gebhart/patrepeval huggingface dataset:
Spurious elevation of automated leukocyte counts induced by Fluosol DA 20%. (1987)

During studies with Fluosol DA 20% (FDA) in rats, an artifactual leukocytosis was observed when an impedance type electronic cell counter was used. The effect was found to be directly related to the duration of the interval between addition of an erythrocyte lysing fluid and counting, observed up to 11 d after transfusion with FDA, blood cell associated, reproducible in vitro, FDA concentration dependent, temperature dependent, and present when human blood was used instead of rat blood. Microscopically, the effect appears to be the result of agglutination of lysed erythrocyte membranes due to the interaction of erythrocytes, the emulsion component of FDA, and the quaternary ammonium salt component of the lysing fluid. These data suggest that FDA causes subtle changes in erythrocytes and raises the possibility that other cells may be similarly affected.
The management of probabilistic data (1992)

It is often desirable to represent in a database, entities whose properties cannot be deterministically classified. The authors develop a data model that includes probabilities associated with the values of the attributes. The notion of missing probabilities is introduced for partially specified probability distributions. This model offers a richer descriptive language allowing the database to more accurately reflect the uncertain real world. Probabilistic analogs to the basic relational operators are defined and their correctness is studied. A set of operators that have no counterpart in conventional relational systems is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Polymorphisms in the Human Inhibitory Signal-regulatory Protein α Do Not Affect Binding to Its Ligand CD47 (2014)

CD47 is a widely distributed membrane protein that interacts with signal-regulatory protein α (SIRPα), an inhibitory receptor on myeloid cells that gives a "don't-eat-me" signal. Manipulation of the interaction is of considerable interest in the immunotherapy of cancer and in xenotransplantation. The amino-terminal ligand binding domain of SIRPα is highly polymorphic in contrast to the single Ig-like domain of CD47. There is confusion as to whether the polymorphisms will affect ligand binding, but this is an important point for this interaction and other paired receptors being considered as targets for therapy. We show by x-ray crystallography that one human SIRPα allele differing in 13 amino acid residues has a very similar binding site and that several different alleles all bind CD47 with similar affinity as expected because the residues are mostly surface-exposed and distant from the binding site. A peptide from the binding site of CD47 has been reported to mimic the CD47 interaction with SIRPα, but we could find no binding. We discuss the possible pitfalls in determining the affinity of weak interactions and also speculate on how SIRPα polymorphisms may have been selected by pathogens and how this may also be true in other paired receptors such as the KIRs.
Nonsteroidal antiinflammatory drugs and colorectal cancer (1994)

The regular use of NSAIDs was associated with an overall significant risk reduction of colorectal cancer in men and in women. Among female patients, the greater protective effect associated with short term NSAID use compared with long term NSAID use may reflect a sampling bias.
Trapping properties of cadmium vacancies inCd1−xZnxTe (1997)

The trapping and thermal emission of holes were studied from a deep acceptor level created during thermal annealing of a ${\mathrm{Cd}}_{1\mathrm{\ensuremath{-}}\mathrm{x}}$${\mathrm{Zn}}_{\mathrm{x}}$Te (x=0.12) crystal grown by the high-pressure Bridgman (HPB) technique using thermoelectric-effect spectroscopy and thermally stimulated current experiments. The deep level, which is usually absent in as-grown HPB ${\mathrm{Cd}}_{1\mathrm{\ensuremath{-}}\mathrm{x}}$${\mathrm{Zn}}_{\mathrm{x}}$Te crystals, is assigned to the 2-/- acceptor level of Cd (Zn) vacancies. The thermal ionization energy of the level is ${\mathrm{E}}_{\mathrm{th}}$ =(0.43\ifmmode\pm\else\textpm\fi{}0.01) eV, and the trapping cross section of holes was found to be \ensuremath{\sigma}=(2.0\ifmmode\pm\else\textpm\fi{}0.2)\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}16}$ ${\mathrm{cm}}^{\mathrm{\ensuremath{-}}2}$.
SIGNAL SCAN 3.O. new database and program features (1993)

