gebhart/patrepeval huggingface dataset:
Effects of systematic variation of the minimal Escherichia coli met consensus operator site: in vivo and in vitro met repressor binding (1996)

We have produced a set of sequence variants based upon the idealized, minimal Escherichia coli met operator in which each position within the basic recognition unit, the 8 bp met box (dAGACGTCT), has been changed to all other possible sequences containing single symmetrical base substitutions. The effects of these sequence variations have been assayed in vivo by monitoring the production of beta-galactosidase from a standard promoter regulated by the operator variants, and in vitro by gel-retardation assay. The two sets of data are consistent and correlate well with expectations based on the three-dimensional structure of the holorepressor bound to a minimal idealized operator and the results of in vitro evolution experiments. Comparison with two natural operators, metA and metC, suggests that in vivo, with non-consensus operators, the repressor binds to at least four consecutive met boxes.
Bioconjugation with Strained Alkenes and Alkynes (2011)

The structural complexity of molecules isolated from biological sources has always served as an inspiration for organic chemists. Since the first synthesis of a natural product, urea, chemists have been challenged to prepare exact copies of natural structures in the laboratory. As a result, a broad repertoire of synthetic transformations has been developed over the years. It is now feasible to synthesize organic molecules of enormous complexity, and also molecules with less structural complexity but prodigious societal impact, such as nylon, TNT, polystyrene, statins, estradiol, XTC, and many more. Unfortunately, only a few chemical transformations are so mild and precise that they can be used to selectively modify biochemical structures, such as proteins or nucleic acids; these are the so-called bioconjugation strategies. Even more challenging is to apply a chemical reaction on or in living cells or whole organisms; these are the so-called bioorthogonal reactions. These fields of research are of particular importance because they not only pose a worthy challenge for chemists but also offer unprecedented possibilities for studying biological systems, especially in areas in which traditional biochemistry and molecular biology tools fall short. Recent years have seen tremendous growth in the chemical biology toolbox. In particular, a rapidly increasing number of bioorthogonal reactions has been developed based on chemistry involving strained alkenes or strained alkynes. Such strained unsaturated systems have the unique ability to undergo (3 + 2) and (4 + 2) cycloadditions with a diverse set of complementary reaction partners. Accordingly, chemistry centered around strain-promoted cycloadditions has been exploited to precisely modify biopolymers, ranging from nucleic acids to proteins to glycans. In this Account, we describe progress in bioconjugation centered around cycloadditions of these strained unsaturated systems. Being among the first to recognize the utility of strain-promoted cycloadditions between alkenes and dipoles, we highlight our report in 2007 of the reaction of oxanobornadienes with azides, which occurs through a sequential cycloaddition and retro Diels-Alder reaction. We further consider the subsequent refinement of this reaction as a valuable tool in chemical biology. We also examine the development of the reaction of cyclooctyne, the smallest isolable cyclic alkyne, with a range of substrates. Owing to severe deformation of the triple bond from ideal linear geometry, the cyclooctynes show high reactivity toward dienes, 1,3-dipoles, and other molecular systems. In the search for bioorthogonal reactions, cycloadditions of cyclic alkenes and alkynes have now established themselves as powerful tools in reagent-free bioconjugations.
Efficacy of Selected Natural Products as Therapeutic Agents against Cancer (2008)

With emerging sophistication in the exploration of ocean environment, a number of marine bioactive products have been identified with promising anticancer activity. Many of these are in active phase I or phase II clinical trials or have been terminated because of adverse side effects, mainly hematological in nature. Nonetheless, the information derived has aided enormously in providing leads for laboratory synthesis with modifications in the parent structure affecting compound solubility, absorption, and toxicity, resulting in less severe toxicity while achieving maximum efficacy in smaller doses. We describe herein, a few of the compounds obtained from marine and terrestrial sources [bryostatin 1 ( 1), dolastatin 10 ( 2), auristatin PE ( 3), and combretastatin A4 ( 4)] that have been extensively investigated in our laboratory and continue to be investigated for their sensitization effects with other cytotoxic agents in several different site-specific tumors employing murine models or human subjects.
New Synthetic Routes to Triazolo-benzodiazepine Analogues: Expanding the Scope of the Bump-and-Hole Approach for Selective Bromo and Extra-Terminal (BET) Bromodomain Inhibition (2015)

