gebhart/patrepeval huggingface dataset:
Pharmacokinetics of S-1 in patients with peritoneal dissemination of gastric cancer (2006)

The response of gastric cancer with peritoneal dissemination to systemic chemotherapy may be negatively affected by poor drug delivery due to the blood-peritoneal barrier. However, S-1 has been reported to be effective. We examined the pharmacokinetics of S-1 in 14 patients who had gastric cancer with peritoneal dissemination. S-1 was given from the morning of the day before surgery to the morning of surgery. Concentrations of 5-fluorouracil (5-FU) and gimeracil (CDHP) were measured in the serum, ascites, disseminated peritoneal nodes, and normal peritoneum. There was a strong correlation between 5-FU and CDHP concentrations in peritoneal tissues. The concentrations of 5-FU and CDHP in the serum were similar to those in ascites. The concentration of 5-FU was significantly higher in disseminated nodes than in the normal peritoneum. After administration of S-1 to gastric cancer patients with peritoneal dissemination, 5-FU and CDHP in the serum linearly pass through the peritoneum and enter the ascites. High concentrations of 5-FU selectively penetrate disseminated peritoneal cells.
Acute hepatic necrosis and fulminant hepatic failure. (1973)

Fulminant hepatic failure' is defined as severe, acute impairment of hepatic function culminating in hepatic encephalopathy, the encephalopathy being the result of hepatocellular failure and supervening within three weeks of the onset of symptoms*. This definition excludes the hepatic encephalopathy of hepatic cirrhosis and of chronic hepatitis, which produces a slightly different clinical picture, but fulminant hepatic failure as defined here may of course occur as a superimposed phenomenon in patients with these conditions. Likewise excluded is encephalopathy caused by sedatives in patients with viral hepatitis or by a direct cerebral action of certain halogenated hydrocarbons in subjects whose livers are already damaged by these compounds.
The Function of Sensory Nerve Fibers in Lumbar Radiculopathy (1998)

Large and small sensory afferent nerve fibers are affected in lumbar radiculopathy. The increase in sensation thresholds in the ipsilateral neighboring dermatome and in the dermatomes in the asymptomatic leg indicates that adjacent nerve roots are involved in the pathophysiology of sciatica in patients with lumbar disc herniation.
Measurements of Tumor Cell Autophagy Predict Invasiveness, Resistance to Chemotherapy, and Survival in Melanoma (2011)

Autophagy is a potential prognostic factor and therapeutic target in melanoma. Three dimensional culture mimics the tumor microenvironment better than monolayer culture and is an appropriate model for studying therapeutic combinations involving autophagy modulators. Autophagy inhibition should be tested clinically in patients with melanoma.
Classification of CAD severity using fusion neural net analysis of multiple exercise ECG waveform representations (2002)

A hierarchical fuzzy neural-net approach has been developed to classify averaged serial ECG waveforms gathered during exercise testing in order to determine the severity of coronary artery disease (CAD). The ST-T complex of each ECG was first transformed on a sample-by-sample basis to form multiple representations (e.g. raw amplitudes, delta-baseline, slope through J-junction) to highlight the salient features of the signal. These representations were then initially classified by individual neural-nets and the resultant CAD-group outputs used as inputs into a secondary fusion-net for final classification. Also at the fusion-net level, additional parameters (e.g., HR and phase) were added to the fusion-net's input dimension space. Using only one lead, the processing gives nearly perfectly discrimination between angiographic normals and patients with severe 3-vessel disease. The use of FMM neural-nets is particularly relevant for this type of medical application since they allow the user to determine why and where the network decided on its results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Regulation of VanB-type vancomycin resistance gene expression by the VanS(B)-VanR (B) two-component regulatory system in Enterococcus faecalis V583 (1996)