SIGNAL SCAN is a program that utilizes a transcription factor database to find potential transcription factor binding sites in DNA sequences. The program is now in its third version. The SIGNAL SCAN transcription factor database format has changed and the program output format has been improved. New features allow the user to update the SIGNAL SCAN database automatically, to retrieve original journal citations and to develop user signal databases. The program now uses an indexing algorithm, improving scanning speed by a factor of 3. SIGNAL SCAN is now network compatible and is available for IBM-compatible PC, Unix and VMS platforms.
Overexpression, site-directed mutagenesis, and mechanism of Escherichia coli acid phosphatase (1992)

Site-directed mutagenesis was used to examine the catalytic importance of 2 histidine and 4 arginine residues in Escherichia coli periplasmic acid phosphatase (EcAP). The residues that were selected as targets for mutagenesis were those that were also conserved in a number of high molecular weight acid phosphatases from eukaryotic organisms, including human prostatic and lysosomal acid phosphatases. Both wild type EcAP and mutant proteins were overproduced in E. coli using an expression system based on the T7 RNA polymerase promoter, and the proteins were purified to homogeneity. Examination of the purified mutant proteins by circular dichroism and proton NMR spectroscopy revealed no significant conformational changes. The replacement of Arg16 and His17 residues that were localized in a conserved N-terminal RHGXRXP motif resulted in the complete elimination of EcAP enzymatic activity. Critical roles for Arg20, Arg92, and His303 were also established because the corresponding mutant proteins exhibited residual activities that were not higher than 0.4% of that of wild type enzyme. In contrast, the replacement of Arg63 did not cause a significant alteration of the kinetic parameters. The results are in agreement with a previously postulated distant relationship between acid phosphatases, phosphoglycerate mutases, and fructose-2,6-bisphosphatase. These and earlier results are also consistent with the conclusion that 2 histidine residues participate in the catalytic mechanism of acid phosphatases, with His17 playing the role of a nucleophilic acceptor of the phospho group, whereas His303 may act as a proton donor to the alcohol or phenol.
Effects of α-deuterium substitution on the mutagenicity of 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)1 (1983)

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a carcinogenic tobacco specific nitrosamine, can be converted to electrophilic diazohydroxide intermediates by metabolic hydroxylation of either the methylene carbon (carbon 4) or the methyl carbon attached to the nitrosamine group. To investigate the relative importance of these two processes in NNK mutagenesis, we synthesized 4,4-dideutero-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone([4,4,-D2]NNK) and 4-(trideuteromethylnitrosamino)-1-(3-pyridyl)-1-butanone ([CD3] NNK), and evaluated their mutagenic activities in Salmonella typhimurium tester strains. In the presence of Aroclor induced rat liver 9000 g supernatant, NNK and [4,4-D2]NNK had comparable mutagenic activities towards S. typhimurium TA 1535 and TA 100, but [CD3]NNK was inactive in both strains. These results suggest that hydroxylation of the methyl group of NNK is more important than hydroxylation of carbon 4 in its activation to a mutagen. To test the inherent mutagenicity of 4-oxo-4-(3-pyridyl)butyldiazohydroxide and methyldiazohydroxide which would be formed by methyl hydroxylation or carbon 4 hydroxylation, respectively, we compared the mutagenicities, without activation, of the corresponding model compounds, 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone and carbethoxynitrosaminomethane (methylnitrosourethane). Both compounds were highly mutagenic toward S. typhimurium TA 1535 and TA 100, but at doses of 4 x 10(-3) to 4 x 10(-4) mumol/plate, only 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone was mutagenic. These results are consistent with those obtained with the deuterium substituted compounds and indicate the importance of 4-oxo-4-(3-pyridyl)butylation of DNA in NNK mutagenesis.
The foxa2 Gene Controls the Birth and Spontaneous Degeneration of Dopamine Neurons in Old Age (2007)

