gebhart/patrepeval huggingface dataset:
Transcriptomics-Based Drug Repurposing Approach Identifies Novel Drugs against Sorafenib-Resistant Hepatocellular Carcinoma (2020)

<i>Objective:</i> Hepatocellular carcinoma (HCC) is frequently diagnosed in patients with late-stage disease who are ineligible for curative surgical therapies. The majority of patients become resistant to sorafenib, the only approved first-line therapy for advanced cancer, underscoring the need for newer, more effective drugs. The purpose of this study is to expedite identification of novel drugs against sorafenib resistant (SR)-HCC. <i>Methods:</i> We employed a transcriptomics-based drug repurposing method termed connectivity mapping using gene signatures from in vitro-derived SR Huh7 HCC cells. For proof of concept validation, we focused on drugs that were FDA-approved or under clinical investigation and prioritized two anti-neoplastic agents (dasatinib and fostamatinib) with targets associated with HCC. We also prospectively validated predicted gene expression changes in drug-treated SR Huh7 cells as well as identified and validated the targets of Fostamatinib in HCC. <i>Results:</i> Dasatinib specifically reduced the viability of SR-HCC cells that correlated with up-regulated activity of SRC family kinases, its targets, in our SR-HCC model. However, fostamatinib was able to inhibit both parental and SR HCC cells in vitro and in xenograft models. Ingenuity pathway analysis of fostamatinib gene expression signature from LINCS predicted JAK/STAT, PI3K/AKT, ERK/MAPK pathways as potential targets of fostamatinib that were validated by Western blot analysis. Fostamatinib treatment reversed the expression of genes that were deregulated in SR HCC. <i>Conclusion:</i> We provide proof of concept evidence for the validity of this drug repurposing approach for SR-HCC with implications for personalized medicine.
A Single N-Linked Glycosylation Site in the Japanese Encephalitis Virus prM Protein Is Critical for Cell Type-Specific prM Protein Biogenesis, Virus Particle Release, and Pathogenicity in Mice (2008)

ABSTRACT The prM protein of Japanese encephalitis virus (JEV) contains a single potential N-linked glycosylation site, N 15 -X 16 -T 17 , which is highly conserved among JEV strains and closely related flaviviruses. To investigate the role of this site in JEV replication and pathogenesis, we manipulated the RNA genome by using infectious JEV cDNA to generate three prM mutants (N15A, T17A, and N15A/T17A) with alanine substiting for N 15 and/or T 17 and one mutant with silent point mutations introduced into the nucleotide sequences corresponding to all three residues in the glycosylation site. An analysis of these mutants in the presence or absence of endoglycosidases confirmed the addition of oligosaccharides to this potential glycosylation site. The loss of prM N glycosylation, without significantly altering the intracellular levels of viral RNA and proteins, led to an ≈20-fold reduction in the production of extracellular virions, which had protein compositions and infectivities nearly identical to those of wild-type virions; this reduction occurred at the stage of virus release, rather than assembly. This release defect was correlated with small-plaque morphology and an N-glycosylation-dependent delay in viral growth. A more conservative mutation, N15Q, had the same effect as N15A. One of the four prM mutants, N15A/T17A, showed an additional defect in virus growth in mosquito C6/36 cells but not human neuroblastoma SH-SY5Y or hamster BHK-21 cells. This cell type dependence was attributed to abnormal N-glycosylation-independent biogenesis of prM. In mice, the elimination of prM N glycosylation resulted in a drastic decrease in virulence after peripheral inoculation. Overall, our findings indicate that this highly conserved N-glycosylation motif in prM is crucial for multiple stages of JEV biology: prM biogenesis, virus release, and pathogenesis.
High‐Throughput Measurement of Binding Kinetics by mRNA Display and Next‐Generation Sequencing (2016)

There is great demand for high-throughput methods to characterize ligand affinity. By combining mRNA display with next-generation sequencing, we determined the kinetic on- and off-rates for over twenty thousand ligands without the need for synthesis or purification of individual members. Our results are reproducible and as accurate as those obtained with other methods of affinity measurement.
1700V, 20A 4H-SiC DMOSFETs Optimized for High Temperature Operation (2011)

