gebhart/patrepeval huggingface dataset:
Cleavage of the antithrombin III binding site in heparin by heparinases and its implication in the generation of low molecular weight heparin (2000)

Heparin has been used as a clinical anticoagulant for more than 50 years, making it one of the most effective pharmacological agents known. Much of heparin's activity can be traced to its ability to bind antithrombin III (AT-III). Low molecular weight heparin (LMWH), derived from heparin by its controlled breakdown, maintains much of the antithrombotic activity of heparin without many of the serious side effects. The clinical significance of LMWH has highlighted the need to understand and develop chemical or enzymatic means to generate it. The primary enzymatic tools used for the production of LMWH are the heparinases from Flavobacterium heparinum, specifically heparinases I and II. Using pentasaccharide and hexasaccharide model compounds, we show that heparinases I and II, but not heparinase III, cleave the AT-III binding site, leaving only a partially intact site. Furthermore, we show herein that glucosamine 3-O sulfation at the reducing end of a glycosidic linkage imparts resistance to heparinase I, II, and III cleavage. Finally, we examine the biological and pharmacological consequences of a heparin oligosaccharide that contains only a partial AT-III binding site. We show that such an oligosaccharide lacks some of the functional attributes of heparin- and heparan sulfate-like glycosaminoglycans containing an intact AT-III site.
Label-free and live cell imaging by interferometric scattering microscopy (2018)

Despite recent remarkable advances in microscopic techniques, it still remains very challenging to directly observe the complex structure of cytoplasmic organelles in live cells without a fluorescent label. Here we report label-free and live-cell imaging of mammalian cell, <i>Escherischia coli</i>, and yeast, using interferometric scattering microscopy, which reveals the underlying structures of a variety of cytoplasmic organelles as well as the underside structure of the cells. The contact areas of the cells attached onto a glass substrate, <i>e.g.</i>, focal adhesions and filopodia, are clearly discernible. We also found a variety of fringe-like features in the cytoplasmic area, which may reflect the folded structures of cytoplasmic organelles. We thus anticipate that the label-free interferometric scattering microscopy can be used as a powerful tool to shed interferometric light on <i>in vivo</i> structures and dynamics of various intracellular phenomena.
Engineered secreted T-cell receptor alpha beta heterodimers. (1991)

We have produced a soluble form of a mouse alpha beta T-cell antigen receptor (TCR) by shuffling its variable (V) and constant (C) domains to the C region of an immunoglobulin kappa light chain. These chimeric molecules composed of V alpha C alpha C kappa and V beta C beta C kappa chains were efficiently secreted (up to 1 micrograms/ml) by transfected myeloma cells as noncovalent heterodimers of about 95-kDa molecular mass. In the absence of direct binding measurement, we have refined the epitopic analysis of the soluble V alpha C alpha C kappa-V beta C beta C kappa dimers and shown that they react with an anti-clonotypic antibody and two antibodies directed to the C domain of the TCR alpha and beta chains. Conversely, we have raised three distinct monoclonal antibodies against the soluble TCR heterodimers and shown that they recognize surface-expressed TCRs. Two of these antibodies were found to react specifically with the products of the V alpha 2 (V delta 8) and V beta 2 gene segments, respectively. When considered together, these data suggest that these soluble TCR molecules are folded in a conformation indistinguishable from that which they assume at the cell surface.
Excretory-Secretory Products Secreted by <i>Paragonimus westermani</i> Delay the Spontaneous Cell Death of Human Eosinophils through Autocrine Production of GM-CSF (2003)

These results suggest that the proteases in the ESP secreted by PwNEM are able to regulate eosinophil survival through the autocrine production of GM-CSF. Thus, the enhanced eosinophil survival induced by Paragonimus-secreted products may contribute to the elicitation of eosinophilic inflammatory responses at the worm-infected lesion in human paragonimiasis.
Synthesis of Poly (2,2′‐(1,4‐phenylene) 5,5′‐bibenzimidazole) (para‐PBI) and Phosphoric Acid Doped Membrane for Fuel Cells (2009)