We describe new synthetic routes developed toward a range of substituted analogues of bromo and extra-terminal (BET) bromodomain inhibitors I-BET762/JQ1 based on the triazolo-benzodiazepine scaffold. These new routes allow for the derivatization of the methoxyphenyl and chlorophenyl rings, in addition to the diazepine ternary center and the side chain methylene moiety. Substitution at the level of the side chain methylene afforded compounds targeting specifically and potently engineered BET bromodomains designed as part of a bump and hole approach. We further demonstrate that marked selectivity for the second over the first bromodomain can be achieved with an indole derivative that exploits differential interaction with an aspartate/histidine conservative substitution on the BC loop of BET bromodomains.
Synthesis of pyrazoline and isoxazoline in triethanolamine medium (2004)

Reactions of chalcones la-u with phenylhydrazine and hydrazine hydrate give pyrazolines 2a-u and with hydroxylamine hydrochloride yield isoxazolines 3a-c in triethanolamine medium. The structures of products are established by melting points, chemical studies and spectral data (IR and 1 HNMR).
Hepatic encephalopathy: the role of inflammation, ammonia andaquaporin expression in the pathogenesis of cerebral oedema (2010)

Current evidence indicates synergy between hyperammonaemia and inflammation in the brain with liver failure. Utilising animal and laboratory experiments, this thesis explored a number of concise questions focused on progression to brain
oedema and coma with hepatic encephalopathy (HE).
STUDY 1: It is unclear whether the background cirrhotic state or hyperammonaemia predisposes to superimposed inflammation. Question 1: Does lipopolysaccharide (LPS)-induced systemic inflammation worsen brain oedema in
cirrhotic bile duct-ligated rats? and is this associated with blood-brain barrier disruption? altered brain ammonia and/or inflammatory pathways? Answer 1: LPSinduced
pre-coma/coma and exacerbated cytotoxic oedema, indicating synergy
between hyperammonaemia and inflammation associated with brain protein nitrosation.
STUDY 2: New ammonia-lowering therapies targeting multiple organs are necessary. Question 2: Does combining L-ornithine and phenylacetate (OP),
synergistically improve ammonia reduction? Answer 2: L-ornithine and
phenylbutyrate synergistically lead to sustained ammonia-lowering and limited
oedema; L-ornithine detoxifying ammonia by providing a substrate for glutamine
synthesis and phenylacetate renally excreting the glutamine as phenylacetylglutamine.
STUDY 3: Despite apparent synergism, therapies for HE target either
hyperammonemia or inflammation, not both. Question 3: Can a reduction in
ammonia in cirrhotic rats prevent LPS-induced worsening of brain oedema and
progression to pre-coma/coma? Does targeting hyperammonaemia and inflammation together provide therapeutic synergy? Answer 3: Ammonia primes
the brain to the deleterious effect of LPS, with the ammonia-lowering effect of OP
preventing LPS-induced coma and brain edema.
STUDY 4: Aquaporin-4 (AQP4), a bi-directional astrocyte water channel, is thought
to provoke brain oedema in neuropathic disorders. Question 4: Is AQP4 causally
involved in the brain oedema associated with models of liver failure? Answer 4:
AQP4 has no causal role in the brain edema associated with hyperammonemia or
inflammation, with or without acute liver dysfunction. However in cirrhosis, AQP4
upregulation, with contemporaneous p38MAPK activation is possibly a compensatory
response to inhibit edema formation.
Different characteristics of InGaN/GaN multiple quantum well heterostructures grown on m- and r-planes of a single n-GaN nanowire using metalorganic chemical vapor deposition (2014)

The growth behavior of coaxial nonpolar (m-plane) and semipolar (r-plane) oriented multiple quantum well (MQW) heterostructures simultaneously deposited under the same experimental conditions on core n-GaN nanowires (NWs) were investigated in this study. The core–shell-type InGaN/GaN MQW/n-GaN heterostructure NWs were grown on Si(111) substrates via the metalorganic chemical vapor deposition technique. We characterized these MQW NW heterostructures and discussed the comparative analyses of the formation of m-plane and r-plane oriented NW structures. Temperature-dependent photoluminescence (PL) measurements showed a distinct InGaN well structure emission wavelength at the m- and r-plane regions owing to the variation of the In composition. Further, the polarization-induced effects of the MQW NW structure were investigated by using power-dependent cathodoluminescence (CL) measurements. The non-radiative recombination located at the defective interface between the m- and r-planes was correlated with the CL mapping image profile and was also evidenced by scanning transmission electron microscopy (STEM) observations. This investigation addresses the understanding of the formation of nonpolar and semipolar oriented MQW NWs and offers insightful details of the structural and optoelectronic characterization of these core–shell NWs.
Production and characterization of three monoclonal antibodies to Candida albicans proteins (1984)