Parkinson disease affects more than 1% of the population over 60 y old. The dominant models for Parkinson disease are based on the use of chemical toxins to kill dopamine neurons, but do not address the risk factors that normally increase with age. Forkhead transcription factors are critical regulators of survival and longevity. The forkhead transcription factor, foxa2, is specifically expressed in adult dopamine neurons and their precursors in the medial floor plate. Gain- and loss-of-function experiments show this gene, foxa2, is required to generate dopamine neurons during fetal development and from embryonic stem cells. Mice carrying only one copy of the foxa2 gene show abnormalities in motor behavior in old age and an associated progressive loss of dopamine neurons. Manipulating forkhead function may regulate both the birth of dopamine neurons and their spontaneous death, two major goals of regenerative medicine.
The Effect of α4β1-Integrin Binding Sequences of Fibronectin on Growth of Cells From Human Hematopoietic Progenitors (1998)

Abstract Highly regulated interactions between adhesion receptors on progenitor cells and their extracellular matrix ligands are essential for the control of hematopoiesis in bone marrow stroma. We have examined the relationship between α4β1-integrin–mediated adhesion and growth of CD34+ cells by assessing their adhesive and migratory patterns of proliferation in a mixture of hematopoietic growth factors in the presence of different recombinant fragments of theHepII/IIICS region of fibronectin. CD34+ cells were isolated from cord blood and placed in culture wells containing serum-free medium and growth factors. Wells were precoated with either the H120 fragment of fibronectin, which contains three α4β1-integrin binding sites, or the H0 fragment, which lacks the two highest affinity α4β1 binding sequences. Proliferation of single cells of CD34+38+DR+and CD34+38−DR+ phenotypes occurred in contact with the H120 substrate and was associated with migration. Larger numbers of cells were used to quantitate proliferative responses. Cells growing in wells coated with H120 formed attachments to the base of the wells throughout the culture period. Higher total cell counts were consistently found in wells coated with H120 compared with H0 and bovine serum albumin controls. The difference was first apparent at day 8 of culture and reached a maximum at days 11 through 13, when expansion with H120 was a mean of 1.8-fold higher than that seen with H0 (P≤ .0001). The greatest expansion (2.25-fold) with H120 compared with H0 was seen when the growth factor concentrations were reduced to 1/16 of the standard levels (P ≤ .001). The increase in total cell numbers was not at the expense of CD34+ cells as numbers of these were similar in H120 and control cultures. These results provide evidence for synergy between growth factors and integrins that may be relevant to understanding hematopoiesis in marrow stroma.
Absorbed fractions for alpha-particles in tissues of cortical bone (2009)

Bone-seeking alpha-particle emitting radionuclides are common health physics hazards. Additionally, they are under consideration as an option for therapeutic molecular radiotherapy applications. Current dose models do not account for energy or bone-site dependence as shown by alpha-particle absorbed fractions given in ICRP Publication 30. Energy-dependent, yet bone-site independent, alpha-particle absorbed fractions have been presented by the models of Stabin and Siegel (2003 Health Phys. 85 294-310). In this work, a chord-based computational model of alpha-particle transport in cortical bone has been developed that explicitly accounts for both the bone-site and particle-energy dependence of alpha-particle absorbed fractions in this region of the skeleton. The model accounts for energy deposition to three targets: cortical endosteum, haversian space tissues and cortical bone. Path length distributions for cortical bone given in Beddoe (1977 Phys. Med. Biol. 22 298-308) provided additional transport regions in the absorbed fraction calculation. Significant variations in absorbed fractions between different skeletal sites were observed. Differences were observed between this model and the absorbed fractions given in ICRP Publication 30, which varied by as much as a factor of 2.1 for a cortical bone surface source irradiating cortical endosteum.
A Variant of t-PA (T103N, KHRR 296-299 AAAA) that, by Bolus, Has Increased Potency and Decreased Systemic Activation of Plasminogen (1993)

