartan subalgebra h. An irreducible finite-dimensional representation V of g splits as a sum of eigenspaces of h, and the highest weight space is 1-dimensional and is an eigenspace of b. The Weyl group W acts on the weights of V, and the conjugates wλ of the highest weight vector λ under this action are the extremal weights, whose weight spaces are all 1-dimensional. A Demazure module is the b-submodule of V generated by the weight space of an extremal vector wλ, so the Demazure submodules of V are parametrized by the Weyl group W. There are two extreme cases: if w is trivial the Demazure module is just 1-dimensional, and if w is the element of maximal length of W then the Demazure module is the whole of the irreducible representation V. Demazure modules can be defined in a similar way for highest weight representations of Kac–Moody algebras, except that one now has 2 cases as one can consider the submodules generated by either the Borel subalgebra b or its opposite subalgebra.
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In addition to earwax phenotype, the ABCC11 genotype has been found to be associated with colostrum secretion from the breasts as well as normal axillary odor and osmidrosis (excessive axillary malodor). A functional ABCC11 protein has been found to be essential for the presence of the characteristic strong axillary odor, with the 538G→A SNP leading to a loss of secretion of axillary malodorous precursors and a nearly complete loss of axillary odor in those who are homozygous for the polymorphism. Specifically, the secretion of the amino-acid conjugates 3M2H-Gln, HMHA-Gln, and Cys-Gly-(S) 3M3SH, which are precursors of key axillary malodorous compounds including the unsaturated or hydroxylated branched-chain fatty acids 3M2H and HMHA and the sulfanylalkanol 3M3SH, has been found to be abolished in homozygotic carriers of the SNP, and the odoriferous androstane steroids androstenone and androstenol and their precursors DHEA and DHEA-S have been found to be significantly reduced as well. Patients with axillary osmidrosis (538G/G or 538G/A genotype) were found to have significantly more numerous and relatively large axillary apocrine glands compared to controls with the A/A genotype.
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Cholestasis means "the slowing or stopping of bile flow" which can be caused by any number of diseases of the liver (which produces the bile), the gallbladder (which stores the bile), or biliary tract (also known as the biliary tree, the conduit that allows the bile to leave the liver and gallbladder and enter the small intestine). When this occurs, conjugated bilirubin and the waste products that usually would be cleared in bile reflux back into the bloodstream. This causes a primarily conjugated hyperbilirubinemia and jaundice; the liver conjugates the bile to make it water-soluble and because the bile has already been processed by the liver, when it gets backed up because of a blockage and is refluxed into the blood, the blood will have high levels of conjugated bilirubin. This is in contrast to primarily unconjugated hyperbilirubinemia which is the water-insoluble form that is bound to serum albumin; the liver has not had a chance to conjugate the bilirubin yet and can be caused either because too much unconjugated bilirubin is made (such as in massive hemolysis or ineffective erythropoiesis) or because too little is conjugated (Gilbert's disease or Crigler–Najjar syndrome).
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This dialect generally preserves intimate or familiar tu, the standard equalizing form você, and the respectful or formal o senhor/a senhora, together with their related possessives, to such an extent that almost all speakers use these forms, according to context. Nevertheless, a minority of educated speakers correctly conjugates all of the tu pronouns formally; otherwise, it is mostly conjugated as você. Standard Portuguese usage has vocês and os senhores/as senhoras as plurals of você and o senhor/a senhora, but the vernacular has also produced new forms with the second-person familiar plural function, such as gente (compare a gente as a possible colloquial variation of nós, "we"/"us", that should be conjugated—but commonly is not—as third-person singular), pessoas, pessoal, [meu] povo, cês (eye dialect for vocês in colloquial pronunciation), and galera (the latter mainly associated with youth slang). It is often said that the gaúcho, nordestino and amazofonia dialects, as well as some sociolects elsewhere, such as that in and around the city of Santos, have preserved tu; but unlike in fluminense, the use of você is very limited, and entirely absent among some speakers, and tu takes its place.
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Little to no parent drug is present in urine, so there is a lot of research to try and identify the major urinary metabolites that could be used as markers of synthetic cannabinoid intake. The major urinary metabolites in most cases are formed by oxidation of the alkyl side-chain to an alcohol and carboxylic acid followed by glucuronide conjugation and also by N-dealkylation and aromatic hydroxylation. For example, the main metabolites of JWH-018, of which there are over 20, include carboxylated, monohydroxylated, dihydroxylated, and trihydroxylated metabolites, but they are mostly excreted in urine as glucuronide conjugates. The presence of synthetic cannabinoids or their metabolites in bodily fluids may be determined using specifically-targeted commercially available immunoassay screening methods (EMIT), while liquid chromatography-mass spectrometry is most often used for confirmation and quantitation. There are commercially available EMIT kits for the screening of the synthetic cannabinoids JWH-018, JWH-073, JWH-398, JWH-200, JWH-019, JWH-122, JWH-081, JWH-250, JWH-203, CP-47,497, CP-47,497-C8, HU-210, HU-211, AM-2201, AM-694, RCS-4, and RCS-8 through companies like NMS Labs, Cayman Chemical, and Immunoanalysis Corporation.
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Quercetin 3-sulfate is a plasma human metabolite of quercetin.Human metabolism of dietary flavonoids: Identification of plasma metabolites of quercetin. Andrea J. Day, Fred Mellon, Denis Barron, Géraldine Sarrazin, Michael R.A. Morgan and Gary Williamson, Free Radical Research, 2001, Vol. 35, No. 6, pages 941-952, Effect of quercetin conjugates on vascular permeability and expression of adhesion molecules. Mika Mochizuki, Katsuko Kajiya, Junji Terao, Kazuhiko Kaji, Shigenori Kumazawa, Tsutomu Nakayama and Kayoko Shimoi, BioFactors, Volume 22, Issue 1-4, pages 201–204, 2004, Metabolism of quercetin-7- and quercetin-3-glucuronides by an in vitro hepatic model: the role of human β-glucuronidase, sulfotransferase, catechol-O-methyltransferase and multi-resistant protein 2 (MRP2) in flavonoid metabolism. Karen A O’Leary, Andrea J Day, Paul W Needs, Fred A Mellon, Nora M O’Brien and Gary Williamson, Biochemical Pharmacology, Volume 65, Issue 3, 1 February 2003, pages 479-491, It is the sulfate conjugate of quercetin. Quercetin-3-sulfate 3'-sulfotransferase is an enzyme that uses 3'-phosphoadenylyl sulfate and quercetin 3-sulfate to produce adenosine 3',5'-bisphosphate and quercetin 3,3'-bissulfate. Quercetin-3-sulfate 4'-sulfotransferase is an enzyme that uses 3'-phosphoadenylyl sulfate and quercetin 3-sulfate to produce adenosine 3',5'-bisphosphate and quercetin 3,4'-bissulfate.
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