DMOSFETs fabricated in 4H-SiC with capabilities for blocking in excess of 1700V and conducting 20A continuous current in the on-state are presented. These SiC DMOSFETs remain functional to temperatures in excess of 225°C, with leakage current at 1700V at 225°C of less than 5 A with VGS = 0V. The DMOSFETs show excellent switching characteristics, with total switching energy of 1.8 to 1.95 mJ over the entire temperature range of testing (25°C to 200°C), when switched from the blocking state at 1200V to conducting at 20A in a clamped inductive load switching circuit. The electrical characteristics are compared to commercially available Si IGBTs rated to 1700V with similar current ratings as the SiC DMOSFET described herein.
Production and Characterization of Cellulose Nanofibers from Wood Pulp (2011)

Cellulose nanofibers with a size range of 5–100 nm have the potential to be a low cost renewable material that has application in a range of products. However, current chemical methods to produce crystalline nanofibers suffer from low yields and high chemical costs, while mechanical methods require high energy costs. Methods to lower the energy costs of the mechanical methods have not been well documented in the literature. A bleached softwood kraft pulp was processed using a mechanical dispersion mill and a homogenizer to produce cellulose nanofibers. Two different commercial enzymes were used to pretreat the wood fibers before the mechanical treatments. The resulting nanofibers were characterized by light microscopy, atomic force microscopy, and inverse gas chromatography. Results indicate that the dispersion mill does not affect the overall pulp fiber fibrillation, but does help prepare the sample for the homogenizer. Most fibrillation occurs after three passes through the homogenizer. The enzyme pretreatment has little effect on the size of the fibers, but does allow for higher solids to pass through the homogenizer without clogging. The dispersion component of surface energy of the resulting nanofibrils is impacted by the type of enzyme used. The measurement of acid–base properties proved to be challenging using current IGC experimental protocols.
On the Inter-Symbol-Interference in several Ultra Wideband systems (2005)

The performance of several ultra-wideband (UWB) transmission schemes is analysed when the channel is frequency selective so that inter-symbol-interference (ISI) arises at the receiver. The UWB schemes considered employ time hopping (TH) and/or direct sequence (DS) as spreading method and a correlation receiver. Analytical expressions for the signal to interference power ratio (SIR) are derived are used to compare the schemes over several channels. Also the bit error rate (BER) is discussed. The theoretical results are compared with simulation results
An adenovirus encoding CuZnSOD protects cultured striatal neurones against glutamate toxicity (1996)

Superoxide dismutase (SOD), a key enzyme in the detoxification of free radicals, catalyses the dismutation of superoxide O2.- to oxygen and hydrogen peroxide (H2O2). It is therefore a promising candidate for gene transfer therapy of neurological diseases in which free radicals are thought to be involved. We have constructed a recombinant adenoviral vector containing the human copper-zinc SOD cDNA. Using this vector we were able to drive the production of an active human copper-zinc SOD protein (hCuZnSOD) in various cell lines and primary cultures. Infection of striatal cells with a recombinant adenovirus expressing hCuZnSOD protected these cells from glutamate-induced cell death.
Production of alcohol from Jerusalem artichokes by yeasts (1982)

Various yeasts such as several strains of Saccharomyces diastaticus, S. cerevisiae, and Kluyveromyces fregilis were investigated for their ability to ferment the carbohydrates from Jerusalem artichokes to alcohol. Juice extracted of the carbohydrates. Fermentation was also carried out with raw artichokes without prior juice extraction. Result indicate that this row material has good potential for fuel alcohol production by fermentation.
Microtubules and Actin Microfilaments Regulate Lipid Raft/Caveolae Localization of Adenylyl Cyclase Signaling Components (2006)

