gebhart/patrepeval huggingface dataset:
Backbone Dynamics of a Domain of Protein L Which Binds to Immunoglobulin Light Chains (1996)

Protein L is a multidomain protein expressed at the surface of some strains of the anaerobic bacterial species Peptostreptococcus magnus. The molecule interacts with the variable domain of immunoglobulin (Ig) light chains through five repeated homologous domains denoted B1 to B5. The fold of the Ig‐light‐chain‐binding B1 domain of protein L (PLB1) has been shown to comprise an α‐helix packed against a four‐stranded β‐sheet and therefore resembles the structure of the IgG‐binding domains of streptococcal protein G. In the present study, amide‐proton exchange and 15 N‐relaxation NMR measurements were performed on the B1 domain to investigate its backbone mobility. It was shown that the folded portion of PLB1 is rigid with no regions of significantly higher flexibility than average. The N‐terminus, however, is highly flexible consistent with earlier studies on the solution structure of PLB1. Comparison of the amide‐proton‐exchange data with similar measurements performed on the IgG‐binding domains of protein G indicates that the two proteins have different exchange behaviors in heir second β‐strands. Both protein G and L employ this region of their structures for binding to immunoglobulins since the interaction of protein G and protein L with IgG Fab and the Ig light chain, respectively, involves residues from the second β‐strand.
Malonyl coenzyme A synthetase. Purification and properties. (1985)

Malonyl coenzyme A synthetase (EC 6.2.1.14) was induced in Pseudomonas fluorescens grown on malonate as a sole carbon source. This enzyme was purified, for the first time, over 30-fold by the combination of ammonium sulfate precipitation, Sephadex G-150 gel filtration, DEAE-Sephacel ion exchange chromatography, and hydroxylapatite chromatography. The purified enzyme, which had a specific activity of about 0.512 mumol/min/mg, appeared to be electrophoretically homogeneous. The molecular size of the enzyme was determined to be 98,000 Da which is composed of two 49,000-Da subunits. The optimum pH for the enzyme was 7.5. Malonyl coenzyme A synthetase requires ATP, CoA, and Mg2+ for the full enzyme activity. With succinate or acetate, the synthetic rate of CoA derivative was 40% of that observed with malonate. The malonyl coenzyme A synthetase showed typical Michaelis-Menten kinetics for the substrate, malonate, ATP, and coenzyme A, from which the Km values were calculated to be 3.8 X 10(-4) M, 2 X 10(-3) M, and 10(-4) M and Vmax values to be 0.117 mumol/min/mg, 0.111 mumol/min/mg, and 0.142 mumol/min/mg, respectively. The purified malonyl coenzyme A synthetase was immunogenic in the rabbit and Ouchterlony double diffusion analysis revealed a single precipitant line with the enzyme. The antiserum inhibited the enzyme activity and the extent of inhibition was dependent on the amount of the serum added.
Increased expression of fibroblast growth factors (FGFs) and their receptor by protamine and suramin on Kaposi's sarcoma-derived cells. (1993)

Growth factors, such as bFGF, have been shown to exert autocrine and paracrine effects on the growth of Kaposi's Sarcoma (KS)-derived cells, which suggested that the inhibitors of angiogenesis may be promising for KS treatment. However, KS lesions have been found to continue to enlarge after patients had been treated with FGF binding antagonists such as suramin. We investigated the effect of protamine and suramine on the growth of KS derived cells in vitro. Although both of these agents which are FGF binding antagonists were found to inhibit the incorporation of 3H thymidine in KS-derived cultured cells, increased expression of bFGF, FGF5 and the FGF receptor was observed after the KS cells were exposed to these substances. These results might explain the clinical observation that FGF binding antagonists such as suramin caused an apparent stimulation of KS tumor growth when administered systemically to patients with AIDS-related KS.
Structural Basis of Enantioselective Inhibition of Cyclooxygenase-1 by S-α-Substituted Indomethacin Ethanolamides (2007)