In the accompanying paper, we reported that the properties of decreased plasma clearance rate, increased fibrin specificity, and resistance to inactivation by PAI-1 could be effectively combined in the t-PA variant T103N, KHRR 296-299 AAAA. In the current study we evaluated the in vivo efficacy of this variant as well as variants containing the individual mutations T103N and KHRR 296-299 AAAA. Plasma clearance and in vivo lysis of whole blood and platelet-rich clots were determined in a rabbit arterio-venous shunt model. The T103N containing variants were administered as an intravenous (i.v.) bolus. KHRR 296-299 AAAA and t-PA were infused i.v. over 90 min. The clearance rate of the KHRR 296-299 AAAA variant was similar to t-PA. However, the clearance of the T103N and T103N, KHRR 296-299 AAAA variants were 8 and 6-fold reduced, respectively. Potency of the variants relative to t-PA on whole blood clots ranged from 0.9 (T103N, KHRR 296-299 AAAA) to 1.7 (T103N). Relative potency on platelet-rich clots ranged from 2.4 (T103N) to 4.2 (T103N, KHRR 296-299 AAAA). Fibrinogen concentrations in rabbits 120 min after dosing with a 2.5 mg/kg bolus were: 24, 16, 82, and 77% of initial for t-PA; T103N; KHRR 296-299 AAAA; and T103N, KHRR 296-299 AAAA treatment groups, respectively. These results suggest that the T103N, KHRR 296-299 AAAA variant of t-PA, given as a bolus, could result in greater efficacy, particularly on refractory platelet-rich clots, without inducing the severe systemic lytic state produced by a bolus of a less fibrin specific variant.
Schizosaccharomyces pombe Has a Novel Eukaryotic Initiation Factor 4F Complex Containing a Cap-binding Protein with the Human eIF4E C-terminal Motif KSGST (1996)

Genetic and biochemical analyses were performed on the cytoplasmic cap-binding complex (eukaryotic initiation factor (eIF) 4F) of Schizosaccharomyces pombe. Genomic and cDNA sequencing of the S. pombe gene (tif1) encoding the cap-binding component eIF4E revealed the presence of two introns in a reading frame of 219 codons. The encoded sequence of 218 amino acids shows a greater degree of identity to the mammalian eIF4E sequence than does its counterpart from Saccharomyces cerevisiae. In particular, unlike its S. cerevisiae counterpart, S.pombe eIF4E has a C-terminal Ser209 within the motif KSGST that is a site of phosphorylation in hamster and rabbit eIF4E. Of relevance to its potential regulatory role, eIF4E was found to be encoded by an mRNA with a six-nucleotide leader and to be of low abundance in vivo. Cross-linking experiments identified S. pombe eIF4E as the major cap-binding protein while a further protein, p36, also showed cap-dependent binding. eIF4A was not associated with the cap-binding complex. While S. pombe eIF4E was shown capable of binding S. cerevisiae p20, an equivalent protein was absent from the eIF4F complex isolated from S. pombe cells. S. pombe 4F therefore shows a remarkable combination of structural and functional properties, some of which it shares with its higher and its lower eukaryotic counterparts.
Genetic Predisposition in NAFLD and NASH: Impact on Severity of Liver Disease and Response to Treatment (2013)

Liver fat deposition related to systemic insulin resistance defines non-alcoholic fatty liver disease (NAFLD) which, when associated with oxidative hepatocellular damage, inflammation, and activation of fibrogenesis, i.e. non-alcoholic steatohepatitis (NASH), can progress towards cirrhosis and hepatocellular carcinoma. Due to the epidemic of obesity, NAFLD is now the most frequent liver disease and the leading cause of altered liver enzymes in Western countries. Epidemiological, familial, and twin studies provide evidence for an element of heritability of NAFLD. Genetic modifiers of disease severity and progression have been identified through genome-wide association studies. These include the Patatin-like phosholipase domain-containing 3 (PNPLA3) gene variant I148M as a major determinant of inter-individual and ethnicity-related differences in hepatic fat content independent of insulin resistance and serum lipid concentration. Association studies confirm that the I148M polymorphism is also a strong modifier of NASH and progressive hepatic injury. Furthermore, a few large multicentre case-control studies have demonstrated a role for genetic variants implicated in insulin signalling, oxidative stress, and fibrogenesis in the progression of NAFLD towards fibrosing NASH, and confirm that hepatocellular fat accumulation and insulin resistance are key operative mechanisms closely involved in the progression of liver damage. It is now important to explore the molecular mechanisms underlying these associations between gene variants and progressive liver disease, and to evaluate their impact on the response to available therapies. It is hoped that this knowledge will offer further insights into pathogenesis, suggest novel therapeutic targets, and could help guide physicians towards individualised therapy that improves clinical outcome.
Chemoprevention of Prostate Cancer (2010)

