gebhart/patrepeval huggingface dataset:
Instabilotyping: comprehensive identification of frameshift mutations caused by coding region microsatellite instability. (2001)

Coding region frameshift mutation caused by microsatellite instability (MSI) is one mechanism contributing to tumorigenesis in cancers with MSI in high frequency. Mutation of TGFBR2 is one example of this process. To identify additional examples, a large-scale genomic screen of coding region microsatellites was conducted. 1115 coding homopolymeric loci with six or more nucleotides were identified in an online genetic database. Mutational screening was performed at 152 of these loci in 46 colorectal tumors with MSI in high frequency. Nine loci were mutated in > or =20% of tumors, 10 loci in 10-20%, 24 loci in 5-10%, 43 loci in <5%, and 66 loci were not mutated in any tumors. The most frequently mutated novel loci were the activin type II receptor gene (58.1%), SEC63 (48.8%), AIM 2 (47.6%), a gene encoding a subunit of the NADH-ubiquinone oxidoreductase complex (27.9%), a homologue of mouse cordon-bleu (23.8%), and EBP1/PA2G4 (20.9%). This genome-wide approach identifies coding region MSI in genes or pathways not implicated previously in colorectal tumorigenesis, which may merit functional study or other additional analysis.
Normal Ureter Size on Unenhanced Helical CT (2004)

Three millimeters should be considered the upper limit of normal size for nonobstructed ureters on unenhanced helical CT.
Autoimmune myocarditis induced in mice by cardiac C-protein. Cloning of complementary DNA encoding murine cardiac C-protein and partial characterization of the antigenic peptides. (1994)

Autoimmune myocarditis is considered to play a major role in the pathogenesis of dilated cardiomyopathy. A new autoimmune myocarditis model was attained by repeated immunization using murine cardiac C-protein with the immunological adjuvant, Klebsiella pneumoniae O3 lipopolysaccharide. For further analysis of a pathological epitope, the cDNA encoding C-protein was isolated; a fusion protein encoded by part of this cDNA induced myocarditis in SMA mice as well as in three other strains: DBA/1J (H-2q), O20/A (H-2pz1), and SJL (H-2s). The nucleotide sequence and its deduced amino acid analysis revealed that this protein had immunoglobulin-like and fibronectin-like repeats. This study provides a new animal model of autoimmune myocarditis which may shed light on the pathogenesis of dilated cardiomyopathy.
Enhanced room-temperature piezoconductance of metal–semiconductor hybrid structures (2003)

Metal–semiconductor hybrids (MSHs) are found to exhibit enhanced room-temperature piezoconductance in the presence of uniaxial tensile strain. The magnitude of the enhanced piezoconductance is more than five times greater than that of the homogeneous semiconductor alone and is strongly dependent on both the location and properties of the metal–semiconductor interface. MSHs may be useful in determining the electrical properties of low-resistance metal contacts on semiconductors.
High-Frequency Ultrasound in the Evaluation of Pharmacological Effects on the Skin (2002)

In 1987, the introduction of two 20-MHz B- (brightness-) scan ultrasound systems with axial and lateral resolution of 200 microm and 75-80 microm, respectively, rendered two-dimensional sonographic imaging in dermatology possible. Since then cutaneous sonography has increasingly been used to investigate drug effects on human skin. Both unwanted and wanted effects have been studied, including skin thinning due to repeated glucocorticoid application and reduction of skin thickening in hyperplastic disorders such as psoriasis vulgaris due to various treatment approaches. The resolution of 20-MHz ultrasound is sufficient for studying pathological changes and pharmacological effects in the dermis and the subcutaneous fat; for assessing the epidermis, frequencies between 50 and 100 MHz may prove to be more effective.
Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans (1997)

