gebhart/patrepeval huggingface dataset:
Linezolid versus Vancomycin in Treatment of Complicated Skin and Soft Tissue Infections (2005)

Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (P=0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (P<0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA.
See-through Integral Imaging Display with Background Occlusion Capability (2015)

An integral imaging display with see-through and background occlusion capabilities is proposed. A symmetric integral imaging system consisting of multiple lens arrays is combined with modulation and masking layers. The system is experimentally verified.
The transcription factor LSF: a novel oncogene for hepatocellular carcinoma. (2012)

The transcription factor LSF (Late SV40 Factor), also known as TFCP2, belongs to the LSF/CP2 family related to Grainyhead family of proteins and is involved in many biological events, including regulation of cellular and viral promoters, cell cycle, DNA synthesis, cell survival and Alzheimer's disease. Our recent studies establish an oncogenic role of LSF in Hepatocellular carcinoma (HCC). LSF overexpression is detected in human HCC cell lines and in more than 90% cases of human HCC patients, compared to normal hepatocytes and liver, and its expression level showed significant correlation with the stages and grades of the disease. Forced overexpression of LSF in less aggressive HCC cells resulted in highly aggressive, angiogenic and multi-organ metastatic tumors in nude mice. Conversely, inhibition of LSF significantly abrogated growth and metastasis of highly aggressive HCC cells in nude mice. Microarray studies revealed that as a transcription factor LSF modulated specific genes regulating invasion, angiogenesis, chemoresistance and senescence. LSF transcriptionally regulates thymidylate synthase (TS) gene, thus contributing to cell cycle regulation and chemoresistance. Our studies identify a network of proteins, including osteopontin (OPN), Matrix metalloproteinase-9 (MMP-9), c-Met and complement factor H (CFH), that are directly regulated by LSF and play important role in LSF-induced hepatocarcinogenesis. A high throughput screening identified small molecule inhibitors of LSF DNA binding and the prototype of these molecules, Factor Quinolinone inhibitor 1 (FQI1), profoundly inhibited cell viability and induced apoptosis in human HCC cells without exerting harmful effects to normal immortal human hepatocytes and primary mouse hepatocytes. In nude mice xenograft studies, FQI1 markedly inhibited growth of human HCC xenografts as well as angiogenesis without exerting any toxicity. These studies establish a key role of LSF in hepatocarcinogenesis and usher in a novel therapeutic avenue for HCC, an invariably fatal disease.
New Insights Into the Role of mTOR Signaling in the Cardiovascular System (2018)

The mTOR (mechanistic target of rapamycin) is a master regulator of several crucial cellular processes, including protein synthesis, cellular growth, proliferation, autophagy, lysosomal function, and cell metabolism. mTOR interacts with specific adaptor proteins to form 2 multiprotein complexes, called mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2). In the cardiovascular system, the mTOR pathway regulates both physiological and pathological processes in the heart. It is needed for embryonic cardiovascular development and for maintaining cardiac homeostasis in postnatal life. Studies involving mTOR loss-of-function models revealed that mTORC1 activation is indispensable for the development of adaptive cardiac hypertrophy in response to mechanical overload. mTORC2 is also required for normal cardiac physiology and ensures cardiomyocyte survival in response to pressure overload. However, partial genetic or pharmacological inhibition of mTORC1 reduces cardiac remodeling and heart failure in response to pressure overload and chronic myocardial infarction. In addition, mTORC1 blockade reduces cardiac derangements induced by genetic and metabolic disorders and has been reported to extend life span in mice. These studies suggest that pharmacological targeting of mTOR may represent a therapeutic strategy to confer cardioprotection, although clinical evidence in support of this notion is still scarce. This review summarizes and discusses the new evidence on the pathophysiological role of mTOR signaling in the cardiovascular system.
Properties of the fatty acid esters of amylose (1962)

Abstract To help establish the suitability of esters of amylose and fatty acids as dip‐coating materials, esters of the evennumbered, saturated fatty acids, acetic through stearic, and of oleic and cottonseed oil fatty acids were prepared, and their properties were determined. The various esters generally were prepared by the interaction of acid chlorides with the amylose suspended in a suitable mixture of solvents. Analyses for content of free fatty acid groups indicated that high proportions of the hydroxyl groups were esterified. Intrinsic viscosity decreased as the chain length of the acyl group increased, a reflection of the changing nature of the products rather than a decrease in the degree of polymerization of the amylose. As the chain length of the saturated fatty acid group increased the softening point at first decreased and then increased, the minimum being obtained with the myristate. The stearate softened at 56.2ŶC. The stearate had a hardness index of 139, which was about equal to the index of 140 for completely hydrogenated cottonseed oil. Densities were greater than those of the corresponding triglycerides and decreased as the chain length of the fatty acid group increased. Permeability to water vapor also decreased as the chain length increased, the index being 620ȕ10 蜢12 for the acetate and 15ȕ10 蜢12 for the stearate. The acetate possessed the highest tensile strength, about 4.40 kg./sq. mm., while the palmitate had a tensile strength of about 0.49 kg./sq. mm. Elongation at the break point varied widely, being 632% for the caprate and 0.95% for the stearate.
A High-Content Screen Identifies Novel Compounds That Inhibit Stress-Induced TDP-43 Cellular Aggregation and Associated Cytotoxicity (2013)

