gebhart/patrepeval huggingface dataset:
Binding of annexin V/placental anticoagulant protein I to platelets. Evidence for phosphatidylserine exposure in the procoagulant response of activated platelets. (1990)

Proteins of the annexin/lipocortin family act as in vitro anticoagulants by binding to anionic phospholipid vesicles. In this study, we investigated whether annexin V (placental anticoagulant protein I) would bind to human platelets. Annexin V bound to unstimulated platelets in a reversible, calcium-dependent reaction with an apparent Kd of 7 nM and 5000-8000 sites/platelet. Additional binding sites could be induced by several platelet agonists in the following order of effectiveness: A23187 greater than collagen + thrombin greater than collagen greater than thrombin. However, neither ADP nor epinephrine induced additional binding sites. Three other proteins of the annexin family (annexins II, III, and IV) competed for annexin V platelets binding sites with the same relative potencies previously observed for binding to phospholipid vesicles. Phospholipid vesicles containing phosphatidylserine completely inhibited binding of annexin V to platelets. Annexin V completely blocked binding of 125I-factor Xa to thrombin-stimulated platelets. These results support the hypothesis that phosphatidylserine exposure occurs during platelet activation and may be necessary for assembly of the prothrombinase complex on platelet membranes.
Immunochemical Properties of the Staphylococcal Poly- N -Acetylglucosamine Surface Polysaccharide (2002)

Staphylococcus aureus and Staphylococcus epidermidis often elaborate adherent biofilms, which contain the capsular polysaccharide-adhesin (PS/A) that mediates the initial cell adherence to biomaterials. Biofilm cells produce another antigen, termed polysaccharide intercellular adhesin (PIA), which is composed of a approximately 28 kDa soluble linear beta(1-6)-linked N-acetylglucosamine. We developed a new method to purify PS/A from S. aureus MN8m, a strain hyperproducing PS/A. Using multiple analytical techniques, we determined that the chemical structure of PS/A is also beta(1-6)-N-acetylglucosamine (PNAG). We were unable to find N-succinylglucosamine residues in any of our preparations in contrast to previously reported findings (D. McKenney, K. Pouliot, Y. Wang, V. Murthy, M. Ulrich, G. Doring, J. C. Lee, D. A Goldmann, and G. B. Pier, Science 284:1523-1527, 1999). PNAG was produced with a wide range of molecular masses that could be divided into three major fractions with average molecular masses of 460 kDa (PNAG-I), 100 kDa (PNAG-II), and 21 kDa (PNAG-III). The purified antigens were not soluble at neutral pH unless first dissolved in 5 M HCl and then neutralized with 5 M NaOH. PNAG-I was very immunogenic in rabbits, but the responses of individual animals were variable. Immunization of mice with various doses (100, 50, or 10 microg) of PNAG-I, -II, and -III demonstrated that only PNAG-I was able to elicit an immunoglobulin G (IgG) immune response with the highest titers obtained with 100-microg dose. When we purified a small fraction of PNAG with a molecular mass of approximately 780 kDa (PNAG-780) from PNAG-I, significantly higher IgG titers than those in mice immunized with the same doses of PNAG-I were obtained, suggesting the importance of the molecular mass of PNAG in the antibody response. These results further clarify the chemical structure of PS/A and help to differentiate it from PIA on the basis of immunogenicity, molecular size, and solubility.
A New Synthetic Route to 5-Aminomethylene Derivatives of Barbituric Acids (1994)

Interaction of barbituric acid and dimethylformamide in the presence of amine salt leads to 5-aminomethylenebarbituric acids in good yield.
Binding of the herpes simplex virus major regulatory protein to viral DNA. (1989)