Abstract A detailed investigation of the polymerisation conditions for poly(2,2′‐(1,4‐phenylene)5,5′‐bibenzimidazole) ( para ‐PBI) in polyphosphoric acid (PPA) led to the preparation of high molecular weight polymer. The polymer solutions could be used directly to produce phosphoric acid (PA)‐doped PBI membranes by the PPA process. These membranes showed very high PA doping levels, i.e., up to ∼30 moles of PA per mole of PBI repeat unit. The ionic conductivity of the membranes was 0.24 S cm –1 at 160 °C. Fuel cell performance was measured at various operating conditions by changing temperature, pressure and gases and verified the high carbon monoxide (CO) tolerance of fuel cells operating at this temperature.
Molybdenum and Tungsten Monoalkoxide Pyrrolide (MAP) Alkylidene Complexes That Contain a 2,6-Dimesitylphenylimido Ligand (2013)

Molybdenum and tungsten bispyrrolide alkylidene complexes that contain a 2,6-dimesitylphenylimido (NAr*) ligand have been prepared, in which the pyrrolide is the parent pyrrolide or 2,5-dimethylpyrrolide. Monoalkoxide pyrrolide (MAP) complexes were prepared through addition of 1 equiv of an alcohol to the bispyrrolide complexes. MAP compounds that contain the parent pyrrolide (NC4H4–) are pyridine adducts, while those that contain 2,5-dimethylpyrrolide are pyridine free. Molybdenum and tungsten MAP 2,5-dimethylpyrrolide complexes that contain O-t-Bu, OCMe(CF3)2, or O-2,6-Me2C6H3 ligands were found to have approximately equal amounts of syn and anti alkylidene isomers, which allowed a study of the interconversion of the two employing 1H–1H EXSY methods. The Keq values ([syn]/[anti]) are all 2–3 orders of magnitude smaller than those observed for a large number of Mo bisalkoxide imido alkylidene complexes, as a consequence of the destabilization of the syn isomer by the sterically demanding NAr* ligand. The rates of interconversion of syn and anti isomers were found to be 1–2 orders of magnitude faster for W MAP complexes than for Mo MAP complexes.
Effects of DX-9065a, an Inhibitor of Factor Xa, on Ellagic Acid-Induced Plantar Skin Thrombosis Assessed in Tetrodotoxin- and Nω-Nitro-L-Arginine-Treated Rats (2003)

Effects of DX-9065a ((+)-2S-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-[7-amidino-2-naphthyl]propanoic acid hydrochloride pentahydrate), a dibasic propanoic acid and an inhibitor of factor Xa, were compared with those of argatroban, a low molecular weight thrombin inhibitor, on the ellagic acid-induced plantar skin thrombosis in the rats treated with tetrodotoxin and Nω-nitro-L-arginine. Plantar skin blood flow was measured with laser Doppler flow meters, and skin temperature of the hindlimb was monitored simultaneously. In order to induce thrombus in plantar skin vasculature, ellagic acid (300 μg, i.a.) was injected into a branch of femoral artery. The formation of thrombus in femoral and plantar vessels was assessed by light microscopy. Ellagic acid decreased plantar skin blood flow and skin temperature. Intravenous injections of DX-9065a (3 mg/kg) and argatroban (1 – 3 mg/kg) significantly inhibited the ellagic acid-induced disturbance of plantar skin blood flow and lowering skin temperature without affecting bleeding time. The oral administration of DX-9065a (30 – 100 mg/kg) significantly prevented the decrease in skin temperature induced by ellagic acid, but it partially inhibited the disturbance of plantar skin blood flow. DX-9065a and argatroban also prolonged prothrombin time in a dose-dependent manner. These results suggest that DX-9065a effectively prevented thrombosis produced by ellagic acid in the skin circulation without a risk of bleeding.
A tetrameric perylene diimide non-fullerene acceptor via unprecedented direct (hetero)arylation cross-coupling reactions (2018)

This study reports on the synthesis of an indancenodithiophene perylene diimide tetramer via unique direct (hetero)arylation reactivity. The thiophene based core structure is shown to be easily functionalized with four perylene diimides at the four active C-H positions. This new reactivity provides a simple synthetic pathway towards tetrameric perylene diimides which have emerged as one of the best classes of electron acceptors for organic solar cells.
GPR expression in the rat taste bud relating to fatty acid sensing (2007)