Glucagon-like peptide 1 (GLP-1) has been shown to inhibit gastric emptying of liquid meals in type 2 diabetic patients. It was the aim of the present study to compare the action of physiological and pharmacological doses of intravenous GLP-1-(7-36) amide and GLP-1-(7-37) on gastric emptying in normal volunteers. Nine healthy subjects participated (26 +/- 3 yr; body mass index 22.9 +/- 1.6 kg/m2; hemoglobin A1C 5.0 +/- 0.2%) in five experiments on separate occasions after an overnight fast. A nasogastric tube was positioned for the determination of gastric volume by use of a dye-dilution technique (phenol red). GLP-1-(7-36) amide (0.4, 0.8, or 1.2 pmol.kg-1.min-1), GLP-1-(7-37) (1.2 pmol.kg-1.min-1), or placebo was infused intravenously from -30 to 240 min. A liquid meal (50 g sucrose, 8% amino acids, 440 ml, 327 kcal) was administered at 0 min. Glucose, insulin, and C-peptide were measured over 240 min. Gastric emptying was dose dependently slowed by GLP-1-(7-36) amide (P < 0.0001). Effects of GLP-1-(7-37) at 1.2 pmol.kg-1.min-1 were virtually identical. GLP.1 dose dependently stimulated fasting insulin secretion (-30 to 0 min) and slightly reduced glucose concentrations. After the meal (0-240 min), integrated incremental glucose (P < 0.0001) and insulin responses (P = 0.01) were reduced (dose dependently) rather than enhanced. In conclusion, 1) GLP-1-(7-36) amide or -(7-37) inhibits gastric emptying also in normal subjects, 2) physiological doses (0.4 pmol.kg-1.min-1) still have a significant effect, 3) despite the known insulinotropic actions of GLP-1-(7-36) amide and -(7-37), the net effect of administering GLP-1 with a meal is no change or a reduction in meal-related insulin responses. These findings suggest a primarily inhibitory function for GLP-1 (ileal brake mechanisms).
Polycomb Antagonizes p300/CREB-binding Protein-associated Factor to Silence FOXP3 in a Kruppel-like Factor-dependent Manner (2012)

Inducible gene expression underlies the epigenetically inherited differentiation program of most immune cells. We report that the promoter of the FOXP3 gene possesses two distinct functional states: an "off state" mediated by the polycomb histone methyltransferase complex and a histone acetyltransferase-dependent "on state." Regulating these states is the presence of a Kruppel-like factor (KLF)-containing Polycomb response element. In the KLF10(-/-) mouse, the FOXP3 promoter is epigenetically silenced by EZH2 (Enhancer of Zeste 2)-mediated trimethylation of Histone 3 K27; thus, impaired FOXP3 induction and inappropriate adaptive T regulatory cell differentiation results in vitro and in vivo. The epigenetic transmittance of adaptive T regulatory cell deficiency is demonstrated throughout more than 40 generations of mice. These results provide insight into chromatin remodeling events key to phenotypic features of distinct T cell populations.
Human antibody response to group A streptococcal teichoic acid (1974)

The immunochemical characteristics and antibody levels in human sera to a specific group A streptococcal teichoic acid (TA) were studied. This phenol-extracted TA had DL-α-glycerophosphate as the major antigen determinant and not N-acetylglucosamine (N-AGA) as measured by an indirect hemagglutination assay (IHA). The group A streptococcal carbohydrate (A-CHO), N-AGA, and staphylococcal TA did not inhibit the streptococcal TA reaction. In studies of patients with or without history of acute rheumatic fever (ARF) or rheumatic heart disease (RHD), there was an inverse relationship between magnitude of TA hemagglutinating and A-CHO precipitating antibody (Ab) titers. Age-specific distribution of TA-Ab titers was not characteristic of titers observed against other streptococcal protein or carbohydrate antigens.
JNICodejail (2013)

The Java Native Interface (JNI) allows Java programmers to inter-operate with code written in other languages like C and C++. One reason to use JNI is to get higher performance. Other reasons are to access low-level implementation features not available in pure Java and facilitate the reuse of existing code and libraries. However, the drawback is that native code can be used to compromise the security of the rest of Java.
Anion Transport in Heart (2000)

Anion transport proteins in mammalian cells participate in a wide variety of cell and intracellular organelle functions, including regulation of electrical activity, pH, volume, and the transport of osmolites and metabolites, and may even play a role in the control of immunological responses, cell migration, cell proliferation, and differentiation. Although significant progress over the past decade has been achieved in understanding electrogenic and electroneutral anion transport proteins in sarcolemmal and intracellular membranes, information on the molecular nature and physiological significance of many of these proteins, especially in the heart, is incomplete. Functional and molecular studies presently suggest that four primary types of sarcolemmal anion channels are expressed in cardiac cells: channels regulated by protein kinase A (PKA), protein kinase C, and purinergic receptors (I(Cl.PKA)); channels regulated by changes in cell volume (I(Cl.vol)); channels activated by intracellular Ca(2+) (I(Cl.Ca)); and inwardly rectifying anion channels (I(Cl.ir)). In most animal species, I(Cl.PKA) is due to expression of a cardiac isoform of the epithelial cystic fibrosis transmembrane conductance regulator Cl(-) channel. New molecular candidates responsible for I(Cl.vol), I(Cl.Ca), and I(Cl.ir) (ClC-3, CLCA1, and ClC-2, respectively) have recently been identified and are presently being evaluated. Two isoforms of the band 3 anion exchange protein, originally characterized in erythrocytes, are responsible for Cl(-)/HCO(3)(-) exchange, and at least two members of a large vertebrate family of electroneutral cotransporters (ENCC1 and ENCC3) are responsible for Na(+)-dependent Cl(-) cotransport in heart. A 223-amino acid protein in the outer mitochondrial membrane of most eukaryotic cells comprises a voltage-dependent anion channel. The molecular entities responsible for other types of electroneutral anion exchange or Cl(-) conductances in intracellular membranes of the sarcoplasmic reticulum or nucleus are unknown. Evidence of cardiac expression of up to five additional members of the ClC gene family suggest a rich new variety of molecular candidates that may underlie existing or novel Cl(-) channel subtypes in sarcolemmal and intracellular membranes. The application of modern molecular biological and genetic approaches to the study of anion transport proteins during the next decade holds exciting promise for eventually revealing the actual physiological, pathophysiological, and clinical significance of these unique transport processes in cardiac and other mammalian cells.
A Platelet-Dependent Serum Factor That Stimulates the Proliferation of Arterial Smooth Muscle Cells In Vitro (1974)