The modification of the nonselective nonsteroidal anti-inflammatory drug, indomethacin, by amidation presents a promising strategy for designing novel cyclooxygenase (COX)-2-selective inhibitors. A series of alpha-substituted indomethacin ethanolamides, which exist as R/S-enantiomeric pairs, provides a means to study the impact of stereochemistry on COX inhibition. Comparative studies revealed that the R- and S-enantiomers of the alpha-substituted analogs inhibit COX-2 with almost equal efficacy, whereas COX-1 is selectively inhibited by the S-enantiomers. Mutagenesis studies have not been able to identify residues that manifest the enantioselectivity in COX-1. In an effort to understand the structural impact of chirality on COX-1 selectivity, the crystal structures of ovine COX-1 in complexes with an enantiomeric pair of these indomethacin ethanolamides were determined at resolutions between 2.75 and 2.85 A. These structures reveal unique, enantiomer-selective interactions within the COX-1 side pocket region that stabilize drug binding and account for the chiral selectivity observed with the (S)-alpha-substituted indomethacin ethanolamides. Kinetic analysis of binding demonstrates that both inhibitors bind quickly utilizing a two-step mechanism. However, the second binding step is readily reversible for the R-enantiomer, whereas for the S-enantiomer, it is not. These studies establish for the first time the structural and kinetic basis of high affinity binding of a neutral inhibitor to COX-1 and demonstrate that the side pocket of COX-1, previously thought to be sterically inaccessible, can serve as a binding pocket for inhibitor association.
Sequences of Escherichia coli uvrA gene and protein reveal two potential ATP binding sites. (1986)

We have determined the nucleotide sequence of the uvrA gene of Escherichia coli. The coding region of the gene is 2820 base pairs which specifies a protein of 940 amino acids and Mr = 103,874. The polypeptide sequence predicted from the DNA sequence was confirmed by analyzing the UvrA protein: the sequence of the first 7 NH2-terminal amino acids as well as the amino acid composition of the pure protein agreed with those predicted from the nucleotide sequence. By comparing the sequence of UvrA protein to the amino acid sequences of other ATPases, we found that two regions in the UvrA protein, separated from one another by about 600 amino acids, have the highly conserved G-X4-GKT(S)-X6-I(V) sequence found at the active sites of many, but not all, ATPases. Our findings suggest that UvrA protein may have two ATP binding sites.
Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats (1998)

Recent evidence in vivo indicates that spontaneously hypertensive rats (SHR) exhibit an increase in oxyradical production in and around microvascular endothelium. This study is aimed to examine whether xanthine oxidase plays a role in overproduction of oxidants and thereby may contribute to hypertensive states as a consequence of the increasing microvascular tone. The xanthine oxidase activity in SHR was inhibited by dietary supplement of tungsten (0.7 g/kg) that depletes molybdenum as a cofactor for the enzyme activity as well as by administration of (-)BOF4272 [(-)-8-(3-methoxy-4-phenylsulfinylphenyl)pyrazolo(1,5-alpha)-1,3, 5-triazine-4-monohydrate], a synthetic inhibitor of the enzyme. The characteristic elevation of mean arterial pressure in SHR was normalized by the tungsten diet, whereas Wistar Koto (WKY) rats displayed no significant alteration in the pressure. Multifunctional intravital videomicroscopy in mesentery microvessels with hydroethidine, an oxidant-sensitive fluoroprobe, showed that SHR endothelium exhibited overproduction of oxyradicals that coincided with the elevated arteriolar tone as compared with WKY rats. The tungsten diet significantly repressed these changes toward the levels observed in WKY rats. The activity of oxyradical-producing form of xanthine oxidase in the mesenteric tissue of SHR was approximately 3-fold greater than that of WKY rats, and pretreatment with the tungsten diet eliminated detectable levels of the enzyme activity. The inhibitory effects of the tungsten diet on the increasing blood pressure and arteriolar tone in SHR were also reproducible by administration of (-)BOF4272. These results suggest that xanthine oxidase accounts for a putative source of oxyradical generation that is associated with an increasing arteriolar tone in this form of hypertension.
Opioids in the Management of ChronicNon-Cancer Pain: An Update of AmericanSociety of the Interventional Pain Physicians’(ASIPP) Guidelines (2008)

Opioids are commonly prescribed for chronic non-cancer pain and may be effective for short-term pain relief. However, long-term effectiveness of 6 months or longer is variable with evidence ranging from moderate for transdermal fentanyl and sustained-release morphine with a Level II-2, to limited for oxycodone with a Level II-3, and indeterminate for hydrocodone and methadone with a Level III. These guidelines included the evaluation of the evidence for the use of opioids in the management of chronic non-cancer pain and the recommendations for that management. These guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Because of the changing body of evidence, this document is not intended to be a "standard of care."
Photochemical Deamination and Demethylation of 5-Methylcytosine (1996)