Three monoclonal antibodies, designated A2C7, C2C7, and F19, were produced which recognize proteins from Candida albicans. All are of the immunoglobulin G1 heavy chain and kappa light chain class. A2C7 and C2C7 immunoprecipitated three proteins contained in a partially purified fraction (region A) of a mycelial cytoplasmic extract of C. albicans. The apparent molecular weights of these proteins are 120,000 (120K) to 135K, 44K to 52K, to 38K. Monoclonal antibody F19 was reactive with proteins of 42K, 43K, and 50K in immunoblotting experiments. F19 was also able to form a precipitin band in agarose gel with protein(s) contained in region A. Limited proteolytic digestion of the three proteins immunoprecipitated by A2C7 and C2C7 demonstrated that both monoclonal antibodies recognized the same three Candida proteins and that there exists a significant degree of relatedness in primary structure among the three proteins. Proteins with apparent molecular weights of 120K to 135K, 44K to 52K, and 35K to 38K that were immunoprecipitated by sera from two patients with invasive candidiasis and by the serum from a rabbit immunized against a 48K (44K to 52K) Candida protein were also analyzed by limited proteolysis. Patterns of peptide fragments generated by enzymatic digestion of these proteins showed that the proteins recognized by the monoclonal antibodies are the same proteins recognized by antibodies in the sera of patients during an invasive Candida infection and by antibodies in the serum of the immune rabbit.
Protein disulfide isomerase a multifunctional protein with multiple physiological roles (2014)

Protein disulfide isomerase (PDI), is a member of the thioredoxin superfamily of redox proteins. PDI has three catalytic activities including, thiol-disulfide oxireductase, disulfide isomerase and redox-dependent chaperone. Originally, PDI was identified in the lumen of the endoplasmic reticulum and subsequently detected at additional locations, such as cell surfaces and the cytosol. This review will provide an overview of the recent advances in relating the structural features of PDI to its multiple catalytic roles as well as its physiological and pathophysiological functions related to redox regulation and protein folding.
Requirement for Tumor Necrosis Factor-Receptor 2 in Alveolar Chemokine Expression Depends upon the Form of the Ligand (2005)

Respiratory virus infection evokes a potent T-cell response that may result in a considerable insult to the structural and functional integrity of the gas exchange units of the lung. Alveolar antigen recognition by CD8+ T lymphocytes results in significant injury that is critically dependent upon tumor necrosis factor (TNF)-alpha expressed by the CD8+ T cells and is largely dependent upon TNF-receptor 1 expression on the alveolar epithelial target cells. TNF-receptor 2 (TNF-R2)-deficient mice were used to demonstrate that CD8+ T-cell-mediated lung injury associated with clearance of experimental influenza requires TNF-R2 for full expression of immunopathology. In vitro analysis indicates that alveolar cell expression of TNF-R2 is critical in the induction of epithelial monocyte chemoattractant protein (MCP)-1 expression specifically in response to soluble TNF-alpha, suggesting an important role for this receptor in bystander lung injury. However, TNF-R2 was dispensable for induction of alveolar MCP-1 expression in response to transmembrane TNF-alpha expressed by antigen-specific CD8+ T cells, and the effects of the two receptors seem to be additive. Because TNF-R2 may be rapidly shed as part of feedback inhibition of bystander inflammation, this suggests a mechanism by which immunopathology in respiratory virus infection may be regulated and by which T-cell receptor-dependent TNF-alpha activity might bypass such negative regulation for contact-dependent antiviral activities.
Transaminase B from Escherichia coli : Quaternary Structure, Amino-Terminal Sequence, Substrate Specificity, and Absence of a Separate Valine-α-Ketoglutarate Activity (1979)