We investigated the expression of G protein-coupled receptor GPR40 and GPR120 in the rat tongue. Using reverse transcription polymerase chain reaction, we detected a significant expression of GPR120 mRNA in the epithelium of the circumvallate papillae but not in the nonsensory epithelium, while the expression of GPR40 mRNA was undetectable in the sensory papillae. Western blotting analysis of colon and circumvallate papillae for GPR120 showed a protein band with a molecular weight that corresponds to that of GPR120, indicating that this antibody could recognize a native form of GPR120. Immunohistochemistry using anti-GPR120 antibody revealed GPR120 immunoreactivity in the enteroendocrine cells of the colon. Furthermore, some cells in each taste bud were stained positively with more intense labeling in the apical part of the cells. These results suggested that GPR120 is expressed in the taste cells of the circumvallate papillae to sense dietary fat, like the receptor expressed in the enteroendocrine cells.
Pharmacokinetics and pharmacodynamics of recombinant factor VIIa (1994)

The pharmacokinetics of rFVIIa are linear in the dose range evaluated. The results suggest potential value of prothrombin time determination in the monitoring of rFVIIa therapy.
The phylogenetic relationships of cyanobacteria inferred from 16S rRNA, gyrB, rpoC1 and rpoD1 gene sequences. (2003)

Phylogenetic analysis of cyanobacteria was carried out using the small subunit rRNA (16S rRNA), DNA gyrase subunit B (gyrB), DNA-dependent RNA polymerase gamma subunit (rpoC1) and a principal sigma factor of E. coli sigma(70) type for DNA-dependent RNA polymerase (rpoD1) gene sequences of 24 strains which contained 5 subgroups of cyanobacteria-3 strains of the Chroococcales, 5 strains of the Pluerocapsales, 7 strains of the Oscillatoriales, 7 strains of the Nostocales and 2 strains of the Stigonematales. Degenerated PCR primers of gyrB, rpoC1 and rpoD1 genes were designed using consensus amino acid sequences registered in GenBank. The phylogenetic positions of cyanobacteria were resolved through phylogenetic analysis based on 16S rDNA, gyrB, rpoC1 and rpoD1 gene sequences. Phylogenies of gyrB, rpoC1 and rpoD1 support 16S rRNA-based classification of cyanobacteria. Interestingly, phylogenies from amino acid sequences deduced from gyrB and combined amino acid sequences deduced from rpoC1 and rpoD1 genes strongly support that of 16S rRNA, but the branching pattens of the trees based on 16S rDNA, GyrB, rpoC1, rpoD1 and combined amino acid sequences deduced from rpoC1 and rpoD1 were not congruent. In this study, we showed the correlation among phylogenetic relationships of 16S rDNA, gyrB, rpoC1 and rpoD1 genes. The phylogenetic trees based on the sequences of 16S rDNA, GyrB, rpoC1, rpoD1 and the combined amino acid sequences deduced from rpoC1 and rpoD1 showed that the lateral gene transfer of rRNA might be suspected for Synechocystis sp. PCC 6803.
Pharmacological PKA Inhibition: All May Not Be What It Seems (2008)

Signaling through the cyclic adenosine monophosphate-dependent protein kinase [protein kinase A (PKA)] is an important and widely studied area of signal transduction research. This signaling pathway is commonly investigated through the use of the pharmacological PKA inhibitors H89 and KT 5720. Both of these compounds are thought to block PKA actions through competitive inhibition of the adenosine triphosphate site on the PKA catalytic subunit. Recently, a number of studies have identified actions of H89 and KT 5720 that are independent of their effects on PKA. These nonspecific effects are widespread; they include actions on other protein kinases and signaling molecules and also on basic cellular functions, such as transcription. Here, I summarize the nonspecific effects of these two compounds and compare their actions with those of other PKA inhibitors.
The complete amino acid sequence of hirudin, a thrombin specific inhibitor (1984)

Color carboxymethylation of cysteine residues with a new chromophoric reagent dimethylaminoazobenzene iodoacetamide, was applied to the micro‐sequence analysis of hirudin, a thrombin specific inhibitor. Six cysteine residues of the reduced hirudin were detected as colored phenylthiohydantoin derivative and 3 tryptic peptides of hirudin (all containing cysteines) were isolated as colored peptide. The complete hirudin sequence, including 6 uncertain positions left in the previous report [Petersen T.E. (1976) in: Protides of the Biological Fluids; 23rd Colloquium, pp. 145, Pergamon Press, London] was established.
Immunogenicity And Safety Of A Live Attenuated Varicella Vaccine (Oka/Sb Bio) In Healthy Children (1996)