Cytosine methylation is believed to play a pivotal role in eucaryotic cellular development as well as in viral latency. We have been investigating chemical mechanisms for the perturbation of methylation patterns, including the effects of ultraviolet radiation. We observed that, upon exposure to UV light, 5-methylcytosine (5mC) was converted to thymine, cytosine, and a series of 5-substituted cytosine derivatives as analyzed by gas chromatography/mass spectrometry. Deamination of 5mC to thymine proceeds via formation of the intermediate photohydrate. Formation of 5-substituted cytosine derivatives results from oxidation of the 5-methyl group with initial formation of 5-(hydroxymethyl)cytosine (hmC). Upon exposure to UV light, hmC is converted to cytosine. The conversion of hmC to cytosine likely results from photohydration and elimination of formaldehyde. It is proposed that endogenous oxidation and hydrolysis could result in demethylation of 5mC residues in DNA. Whereas hydrolytic deamination of 5mC to thymine has been widely discussed, demethylation of 5mC has not as yet been described.
The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA‐PCa‐2b and LuCaP‐35 prostate cancers (2007)

Our findings suggest that the use of a combination of antagonists of GHRH and LHRH could improve the therapy for androgen sensitive prostate cancer. Antagonists of GHRH could be also considered for treatment of androgen-independent prostate cancers.
The rate of early fetal growth in the human subject (1972)

Data from 354 embryos and fetuses between 20 and 200 mm crown rump length obtained by therapeutic abortion in 3 different countries were evaluated. All Danich and Hungarian and the majority of American specimens were measured immeditely after delivery in the fresh condition. In the mathematical evaluation linear regressions were calculated by the method of least squares for arbitrarily defined ranges to 20-50 mm and 50-200 mm crown rump lenghts. The material was analyzed statistically so that confidence limits could be drawn for the estimation of gestational age from crown rump length measurements. All data in the 20-50 mm range were combined, but beyond that fetal length the statistics for the Hungarian group were calculated separatley. The equation calculated to fit the data in the 20-50 mm rage is A = 46 + 0.71 L where A is gestational age in days and L is crown rump lenght in mm. The 95% confidence limits of regression are 0.57-0.83 days/mm and the correlation between gestational age and crown rump length is 0.65. Estimates of gestational age from sitting height measurements can be made + or - 15 days with 95% confidence. The equation for the combined Danish and American data in the range 50-200 mm is A = 64 + 0.41 L. The 95% confidence limits for the regression are 0.36-0.46 days mm and the correlation between gestational age and crown rump length is 0.70. Estimates of gestational age from crown rump length can be made + or - 26 days with 95% confidence. The data from the Hungarian study in the 50-200 mm sitting height range differ from those of the combined Danish and American material. The regression of days/mm (0.22) was significantly less at p. 01 level supporting the suspected bias in the Hungarian material, but the correlation between gestational age and crown rump length, 0.62, was not significantly less than that of the combined Danish and American data. Thus, if the difference in the slope was due to a bias, the bias was relatively consistent from patient to patient. Comparison of the results with those of Streeter (1920, 1951) indicates that the considerable discrepancy at the embryonic stages diminishes gradually in the fetal period and eventually becomes quite insignificant.
Angiotensin II-induced proliferation of aortic myocytes in spontaneously hypertensive rats (1990)

In order to determine whether the morphological modifications observed in arterial media of spontaneously hypertensive rats (SHR) could be induced by an abnormal response of the smooth muscle cells to vasoactive agents, we studied the action of angiotensin (Ang) II on cultured aortic smooth muscle cells from both SHR and Wistar-Kyoto rats (WKY). Under our experimental conditions, Ang II exerts a mitogenic action on SHR cells, whereas its effect is very weak on WKY cells. Phospholipase C activation and c-fos and c-myc proto-oncogene expressions induced by Ang II are considerably enhanced in SHR cells, and these abnormalities may be linked to an increased number of Ang II receptors.
Recombinant Mouse-Human Chimeric Antibodies as Calibrators in Immunoassays That Measure Antibodies toToxoplasma gondii (1998)