Acquired VanA- and VanB-type glycopeptide resistance in enterococci is due to synthesis of modified peptidoglycan precursors terminating in D-lactate. As opposed to VanA-type strains which are resistant to both vancomycin and teicoplanin, VanB-type strains remain teicoplanin susceptible. We have determined the sequence of a 7,160-bp DNA fragment associated with VanB-type resistance in Enterococcus faecalis V583 that contains seven open reading frames. The distal part encoded the VanH (B), VanB, and VanX (B) proteins that are highly similar to the putative VanH, VanA, and VanX proteins responsible for VanA-type resistance. Upstream from the structural genes for these proteins were the vanY(B) gene encoding a D,D-carboxypeptidase and an open reading frame vanW with an unknown function. The proximal part of the gene cluster coded for the apparent VanS(B)-VanR (B) two-component regulatory system. VanR (B) was related to response regulators of the OmpR subclass, and VanS (B) was related to membrane-associated histidine protein kinases. Analysis of transcriptional fusions with a reporter gene and promoter mapping indicated that the VanR B-VanS B two-component regulatory system activates a promoter located immediately downstream from the vanS B gene. Vancomycin, but not teicoplanin, was an inducer, which explains teicoplanin susceptibility of VanB-type enterococci.
Mode of action of liver tumor induction by trichloroethylene and its metabolites, trichloroacetate and dichloroacetate. (2000)

Trichloroethylene (TCE) induces liver cancer in mice but not in rats. Three metabolites of TCE may contribute--chloral hydrate (CH), dichloroacetate (DCA), and trichloroacetate (TCA). CH and TCA appear capable of only inducing liver tumors in mice, but DCA is active in rats as well. The concentrations of TCA in blood required to induce liver cancer approach the mM range. Concentrations of DCA in blood associated with carcinogenesis are in the sub-microM range. The carcinogenic activity of CH is largely dependent on its conversion to TCA and/or DCA. TCA is a peroxisome proliferator in the same dose range that induces liver cancer. Mice with targeted disruptions of the peroxisome proliferator-activated receptor alpha (PPAR-alpha) are insensitive to the liver cancer-inducing properties of other peroxisome proliferators. Human cells do not display the responses associated with PPAR-alpha that are observed in rodents. This may be attributed to lower levels of expressed PPAR-alpha in human liver. DCA treatment produces liver tumors with a different phenotype than TCA. Its tumorigenic effects are closely associated with differential effects on cell replication rates in tumors, normal hepatocytes, and suppression of apoptosis. Growth of DCA-induced tumors has been shown to arrest after cessation of treatment. The DCA and TCA adequately account for the hepatocarcinogenic responses to TCE. Low-level exposure to TCE is not likely to induce liver cancer in humans. Higher exposures to TCE could affect sensitive populations. Sensitivity could be based on different metabolic capacities for TCE or its metabolites or result from certain chronic diseases that have a genetic basis.
Contextual Gaussian Process Bandit Optimization (2011)

How should we design experiments to maximize performance of a complex system, taking into account uncontrollable environmental conditions? How should we select relevant documents (ads) to display, given information about the user? These tasks can be formalized as contextual bandit problems, where at each round, we receive context (about the experimental conditions, the query), and have to choose an action (parameters, documents). The key challenge is to trade off exploration by gathering data for estimating the mean payoff function over the context-action space, and to exploit by choosing an action deemed optimal based on the gathered data. We model the payoff function as a sample from a Gaussian process defined over the joint context-action space, and develop CGP-UCB, an intuitive upper-confidence style algorithm. We show that by mixing and matching kernels for contexts and actions, CGP-UCB can handle a variety of practical ap-plications. We further provide generic tools for deriving regret bounds when using such composite kernel functions. Lastly, we evaluate our algorithm on two case studies, in the context of automated vaccine design and sensor management. We show that context-sensitive optimization outperforms no or naive use of context. 1
Mutation in Glycerol-3-Phosphate Dehydrogenase 1–Like Gene ( GPD1-L ) Decreases Cardiac Na + Current and Causes Inherited Arrhythmias (2007)

GPD1-L is a novel gene that may affect trafficking of the cardiac Na+ channel to the cell surface. A GPD1-L mutation decreases SCN5A surface membrane expression, reduces inward Na+ current, and causes Brugada syndrome.
Dose and Temporal Pattern of Estrogen Exposure Determines Neuroprotective Outcome in Hippocampal Neurons: Therapeutic Implications (2006)

