gebhart/patrepeval huggingface dataset:
Association of Single Nucleotide Polymorphisms in TCF2 with Type 2 Diabetes Susceptibility in a Han Chinese Population (2012)

Hepatocyte nuclear factor 1β (HNF1β), a transcription factor encoded by the transcription factor 2 gene (TCF2), plays a critical role in pancreatic cell formation and glucose homeostasis. It has been suggested that single nucleotide polymorphisms (SNPs) of TCF2 are associated with susceptibility to type 2 diabetes (T2D). However, published results are inconsistent and inclusive. To further investigate the role of these common variants, we examined the association of TCF2 polymorphisms with the risk of T2D in a Han population in northeastern China. We genotyped five SNPs in 624 T2D patients and 630 healthy controls by using a SNaPshot method, and evaluated the T2D risk conferred by individual SNPs and haplotypes. In the single-locus analysis, we found that rs752010, rs4430796 and rs7501939 showed allelic differences between T2D patients and healthy controls, with an OR of 1.26 (95% CI 1.08-1.51, P = 0.003), an OR of 1.23 (95% CI 1.06-1.55, P = 0.001) and an OR of 1.28 (95% CI 1.10-1.61, P = 0.001), respectively. Genotype association analysis of each locus also revealed that the homozygous carriers of the at-risk allele had a significant increased T2D risk compared to homozygous carriers of the other allele (OR 1.78, 95% CI 1.20-2.64 for rs752010; OR 1.82, 95% CI 1.24-2.67 for rs4430796; OR 1.95, 95% CI 1.31-2.90 for rs7501939), even after Bonferroni correction for multiple comparisons. Besides, the haplotype-based analysis demonstrated that AGT in block rs752010-rs4430796-rs7501939 was associated with about 30% increase in T2D risk (OR 1.31, 95% CI 1.09-1.57, P = 0.01). Our findings suggested that TCF2 variants may be involved in T2D risk in a Han population of northeastern China. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation.
Lithium glass scintillator neutron detector as an improved alternative to the standard <sup>3</sup> he proportional counter (2010)

Lithium glass scintillator made from <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> Li-enriched substrate is a well known for its neutron detection capability. In spite of neutron interaction, cross section of <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> Li happens to be lower than that of <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> He. However, the neutron detection efficiency could be higher due to higher volume content of <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> Li nuclear in the solid scintillator vs. gas filled proportional counter. At the same time, as lithium glass is sensitive to gamma and charge particle radiation, non-neutron radiation discrimination is required. Our detector is composed of two equal-size cylindrical Li(Ce) glass scintillators. The first one is high-sensitive to thermal neutrons GS-20 ( <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> Li doped), the second one is GS-30 ( <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7</sup> Li doped) type Scint-Gobain made lithium glass scintillator. Each of scintillators is coupled with R7400U Hamamatsu subminiature photomultiplier tube, and all assembly is fitted into NP100H <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> He tube size. <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> Li absorbs thermal neutrons releasing alpha particles and triton with 4.8 MeV total energy deposit inside the scintillator (equivalent to about ~1.3 MeV gamma energy depositions). Because <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7</sup> Li isotope does not absorb thermal neutrons, and the physical properties of the two scintillators are virtually identical, the difference between these two scintillators could be used to provide neutron dose rate information. Results of study of neutron detector assembled of two Li(Ce) scintillators and NP100H moderator are presented.
STUDIES ON THE MECHANISM OF ERYTHROPOIETIC STIMULATION IN PARABIOTIC RATS DURING HYPOXIA (1950)

Abstract Chronic hypoxemia was induced in one partner of a pair of parabiotic rats by exposure to defined gas mixtures with low oxygen content. The other partner of the pair was kept in normal atmosphere throughout the experiment and showed normal values of the oxygen saturation of the blood. The erythropoiesis, estimated by the percentage of nucleated red cells in the bone marrow, showed a statistically significant stimulation in both animals. It is, therefore, concluded that under these experimental conditions, the stimulus is not the partial pressure of oxygen in the bone marrow directly but a humoral factor elicited by the hypoxemia in the one partner and transferred to the other one.
Regulation of Gene Expression (1994)