In the present study, we examined the feasibility of using recombinant antibodies containing murine variable regions and human constant regions as calibrators or controls in immunoassays. As a model system, we chose the Abbott IMx Toxo immunoglobulin M (IgM) and Toxo IgG assays designed to detect antibodies to Toxoplasma gondii. Two mouse monoclonal antibodies were selected based on their reactivity to the T. gondii antigens P30 and P66. Heavy- and light-chain variable-region genes were cloned from both hybridomas and transferred into immunoglobulin expression vectors containing human kappa and IgG1 or IgM constant regions. The constructs were stably transfected into Sp2/0-Ag14 cells. In the IMx Toxo IgG assay, immunoreactivity of the anti-P30 chimeric IgG1 antibody paralleled that of the positive human plasma-derived assay calibrators. Signal generated with the anti-P66 chimeric IgG1 antibody was observed to plateau below the maximal reactivity observed for the assay calibrator. Examination of the IgM chimeric antibodies in the IMx Toxo IgM assay revealed that both the anti-P30 and anti-P66 antibodies matched the assay index calibrator manufactured with human Toxo IgM-positive plasma. When evaluated with patient samples, the correlation between results obtained with the chimeric antibody calibrators and the positive human plasma calibrators was > or =0.985. These data demonstrate that chimeric mouse-human antibodies are a viable alternative to high-titer positive human plasma for the manufacture of calibrators and controls for diagnostic assays.
Tissue Engineering of the Cornea (2003)

Tissue engineering of the cornea represents a paradigm shift in medical treatment to overcome the present disadvantages of corneal transplantation, primarily immune rejection and the shortage of donor corneas. Transplantation of cultivated corneal epithelial cells expanded ex vivo from corneal epithelial stem cells has been developed and has already entered the clinical realm. However, there remain many hurdles to be overcome. The author and colleagues are developing a method to transplant cultivated cell sheets that uses a temperature-responsive culture dish. This article reviews the present situation regarding tissue-engineered corneal epithelium and introduces the results of this program of research.
Marketing Models (Маркетинговые модели) (1992)

A comprehensive, quantitative analysis of marketing models for marketing decisions. Всесторонний, количественный анализ моделей, используемых для принятия маркетинговых решений.
Comparative In Vitro Activities and Postantibiotic Effects of the Oxazolidinone Compounds Eperezolid (PNU-100592) and Linezolid (PNU-100766) versus Vancomycin against Staphylococcus aureus , Coagulase-Negative Staphylococci, Enterococcus faecalis , and Enterococcus faecium (1998)

The activities of the oxazolidinone antibacterial agents eperezolid (PNU-100592) and linezolid (PNU-100766) were compared with that of vancomycin against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus (n = 200), coagulase-negative staphylococci (n = 100), and vancomycin-susceptible and -resistant Enterococcus faecalis and Enterococcus faecium (n = 50). Eperezolid and linezolid demonstrated good in vitro inhibitory activity, regardless of methicillin susceptibility for staphylococci (MIC at which 90% of the isolates are inhibited [MIC90] range, 1 to 4 microg/ml) or vancomycin susceptibility for enterococci (MIC90 range, 1 to 4 microg/ml). In time-kill studies, eperezolid and linezolid were bacteriostatic in action. A postantibiotic effect of 0.8+/-0.5 h was demonstrated for both eperezolid and linezolid against S. aureus, S. epidermidis, E. faecalis, and E. faecium.
Experimental interrogation of the path dependence and stochasticity of protein evolution using phage-assisted continuous evolution (2013)

To what extent are evolutionary outcomes determined by a population's recent environment, and to what extent do they depend on historical contingency and random chance? Here we apply a unique experimental system to investigate evolutionary reproducibility and path dependence at the protein level. We combined phage-assisted continuous evolution with high-throughput sequencing to analyze evolving protein populations as they adapted to divergent and then convergent selection pressures over hundreds of generations. Independent populations of T7 RNA polymerase genes were subjected to one of two selection histories ("pathways") demanding recognition of distinct intermediate promoters followed by a common final promoter. We observed distinct classes of solutions with unequal phenotypic activity and evolutionary potential evolve from the two pathways, as well as from replicate populations exposed to identical selection conditions. Mutational analysis revealed specific epistatic interactions that explained the observed path dependence and irreproducibility. Our results reveal in molecular detail how protein adaptation to different environments, as well as stochasticity among populations evolved in the same environment, can both generate evolutionary outcomes that preclude subsequent convergence.
Predictive Torque Control - A solution for mono inverter-dual parallel PMSM system (2011)