TDP-43 is an RNA binding protein found to accumulate in the cytoplasm of brain and spinal cord from patients affected with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Nuclear TDP-43 protein regulates transcription through several mechanisms, and under stressed conditions, it forms cytoplasmic aggregates that co-localize with stress granule (SG) proteins in cell culture. These granules are also found in the brain and spinal cord of patients affected with ALS and FTLD. The mechanism through which TDP-43 might contribute to neurodegenerative diseases is poorly understood. To investigate the pathophysiology of TDP-43 aggregation and to isolate potential therapeutic targets, we screened a chemical library of 75,000 compounds using high-content analysis with PC12 cells that inducibly express human TDP-43 tagged with green fluorescent protein (GFP). The screen identified 16 compounds that dose-dependently decreased the TDP-43 inclusions without significant cellular toxicity or changes in total TDP-43 expression levels. To validate the effect, we tested compounds by Western blot analysis and in a Caenorhabditis elegans model that replicates some of the relevant disease phenotypes. The hits from this assay will be useful for elucidating regulation of TDP-43, stress granule response, and possible ALS therapeutics.
Effects of Gastrin, Glutamine, and Somatostatin on the In Vitro Growth of Normal and Malignant Human Gastric Mucosal Cells (1986)

This study evaluated the dose-related trophic effects of glutamine, gastrin, and somatostatin on the in vitro growth of human gastric cancer cells and normal human gastric mucosal cells. Quadruplicate cell cultures were seeded into growth medium with or without glutamine, gastrin, or somatostatin. After 72 hours' incubation, cells were counted and their numbers compared with those of controls. Glutamine and gastrin stimulated the growth of both normal and malignant gastric mucosal cells. Compared with normal cells, the malignant cells responded to these growth factors at lower concentrations. Somatostatin enhanced growth of gastric cancer cells at all concentrations and inhibited growth of normal cells at high concentrations. Further studies on the responsiveness of gastric adenocarcinoma to gastrointestinal tract hormones may elucidate mechanisms of oncogenesis and suggest new therapeutic avenues for patients with gastric cancer.
Nature of the SOS-inducing signal in Escherichia coli (1990)

The SOS genes of Escherichia coli, which include many DNA repair genes, are induced by DNA damage. Although the central biochemical event in induction, activation of RecA protein through binding of single-stranded DNA and ATP to promote cleavage of the LexA repressor, is known, the cellular event that provides this activation following DNA damage has not been well understood. We provide evidence here that the major pathway of induction after damage by a typical agent, ultraviolet light, requires an active replication fork; this result supports the model that DNA replication leaves gaps where elongation stops at damage-induced lesions, and thus provides the single-stranded DNA that activates RecA protein. In order to detect quantitatively the immediate product of the inducing signal, activated RecA protein, we have designed an assay to measure the rate of disappearance of intact LexA repressor. With this assay, we have studied the early phase of the induction process. LexA cleavage is detectable within minutes after DNA damage and occurs in the absence of protein synthesis. By following the reaccumulation of LexA in the cell, we detect repair of DNA and the disappearance of the inducing signal. Using this assay, we have measured the LexA content of wild-type and various mutant cells, characterized the kinetics and conditions for development of the inducing signal after various inducing treatments and, finally, have shown the requirement for DNA replication in SOS induction by ultraviolet light.
Low Probability of Detection Communication: Opportunities and Challenges (2019)

LPD communication has recently emerged as a new transmission technology to address privacy and security in wireless networks. Recent studies have established the fundamental limits of LPD communication in terms of the amount of information that can be conveyed from a transmitter to a receiver subject to a constraint on a warden's detection error probability. The established information- theoretic metric enables analytical studies on the design and performance of LPD communication under various channel conditions. In this article, we present the key features of LPD communication and discuss various important design considerations. First, we clarify the differences between LPD communication and well-known physical-layer security. Then, from an information-theoretic point of view, we discuss the optimal signaling strategies for transmitting the message-carrying signal and artificial noise signal for LPD communication. Finally, we identify the key challenges in the design of practical LPD communication systems and point out future research directions in this context. This article provides guidelines for designing practical LPD communication strategies in wireless systems and networks.
Development of TAP, a non-invasive test for qualitative and quantitative measurements of biomarkers from the skin surface (2014)

