gebhart/patrepeval huggingface dataset:
Farnesol modification of Kirsten-ras exon 4B protein is essential for transformation. (1990)

Oncogenic forms of ras proteins are synthesized in the cytosol and must become membrane associated to cause malignant transformation. Palmitic acid and an isoprenoid (farnesol) intermediate in cholesterol biosynthesis are attached to separate cysteine residues near the C termini of H-ras, N-ras, and Kirsten-ras (K-ras) exon 4A-encoded proteins. These lipid modifications have been suggested to promote or stabilize the association of ras proteins with membranes. Because preventing isoprenylation also prevents palmitoylation, examining the importance of isoprenylation alone has not been possible. However, the oncogenic human [Val12]K-ras 4B protein is not palmitoylated but is isoprenylated, membrane associated, and fully transforming. We therefore constructed mutant [Val12]K-ras 4B proteins that were not isoprenylated to examine the effects of isoprenylation in the absence of palmitoylation. The nonisoprenylated mutant proteins both failed to associate with membranes and did not transform NIH 3T3 cells. In addition, inhibition of isoprenoid and cholesterol synthesis with the drug compactin also decreased [Val12]K-ras 4B protein isoprenylation and membrane association. These results unequivocally demonstrate that isoprenylation, rather than palmitoylation, is essential for ras membrane binding and ras transforming activity. These findings clearly indicate the biological significance of ras protein modification by farnesol and suggest that this modification may be important for facilitating the processing, trafficking, and biological activity of other isoprenylated proteins. Because K-ras is the most frequently activated oncogene in a wide spectrum of human malignancies, study of this pathway could lead to important therapeutic treatments.
Automatic verification of implementations of large circuits against HDL specifications (1997)

This paper addresses the problem of verifying the correctness of gate-level implementations of large synchronous sequential circuits with respect to their higher level specifications in a hardware description language (HDL). The verification strategy is to verify containment of the finite state machine (FSM) represented by the HDL description in the gate-level FSM by computing pairs of compatible states. This formulation of the verification problem dissociates the verification process from the specification of initial states, whose encoding may be unknown or obscured during optimization and also enables verification of reset circuitry. To make verification of large circuits with merged data path and control tractable, the concept of strong containment is introduced. This is a conservative approach which exploits correspondence between data path-registers in the two descriptions without requiring any correspondence between the control units. We also present an important result and associated proof that computation of pairs of equivalent or compatible states can be achieved by considering subsets of the circuit outputs. Consequently, verification of circuits with large and diverse input-output sets, which was previously intractable due to lack of a single effective variable order for the binary decision diagrams (BDD's), is now feasible. Experimental results are presented for the verification of several industry level circuits.
A pivotal involvement of IFN‐' in the pathogenesis of acetaminophen‐induced acute liver injury (2002)

In wild-type BALB/c mice, i.p. administration of acetaminophen (APAP; 750 mg/kg) induced intrahepatic IFN-gamma mRNA expression and a marked increase in serum transaminase levels, leading to acute lethality of approximately 45%. Histopathological examination showed centrilobular hepatic necrosis with leukocyte infiltration and a large number of apoptotic hepatocytes 10 and 24 h after APAP challenge. mRNA expression of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, interleukin (IL) 1alpha, IL-1beta, IL-6, tumor necrosis factor alpha, monocyte chemoattractant protein 1, macrophage inflammatory protein (MIP) 1alpha, MIP-2, KC, IP-10, Mig, Fas, and inducible nitric oxide synthase was enhanced in the liver of wild-type mice injected with APAP. To clarify the role of IFN-gamma in this process, IFN-gamma-deficient mice were treated in the same manner. All IFN-gamma-deficient mice survived with reduced serum transaminase elevation and attenuated hepatic necrosis, leukocyte infiltration, and hepatocyte apoptosis. The gene expression of all molecules was significantly attenuated in IFN-gamma-deficient mice. Administration of an anti-IFN-gamma neutralizing antibody even 2 or 8 h after APAP challenge to wild-type mice alleviated APAP-induced liver injury, and all mice survived. Thus, IFN-gamma is responsible for APAP-induced liver injury by mediating leukocyte infiltration, hepatocyte apoptosis, and NO production as well as cytokine and chemokine production. Moreover, immunoneutralization of IFN-gamma may be therapeutically effective for developing APAP-induced liver injury.
Comparative single-dose pharmacokinetics of amantadine hydrochloride and rimantadine hydrochloride in young and elderly adults (1985)