An Oka strain varicella vaccine developed by SmithKline Beecham Biologicals in the early 1980s is registered for immunization of high-risk groups in nine European countries. Because the preparation must be stored at -20 degrees C, it was reformulated to facilitate its use for general vaccination in healthy children with storage at 2-8 degrees C for 2 years. Studies using production lots of the reformulated vaccine in approximately 1400 healthy children are summarized. During the 42-day follow-up, no vaccine-related serious adverse events were reported. Unsolicited reactogenicity rates were low: 14.2% in children ages 9-36 months (the main target age group for the vaccine). Seroconversion rates were 98.6% after a single dose. Consistent reactogenicity and immunogenicity were observed across vaccine lots. After efficacy is demonstrated in other studies, widespread use of this vaccine will prevent a common and potentially serious childhood illness.
Altering the Genome by Homologous Recombination (1989)

Homologous recombination between DNA sequences residing in the chromosome and newly introduced, cloned DNA sequences (gene targeting) allows the transfer of any modification of the cloned gene into the genome of a living cell. This article discusses the current status of gene targeting with particular emphasis on germ line modification of the mouse genome, and describes the different methods so far employed to identify those rare embryonic stem cells in which the desired targeting event has occurred.
Quantifying single nucleotide variant detection sensitivity in exome sequencing (2013)

Non-reference alleles in the heterozygote state have a high chance of being missed when commonly applied read coverage thresholds are used despite the widely held assumption that there is good polymorphism detection at these coverage levels. Such alleles are likely to be of functional importance in population based studies of rare diseases, somatic mutations in cancer and explaining the "missing heritability" of quantitative traits.
Evolution of Switching Characteristics from Tristable to V-Shaped in an Apparently Antiferroelectric Liquid Crystal (1997)

We have identified three smectic phases, smectic A, ferrielectric and antiferroelectric, in a free-standing film of the first component compound of the mixture which was reported to show the V-shaped switching usable for realizing attractive displays [Inui et al. .: J. Mater. Chem. 6 (1996) 671]. The switching in the antiferroelectric phase, observed by applying a triangular waveform electric field to a homogeneous cell, evolves from tristable to V-shaped with increasing temperature and frequency; the V-shaped switching occurs uniformly without accompanying any domain boundary movement. The results have been discussed in terms of thresholdless antiferroelectricity in liquid crystals.
Microbial Communities Associated with Anaerobic Benzene Degradation in a Petroleum-Contaminated Aquifer (1999)

Microbial community composition associated with benzene oxidation under in situ Fe(III)-reducing conditions in a petroleum-contaminated aquifer located in Bemidji, Minn., was investigated. Community structure associated with benzene degradation was compared to sediment communities that did not anaerobically oxidize benzene which were obtained from two adjacent Fe(III)-reducing sites and from methanogenic and uncontaminated zones. Denaturing gradient gel electrophoresis of 16S rDNA sequences amplified with bacterial or Geobacteraceae-specific primers indicated significant differences in the composition of the microbial communities at the different sites. Most notable was a selective enrichment of microorganisms in the Geobacter cluster seen in the benzene-degrading sediments. This finding was in accordance with phospholipid fatty acid analysis and most-probable-number-PCR enumeration, which indicated that members of the family Geobacteraceae were more numerous in these sediments. A benzene-oxidizing Fe(III)-reducing enrichment culture was established from benzene-degrading sediments and contained an organism closely related to the uncultivated Geobacter spp. This genus contains the only known organisms that can oxidize aromatic compounds with the reduction of Fe(III). Sequences closely related to the Fe(III) reducer Geothrix fermentans and the aerobe Variovorax paradoxus were also amplified from the benzene-degrading enrichment and were present in the benzene-degrading sediments. However, neither G. fermentans nor V. paradoxus is known to oxidize aromatic compounds with the reduction of Fe(III), and there was no apparent enrichment of these organisms in the benzene-degrading sediments. These results suggest that Geobacter spp. play an important role in the anaerobic oxidation of benzene in the Bemidji aquifer and that molecular community analysis may be a powerful tool for predicting a site's capacity for anaerobic benzene degradation.
Single-injection HPLC analysis of acids, sugars, and alcohols in cucumber fermentations (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSingle-injection HPLC analysis of acids, sugars, and alcohols in cucumber fermentationsRoger F. McFeetersCite this: J. Agric. Food Chem. 1993, 41, 9, 1439–1443Publication Date (Print):September 1, 1993Publication History Published online1 May 2002Published inissue 1 September 1993https://doi.org/10.1021/jf00033a016RIGHTS & PERMISSIONSArticle Views991Altmetric-Citations38LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (583 KB) Get e-Alerts Get e-Alerts
Synthesis and analysis of the membrane proximal external region epitopes of HIV‐1 (2010)