Genetics is a language with rules of composition that give the tissues of the body their special traits. These rules govern the activation of particular subgroups of genes, which determine not only the unique characteristics of a cell type but also whether it remains quiescent, divides, or dies. The timing of gene activation is very important. If genes are activated in the wrong order, a cell may miss a critical step in its development. Moreover, the expression of a gene at the wrong time in the cell's life cycle is a frequent misstep in the progression toward cancer. Understanding the . . .
Heterogeneity of glutathione S-transferase enzyme and gene expression in ovarian carcinoma (1992)

Expression of the three major cytosolic classes of glutathione S-transferases (GST; Pi, Alpha and Mu) was examined by 2D gel analysis and Western blotting of biopsies from 26 patients diagnosed with ovarian carcinoma. In contrast to other tissues, at least one 'constitutive' subunit from each of the three major cytosolic GST classes was expressed. In most cases, pi appeared to be the major form present, although levels of alpha and mu subunit expression were approximately equal to pi in some patients. There was no detectable effect of prior chemotherapy on enzyme activity. Mean transferase activity for primary carcinoma was 79.9 +/- 11.9 (mean +/- SEM; nmol min-1 mg-1), with three pair-matched normal tissues showing minor decreases in transferase activity. One sample, in which a 32% increase in tumour enzyme activity was noted, was from a patient with primary disease and was associated with marked overexpression of a relatively basic form of alpha which was absent from the matching normal tissue, but present in 20% of all tumours examined. RFLP analysis of genomic tumour DNA using a human mu class cDNA probe indicated that at least two of the three mu forms (the 'constitutive' form and one other) observed in ovarian tissue were allelic variants, as a one-to-one correlation was observed between the presence of two Hind III fragments at 13.1 and 2.2 kb and expression of a second, more basic, variable form. This latter form was positively identified as the mu class subunit mu based on Southern analysis and was seen to be present in 40% of the samples examined. However, in the absence of mu expression, at least one other mu class subunit probably corresponding to GST psi, was seen to be present. Thus, at least in ovarian tissues, absence of the mu subunit does not necessarily imply a lack of ability to metabolize mu substrates, as psi has similar catalytic activity. A third mu subunit, probably corresponding to GST phi based on its relatively acidic pI, was also noted in 72% of samples examined, but has unknown substrate specificity. Increased expression of both alpha and mu forms may be of relevance to disease diagnosis and drug response.
Src and phosphatidylinositol 3–kinase mediate soluble E-selectin–induced angiogenesis (2003)

Angiogenesis plays an important role in a variety of pathophysiologic processes, including tumor growth and rheumatoid arthritis. We have previously shown that soluble E-selectin (sE-selectin) is an important angiogenic mediator. However, the mechanism by which sE-selectin mediates angiogenesis is still unknown. In this study, we show that sE-selectin is a potent mediator of human dermal microvascular endothelial cell (HMVEC) chemotaxis, which is predominantly mediated through the Src and the phosphatidylinositiol 3-kinase (PI3K) pathways. Further, sE-selectin induced a 2.2-fold increase in HMVEC tube formation in the Matrigel in vitro assay. HMVECs pretreated with the Src inhibitor (PP2) and the PI3K inhibitor (LY294002) or transfected with Src antisense oligonucleotides or Akt dominant-negative mutants significantly inhibited sE-selectin-mediated HMVEC tube formation. In contrast, HMVECs transfected with an extracellular signal-related kinase 1/2 (ERK1/2) mutant or pretreated with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 failed to show sE-selectin-mediated HMVEC tube formation. Similarly, in the Matrigel-plug in vivo assay, sE-selectin induced a 2.2-fold increase in blood vessel formation, which was significantly inhibited by PP2 and LY294002 but not by PD98059. sE-selectin induced a marked increase in Src, ERK1/2, and PI3K phosphorylation. PI3K and ERK1/2 phosphorylation was significantly inhibited by PP2, thereby suggesting that both of these pathways may be activated via Src kinase. Even though the ERK1/2 pathway was activated by sE-selectin in HMVECs, it seems not to be essential for sE-selectin-mediated angiogenesis. Taken together, our data clearly show that sE-selectin-induced angiogenesis is predominantly mediated through the Src-PI3K pathway.
The CD14 bright CD16+ monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population (2011)