Dialyzed serum from clotted monkey blood ("blood serum") promotes the proliferation of monkey arterial smooth muscle cells in culture, but dialyzed serum prepared from recalcified platelet-poor plasma ("plasma serum") is much less effective. Addition of platelets and calcium to platelet-poor plasma increases the activity of plasma serum to the same level achieved with blood serum. Furthermore, addition to plasma serum of a platelet-free supernatant prepared by exposing purified platelets to thrombin also stimulates the proliferation of smooth muscle cells. Thus, much of the growth-promoting activity of dialyzed serum is directly or indirectly derived from platelets. This finding has important implications for the response of arteries to localized injury and provides a key to further understanding of the role of factors derived from blood serum in promoting cell proliferation in vitro.
Lipid hydroperoxides greatly increase the rate of oxidative catabolism of all-trans-retinoic acid by human cell culture microsomes genetically enriched in specified cytochrome P-450 isoforms. (1993)

Cytochrome P-450 enzymes have been implicated in the oxidative catabolism of all-trans-retinoic acid (RA), a process that is accelerated by exposure to RA in cultured cells and rodents, and also in patients receiving RA as treatment for cancer (J.F.R. Muindi et al., Cancer Res., 52: 2138, 1992; Blood, 79: 299, 1992). Accelerated oxidation of RA could arise from an induction of RA-catabolizing P-450 isoforms or from an increase in oxidative cofactors. We have examined the efficiency of NADPH/O2 and lipid hydroperoxides (LOOH) to support oxidation of RA using human cell microsomes genetically enriched in different P-450 isoforms. The observed rate of RA oxidation using the NADPH/O2 system was slow for all isoforms (6-23 pmol/mg protein/min). LOOH-mediated oxidation was much faster (24-1078 pmol/mg protein/min), not isoform specific, but dependent upon the chemical nature of the LOOH. The order of efficiency of RA oxidation using LOOH was 13-hydroperoxy[S-(E,Z)]-9,11-octadecadienoic acid > 5-hydroperoxy[S-(E,Z,Z,Z)]-6,6,11,14-eicosatetraenoic acid > prostaglandin G2 > cumene hydroperoxide > tert-butylhydroperoxide > H2O2. Whereas submicromolar concentrations of 13-hydroperoxy[S-(E,Z)]- 9,11-octadecadienoic and 5-hydroperoxy[S-(E,Z,Z,Z)]-6,6,11,14- eicosatetraenoic acid oxidized RA at appreciable rates, micromolar concentrations were required for the other LOOH. These observations suggest that physiological LOOH, generated by the arachidonic acid-lipoxygenase system, may be involved in the self-induced oxidative catabolism of RA.
HIGH CONDUCTIVITY COPPER-RICH Cu-Zr ALLOYS (1960)

A high-purity Cu--Zr alloy system was investigated. The Zr content of the alloys studied varied from 0.003 to 0.23%. The Solid solubility of Zr in Cu and some physical and mechanical properties of the alloys were determined. By proper heat treatment, Cu-- Zr alloy can develop a high electrical conductivity and resistance to softening at temperatures up to 500 deg C. This combination of desirable properties makes this alloy superior to other commercial copper base alloys for use in the electrical conductor field. (auth)
Role of cyclic GMP in gene regulation (2005)