The single-dose pharmacokinetics of amantadine hydrochloride and rimantadine hydrochloride were compared in a randomized, two-period, crossover study involving six young (less than or equal to 35 years) and six elderly (less than or equal to 60 years) adults. Subjects ingested single 200-mg oral doses after an overnight fast, and serial plasma (0 to 96 h), nasal mucus (0 to 8 h), and urine (0 to 24 h) samples were collected for assay of drug concentration by electron capture gas chromatography. For both groups combined, rimantadine differed significantly from amantadine in peak plasma concentration (mean +/- standard deviation, 0.25 +/- 0.06 versus 0.65 +/- 0.22 micrograms/ml), plasma elimination half-life (36.5 +/- 15 versus 16.7 +/- 7.7 h), and percentage of administered dose excreted unchanged in urine (0.6 +/- 0.8 versus 45.7 +/- 15.7%). No significant age-related differences were noted for rimantadine. Urinary excretion (0 to 24 h) of rimantadine and its hydroxylated metabolites averaged 19% of the administered dose. The maximum nasal mucus drug concentration was similar for both drugs (0.42 +/- 0.25 versus 0.45 +/- 0.32 micrograms/g), and the ratio of maximum nasal mucus to plasma concentration was over twofold higher after rimantadine than after amantadine. These findings may in part explain the clinical effectiveness of rimantadine in influenza A virus infections at dosages that have lower toxicity than those of amantadine.
Terbium and Rhodamine as Labels in a Homogeneous Time-resolved Fluorometric Energy Transfer Assay of the β Subunit of Human Chorionic Gonadotropin in Serum (1999)

Although less sensitive than heterogeneous, dissociation-enhanced europium-based separation assays, the presented assay format has advantages such as speed and simplicity, which make the assay format ideal for assays requiring a high throughput.
Sacral Nerve Stimulation Can Be Successful in Patients With Ultrasound Evidence of External Anal Sphincter Disruption (2005)

Sacral nerve stimulation may successfully restore bowel continence in some patients with endoanal ultrasound evidence of a defect in their external anal sphincter.
Characterization of single magnetic particles with InAs quantum-well Hall devices (2004)

We have measured the magnetic dipolar field from individual micron-sized spherical ferromagnetic particles. The particles were positioned using an atomic force microscope and measured using submicron Hall sensors fabricated from an InAs single-quantum-well heterostructure with lateral dimensions of 0.5–2.5μm. The magnetic moment of individual particles has been measured, verifying their dipolar moment. We also demonstrate a scaling rule for the detection of individual particles which is relevant to the design of biosensors.
Oxidation of Linseed Oil (1950)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidation of Linseed OilP. S. Hess and G. A. O'HareCite this: Ind. Eng. Chem. 1950, 42, 7, 1424–1431Publication Date (Print):July 1, 1950Publication History Published online1 May 2002Published inissue 1 July 1950https://pubs.acs.org/doi/10.1021/ie50487a044https://doi.org/10.1021/ie50487a044research-articleACS PublicationsRequest reuse permissionsArticle Views651Altmetric-Citations55LEARN 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 options Get e-Alerts
Improving ethanol yield in acetate-reducing Saccharomyces cerevisiae by cofactor engineering of 6-phosphogluconate dehydrogenase and deletion of ALD6 (2016)