This study is the first to provide a link between the increased frequency of the CD14(bright) CD16+ monocyte subpopulation in RA and the expansion of Th17 cells, which are likely to have a role in the pathogenesis of autoimmunity.
Thymus-dependent antiidiotype and anti-antiidiotype responses to a dinitrophenyl-specific monoclonal antibody. (1990)

BALB/c mice were inoculated i.p. with graded doses of a DNP-specific, IgM mAb (designated 57.1). Injection with unmodified 57.1 in the absence of adjuvants resulted in the generation of an anti-Id response (Ab2) and an anti-anti-Id response (Ab3). The generation of serum anti-Id antibodies was found to be thymus dependent. Nude mice immunized with 57.1 were unable to produce a serum Ab2 response above nonimmunized controls whereas euthymic mice receiving identical doses of 57.1 produced strong Ab2 responses. To examine the specificity of serum anti-Id, sera from mice receiving 57.1 were screened against a panel of mAb representing at least five distinct VH gene families. Serum titers were significantly higher against 57.1 than against any of the other antibodies in the panel. Three of the antibodies in this panel bind FD5-1, a monoclonal anti-Id (Ab2) that also binds 57.1. However, sera from mice receiving 57.1 bound 57.1 only. Thus, the serum Ab2 response appears to be highly specific for idiotopes on 57.1. The predominant isotype of these anti-Id antibodies was IgG1. The number of isotypes detected increased in a dose dependent manner with all IgG subclasses having anti-Id specificity in sera from animals receiving the higher doses of 57.1. Further analysis of the serum demonstrated that approximately 8% of the Ab2 response was paratope-specific (inhibitable by the monovalent hapten DNP-lysine). The same sera were analyzed for the presence of Ab3 by binding to the monoclonal anti-Id antibody FD5-1. Lower serum titers of Ab3 were generated in comparison to serum titers of Ab2. Analysis of the binding specificity of the Ab3 response revealed that DNP-BSA was able to partially inhibit the binding of serum IgM and IgG Ab3 to FD5-1. A subset of the Ab3 response. Ab1' that is specific for DNP was observed in a direct binding assay where detectable amounts of DNP binding IgM, IgG1, and IgG3 isotypes were present. We have thus described a complete circuit (Ab1----Ab2----Ab3) of antibodies within the Id network by immunizing animals with an unmodified mAb in the absence of Ag or adjuvants.
Expression of oncostatin M in hematopoietic organs (2002)

Murine oncostatin M (OSM), a member of the interleukin-6 (IL-6) -related cytokine subfamily, stimulates definitive hematopoiesis and liver development. The OSM gene was cloned as a cytokine-inducible early response gene in some hematopoietic cell lines. In this study, we performed in situ hybridization to examine the tissue distribution of cells expressing OSM mRNA in the developing and the adult mice. Its gene expression was seen in hematopoietic cells of developing liver from 11.5 days postcoitum (dpc), and persisted to the neonates. From 17.5 dpc, OSM mRNA-positive cells were found in other hematopoietic organs, including bone marrow, thymus, and spleen. The highest levels of gene expression were observed in the adult bone marrow. Most OSM-expressing cells expressed IL-5 receptor alpha subunit, a marker for eosinophil lineage. In addition, some positive cells expressed neutrophil elastase, which was used as a polymorphonuclear neutrophil (PMN) marker. After birth, OSM mRNA was expressed in tissue eosinophils in nonhematopoietic organs, including small intestine, lung, and skin. Our data revealed that eosinophil progenitors and eosinophils as well as PMNs are also an important cellular source of OSM in mice.
C-reactive protein and paroxysmal atrial fibrillation (2001)

These results suggest that CRP has a strong association with PAF and support the hypothesis that CRP is a potent determinant of successful cardioversion of PAF in sinus rhythm.
<title>Investigation of methods for the computerized detection and analysis of mammographic masses</title> (1990)