Infected-cell protein 4 (ICP4), the major regulatory protein specified by herpes simplex virus 1 in infected cells, binds to homologs of the sequence ATCGTCnnnnYCGRC (A sites, where n is any nucleotide, Y is a pyrimidine, and R is a purine) and to unrelated sequences for which no consensus sequence has been derived (B sites). We have examined the binding of ICP4 to each of two A and two B binding sites by using Fab fragments of a monoclonal antibody that is reactive with an epitope located at the N terminus of ICP4 and that decreases the mobility of ICP4-DNA complexes in non-denaturing gels. The results indicate that each type of site binds two monomers of ICP4. Methylation-interference studies on the type B sites mapped the guanines whose methylation interfered with the binding of ICP4. The methylation-interference pattern obtained with one of the B sites was similar to that obtained on an A site but differed from that of the other B site. The ability of ICP4 to bind to DNA fragments containing the binding site appears to be dependent on length and on the proximity of the binding site to the fragment end. Short DNA fragments did not form stable complexes with ICP4 even though they contained all of the purines whose methylation interfered with the binding of the regulatory protein.
Pharmacokinetics of Mercaptopurine (1997)

Measurement of red cell 6-mercaptopurine (MP) derived 6-thioguanine nucleotide (TGN) and methylmercaptopurine metabolites (MeMPs) can be used to monitor therapy in children who are administered MP for childhood lymphoblastic leukemia. Red cell TGNs are not influenced by the time of blood sampling in relation to the last MP dose. The purpose of this study was to find out whether the same is true for the MeMPs. Plasma MP and red cell MP metabolite pharmacokinetics were studied in seven children immediately before and for 4 hours after a protocol standardized dose of MP. Duplicate blood samples were taken, one was processed immediately whereas one was left at an ambient temperature for 24 hours. The variation in TGN and MeMP metabolites over the 0- to 4-hour period (10 time points per child) was within the error of the assays used. The coefficients of variation for the TGNs ranged from 2.7% to 7% and for the MeMPs, 4% to 10.7%. There was no difference in the TGN and MeMP concentrations measured when the blood samples were left for 24 hours. If a child takes a MP tablet immediately before a clinic appointment, it has no major influence on MeMP measurements.
Dynamic 3D avatar creation from hand-held video input (2015)

We present a complete pipeline for creating fully rigged, personalized 3D facial avatars from hand-held video. Our system faithfully recovers facial expression dynamics of the user by adapting a blendshape template to an image sequence of recorded expressions using an optimization that integrates feature tracking, optical flow, and shape from shading. Fine-scale details such as wrinkles are captured separately in normal maps and ambient occlusion maps. From this user- and expression-specific data, we learn a regressor for on-the-fly detail synthesis during animation to enhance the perceptual realism of the avatars. Our system demonstrates that the use of appropriate reconstruction priors yields compelling face rigs even with a minimalistic acquisition system and limited user assistance. This facilitates a range of new applications in computer animation and consumer-level online communication based on personalized avatars. We present realtime application demos to validate our method.
Synthetic peptides comprising sequences of the human immunoglobulin E heavy chain capable of releasing histamine (1979)

On the basis of previous studies on the structure-activity relationship of model polypeptide histamine liberators, a site within the Fc region of immunoglobulin E antibody molecules has been proposed as that responsible for the direct triggering of target mast cells after antigen challenge. Peptides comprising this region of the epsilon-chain have now been synthesized and shown to induce histamine release from normal rat peritoneal mast cells in a selective manner essentially similar to that mediated by anaphylactic antibody-antigen interaction.
CENP-A Is Required for Accurate Chromosome Segregation and Sustained Kinetochore Association of BubR1 (2005)

CENP-A is an evolutionarily conserved, centromere-specific variant of histone H3 that is thought to play a central role in directing kinetochore assembly and in centromere function. Here, we have analyzed the consequences of disrupting the CENP-A gene in the chicken DT40 cell line. In CENP-A-depleted cells, kinetochore protein assembly is impaired, as indicated by mislocalization of the inner kinetochore proteins CENP-I, CENP-H, and CENP-C as well as the outer components Nuf2/Hec1, Mad2, and CENP-E. However, BubR1 and the inner centromere protein INCENP are efficiently recruited to kinetochores. Following CENP-A depletion, chromosomes are deficient in proper congression on the mitotic spindle and there is a transient delay in prometaphase. CENP-A-depleted cells further proceed through anaphase and cytokinesis with unequal chromosome segregation, suggesting that some kinetochore function remains following substantial depletion of CENP-A. We furthermore demonstrate that CENP-A-depleted cells exhibit a specific defect in maintaining kinetochore localization of the checkpoint protein BubR1 under conditions of checkpoint activation. Our data thus point to a specific role for CENP-A in assembly of kinetochores competent in the maintenance of mitotic checkpoint signaling.
Alzheimer's disease untangled (1992)