To address controversies of estrogen therapy, in vitro models of perimenopause and prevention vs. treatment modes of 17beta-estradiol (E(2)) exposure were developed and used to assess the neuroprotective efficacy of E(2) against beta-amyloid-1-42 (Abeta(1-42))-induced neurodegeneration in rat primary hippocampal neurons. Low E(2) (10 ng/ml) exposure exerted neuroprotection in each of the perimenopausal temporal patterns, acute, continuous, and intermittent. In contrast, high E(2) (200 ng/ml) was ineffective at inducing neuroprotection regardless of temporal pattern of exposure. Although high E(2) alone was not toxic, neurons treated with high-dose E(2) resulted in greater Abeta(1-42)-induced neurodegeneration. In prevention vs. treatment simulations, E(2) was most effective when present before and during Abeta(1-42) insult. In contrast, E(2) treatment after Abeta(1-42) exposure was ineffective in reversing Abeta-induced degeneration, and exacerbated Abeta(1-42)-induced cell death when administered after Abeta(1-42) insult. We sought to determine the mechanism by which high E(2) exacerbated Abeta(1-42)-induced neurodegeneration by investigating the impact of low vs. high E(2) on Abeta(1-42)-induced dysregulation of calcium homeostasis. Results of these analyses indicated that low E(2) significantly prevented Abeta(1-42)-induced rise in intracellular calcium, whereas high E(2) significantly increased intracellular calcium and did not prevent Abeta(1-42)-induced calcium dysregulation. Therapeutic benefit resulted only from low-dose E(2) exposure before, but not after, Abeta(1-42)-induced neurodegeneration. These data are relevant to impact of perimenopausal E(2) exposure on protection against neurodegenerative insults and the use of estrogen therapy to prevent vs. treat Alzheimer's disease. Furthermore, these data are consistent with a healthy cell bias of estrogen benefit.
Structure-Function Analysis of T4 RNA Ligase 2 (2003)

Bacteriophage T4 RNA ligase 2 (Rnl2) exemplifies a polynucleotide ligase family that includes the trypanosome RNA-editing ligases and putative RNA ligases encoded by eukaryotic viruses and archaea. Here we analyzed 12 individual amino acids of Rnl2 that were identified by alanine scanning as essential for strand joining. We determined structure-activity relationships via conservative substitutions and examined mutational effects on the isolated steps of ligase adenylylation and phosphodiester bond formation. The essential residues of Rnl2 are located within conserved motifs that define a superfamily of nucleotidyl transferases that act via enzyme-(lysyl-N)-NMP intermediates. Our mutagenesis results underscore a shared active site architecture in Rnl2-like ligases, DNA ligases, and mRNA capping enzymes. They also highlight two essential signature residues, Glu(34) and Asn(40), that flank the active site lysine nucleophile (Lys(35)) and are unique to the Rnl2-like ligase family.
Is Multiple Sclerosis Caused by a Dual Infection with Retrovirus and Epstein-Barr Virus? (1992)

Although the etiology of multiple sclerosis is as yet unknown, epidemiological observations strongly point toward one or more infectious agent(s) being involved in the disease. In recent years some studies have indicated involvement of retrovirus in multiple sclerosis (MS). However, an intrafamilial epidemiological study revealed that MS and the known human retroviruses had a divergent epidemiology. Some studies have shown the association of Epstein-Barr virus (EBV) with MS and one recent study revealed dual infection by retrovirus and EBV in a cell line established from a patient with an MS-like disease. Our hypothesis for the development of MS and MS-like diseases is that a hitherto uncharacterized retrovirus is the etiological agent, but development of neurologic disease is related to or even dependent on a delayed EBV infection. The dual infection hypothesis is analyzed and found to be consistent with the epidemiological characteristics of MS.
Use of human Dihydroorotate Dehydrogenase (hDHODH) Inhibitors in Autoimmune Diseases and New Perspectives in Cancer Therapy (2018)

The review will describe a variety of specific inhibitor classes and conclude on recent and future therapeutic perspectives for this target.
Prophages and bacterial genomics: what have we learned so far? (2003)