At present mammography is the most effective method for the early detection of breast cancer1 . Detection and classification of masses in mammograms are among the most important and difficult tasks performed by radiologists. Various studies have indicated that regular mammographic screening can reduce the mortality from breast cancer in women2. Thus mammography may become one of the largest volume x-ray procedures routinely interpreted by radiologists. The miss rate for the radiographic detection of malignant masses ranges from 12 to 30 percent. In addition although general rules exist for the visual differentiation of benign and malignant masses error does occur in the classification of masses with the current methods of radiologic characterization. Thus it is apparent that the efficiency and effectiveness of screening procedures could be increased by use of a computer system that successfully aids the radiologist in detecting and characterizing mammographic masses. We are developing computerized schemes for the automated detection and classification of masses in digital mammograms. The detection scheme utilizes the architectural symmeiry of the left and right breasts and digital bilateralsubtraction techniques in order to increase the conspicuity of the mammographic mass prior to the application of featureextraction techniques. The classification scheme involves the extraction of border information from the mammographic mass in order to quantify the degree of spiculation which is related to the likelihood of malignancy. METHODS Clinical screen/film mammograms were used in the
Three-TFT image sensor for real-time digital X-ray imaging (2006)

A new current-programmed, current-output active TFT image sensor suitable for real-time X-ray imaging (e.g. fluoroscopy) using hydrogenated amorphous silicon (a-Si:H) thin-film-transistor (TFT) technology is introduced. The proposed pixel circuit can successfully compensate for characteristic variations such as mobility and threshold voltage shift in a-Si:H TFTs. Simulation and measurement results show that high on-pixel amplification can be accomplished with this pixel circuit.
The Major Synovial Targets of the Rheumatoid Arthritis-Specific Antifilaggrin Autoantibodies Are Deiminated Forms of the α- and β-Chains of Fibrin (2001)

IgG antifilaggrin autoantibodies (AFA) are the most specific serological markers of rheumatoid arthritis. In epithelial tissues, they recognize citrulline-bearing epitopes present on various molecular forms of (pro)filaggrin. Histological analysis of rheumatoid synovial membranes with an Ab to citrulline showed labeling of interstitial amorphous deposits and mononuclear cells of various types. Immunochemical analysis of exhaustive sequential extracts of the same tissues showed that they contain several deiminated (citrulline containing) proteins. Among them, two proteins, p64--78 and p55--61, present in urea-DTT and guanidine extracts, were shown by immunoblotting to be specifically targeted by AFA. By amino-terminal sequencing the proteins were identified as deiminated forms of the alpha- and beta-chains of fibrin, respectively. Their identity was confirmed using several Abs specific for the A alpha- and/or to the B beta-chain of fibrin(ogen). Moreover, AFA-positive rheumatoid arthritis (RA) sera and purified AFA were highly reactive to the A alpha- and B beta-chains of human fibrinogen only after deimination of the molecules by a peptidylarginine deiminase. Autoantibodies affinity purified from a pool of RA sera onto deiminated fibrinogen were reactive toward all of the epithelial and synovial targets of AFA. This confirmed that the autoantibodies to the deiminated A alpha-and B beta-chains of fibrinogen, the autoantibodies to the synovial proteins p64--78 and p55--61, and, lastly, AFA, constitute largely overlapping autoantibody populations. These results show that deiminated forms of fibrin deposited in the rheumatoid synovial membranes are the major target of AFA. They suggest that autoimmunization against deiminated fibrin is a critical step in RA pathogenesis.
Molecular cloning and expression in Escherichia coli of the Bacillus licheniformis bacitracin synthetase 2 gene (1989)

The structural genes for the entire bacitracin synthetase 2 (component II) and for a part of the putative bacitracin synthetase 3 (component III) from Bacillus licheniformis ATCC 10716 were cloned and expressed in Escherichia coli. A cosmid library of B. licheniformis DNA was constructed. The library was screened for the ability to produce bacitracin synthetase by in situ immunoassay using anti-bacitracin synthetase antiserum. A positive clone designated B-15, which has a recombinant plasmid carrying about a 32-kilobase insert of B. licheniformis DNA, was further characterized. Analysis of crude cell extract from B-15 by polyacrylamide gel electrophoresis and Western blotting (immunoblotting) showed that the extract contains two immunoreactant proteins with high molecular weight. One band with a molecular weight of about 240,000 comigrates with bacitracin synthetase 2; the other band is a protein with a molecular weight of about 300,000. Partial purification of the gene products encoded by the recombinant plasmid by gel filtration and hydroxyapatite column chromatography revealed that one gene product catalyzes L-lysine- and L-ornithine-dependent ATP-PPi exchange reactions which are characteristic of bacitracin synthetase 2, and the other product catalyzes L-isoleucine-, L-leucine, L-valine-, and L-histidine-dependent ATP-PPi exchange activities, suggesting the activities of a part of bacitracin synthetase 3. Subcloning experiments indicated that the structural gene for bacitracin synthetase 2 is located near the middle of the insert.
Telodendrimer-based Nanocarriers for the Treatment of Ovarian Cancer (2013)