The last year has seen major advances in the study of Alzheimer's disease (AD). Four mutations involving amino acid substitutions in exons 16 and 17 of the amyloid precursor protein (APP) gene, have been identified which co-segregate with the disease in some families multiply affected by early onset Alzheimer's disease. These mutations are strongly suggestive of a causative role for the amyloid precursor protein in Alzheimer's disease. Despite their rarity, these mutations are important because they represent the first known cause of Alzheimer's disease. Processing of APP must be central to the pathogenesis of the disease although the precise effects of these amino acid substitutions are not understood. Work is now being undertaken to characterise the processing pathways of APP and to identify other causes of AD. The development of models of AD using the APP mutations offers the possibility of identifying drug targets and developing more effective treatments than are presently available.
Crystal Structure of Fungal Lectin (2003)

Aleuria aurantia lectin is a fungal protein composed of two identical 312-amino acid subunits that specifically recognizes fucosylated glycans. The crystal structure of the lectin complexed with fucose reveals that each monomer consists of a six-bladed beta-propeller fold and of a small antiparallel two-stranded beta-sheet that plays a role in dimerization. Five fucose residues were located in binding pockets between the adjacent propeller blades. Due to repeats in the amino acid sequence, there are strong similarities between the sites. Oxygen atoms O-3, O-4, and O-5 of fucose are involved in hydrogen bonds with side chains of amino acids conserved in all repeats, whereas O-1 and O-2 interact with a large number of water molecules. The nonpolar face of each fucose residue is stacked against the aromatic ring of a Trp or Tyr amino acid, and the methyl group is located in a highly hydrophobic pocket. Depending on the precise binding site geometry, the alpha- or beta-anomer of the fucose ligand is observed bound in the crystal. Surface plasmon resonance experiments conducted on a series of oligosaccharides confirm the broad specificity of the lectin, with a slight preference for alphaFuc1-2Gal disaccharide. This multivalent carbohydrate recognition fold is a new prototype of lectins that is proposed to be involved in the host recognition strategy of several pathogenic organisms including not only the fungi Aspergillus but also the phytopathogenic bacterium Ralstonia solanacearum.
Regulation of bacterial glycogen synthesis. Stimulation of glycogen synthesis by endogenous and exogenous cyclic adenosine 3':5'-monophosphate in Escherichia coli and the requirement for a functional CRP gene. (1983)

In Escherichia coli cya mutants, deficient in adenylate cyclase (EC 4.6.1.1), basal cellular rates of glycogen synthesis were lower and the relative increases produced by exogenous cyclic adenosine 3',5'-monophosphate during growth on glucose were greater than in their respective parent strains. These observations provide strong evidence that endogenous cyclic AMP is one of the key regulators of glycogen synthesis in growing E. coli. In crp mutants, deficient in cyclic AMP receptor protein (CRP), the basal cellular rates of glycogen synthesis were much lower than in their respective parent strains. Stimulation of glycogen synthesis by exogenous cyclic AMP was markedly attenuated in the three crp mutants. Thus, stimulation of glycogen synthesis by either endogenous or exogenous cyclic AMP appears to require CRP. Functional CRP appeared to be required for all three responses observed after cyclic AMP addition: an abrupt step-up in the cellular rate of glycogen synthesis, a continuing exponential increase in rate, and a stimulation of the rate during a subsequent nitrogen starvation. To account for these responses, we derived a mathematical model in which the cyclic AMP-CRP complex regulates the differential rate of synthesis of an enzyme metabolizing an effector of the rate-limiting enzyme of glycogen synthesis.
Effects ofGPD1Overexpression inSaccharomyces cerevisiaeCommercial Wine Yeast Strains LackingALD6Genes (2006)