Cyclic GMP is produced in response to nitric oxide and natriuretic peptides; cGMP is a key regulator of cell proliferation, differentiation, and apoptosis, and plays an important role in many (patho)physiological processes such as synaptic plasticity, angiogenesis, inflammation, and cardiac hypertrophy. The regulation of gene expression by cGMP has been recognized relatively recently, but cGMP-mediated increases or decreases in the mRNA expression of >60 different genes have been described, and gene expression profiling is just beginning to contribute to the growing list of cGMP-regulated genes. Deletion or over-expression experiments in mice involving components of the cGMP signaling pathway have contributed to our understanding of long-term effects of altered cGMP signaling, including the regulation of gene expression. We will discuss transcriptional and post-transcriptional mechanisms of gene regulation by cGMP, and review specific transcription factors and RNA binding proteins targeted by cGMP. Some of the effects of cGMP on gene expression are indirect, through cGMP modulation of other signaling pathways, e. g. mitogen-activated protein kinase pathways. However, some effects of cGMP can be directly attributed to cGMP regulation of specific transcription factors such as CREB, TFII-I or c-Fos, and are mediated by cGMP-dependent protein kinases. We will discuss specific genes regulated by cGMP in the context of their contribution to particular (patho)physiologic processes regulated by cGMP.
Use of Species-Directed 16S rRNA Gene PCR Primers for Detection of Atopobium vaginae in Patients with Bacterial Vaginosis (2004)

Recent studies suggest that the association between a metronidazole-resistant anaerobe, Atopobium vaginae, and bacterial vaginosis (BV) warrants further investigation. In the present study, specific primers enhanced detection of A. vaginae and provided additional evidence that this bacterium is prevalent among patients with BV but absent among patients with normal vaginal flora.
Progestins Both Stimulate and Inhibit Breast Cancer Cell Cycle Progression while Increasing Expression of Transforming Growth Factor α, Epidermal Growth Factor Receptor, c- fos, and c- myc Genes (1991)

This study documents a biphasic change in the rate of cell cycle progression and proliferation of T-47D human breast cancer cells treated with synthetic progestins, consisting of an initial transient acceleration in transit through G1, followed by cell cycle arrest and growth inhibition. Both components of the response were mediated via the progesterone receptor. The data are consistent with a model in which the action of progestins is to accelerate cells already progressing through G1, which are then arrested early in G1 after completing a round of replication, as are cells initially in other phases of the cell cycle. Such acceleration implies that progestins act on genes or gene products which are rate limiting for cell cycle progression. Increased production of epidermal growth factor and transforming growth factor alpha, putative autocrine growth factors in breast cancer cells, does not appear to account for the initial response to progestins, since although the mRNA abundance for these growth factors is rapidly induced by progestins, cells treated with epidermal growth factor or transforming growth factor alpha did not enter S phase until 5 to 6 h later than those stimulated by progestin. The proto-oncogenes c-fos and c-myc were rapidly but transiently induced by progestin treatment, paralleling the well-known response of these genes to mitogenic signals in other cell types. The progestin antagonist RU 486 inhibited progestin regulation of both cell cycle progression and c-myc expression, suggesting that this proto-oncogene may participate in growth modulation by progestins.
High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. (2003)

Thyroid papillary cancers (PTCs) are associated with activating mutations of genes coding for RET or TRK tyrosine kinase receptors, as well as of RAS genes. Activating mutations of BRAF were reported recently in most melanomas and a small proportion of colorectal tumors. Here we show that a somatic mutation of BRAF, V599E, is the most common genetic change in PTCs (28 of 78; 35.8%). BRAF(V599E) mutations were unique to PTCs, and not found in any of the other types of differentiated follicular neoplasms arising from the same cell type (0 of 46). Moreover, there was no overlap between PTC with RET/PTC, BRAF, or RAS mutations, which altogether were present in 66% of cases. The lack of concordance for these mutations was highly unlikely to be a chance occurrence. Because these signaling proteins function along the same pathway in thyroid cells, this represents a unique paradigm of human tumorigenesis through mutation of three signaling effectors lying in tandem.
Modulation of Gemcitabine (2′,2′-Difluoro-2′-Deoxycytidine) Pharmacokinetics, Metabolism, and Bioavailability in Mice by 3,4,5,6-Tetrahydrouridine (2008)