Microtubules and actin filaments regulate plasma membrane topography, but their role in compartmentation of caveolae-resident signaling components, in particular G protein-coupled receptors (GPCR) and their stimulation of cAMP production, has not been defined. We hypothesized that the microtubular and actin cytoskeletons influence the expression and function of lipid rafts/caveolae, thereby regulating the distribution of GPCR signaling components that promote cAMP formation. Depolymerization of microtubules with colchicine (Colch) or actin microfilaments with cytochalasin D (CD) dramatically reduced the amount of caveolin-3 in buoyant (sucrose density) fractions of adult rat cardiac myocytes. Colch or CD treatment led to the exclusion of caveolin-1, caveolin-2, beta1-adrenergic receptors (beta1-AR), beta2-AR, Galpha(s), and adenylyl cyclase (AC)5/6 from buoyant fractions, decreasing AC5/6 and tyrosine-phosphorylated caveolin-1 in caveolin-1 immunoprecipitates but in parallel increased isoproterenol (beta-AR agonist)-stimulated cAMP production. Incubation with Colch decreased co-localization (by immunofluorescence microscopy) of caveolin-3 and alpha-tubulin; both Colch and CD decreased co-localization of caveolin-3 and filamin (an F-actin cross-linking protein), decreased phosphorylation of caveolin-1, Src, and p38 MAPK, and reduced the number of caveolae/mum of sarcolemma (determined by electron microscopy). Treatment of S49 T-lymphoma cells (which possess lipid rafts but lack caveolae) with CD or Colch redistributed a lipid raft marker (linker for activation of T cells (LAT)) and Galpha(s) from lipid raft domains. We conclude that microtubules and actin filaments restrict cAMP formation by regulating the localization and interaction of GPCR-G(s)-AC in lipid rafts/caveolae.
Design Method of Software Test Case (2012)

The software test case design technique were inreoduced,including the black-box test case design technique,and the white-box test case design technique.Introduced in the test design process standardization,conducted a study on the standardization of test design cases.
Prephenate dehydratase of the actinomycete <i>Amycolatopsis methanolica</i>: purification and characterization of wild-type and deregulated mutant proteins (1995)

Prephenate dehydratase (PDT) is a key regulatory enzyme in L-phenylalanine biosynthesis in the Gram-positive bacterium Amycolatopsis methanolica. The PDT protein was purified to homogeneity (1957-fold) from wild-type cells with a final yield of 6.5%. It was characterized as a 150 kDa homotetrameric protein with a subunit size of 34 kDa. The first 35 N-terminal amino acids were identified, revealing highest similarity to the PDT proteins from Corynebacterium glutamicum and Bacillus subtilis. Kinetic studies showed that the A. methanolica PDT is allosterically inhibited by phenylalanine and activated by tyrosine. Phenylalanine caused an increase in the S0.5 for prephenate and a decrease in the Vmax. Tyrosine caused a decrease in the S0.5 for prephenate and an increase in the Vmax. Spontaneous o-fluoro- and p-fluoro-DL-phenylalanine-resistant mutants of A. methanolica were isolated. Kinetic studies with the partially purified PDT proteins of strains pFPhe32 and oFPhe84 showed that these mutant proteins had become (partly) insensitive to both phenylalanine inhibition and tyrosine activation.
Mutator Genes Giving Rise to Decreased Antibiotic Susceptibility in <i>Pseudomonas aeruginosa</i> (2008)

Screening of the PA14 genomic transposon mutant library for resistance to ceftazidime, tobramycin, and ciprofloxacin led to the discovery of several mutants that appeared in more than one screen. Testing of the frequency of mutation to ciprofloxacin resistance revealed previously known mutator genes, including mutS and mutL, as well as mutators that have not yet been described for P. aeruginosa, including PA3958 and RadA (PA4609).
LiDAR Panoptic Segmentation for Autonomous Driving (2020)

Truly autonomous driving without the need for human intervention can only be attained when self-driving cars fully understand their surroundings. Most of these vehicles rely on a suite of active and passive sensors. LiDAR sensors are a cornerstone in most of these hardware stacks, and leveraging them as a complement to other passive sensors such as RGB cameras is an enticing goal. Understanding the semantic class of each point in a LiDAR sweep is important, as well as knowing to which instance of that class it belongs to. To this end, we present a novel, single-stage, and real-time capable panoptic segmentation approach using a shared encoder with a semantic and instance decoder. We leverage the geometric information of the LiDAR scan to perform a novel, distance- aware tri-linear upsampling, which allows our approach to use larger output strides than using transpose convolutions leading to substantial savings in computation time. Our experimental evaluation and ablation studies for each module show that combining our geometric and semantic embeddings with our learned, variable instance thresholds, a category-specific loss, and the novel trilinear upsampling module leads to higher panoptic quality. We will release the code of our approach in our LiDAR processing library LiDAR-Bonnetal [27].
Geometric Calibration and Radiometric Correction of LiDAR Data and Their Impact on the Quality of Derived Products (2011)