Transaminase B (branched-chain amino acid aminotransferase, EC 2.6.1.42), the ilvE gene product, was purified to apparent homogeneity from an Escherichia coli K-12 strain which carries the ilvE gene both on the host chromosome and on a plasmid. The oligomeric structure of the enzyme, as determined by analytical ultracentrifugation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was confirmed to be that of a hexamer with a molecular weight of about 182,000 and apparently identical subunits. Cross-linking with dimethylsuberimidate yielded trimers, dimers, and monomers, but essentially no species of higher molecular weight. These results are consistent with a double-trimer arrangement of the subunits in native enzyme. The amino-terminal sequence was found to be: Gly Thr Lys Lys Ala Asp Tyr Ile (Trp) Phe Asn Gly (Thr) (Met) Val. Purified transaminase B catalyzed transamination between alpha-ketoglutarate and l-isoleucine, l-leucine, l-valine, and, to a lesser extent, l-phenylalanine and l-tyrosine, the latter reacting very sluggishly. The enzyme was free of aspartate transaminase and of transaminase C. The apparent K(m) values for the branched-chain alpha-ketoacids were smaller than those for the corresponding amino acids. The lowest K(m) was recorded for dl-alpha-keto-beta-methyl-n-valerate, and the highest was recorded for l-valine. The ratio of the valine- and isoleucine-alpha-ketoglutarate activities did not change significantly during purification, and both activities were quantitatively removed from crude extract by antibody raised against purified transaminase B. These observations argue against the existence of a separate valine-alpha-ketoglutarate transaminase. Anti-E. coli transaminase B antibody cross-reacted with crude extract from Salmonella typhimurium, but not with extract obtained from Pseudomonas aeruginosa.
Burden of Disease—Implications for Future Research (2001)

One overall challenge for public health and medicine in the future is to allocate available resources effectively to reduce major causes of disease burden globally and to decrease health disparities between poor and affluent populations. The major risk factors for death and disability worldwide are malnutrition; poor water supply, sanitation, and personal and domestic hygiene; unsafe sexual behavior; tobacco use; alcohol use; occupational hazards; hypertension; physical inactivity; illicit drugs; and air pollution. The challenge for research in the 21st century is to maintain and improve life expectancy and the quality of life that was achieved for most of the world's population during the 20th century.
A New Synthesis of the Potent 5-HT1Receptor Ligand, 5-Carboxyamidotryptamine (5-CT) (1993)

Abstract A short, convenient and relatively efficient synthesis of 5-CT is developed through a modified Michael reaction. This method represents a new general synthesis for tryptamines with labile indole substituents.
Induction of growth factor RNA expression in human malignant melanoma: markers of transformation. (1991)

Alteration in the expression of growth factors is widely accepted as being one of several critical defects in the generation of the malignant cell. In the present study, 19 human metastatic melanoma cell lines were compared to 14 normal human foreskin melanocyte cell lines for the production of RNA transcripts specific for 11 different growth factors. Using the extremely sensitive technique of polymerase chain reaction to amplify growth factor-specific complementary DNAs, we analyzed the following: transforming growth factor (TGF) types alpha, beta 1, beta 2, and beta 3, acidic (a) fibroblast growth factor (FGF), basic (b) FGF, FGF-5, keratinocyte growth factor (KGF), HST, and platelet-derived growth factor (PDGF) types A and B. There were clear distinctions among the patterns of growth factor RNA expression by normal melanocytes and malignant melanoma cells. The prototypic melanocyte pattern of expression included TGF beta 1, TGF beta 3, and KGF. A subset of melanocyte cell lines also expressed PDGFA transcripts. In contrast, melanoma cells characteristically expressed RNA transcripts of TGF beta 1, TGF beta 2, TGF beta 3, TGF alpha, bFGF, KGF, and PDGFA. Subsets of melanoma cell lines also expressed aFGF, FGF-5, and PDGFB. The results presented indicated that TGF beta 2, TGF alpha, and bFGF may be particularly important in melanomagenesis and that these, as well as FGF-5, aFGF, and PDGFB, can be used as markers of transformation in this tumor type.
Cross-Reactive Influenza-Specific Antibody-Dependent Cellular Cytotoxicity Antibodies in the Absence of Neutralizing Antibodies (2013)