The utilization of Saccharomyces cerevisiae strains overproducing glycerol and with a reduced ethanol yield is a potentially valuable strategy for producing wine with decreased ethanol content. However, glycerol overproduction is accompanied by acetate accumulation. In this study, we evaluated the effects of the overexpression of GPD1, coding for glycerol-3-phosphate dehydrogenase, in three commercial wine yeast strains in which the two copies of ALD6 encoding the NADP+-dependent Mg2+-activated cytosolic acetaldehyde dehydrogenase have been deleted. Under wine fermentation conditions, the engineered industrial strains exhibit fermentation performance and growth properties similar to those of the wild type. Acetate was produced at concentrations similar to that of the wild-type strains, whereas sugar was efficiently diverted to glycerol. The ethanol yield of the GPD1 ald6 industrial strains was 15 to 20% lower than that in the controls. However, these strains accumulated acetoin at considerable levels due to inefficient reduction to 2,3-butanediol. Due to the low taste and odor thresholds of acetoin and its negative sensorial impact on wine, novel engineering strategies will be required for a proper adjustment of the metabolites at the acetaldehyde branch point.
Polyalanine and polyserine frameshift products in Huntington’s disease (2006)

Codon reiteration disorders are caused by abnormal expansions of either polyglutamine or polyalanine tracts within the coding region of a protein. These mutations impair normal protein folding, resulting in aggregate formation in the affected tissues. Huntington's disease is the most common of the nine disorders caused by polyglutamine expansion mutations. The most extensively studied polyalanine expansion disorder is oculopharyngeal muscular dystrophy. There may be a link between diseases caused by polyglutamine and polyalanine expansion mutations as it has been shown that the expanded CAG/polyglutamine tract within the SCA3 gene can shift to the GCA[corrected]/polyalanine frame. Here, we show that this frameshifting phenomenon is more widespread and occurs in Huntington's disease. We have shown both +1 frameshift and +2 frameshift products (which may contain polyalanine or polyserine tracts, respectively) in human postmortem Huntington's disease brains and in a transgenic mouse model of Huntington's disease. Our data suggest that +1 and +2 frameshift products are generated at low levels. This may be relevant to the pathogenesis of human Huntington's disease, as we have previously shown that both polyserine and polyalanine-containing proteins are modifiers of mutant huntingtin toxicity, with low expression levels of polyalanine-containing proteins having a protective effect.
Characterization of the l‐arginine: nitric oxide pathway in human platelets (1990)

1. The activation of the L-arginine: nitric oxide (NO) pathway during aggregation of human platelets by adenosine 5'-diphosphate (ADP), arachidonic acid, thrombin and the calcium ionophore A23187 and its inhibition by NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME) and N-iminoethyl-L-ornithine (L-NIO) were studied. The inhibition of the cytosolic platelet NO synthase by these compounds was also examined. 2. Platelet aggregation induced by ADP (1-10 microM) and arachidonic acid (0.1-10 microM), but not that induced by thrombin (1-30 mu ml-1) or A23187 (1-10 nM), was inhibited by L-, but not D-arginine (1-30 microM). However, in the presence of a subthreshold concentration of prostacyclin (0.1 nM) or of M & B 22948 (1 microM), a selective inhibitor of guanosine 3':5'-cyclic monophosphate (cyclic GMP) phosphodiesterase, L-arginine caused concentration-dependent inhibition of aggregation induced by all of these aggregating agents. 3. L-NMMA, L-NAME and L-NIO (all at 1-30 microM), but not their D-enantiomers, enhanced to the same extent platelet aggregation induced by ADP, arachidonic acid and thrombin without affecting that induced by A23187. 4. In the presence of 300 microM L-arginine, the NO synthase in platelet cytosol was inhibited by L-NMMA, L-NAME and L-NIO with IC50s of 74 +/- 9, 79 +/- 8 and 8.5 +/- 1.5 microM (n = 3), respectively. 5. These results indicate that the L-arginine: NO pathway in human platelets plays a role in the modulation of platelet aggregation.
A General Method of Terminal Truncation, Evolution, and Re-Elongation to Generate Enzymes of Enhanced Stability (2006)