Bacterial genome nucleotide sequences are being completed at a rapid and increasing rate. Integrated virus genomes (prophages) are common in such genomes. Fifty-one of the 82 such genomes published to date carry prophages, and these contain 230 recognizable putative prophages. Prophages can constitute as much as 10-20% of a bacterium's genome and are major contributors to differences between individuals within species. Many of these prophages appear to be defective and are in a state of mutational decay. Prophages, including defective ones, can contribute important biological properties to their bacterial hosts. Therefore, if we are to comprehend bacterial genomes fully, it is essential that we are able to recognize accurately and understand their prophages from nucleotide sequence analysis. Analysis of the evolution of prophages can shed light on the evolution of both bacteriophages and their hosts. Comparison of the Rac prophages in the sequenced genomes of three Escherichia coli strains and the Pnm prophages in two Neisseria meningitidis strains suggests that some prophages can lie in residence for very long times, perhaps millions of years, and that recombination events have occurred between related prophages that reside at different locations in a bacterium's genome. In addition, many genes in defective prophages remain functional, so a significant portion of the temperate bacteriophage gene pool resides in prophages.
Plants, Genes, And Crop Biotechnology (2002)

Jones and Bartlett Publishers and the American Society of Plant Biologists have teamed up for the Second Edition of Plants, Genes, and Crop Biotechnology. The essays collected in this text bring together aspects of genetics and plant breeding, molecular biology and genetic engineering, plant development and reproduction, soils and plant nutrition, agro-ecology and the sustainability of agricultural practices, population increases and the difficulty of eradicating hunger, pest control practices and their environmental consequences, and the role of biotechnology in modern crop production.
EEG-triggered echo-planar functional MRI in epilepsy (1996)

We investigated whether: (1) EEG recordings could be successfully performed in an MRI imager, (2) subclinical epileptic discharges could be used to trigger ultrafast functional MRI images, (3) artifact-free functional MRI images could be obtained while the patient was having the EEG monitored, and (4) the functional MRI images so obtained would show focal signal increases in relation to epileptic discharges. We report our results in two patients who showed focally higher signal intensity, reflective of increased local blood flow, in ultrafast functional MRI timed to epileptic discharges recorded while the patients were in the imager and compared with images not associated with discharges. One patient showed a focal increase despite a clinical and EEG history of generalized discharges. This approach may have the potential to identify brain regions activated during brief focal epileptic discharges.
Emulation learning: the integration of technical and social cognition (2007)

A decade ago, the term emulation had been used by Tomasello (1990) to describe the performance of chimpanzees that seemed to him neither imitative nor a result of simple motivational or attentional influences. However, some researchers have questioned if emulation has been sufficiently well established to be used as a valid alternative in attempts to discover imitation, and whether its definition is precise enough for reliable identification of its operation (Byrne, 1998). As is a common feature of the social learning literature, the term has different meanings in different domains (e.g. Wood, 1989; Whiten and Ham, 1992). Let me first recall what Tomasello and his colleagues (Tomasello et al., 1987; Tomasello, 1990, 1996, 1998) have found and then add some recent evidence, including our findings, for this underestimated learning phenomenon. This endeavour will not only reveal that many findings reported in the literature support the emulation learning account if re-evaluated by recent methodological and theoretical developments (Huang et al., 2002; Want and Harris, 2002; Horowitz, 2003; Whiten et al., 2004; Zentall, 2004), but also that imitation has been dramatically overestimated in terms of occurrence and importance.
Eculizumab treatment: stochastic occurrence of C3 binding to individual PNH erythrocytes (2017)

This study indicates that the distinct (C3+ and C3-) PNH RBC populations are not intrinsically different; rather, they result from a stochastic all-or-nothing phenomenon linked to the time-dependent cumulative probability of each individual PNH red cell to be exposed to levels of complement activation able to trigger C3 binding. These findings may envision novel approaches to reduce C3 opsonization and the subsequent extravascular hemolysis in PNH patients on eculizumab.
Component-based track inspection using machine-vision technology (2011)