The combination of NAD(+)-dependent 6-phosphogluconate dehydrogenase expression and deletion of ALD6 resulted in a marked increase in the amount of acetate that was consumed in these proof-of-principle experiments, and this concept is ready for further testing in industrial strains as well as in hydrolysates. Altering the cofactor specificity of the oxidative branch of the pentose-phosphate pathway in S. cerevisiae can also be used to increase glycerol production in wine fermentation and to improve NADH generation and/or generation of precursors derived from the pentose-phosphate pathway in other industrial applications of this yeast.
Efficacy of Continuous Low-Dose hANP Administration in Patients Undergoing Emergent Coronary Artery Bypass Grafting for Acute Coronary Syndrome (2007)

It is therefore considered that hANP might not only be effective for overcoming some major shortcomings of cardiopulmonary bypass, but also might be effective to attenuate ischemia-reperfusion injury, protect the myocardium, have an anti-arrhythmic effect, and suppress left ventricular remodeling.
Mode of action of AraR, the key regulator of l‐arabinose metabolism in Bacillus subtilis (1999)

The AraR protein is a negative regulator involved in L-arabinose-inducible expression of the Bacillus subtilis araABDLMNPQ-abfA metabolic operon and of the araE/araR genes that are organized as a divergent transcriptional unit. The two ara gene clusters are found at different positions in the bacterial chromosome. AraR was overproduced in Escherichia coli and purified to more than 95% homogeneity. AraR binds specifically to DNA fragments carrying the promoter region of the ara genes. DNase I protection assays showed that AraR binds to two sequences within the promoters of the araABDLMNPQ-abfA operon and the araE gene, and to one sequence in the araR promoter. The AraR target sequences are palindromic and share high identity, defining a 16 bp AraR consensus operator sequence showing half-symmetry, ATTTGTAC. Binding of AraR to DNA was inhibited by L-arabinose but not by other sugars. The two operator sites within the araABDLMNPQ-abfA operon and araE promoters are located on the same side of the DNA helix, and a pattern of enhanced and diminished DNase I cleavage was observed between them, but not in the araR promoter. Quantitative DNase I footprinting in DNA templates containing one, two or three AraR binding sites showed that the repressor binds cooperatively to the two operator sites within the metabolic operon and araE promoters but not to the site located in the araR promoter. These results are consistent with two modes for AraR transcriptional repression that might correlate with different physiological requirements: a high level of repression is achieved by DNA bending requiring two in-phase operator sequences (metabolic operon and araE transport gene), whereas binding to a single operator, which autoregulates araR expression, is 10-fold less effective.
Hyperglycemia and cardiovascular disease in type 2 diabetes. (1999)

Cardiovascular disease (coronary heart disease, stroke, peripheral vascular disease) is the most important cause of mortality and morbidity among patients with type 2 diabetes. Conventional risk factors contribute similarly to macrovascular complications in patients with type 2 diabetes and nondiabetic subjects, and therefore, other explanations have been sought for enhanced atherothrombosis in type 2 diabetes. Among characteristics specific for type 2 diabetes, hyperglycemia has recently been a focus of keen research. A recent meta-analysis of 20 studies on nondiabetic subjects has demonstrated that in the nondiabetic range of glycemia (<6.1 mmol/l), increased glucose is already associated with an increased risk for cardiovascular disease. Similarly, 12 recent prospective studies have convincingly indicated that hyperglycemia contributes to cardiovascular complications in patients with type 2 diabetes. The recently published U.K. Prospective Diabetes Study has shown that intensive glucose control reduces effectively microvascular complications among patients with type 2 diabetes, but that its effect on the prevention of cardiovascular complications was limited. Given the fact that in the U.K. Prospective Diabetes Study, none of the treatment modalities was particularly effective in reducing glucose, this underestimates the true potential of the correction of hyperglycemia in the prevention of cardiovascular disease in type 2 diabetes. However, in addition to intensive therapy of hyperglycemia, other conventional risk factors should also be normalized to prevent cardiovascular disease in patients with type 2 diabetes.
SAGD Optimization With Air Injection (2007)