Improving enzyme stability is a highly desirable design step in generating enzymes able to function under extreme conditions, such as elevated temperatures, while having the additional benefit of being less susceptible to cleavage by proteases. For these reasons, many different approaches and techniques have been devised in constructing such proteins, but the results to date have been of mixed success. Here, we present a robust method involving the terminal truncation, random mutagenesis and fragmentation, recombination, elongation, and finally, selection at physiological temperatures, to generate an enzyme with improved stability. Three cycles of directed evolution comprising of random mutagenesis, DNA shuffling, and selection at 37 degrees C were used, using the bacterial enzyme TEM-1 beta-lactamase as a model protein to yield deletion mutants with in vivo ampicillin resistance levels comparable to wild-type (wt) enzyme. Kinetic studies demonstrate the selected mutant to have a significantly improved thermostability relative to its wt counterpart. Elongation of this mutant to the full-length gene resulted in a beta-lactamase variant with dramatically increased thermostability. This technique was so fruitful that the evolved enzyme retained its maximum catalytic activity even 20 degrees C above its wt parent protein optimum. Thus, structural perturbation by terminal truncation and subsequent compensation by directed evolution at physiological temperatures is a fast, efficient, and highly effective way to improve the thermostability of proteins without the need for selecting at elevated temperatures.
Clinical usefulness of carbohydrate antigen 19‐9 as a screening test for pancreatic cancer in an asymptomatic population (2004)

Mass screening for pancreatic cancer using CA 19-9 levels in asymptomatic subjects is ineffective because of a very low positive predictive value, despite its high sensitivity and specificity.
Bilateral atrial appendectomy abolishes increased plasma atrial natriuretic peptide release and blunts sodium and water excretion during volume loading in conscious dogs. (1992)

The atrial appendages contain most of the atrial natriuretic factor (ANF) in the mammalian heart, and atrial appendage mechanical function predicts ANF secretion during volume loading. To demonstrate the crucial role of the atrial appendages in ANF release, we first measured hemodynamics and changes in plasma ANF after injection of 1,000 ml i.v. normal saline in conscious dogs and again after bilateral atrial appendectomy; we next measured changes in renal function using infusions of atriopeptin 24 to achieve plasma levels corresponding to levels achieved during volume loading; and we lastly measured renal function during acute volume expansion and also after atrial appendectomy. Plasma ANF increased from 65 +/- 11 to 246 +/- 54 pg/ml after volume loading but did not increase after atrial appendectomy. Atrial appendectomy did not alter the tachycardia or hemodynamic effects of volume loading. Infusion of 10 ng/kg/min atriopeptin 24 increased plasma ANF from 50 +/- 9 to 234 +/- 54 pg/ml, increased urine output 34 +/- 10%, and increased sodium excretion 62 +/- 10% in dogs with intact atrial appendages. Renal function was compared in dogs before atrial appendectomy: 20, 40, and 60 minutes after volume loading, urine flow rate increased by 5.9 +/- 0.5, 6.9 +/- 0.4, and 4.4 +/- 0.8 ml/min, while sodium excretion increased by 717 +/- 60, 839 +/- 84, and 582 +/- 57 mueq/min. After atrial appendectomy urine flow rate increased 2.1 +/- 0.7, 2.7 +/- 0.7, and 2.0 +/- 0.6 ml/min, and sodium excretion increased only by 327 +/- 110, 324 +/- 77, and 340 +/- 92 mueq/min (p less than 0.01) during volume loading.(ABSTRACT TRUNCATED AT 250 WORDS)
Image multiplexer using a planar microlens array (1990)

An image multiplexer (IMX) composed of a planar microlens array is proposed for an input device of an optical parallel processing system. Imaging properties were evaluated experimentally and numerically to find a design rule and the limitations of use of the IMX. As a result, it was found that a planar microlens has a relatively good distortion property and low MTF sensitivity for oblique imaging, even if an image height goes to as high as 60% of the lens radius. Furthermore, a compensation method for image shift nonlinearity is proposed. The effective lens number in an array is estimated.