Are we making progress in the chemoprevention of prostate cancer? The disease is an ideal target: not only is it the most common cancer among men in the United States, it has the highest age-specific incidence of any cancer. If we could prevent the disease or delay its progression, many men could be spared the burden of diagnostic procedures and treatments, and costs to the health care system could be reduced substantially. Because we lack a complete understanding of the pathophysiology of prostate cancer, chemopreventive strategies have empirically focused on two approaches: treatment with antioxidants to reduce damage to DNA . . .
Swelling behavior of hyaluronic acid gels (1992)

Abstract Hyaluronic acid is a naturally occurring mucopolysaccharide. It is an important component of the intercellular matrix. It controls the permeability of tissues by means of the highly entangled network which can be formed because of its high molecular weight. To be able to use hyaluronic acid for several biomedical applications it is necessary to have an understanding of its swelling properties. Equilibrium swelling properties of hyaluronic acid gels were investigated by varying the temperature, pH, ionic strength, and composition of the surrounding solution. Swelling was found to depend on pH and ionic strength and to be reversible. The gel was highly swollen at high pH, but it shrank continuously as the pH was lowered to 10% of its maximum volume. The gel was comparatively insensitive to temperature. Drying affected the swelling capacity of the gel significantly. Gel swelling was also affected by a high concentration of acetone or propyl alcohol in the aqueous swelling solutions.
Engineered biosynthesis of a triketide lactone from an incomplete modular polyketide synthase (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEngineered biosynthesis of a triketide lactone from an incomplete modular polyketide synthaseCamilla M. Kao, Guanglin Luo, Leonard Katz, David E. Cane, and Chaitan KhoslaCite this: J. Am. Chem. Soc. 1994, 116, 25, 11612–11613Publication Date (Print):December 1, 1994Publication History Published online1 May 2002Published inissue 1 December 1994https://pubs.acs.org/doi/10.1021/ja00104a069https://doi.org/10.1021/ja00104a069research-articleACS PublicationsRequest reuse permissionsArticle Views483Altmetric-Citations81LEARN 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 InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Monodeazacinchona Alkaloid Derivatives: Synthesis and Preliminary Applications as Phase-Transfer Catalysts (2002)

Four analogues of cinchona alkaloids (5−8) lacking the quinoline nitrogen atom have been prepared. Quaternization afforded the phase-transfer catalysts 10a, 10b, 11a, and 12d. Other optically active catalyst salts were prepared from the cinchona alkaloids themselves (compounds 13, 14, 15). The performances of these PT catalysts and of some others were compared in three test reactions. The deazacinchona derivatives exhibited selectivities similar to or sometimes even better than those of the natural product-derived compounds. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)
Parallel speech recognition (1997)

Computer speech recognition has been very successful in limited domains and for isolated word recognition. However, widespread use of large-vocabulary continuous-speech recognizers is limited by the speed of current recognizers, which cannot reach acceptable error rates while running in real time. This paper shows how to harness shared memory multiprocessors, which are becoming increasingly common, to increase the speed significantly, and therefore the accuracy or vocabulary size, of a speech recognizer. To cover the necessary background, we begin with a tutorial on speech recognition. We then describe the parallelization of an existing high-quality speech recognizer, achieving a speedup of a factor of 3, 5, and 6 on 4-, 8-, and 12-processors respectively for the benchmark North American business news (NAB) recognition task.
Association of C677T Polymorphism in MTHFR Gene, High Homocysteine and Low HDL Cholesterol Plasma Values in Heterozygous Familial Hypercholesterolemia (2009)

In hFH subjects, the genotype TT and higher plasma Hcy levels were associated with lower HDL-C plasma values in FH subjects. More studies are needed to confirm our results and also to elucidate the exact mechanism of interaction between plasma homocysteine and lipid metabolism.