In this paper, we present our latest research engagement with a railroad company to apply machine vision technologies to automate the inspection and condition monitoring of railroad tracks. Specifically, we have proposed a complete architecture including imaging setup for capturing multiple video streams, important rail component detection such as tie plate, spike, anchor and joint bar bolt, defect identification such as raised spikes, defect severity analysis and temporal condition analysis, and long-term predictive assessment. This paper will particularly present various video analytics that we have developed to detect rail components, which form the building block of the entire framework. Our preliminary performance study has achieved an average of 98.2% detection rate, 1.57% false positive rate and 1.78% false negative rate on the component detection. Finally, with the lack of sufficient representative data and annotations to evaluate system performance on exception detection at both sequence and compliance levels, we proposed a mathematical modeling approach to calculate the probabilities of detecting such exceptions. Such analysis shows that there is still big room for us to improve our approaches in order to achieve desired false positive rate and miss detection rate at the sequence level.
Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms (2015)

JAK2 kinase inhibitors are a promising new class of agents for the treatment of myeloproliferative neoplasms and have potential for the treatment of other diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME guided refinement of C-4 heterocycles to address metabolic liability present in dialkylthiazole 1 led to the discovery of a clinical candidate, BMS-911543 (11), with excellent kinome selectivity, in vivo PD activity, and safety profile.
Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region (1999)

The cellular target of leptomycin B (LMB), a nuclear export inhibitor, has been identified as CRM1 (exportin 1), an evolutionarily conserved receptor for the nuclear export signal of proteins. However, the mechanism by which LMB inhibits CRM1 still remains unclear. CRM1 in a Schizosaccharomyces pombe mutant showing extremely high resistance to LMB had a single amino acid replacement at Cys-529 with Ser. The mutant gene, named crm1-K1, conferred LMB resistance on wild-type S. pombe, and Crm1-K1 no longer bound biotinylated LMB. (1)H NMR analysis showed that LMB bound N-acetyl-L-cysteine methyl ester through a Michael-type addition, consistent with the idea that LMB binds covalently via its alpha, beta-unsaturated delta-lactone to the sulfhydryl group of Cys-529. When HeLa cells were cultured with biotinylated LMB, the only cellular protein bound covalently was CRM1. Inhibition by N-ethylmaleimide (NEM), an alkylating agent, of CRM1-mediated nuclear export probably was caused by covalent binding of the electrophilic structure in NEM to the sulfhydryl group of Cys-529, because the crm1-K1 mutant showed the normal rate for the export of Rev nuclear export signal-bearing proteins in the presence of not only LMB but also NEM. These results show that the single cysteine residue determines LMB sensitivity and is selectively alkylated by LMB, leading to CRM1 inactivation.
Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. (1992)

The vascular endothelial growth factor (VEGF) family encompasses four polypeptides that result from alternative splicing of mRNA. We have previously demonstrated differences in the secretion pattern of these polypeptides. Stable cell lines expressing VEGFs were established in human embryonic kidney CEN4 cells. VEGF121, the shortest form, was secreted and freely soluble in tissue culture medium. VEGF189 was secreted, but was almost entirely bound to the cell surface or extracellular matrix. VEGF165 displayed an intermediary behavior. Suramin induced the release of VEGF189, permitting its characterization as a more basic protein with higher affinity for heparin than VEGF165 or VEGF121, but with similar endothelial cell mitogenic activity. Heparin, heparan sulfate, and heparinase all induced the release of VEGF165 and VEGF189, suggesting heparin-containing proteoglycans as candidate VEGF-binding sites. Finally, VEGF165 and VEGF189 were released from their bound states by treatment with plasmin. The released 34-kDa dimeric species are active as endothelial cell mitogens and as vascular permeability agents. We conclude that the bioavailability of VEGF may be regulated at the genetic level by alternative splicing that determines whether VEGF will be soluble or incorporated into a biological reservoir and also through proteolysis following plasminogen activation.
ChemInform Abstract: Sr5Al2Sb6 (I) and Ba5In2Sb6 (II), Two New Zintl Phases with Different Chain Anions. (1988)

Abstract The title compounds are obtained by heating appropriate mixtures of the elements to 1270 K under argon.
The risk of colorectal cancer in ulcerative colitis: a meta-analysis (2001)

Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.