The objective of this paper is to present a Predictive Torque Control (PTC) algorithm for controlling system composed by two Permanent Magnet Synchronous Motors (PMSM) operating in parallel, fed by a single power inverter. In this system, it is expected that both motors will get the same speed even if they have different conditions of load torque. The principle of PTC algorithm is considered as follows: a model of the system is used to predict the system behavior under a set of configurations of a power inverter, a cost function is built from the predicted values and their references and an optimal algorithm will be solved to find the best configuration to apply to the system in the next time step. Simulation results in Matlab/Simulink indicated that the algorithm (PTC) is well adapted for the synchronism of this system over a wide range of operations.
Single‐Face/All‐cis Arene Hydrogenation by a Supported Single‐Site d0 Organozirconium Catalyst (2016)

The single-site supported organozirconium catalyst Cp*ZrBz2 /ZrS (Cp*=Me5 C5 , Bz=benzyl, ZrS=sulfated zirconia) catalyzes the single-face/all-cis hydrogenation of a large series of alkylated and fused arene derivatives to the corresponding all-cis-cyclohexanes. Kinetic/mechanistic and DFT analysis argue that stereoselection involves rapid, sequential H2 delivery to a single catalyst-bound arene face, versus any competing intramolecular arene π-face interchange.
cDNA for Mo3, a monocyte activation antigen, encodes the human receptor for urokinase plasminogen activator (1992)

We have cloned the cDNA for Mo3, an activation Ag expressed by human monocytes and myelomonocytic cell lines after stimulation by PMA, LPS, muramyl dipeptide, certain cytokines, and cAMP agonists. We have previously shown that Mo3 expression in vivo is associated predominantly with macrophages in inflammatory sites. Mo3 is a highly glycosylated protein of about 50 kDa in monocytes and U-937 cells and is anchored to the plasma membrane by glycosyl-phosphatidylinositol linkage. We purified Mo3 protein by cleavage from the U-937 cell surface with phosphatidylinositol-specific phospholipase C, followed by affinity chromatography using a mAb. An internal peptide sequence was determined and used to design oligonucleotide probes for screening an expression cDNA library. Nucleotide sequencing indicated that the complete coding sequence encodes 335 amino acids, including a predicted signal peptide of 22 residues and a hydrophobic C-terminal portion that is probably cleaved during formation of the GPI linkage. The resulting mature protein of about 290 amino acids is consistent with the 29-kDa molecular mass of deglycosylated Mo3. A Northern blot of RNA from U-937 cells revealed a 1.5-kb band that was induced by PMA treatment. Mo3 cDNA was transfected into Cos cells and surface expression of Mo3 was detected by ELISA using various anti-Mo3 mAb. We performed a computer search of the National Biomedical Research Foundation database and found that Mo3 is identical to the human receptor for the urokinase plasminogen activator (uPA-R). Purified soluble Mo3, as well as anti-Mo3 antibodies, were able to block uPA binding to its receptor on U-937 cells, indicating that Mo3 is indeed uPA-R. The use of these anti-Mo3 antibodies may be helpful in assessing the role of uPA-R in processes such as inflammation and tumor invasion.
Neuron Loss in Transgenic Mouse Models of Alzheimer's Disease (2010)

Since their initial generation in the mid 1990s, transgenic mouse models of Alzheimers's disease (AD) have been proven to be valuable model systems which are indispensable for modern AD research. Whereas most of these models are characterized by extensive amyloid plaque pathology, inflammatory changes and often behavioral deficits, modeling of neuron loss was much less successful. The present paper discusses the current achievements of modeling neuron loss in transgenic mouse models based on APP/Aβ and Tau overexpression and provides an overview of currently available AD mouse models showing these pathological alterations.
Pragmatic, adaptive clinical trials: Is 2020 the dawning of a new age? (2020)

Given the high case fatality rate of SARS-CoV-2, for which there is no cure and no vaccine, clinicians are forced to make decisions about how best to manage patients with limited high-quality evidence to guide treatment. Traditional randomized controlled trials provide strong experimental evidence, however, tend to be slow, inflexible, and have limited generalizability. Adaptive and pragmatic designs are an attractive alternative, which meet our ethical obligation during the SARS-CoV-2 pandemic to balance speed, agility, and generalizability with both prospective study and scientific rigor.