Abstract This paper discusses the recent patent application filed by EnCana Corporation on the use of air injection to improve the performance of steam assisted gravity drainage (SAGD). EnCana's SAGD/Air Injection process employs standard SAGD well-pair infrastructure. It optimizes between the ability of steam to preheat the reservoir during SAGD and the superior (follow-up) oil displacement efficiency of in-situ combustion. Operationally, air injection is initiated after thermal communication has been established between well-pairs with steam. One interesting feature of this operating strategy is that down-hole bulk separation of oil and gas occurs which facilitates (a) efficient monitoring and control of the combustion, (b) design of surface facilities, and (c) corrosion mitigation. Laboratory combustion tube tests are presented that confirm the ability to initiate and sustain combustion, as well as mobilize residual oil saturation to steam, within a SAGD chamber. These experiments were initialized at oil saturations and conditions representative of those in a steam chamber. The residual oil saturations were determined from a full-hole core taken in the vicinity of a mature SAGD well-pair at Foster Creek. Numerical simulations of post-SAGD air injection are presented that suggest the ability to displace and produce oil banks between well-pairs and that recovery factor can be increased up to 8% of the original oil-in-place over conventional SAGD. The simulations show oil production rates and recovery factor are expected to increase with higher air injection rates. However, instantaneous air-oil ratios, which are indicative of operating costs, also increase. Thus there is an optimum continuous air injection rate that maximizes profitability. Simulations further indicate that it is possible to recycle flue gases in the injection stream without affecting oil recovery.
MPEG-H 3D Audio—The New Standard for Coding of Immersive Spatial Audio (2015)

The science and art of Spatial Audio is concerned with the capture, production, transmission, and reproduction of an immersive sound experience. Recently, a new generation of spatial audio technology has been introduced that employs elevated and lowered loudspeakers and thus surpasses previous `surround sound' technology without such speakers in terms of listener immersion and potential for spatial realism. In this context, the ISO/MPEG standardization group has started the MPEG-H 3D Audio development effort to facilitate high-quality bitrate-efficient production, transmission and reproduction of such immersive audio material. The underlying format is designed to provide universal means for carriage of channel-based, object-based and Higher Order Ambisonics based input. High quality reproduction is provided for many output formats from 22.2 and beyond down to 5.1, stereo and binaural reproduction-independently of the original encoding format, thus overcoming the incompatibility between various 3D formats. This paper provides an overview of the MPEG-H 3D Audio project and technology and an assessment of the system capabilities and performance.
性别、职业与亲密伴侣间的暴力——男性职业在家庭暴力中的延伸和暴力代偿 (2005)

男性所从事的工作是否会影响他们在家庭中对其女伴实施暴力?研究者们采用多种理论视角，分析了影响暴力行为的多个变量，但他们大都忽视了男性工作职业对向女性实施暴力的潜在影响(Johnson&Ferraro，2000)。同样，“职业——家庭”关系研究者虽然就职业对家庭生活的影响有很多分析，
Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells (2011)

Drugs that target novel surfaces on the androgen receptor (AR) and/or novel AR regulatory mechanisms are promising alternatives for the treatment of castrate-resistant prostate cancer. The 52 kDa FK506 binding protein (FKBP52) is an important positive regulator of AR in cellular and whole animal models and represents an attractive target for the treatment of prostate cancer. We used a modified receptor-mediated reporter assay in yeast to screen a diversified natural compound library for inhibitors of FKBP52-enhanced AR function. The lead compound, termed MJC13, inhibits AR function by preventing hormone-dependent dissociation of the Hsp90-FKBP52-AR complex, which results in less hormone-bound receptor in the nucleus. Assays in early and late stage human prostate cancer cells demonstrated that MJC13 inhibits AR-dependent gene expression and androgen-stimulated prostate cancer cell proliferation.
Oncolytic Specificity of Newcastle Disease Virus Is Mediated by Selectivity for Apoptosis-Resistant Cells (2011)