Abstract Purpose: In vivo, 2′,2′-difluoro-2′-deoxycytidine (dFdC) is rapidly inactivated by gut and liver cytidine deaminase (CD) to 2′,2′-difluoro-2′-deoxyuridine (dFdU). Consequently, dFdC has poor oral bioavailability and is administered i.v., with associated costs and limitations in administration schedules. 3,4,5,6-Tetrahydrouridine (THU) is a potent CD inhibitor with a 20% oral bioavailability. We investigated the ability of THU to decrease elimination and first-pass effect by CD, thereby enabling oral dosing of dFdC. Experimental Design: A liquid chromatography-tandem mass spectrometry assay was developed for plasma dFdC and dFdU. Mice were dosed with 100 mg/kg dFdC i.v. or orally with or without 100 mg/kg THU i.v. or orally. At specified times between 5 and 1,440 min, mice (n = 3) were euthanized. dFdC, dFdU, and THU concentrations were quantitated in plasma and urine. Results: THU i.v. and orally produced concentrations &amp;gt;4 μg/mL for 3 and 2 h, respectively, whereas concentrations of &amp;gt;1 μg/mL have been associated with near-complete inhibition of CD in vitro. THU i.v. decreased plasma dFdU concentrations but had no effect on dFdC plasma area under the plasma concentration versus time curve after i.v. dFdC dosing. Both THU i.v. and orally substantially increased oral bioavailability of dFdC. Absorption of dFdC orally was 59%, but only 10% passed liver and gut CD and eventually reached the systemic circulation. Coadministration of THU orally increased dFdC oral bioavailability from 10% to 40%. Conclusions: Coadministration of THU enables oral dosing of dFdC and warrants clinical testing. Oral dFdC treatment would be easier and cheaper, potentially prolong dFdC exposure, and enable exploration of administration schedules considered impractical by the i.v. route.
GAD2 on Chromosome 10p12 Is a Candidate Gene for Human Obesity (2003)

The gene GAD2 encoding the glutamic acid decarboxylase enzyme (GAD65) is a positional candidate gene for obesity on Chromosome 10p11-12, a susceptibility locus for morbid obesity in four independent ethnic populations. GAD65 catalyzes the formation of gamma-aminobutyric acid (GABA), which interacts with neuropeptide Y in the paraventricular nucleus to contribute to stimulate food intake. A case-control study (575 morbidly obese and 646 control subjects) analyzing GAD2 variants identified both a protective haplotype, including the most frequent alleles of single nucleotide polymorphisms (SNPs) +61450 C>A and +83897 T>A (OR = 0.81, 95% CI [0.681-0.972], p = 0.0049) and an at-risk SNP (-243 A>G) for morbid obesity (OR = 1.3, 95% CI [1.053-1.585], p = 0.014). Furthermore, familial-based analyses confirmed the association with the obesity of SNP +61450 C>A and +83897 T>A haplotype (chi(2) = 7.637, p = 0.02). In the murine insulinoma cell line betaTC3, the G at-risk allele of SNP -243 A>G increased six times GAD2 promoter activity (p < 0.0001) and induced a 6-fold higher affinity for nuclear extracts. The -243 A>G SNP was associated with higher hunger scores (p = 0.007) and disinhibition scores (p = 0.028), as assessed by the Stunkard Three-Factor Eating Questionnaire. As GAD2 is highly expressed in pancreatic beta cells, we analyzed GAD65 antibody level as a marker of beta-cell activity and of insulin secretion. In the control group, -243 A>G, +61450 C>A, and +83897 T>A SNPs were associated with lower GAD65 autoantibody levels (p values of 0.003, 0.047, and 0.006, respectively). SNP +83897 T>A was associated with lower fasting insulin and insulin secretion, as assessed by the HOMA-B% homeostasis model of beta-cell function (p = 0.009 and 0.01, respectively). These data support the hypothesis of the orexigenic effect of GABA in humans and of a contribution of genes involved in GABA metabolism in the modulation of food intake and in the development of morbid obesity.
Fluorescence study of the topology of messenger RNA bound to the 30S ribosomal subunit of Escherichia coli (1991)

Short RNAs (25-36 nucleotides in length) with sequences of the translational initiation region of bacteriophage R17 protein A mRNA were produced by chemical and in vitro transcription techniques and labeled at their 5' or 3' ends with fluorescent probes. The interaction of these labeled RNAs with the 30S subunit of Escherichia coli was studied by using fluorescence spectroscopic techniques. All the RNAs bound tightly to 30S subunits (Kd less than or equal to 200 nM). Resonance energy transfer experiments demonstrated the proximity of the ends of the RNAs to each other and to two fluorescently labeled sites on the 30S subunit: the 3' end of 16S rRNA and the cysteine residue of ribosomal protein S21. By using the distances calculated from energy transfer between the 3' end of 16S rRNA and the ends of RNAs of varying lengths, a topological map of this region of mRNA on the 30S subunit was constructed.