TAP is a practical and valuable new skin diagnostic tool for measuring protein-based biomarkers from skin, which is convenient to use for operators, with minimal burden for patients.
Gene Targeting in Drosophila and Caenorhabditis elegans With Zinc-Finger Nucleases (2008)

Zinc-finger nucleases (ZFNs) are promising new tools for enhancing the efficiency of gene targeting in many organisms. Because of the flexibility of zinc finger DNA recognition, ZFNs can be designed to bind many different genomic sequences. The double-strand breaks they create are repaired by cellular processes that generate new mutations at the cleavage site. In addition, the breaks can be repaired by homologous recombination with an exogenous donor DNA, allowing the experimenter to introduce designed sequence alterations. We describe the construction of ZFNs for novel targets and their application to targeted mutagenesis and targeted gene replacement in Drosophila melanogaster and Caenorhabditis elegans.
Radioimmunotherapy: recent results and future directions. (1996)

Although radioimmunotherapy is a relatively new field, substantial progress has been made. Additional research will ultimately resolve many of the challenges that currently face radioimmunotherapy and hopefully lead to the cure of some currently incurable malignancies.
Role of antibiotic production by Erwinia herbicola Eh252 in biological control of Erwinia amylovora (1992)

Erwinia herbicola Eh252 is a nonpathogenic epiphytic bacterium that reduces fire blight incidence when sprayed onto apple blossoms before inoculation with Erwinia amylovora, the causal agent of fire blight. Eh252 was found to produce on minimal medium an antibiotic that inhibited the growth of E. amylovora. This antibiotic was inactivated by histidine but not by Fe(II), was sensitive to proteolytic enzymes, and showed a narrow host range of activity. To determine the role of this antibiotic in the control of fire blight, two prototrophic Tn5-induced mutants, 10:12 and 17:12, that had lost their ability to inhibit E. amylovora on plates (Ant- mutants) were compared with the wild-type strain for their ability to suppress fire blight in immature pear fruits. The two mutants had single Tn5 insertions in the chromosome; although they grew in immature pear fruits at a rate similar to that of the wild-type strain, neither of these mutants suppressed fire blight as well as Eh252 did. The Tn5-containing fragment isolated from 10:12 was used to mutagenize Eh252 by marker exchange. Derivatives that acquired the Tn5-containing fragment by homologous recombination lost the ability to inhibit E. amylovora on minimal medium. Furthermore, the three Ant- derivatives tested were also affected in their ability to inhibit E. amylovora in immature pear fruits. The results obtained suggest that antibiotic production is a determinant of the biological control of E. amylovora by Eh252, but that another mechanism(s) is involved.
A null mutation in the Bacillus subtilis aconitase gene causes a block in Spo0A-phosphate-dependent gene expression (1997)

The citB gene of Bacillus subtilis encodes aconitase, the enzyme of the Krebs citric acid cycle, which is responsible for the interconversion of citrate and isocitrate. A B. subtilis strain with an insertion mutation in the citB gene was devoid of aconitase activity and aconitase protein, required glutamate for growth in minimal medium, and was unable to sporulate efficiently in nutrient broth sporulation medium. Mutant cells failed to form the asymmetric septum characteristic of sporulating cells and were defective in transcription of the earliest-expressed spo genes, that is, the genes dependent on the Spo0A phosphorelay. However, this early block in sporulation was partially overcome when cells of the citB mutant were induced to sporulate by resuspension in a poor medium. Accumulation of citrate in the mutant cells or in their culture fluid may be responsible for the early block, possibly because citrate can chelate divalent cations needed for the activity of the phosphorelay.
Sialic acid levels and lag time of growth in chemically defined medium containing 200 mM phosphate among strains of various serotypes of Streptococcus agalactiae (1989)