Newcastle disease virus (NDV) is a negative-sense RNA virus that has been shown to possess oncolytic activity. NDV's selective replication in tumor cells has been previously suggested to be due to the lack of a proper antiviral response in these cells. Here we demonstrate that NDV possesses oncolytic activity in tumor cells capable of a robust type I interferon (IFN) response, suggesting that another mechanism underlies NDV's tumor specificity. We show that the oncolytic selectivity of NDV for tumor cells is dependent upon tumor cell resistance to apoptosis. Utilizing the human non-small-cell lung cancer cell line A549 overexpressing the antiapoptotic protein Bcl-xL, we show significant enhancement of oncolytic activity and NDV replication. Interestingly, while the Bcl-xL-overexpressing cells were resistant to apoptotic stimuli induced by chemotherapeutic agents and early viral replication, during the subsequent viral cycles, we observed a paradoxical increase in apoptosis in response to NDV. The increased oncolytic activity seen was secondary to enhanced viral replication and syncytium formation. The induction of a type I IFN response was enhanced in Bcl-xL cells. Overall, these findings propose a new mechanism for cancer cell specificity for NDV, making it an attractive anticancer agent for chemoresistant tumors with enhanced antiapoptotic activity.
Humanized Anti-IgE mAb Hu-901 Prevents the Activation of Allergen-Specific T Cells (2001)

These data clearly indicate that anti-IgE antibodies for the treatment of allergy exert their effect not only by inhibiting mast cell/basophil degranulation, but also by preventing T cell activation, which possibly explains the effect of anti-IgE treatment on late-phase reactions noted in clinical studies.
Genomics of Preterm Birth (2015)

The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms.
Mouse lymphotoxin-beta receptor. Molecular genetics, ligand binding, and expression (1995)

Lymphotoxin (LT) -alpha beta heterotrimer is a membrane-anchored ligand expressed by activated T cells which binds specifically to the LT beta receptor (LT beta R), a member of the TNFR family. The LT beta R is implicated as a critical element in controlling lymph node development and cellular immune reactions. To address this hypothesis we have isolated a mouse cDNA encoding a single transmembrane protein of 415 amino acids with 76% identity to human LT beta R. The receptor function of this molecule was demonstrated by the ability of the extracellular domain, constructed as a chimera with the Fc region of IgG7, to bind to LT alpha beta complexes expressed on the surface of activated T cells or insect cells infected with baculoviruses containing LT alpha and LT beta cDNAs. The gene encoding mouse LT beta R, Ltbr, contains 10 exons spanning 6.9 kb and maps to mouse chromosome 6, which is closely linked to Tnfr1, consistent with the tight linkage of the human homologue of these genes on chromosome 12p13. Mouse LT beta R mRNA is expressed by cell lines of monocytic and epithelial origin but not by a CTL line, and in vivo it is constitutively expressed in visceral and lymphoid tissues. The delineation of the structure of the mouse LT beta R will aid investigations into the role of this cytokine-receptor system in immune function and development.
Purine-scaffold Hsp90 inhibitors. (2006)

Heat shock protein 90 (Hsp90) has emerged as an important target, the inhibition of which is aimed at a wide range of cell transformations that lead to malignancy. A clinical evaluation of 17-AAG, the first Hsp90 inhibitor to enter the clinic, revealed evidence of activity for the compound at a manageable level of toxicity. However, clinical results have also demonstrated the limitations of this drug. The identification of novel Hsp90 inhibitor classes with improved structural characteristics and better pharmacological profiles has therefore become a major focus of interest in the field of cancer therapeutics. This feature describes the purine-scaffold class of Hsp90 inhibitors, focusing on research efforts from the discovery stage to the clinical translation of such compounds.