LiDAR (Light Detection And Ranging) systems are capable of providing 3D positional and spectral information (in the utilized spectrum range) of the mapped surface. Due to systematic errors in the system parameters and measurements, LiDAR systems require geometric calibration and radiometric correction of the intensity data in order to maximize the benefit from the collected positional and spectral information. This paper presents a practical approach for the geometric calibration of LiDAR systems and radiometric correction of collected intensity data while investigating their impact on the quality of the derived products. The proposed approach includes the use of a quasi-rigorous geometric calibration and the radar equation for the radiometric correction of intensity data. The proposed quasi-rigorous calibration procedure requires time-tagged point cloud and trajectory position data, which are available to most of the data users. The paper presents a methodology for evaluating the impact of the geometric calibration on the relative and absolute accuracy of the LiDAR point cloud. Furthermore, the impact of the geometric calibration and radiometric correction on land cover classification accuracy is investigated. The feasibility of the proposed methods and their impact on the derived products are demonstrated through experimental results using real data.
Cloning of a Chitinase Gene chiSH1 Cloned from Gram-positive Bacterium Kurthia zopfii and Control of Powdery Mildew of Barley. (1996)

The bacterium capable of efficiently digesting chitin was isolated from chitin-amended field soil. It was identified as Kurthia zopfii, and extracellular chitinases secreted into respective culture filtrates were electrophoretically analyzed using a polyacrylamide gel containing glycol chitin. The result indicated that K. zopfii produced the 72, 58, and 44 kilodalton chitinases. The gene (chiSH1) encoding chitinase was cloned from K. zopfii KI2-119 and the entire nucleotide sequence (2097 bases) was determined. In order to evaluate the feasibility of chitinolytic microbes on the protection of chitinous fungal diseases, viable cells of E. coli transformed with the chiSH1 were applied to barley leaves inoculated with the powdery mildew pathogen. The result indicated that the growth of the pathogen was effectively suppressed by the present treatment, suggesting the importance and effectiveness of chitinolytic microbes as a biocontrol agent.
Cytokine production in patients with inflammatory bowel disease. (1992)

The production of cytokines in peripheral blood mononuclear leukocytes of patients with inflammatory bowel disease was investigated. T cell subset analysis and differential white blood cell counts were also performed. Thirty five patients with ulcerative colitis, 14 with Crohn's disease, and 15 age matched healthy volunteers were studied. No differences were observed in T cell subsets and OKT4/OKT8 ratios in patients with ulcerative colitis or Crohn's disease compared with controls. Interleukin 1 beta production was significantly increased in active ulcerative colitis and Crohn's disease, compared with values in controls, but returned to control levels in the inactive stages. In addition, in active ulcerative colitis and Crohn's disease, there were significant correlations between the interleukin 1 beta production and the ulcerative colitis activity index or Crohn's disease activity index. Interleukin 2 production was also significantly increased in the active ulcerative colitis and significantly correlated to the activity index, but there was no change in Crohn's disease patients compared with controls. Gamma interferon production in patients was the same as that in controls. This study suggests that the interleukin 1 beta and 2 values in peripheral mononuclear leukocytes of active untreated inflammatory bowel disease are indicators of the disease states of ulcerative colitis or Crohn's disease, or both.
REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19 (2020)

In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.).
Stitching of off-axis sub-aperture null measurements of an aspheric surface (2008)

Optical testing of a large convex aspheric surface, such as the secondary of a Ritchey-Chretien telescope, can be performed with a Fizeau interferometer that utilizes subaperture aspheric reference plates, each providing a null test of a subaperture of the larger mirror. The subaperture data can be combined or stitched together to create a map of the full surface. The region of the secondary mirror surface under test in each sub-aperture is an off-axis segment of the parent aspheric surface, therefore, the Fizeau reference requires a non-axi-symmetric aspheric surface to match it. Misalignment of the Fizeau reference relative to the parent in each sub-aperture will then result in aberrations in the measurements other than the ordinary terms of piston and tilt. When stitching sub-aperture measurements together, the apparent aberrations due to the null lens misalignment need to be fitted and subtracted. This paper presents an algorithm to perform this particular type of stitching.
A Low-Cost Multi-Parameter Water Quality Monitoring System (2021)