The type-specific capsular polysaccharide antigen of Streptococcus agalactiae has in previous experimental studies been considered a significant antiphagocytic factor, whereas the lipoteichoic acid moiety has been suggested to be a factor in adherence to human fetal cell lines. Since epidemiological data concerning these cell constituents in strains from the genital tract are lacking, we attempted serotyping and analysis of these constituents of 100 vaginal isolates. The capsular polysaccharide level was shown to be the amount of sialic acid that occupied the terminal side chains of the polysaccharide. We carried out a study to ascertain whether strains exhibited a lag time of growth in a chemically defined medium containing 200 mM phosphate, which has been suggested to be characteristic of strains with high lipoteichoic acid levels. Strains were classified, on the basis of the results of distribution of sialic acid levels, into three categories: (i) strains with a low sialic acid content of equal to or less than 9 micrograms/mg of cell dry weight; (ii) strains with a moderate sialic acid content of more than 9 but less than 12 micrograms/mg of cell dry weight; and (iii) strains with a high sialic acid content of equal to or more than 12 micrograms/mg of cell dry weight. Strains that belonged to the last category, which, as previous experimental data indicate, are potentially virulent strains, were significantly distributed among isolates of types Ia (P less than 0.001) and III (P less than 0.05). On the other hand, strains exhibiting a lag time of growth in the above-mentioned medium were detected to a significant extent in type III isolates (P <0.02). These results may be related to the epidemiological finding that isolates from neonates with late-onset infection were more frequently serotype Ia and III isolates.
Abstract 1023: Proprotein Convertase Subtilisin Kexin type 9 is repressed by the Peroxisome Proliferator Activated Receptor alpha ligand fenofibric acid. (2006)

Familial autosomal dominant hypercholesterolemia is characterized by high levels of cholesterol associated to LDL (LDLc), secondary to mutations in the LDL receptor, its ligand the apolipoprotein B or the Proprotein Convertase Subtilisin Kexin type 9 (PCSK9). PCSK9 is a natural inhibitor of the LDLr and its absence reduces the risk for cardiovascular disease and increases sensitivity to statins. We recently showed that PCSK9’s expression is upregulated by insulin and the Liver X Receptor ligand T0901317, via SREBP-1c, and that it is downregulated by fasting. Here we show that the SREBP-1c response element we isolated in PCSK9 proximal promoter is also a sterol responsive element and mediates a large part of the promoter’s activation by statins. The decrease observed in PCSK9 expression during fasting couldn’t be entirely attributed to variations in SREBPs. New investigations show that this down regulation also involves an active repression by PPARalpha. Indeed PCSK9 mRNA is 4 fold (p = 0.01) more abundant in wild type mice than in PPARalpha -/- mice, after a 24h-long fasting, although fed mice present similar mRNA and protein levels. In vitro, in human immortalized hepatocytes, the PPARalpha agonist fenofibric acid (250 μM) diminished PCSK9 mRNA content by 75% (p = 0.002), its protein content by 65 % (p = 0.006), and its autocatalytic activity by −30%, (p = 0.02), as reflected by the cleavage of a peptide corresponding to the autocatalytic cleavage site ( Naureckiene S. et al. 2003 Arch. Biochem. Biophys. 420 : 55 –67. ). Fenofibric acid also prevented the Liver X Receptor-mediated activation of PCSK9 by T0901317. Among several PPAR agonist (ciprofibrate, clofibrate, gemfibrozil), fenofibric acid was the most efficient in reducing PCSK9 autocatalytic activity. These results suggest that fenofibric acid, or the next generation of PPARalpha agonists, might constitute good repressors of PCSK9 in humans.
User performance in relation to 3D input device design (1998)

Based mainly on a series of studies the author conducted at the University of Toronto, this article reviews the usability of various six degrees of freedom (6 DOF) input devices for 3D user interfaces. The following issues are covered in the article: the multiple aspects of input device usability (performance measures), mouse based 6 DOF interaction, mouse modifications for 3D interfaces, free-moving isotonic 6 DOF devices, desktop isometric and elastic 6 DOF devices, armature-based 6 DOF devices, position vs. rate control and the form factors of 6 DOF control handle. These issues are treated at an introductory and practical level, with pointers to more technical and theoretical references.
Advanced glycation end-products in diabetic nephropathy (1999)

Throughout the industrialized (well-fed) world, diabetes mellitus is the most prevalent cause of end-stage renal disease (ESRD). Diabetic nephropathy is as likely to develop in long-duration non-insulin-dependent diabetes (type 2) as in insulin-dependent diabetes mellitus (type 1). Nephropathy in diabetes follows a well outlined course, starting with microalbuminuria through proteinuria, azotaemia and culminating in ESRD. Renal functional decline in diabetic nephropathy is slowed by establishment of euglycaemia and normalization of hypertensive blood pressure. Diabetic ESRD patients, compared with other causes of ESRD, sustain greater mortality and morbidity due to concomitant systemic disorders, especially coronary artery and cerebrovascular disease. A central role for glucose toxicity, especially the adverse impact of accumulated advanced glycosylated end-products (AGEs), appears likely from experimental data generated both in induced diabetic rodents and diabetic individuals. Treatment with aminoguanidine raises the possibility of blocking end-organ damage in diabetes without the necessity for correcting hyperglycaemia.