PEG-dendritic block copolymer (telodendrimer) is a unique class of polymers with well-defined structures and tunable aggregation properties, which have been recently developed as novel micelle-based nanocarriers. This new class of nanocarrier is highly versatile, robust, multifunctional and has many unique properties for drug delivery that are superior to most other nanocarriers reported in the literature. Reversible crosslinking of micelles is able to minimize the premature drug release during circulation. These crosslinks can be reversed with endogenous and/or exogenous stimuli. To further facilitate the precise delivery of nanoparticle drugs to cancer cells, the nanoparticles surface can be decorated with ovarian cancer targeting ligands. This review is focused on the various strategies used for the design, preparation, pharmacokinetic, biodistribution and preclinical therapeutic applications of telodendrimer-based nanocarriers for drug delivery in the treatment of ovarian cancer. Lastly, future perspectives for the development of ovarian cancer-targeting telodendrimer nanotherapeutics are also explored.
A randomized, double-blind, placebo-controlled phase 3 study of the relative efficacy and tolerability of tapentadol IR and oxycodone IR for acute pain (2009)

Clinically meaningful and statistically significant improvements were observed with tapentadol IR 50 mg and 75 mg compared with placebo for the relief of moderate-to-severe acute pain after orthopedic surgery. Tapentadol IR 50 mg and 75 mg were non-inferior to oxycodone HCl IR 10 mg for the treatment of acute pain based on the primary efficacy endpoint of SPID(48) and the pre-specified margin of 48 points. The incidence of nausea and/or vomiting was statistically significantly lower for tapentadol IR 50 mg and numerically lower for tapentadol IR 75 mg than for oxycodone HCl IR 10 mg.
Cleavage-Sensing Redox Peptide Monolayers for the Rapid Measurement of the Proteolytic Activity of Trypsin and α-Thrombin Enzymes (2010)

Ferrocene (Fc)-labeled peptides are end-grafted onto gold electrodes via a flexible polyethylene glycol (PEG) linker, and their ability to act as substrates for proteolytic enzymes trypsin and alpha-thrombin is investigated by cyclic voltammetry. It is shown that whereas a short Fc-tetrapeptide substrate is rapidly cleaved by trypsin, a longer Fc-heptapeptide substrate is required for alpha-thrombin detection. However, in both cases it is observed that not all of the Fc-peptide chains present on the electrode surface are cleavable by the proteases and that the cleavage yield is actually controlled by the surface coverage in the Fc-peptide. Surface dilution of the Fc-peptide using a backfilling molecule such as MCH (6-mercapto-1-hexanol) was required to obtain a cleavage yield larger than 80%. The kinetics of Fc-peptide cleavage by trypsin or alpha-thrombin is then shown to be adequately described by Michaelis Menten kinetics, allowing enzymatic constants k(cat) and K(M) to be determined. The obtained rate constant values showed that the affinity of the enzymes for their respective Fc-peptide substrates is very high (i.e., low K(M) values) whereas that for the cleavage step itself is relatively low (low k(cat) values). Partial compensation of these parameters yields a fast response of the Fc-peptide electrodes to the proteases in solution in the 1-1000 nM range. The type of molecule used to backfill the Fc-peptide layers, either MCH or PEG(6) chains, is shown to modulate the activity of the proteases versus the Fc-peptide layers: in particular, the PEG(6) diluent is specifically shown to decrease the ability of alpha-thrombin to cleave its Fc-peptide substrate whereas trypsin activity is unaffected by the presence of PEG chains.