The membrane proximal external region (MPER) of gp41 abuts the viral membrane at the base of HIV-1 envelope glycoprotein spikes. The MPER is highly conserved and is rich in Trp and other lipophilic residues. The MPER is also required for the infection of host cells by HIV-1 and is the target of the broadly neutralizing antibodies, 4E10, 2F5, and Z13e1. These neutralizing antibodies are valuable tools for understanding relevant conformations of the MPER and for studying HIV-1 neutralization, but multiple approaches used to elicit MPER binding antibodies with similar neutralization properties have failed. Here we report our efforts to mimic the MPER using linear as well as constrained peptides. Unnatural amino acids were also introduced into the core epitope of 4E10 to probe requirements of antibody binding. Peptide analogs with C-terminal Api or Aib residues designed to be helical transmembrane (TM) domain surrogates exhibit enhanced binding to the 4E10 and Z13e1 antibodies. However, we find that placement of constrained amino acids at nonbinding sites within the core epitope significantly reduce binding. These results are relevant to an understanding of native MPER structure on HIV-1, and form a basis for a chemical synthesis approach to mimic MPER stricture and to construct an MPER-based vaccine.
Crystal structures of the apo form of β‐fructofuranosidase from Bifidobacterium longum and its complex with fructose (2011)

We solved the 1.8 Å crystal structure of β-fructofuranosidase from Bifidobacterium longum KN29.1 - a unique enzyme that allows these probiotic bacteria to function in the human digestive system. The sequence of β-fructofuranosidase classifies it as belonging to the glycoside hydrolase family 32 (GH32). GH32 enzymes show a wide range of substrate specificity and different functions in various organisms. All enzymes from this family share a similar fold, containing two domains: an N-terminal five-bladed β-propeller and a C-terminal β-sandwich module. The active site is located in the centre of the β-propeller domain, in the bottom of a 'funnel'. The binding site, -1, responsible for tight fructose binding, is highly conserved among the GH32 enzymes. Bifidobacterium longum KN29.1 β-fructofuranosidase has a 35-residue elongation of the N-terminus containing a five-turn α-helix, which distinguishes it from the other known members of the GH32 family. This new structural element could be one of the functional modifications of the enzyme that allows the bacteria to act in a human digestive system. We also solved the 1.8 Å crystal structure of the β-fructofuranosidase complex with β-D-fructose, a hydrolysis product obtained by soaking apo crystal in raffinose.
Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. (1994)

An aggressive smoking intervention program significantly reduces the age-related decline in FEV1 in middle-aged smokers with mild airways obstruction. Use of an inhaled anticholinergic bronchodilator results in a relatively small improvement in FEV1 that appears to be reversed after the drug is discontinued. Use of the bronchodilator did not influence the long-term decline of FEV1.
Carotid plaque assessment using fast 3D isotropic resolution black‐blood MRI (2010)

Black-blood MRI is a promising tool for carotid atherosclerotic plaque burden assessment and compositional analysis. However, current sequences are limited by large slice thickness. Accuracy of measurement can be improved by moving to isotropic imaging but can be challenging for patient compliance due to long scan times. We present a fast isotropic high spatial resolution (0.7×0.7×0.7 mm3) three-dimensional black-blood sequence (3D-MERGE) covering the entire cervical carotid arteries within 2 min thus ensuring patient compliance and diagnostic image quality. The sequence is optimized for vessel wall imaging of the carotid bifurcation based on its signal properties. The optimized sequence is validated on patients with significant carotid plaque. Quantitative plaque morphology measurements and signal-to-noise ratio measures show that 3D-MERGE provides good blood suppression and comparable plaque burden measurements to existing MRI protocols. 3D-MERGE is a promising new tool for fast and accurate plaque burden assessment in patients with atherosclerotic plaque.