A better understanding of immunity to influenza virus is needed to generate cross-protective vaccines. Engagement of Ab-dependent cellular cytotoxicity (ADCC) Abs by NK cells leads to killing of virus-infected cells and secretion of antiviral cytokines and chemokines. ADCC Abs may target more conserved influenza virus Ags compared with neutralizing Abs. There has been minimal interest in influenza-specific ADCC in recent decades. In this study, we developed novel assays to assess the specificity and function of influenza-specific ADCC Abs. We found that healthy influenza-seropositive young adults without detectable neutralizing Abs to the hemagglutinin of the 1968 H3N2 influenza strain (A/Aichi/2/1968) almost always had ADCC Abs that triggered NK cell activation and in vitro elimination of influenza-infected human blood and respiratory epithelial cells. Furthermore, we detected ADCC in the absence of neutralization to both the recent H1N1 pandemic strain (A/California/04/2009) as well as the avian H5N1 influenza hemagglutinin (A/Anhui/01/2005). We conclude that there is a remarkable degree of cross-reactivity of influenza-specific ADCC Abs in seropositive humans. Targeting cross-reactive influenza-specific ADCC epitopes by vaccination could lead to improved influenza vaccines.
Platinum-Iridium Alloys as Oxygen Reduction Electrocatalysts for Polymer Electrolyte Fuel Cells (2005)

Platinum-iridium (Pt-Ir) alloy electrocatalysts for polymer electrolyte fuel cell (PEFC) cathodes were prepared, and their physical and electrochemical properties were examined. A variety of unsupported Pt-Ir alloy catalysts was prepared in hot KOH solution, and the obtained Pt-Ir alloy catalysts were aggregates of fine particles ; the structure of the alloy was a uniform solid solution phase between Pt and Ir. Evaluation of the activity for the oxygen reduction reaction (ORR) was performed by both the rotating disk electrode (RDE) method in 0.1 M solution and determination of the specific activity during PEFC single-cell operations. The ORR kinetic analysis by the RDE showed that alloying Pt with Ir, especially with 5-20 wt % Ir, enhanced the catalytic activity for the ORR by a factor of more than 1.5 at 0.8 V vs RHE. The relationship between the specific current density and Ir content under PEFC operating conditions also showed enhanced ORR activity at 5-20 wt % Ir, which was consistent with the RDE results.
Towards Better Brain Management: Nootropics (2006)

The learning and memory deficits have been recognized as severe and consistent neurological disorders associated with numerous neurodegenerative states. Research in this area has gained momentum only in the recent past after the biochemical and physiological basis of these processes have been understood. A considerable alteration in the neurotransmission is a consistent finding in cognitive disorders. Therefore, many therapeutic strategies to augment the concentration of neurotransmitters in brain such as cholinergic agents, biogenic amines and neuropeptides etc. have been evaluated in cognitive deficits. CNS modulators are the type of antiamnesics that act via modulation of the neurological processes underlying memory storage. These include psychostimulants, excitatory amino acids and most important of all "nootropics". Nootropics are a heterogeneous group of compounds of diverse chemical composition and biological function that allegedly facilitate learning and memory or overcome natural or induced cognitive impairments. The literature survey incorporated in this article hallmarks the success achieved in the design and development of potential nootropic agents. Additionally, this review is an attempt towards discussing various approaches available to enhance memory, along with the classification of the known memory enhancers, authors research work towards various structural modifications carried out and the biological screening.
Antisense of human peroxiredoxin II enhances radiation-induced cell death. (2000)

Human peroxiredoxin II (Prx II) has been known to function as an antioxidant enzyme in cells. Using head-and-neck cancer cell lines, we investigated whether Prx II expression is related to the resistance of cells to radiation therapy in vivo and in vitro, and whether a Prx II antisense serves as a radiosensitizer. Increased expression of Prx II was observed in tissues isolated from the patients who did not respond to radiation therapy, whereas Prx II expression was weak in tissues from the patients with regressed tumors. Enhanced expression of Prx II in UMSCC-11A (11A) cells was also observed after treatment with gamma radiation. This increased expression conferred radiation resistance to cancer cells because overexpression of Prx II protected 11A cells from radiation-induced cell death, suggesting that blocking Prx II expression could enhance radiation sensitivity. Treatment of 11A cells with a Prx II antisense decreased induction of Prx II, enhancing the radiation sensitivity. From these results, we suggest that stress-induced overexpression of Prx II increases radiation resistance via protection of cancer cells from radiation-induced oxidative cytolysis and that a Prx II antisense can be used as a radiosensitizer.