Multi-parameter water quality monitoring is crucial in resource-limited areas to provide persistent water safety. Conventional water monitoring techniques are time-consuming, require skilled personnel, are not user-friendly and are incompatible with operating on-site. Here, we develop a multi-parameter water quality monitoring system (MWQMS) that includes an array of low-cost, easy-to-use, high-sensitivity electrochemical sensors, as well as custom-designed sensor readout circuitry and smartphone application with wireless connectivity. The system overcomes the need of costly laboratory-based testing methods and the requirement of skilled workers. The proposed MWQMS system can simultaneously monitor pH, free chlorine, and temperature with sensitivities of 57.5 mV/pH, 186 nA/ppm and 16.9 mV/°C, respectively, as well as sensing of BPA with <10 nM limit of detection. The system also provides seamless interconnection between transduction of the sensors' signal, signal processing, wireless data transfer and smartphone app-based operation. This interconnection was accomplished by fabricating nanomaterial and carbon nanotube-based sensors on a common substrate, integrating these sensors to a readout circuit and transmitting the sensor data to an Android application. The MWQMS system provides a general platform technology where an array of other water monitoring sensors can also be easily integrated and programmed. Such a system can offer tremendous opportunity for a broad range of environmental monitoring applications.
Utilization of Eggshell Powder as Excipient in Fast and Sustained Release Acetaminophen Tablets (2018)

Eggshell powder has been investigated for the new application as pharmaceutical excipient in tablet dosage form. Acetaminophen was used as a model drug in this study. Four different eggshell powders were prepared. These included untreated eggshell powder, water treated, ethanol treated and chloroform treated eggshell powders. The treated samples were prepared by surface modification using 1.0 % w/v stearic acid in solvent namely deionized water, 95 % ethanol and chloroform. The tablets containing acetaminophen, eggshell powder and microcrystalline cellulose were prepared by direct compression method. Dissolution studies of four acetaminophen formulations in pH 5.8 phosphate buffer were performed using USP Dissolution Apparatus II. The results show that immediate release of acetaminophen was obtained from tablets containing untreated eggshell powder whereas sustained release of the drug was obtained from the tablet formulations containing three different treated eggshell powders. Sustained release of the drug may be due to hydrophobic nature of the treated eggshell powders. It was also found that the degree of hydrophobicity of the treated eggshell powders depends on the type of solvent used in surface modification process. The results obtained from this study show that eggshell powder appears to be applicable as a pharmaceutical excipient to control the drug release from the tablet. Additionally, this finding may be useful to generate public interest in development of biomaterials from eggshell waste by proposing the new application of eggshell powder in pharmaceutical industry. Keyword: Eggshell, Drug release, Acetaminophen, Excipient, Bioresource utilization
True Random Number Generator circuits based on single- and multi-phase beat frequency detection (2014)

A fully-digital True Random Number Generator (TRNG) measures the frequency difference between two free-running ring oscillators, or in other words the beat frequency, to extract random frequency jitter. For generating a continuous stream of random bits with a high entropy level, the lower significant bits meeting the NIST randomness criteria are concatenated. The generation efficiency is further improved by utilizing a multi-phase structure. The proposed circuit fabricated in 65nm achieves an energy efficiency of 15.1Mb/mW at 0.8V. Experimental data collected from eight TRNG test chips passed all 15 NIST tests without the use of any feedback or tracking scheme.
Differences in Peripheral and Autonomic Nerve Function Measurements in Painful and Painless Neuropathy: A clinical study (1994)

We conclude that no difference could be found in the function of small and large nerve fibers between painful and painless diabetic neuropathy using conventional tests currently used. The CPT evaluation failed to quantify painful symptoms, but it compared favorably with other quantitative sensory tests in quantifying peripheral neuropathy.