gebhart/patrepeval huggingface dataset:
Multimedia database management-requirements and issues (1997)

The spatial, temporal, storage, retrieval, integration and presentation requirements of multimedia data differ significantly from those for traditional data. A multimedia database management system provides for the efficient storage and manipulation of multimedia data in all its varied forms. We look into the basic nature of multimedia data, highlight the need for multimedia DBMSs, and discuss the requirements and issues necessary for developing such systems.
Towards an adaptive natural language interface to command languages (1996)

Operating system command languages assist the user in executing commands for a significant number of common everyday tasks. On the other hand, the introduction of textual command languages for robots has provided the opportunity to perform some important functions that leadthrough programming cannot readily accomplish. However, such command languages assume the user to be expert enough to carry out a specific task in these application domains. On the contrary, a natural language interface to such command languages, apart from being able to be integrated into a future speech interface, can facilitate and broaden the use of these command languages to a larger audience. In this paper, advanced techniques are presented for an adaptive natural language interface that can (a) be portable to a large range of command languages, (b) handle even complex commands thanks to an embedded linguistic parser, and (c) be expandable and customizable by providing the casual user with the opportunity to specify some types of new words as well as the system developer with the ability to introduce new tasks in these application domains. Finally, to demonstrate the above techniques in practice, an example of their application to a Greek natural language interface to the MS-DOS operating system is given.
Addition of Atrasentan to Renin-Angiotensin System Blockade Reduces Albuminuria in Diabetic Nephropathy (2011)

Although endothelin-receptor antagonists reduce albuminuria in diabetic nephropathy, fluid retention limits their use. Here, we examined the effect of atrasentan, a selective endothelin A receptor (ET(A)R) antagonist, on albuminuria in a randomized, double-blind, placebo-controlled trial of subjects with diabetic nephropathy already receiving stable doses of renin-angiotensin system (RAS) inhibitors. We randomly assigned 89 subjects with eGFR >20 ml/min per 1.73 m(2) and a urinary albumin-to-creatinine ratio (UACR) of 100 to 3000 mg/g to placebo or atrasentan (0.25, 0.75, or 1.75 mg daily) for 8 weeks. Compared with placebo, atrasentan significantly reduced UACR only in the 0.75- and 1.75-mg groups (P=0.001 and P=0.011, respectively). Compared with the 11% reduction in the geometric mean of the UACR from baseline to final observation in the placebo group during the study, the geometric mean of UACR decreased by 21, 42, and 35% in the 0.25-, 0.75-, and 1.75-mg atrasentan groups (P=0.291, P=0.023, and P=0.073, respectively). In the placebo group, 17% of subjects achieved ≥40% reduction in UACR from baseline compared with 30, 50, and 38% in the 0.25-, 0.75-, and 1.75-mg atrasentan groups, respectively (P=0.029 for 0.75 mg versus placebo). Peripheral edema occurred in 9% of subjects receiving placebo and in 14, 18, and 46% of those receiving 0.25, 0.5, and 1.75 mg atrasentan, respectively (P=0.007 for 1.75 mg versus placebo). In summary, atrasentan, at the doses tested, is generally safe and effective in reducing residual albuminuria and may ultimately improve renal outcomes in patients with type 2 diabetic nephropathy.
Mapping a gene for neuropathic pain-related behavior following peripheral neurectomy in the mouse (2001)

Total hindpaw denervation in rodents elicits an abnormal behavior of licking, scratching and self-injury of the anesthetic limb ("autotomy"). Since the same denervation produces phantom limb pain and anesthesia dolorosa in humans, autotomy has been used as a model of human neuropathic pain. Autotomy is an inherited trait in rodents, attributable to a few genes of major effect. Here we used recombinant inbred (RI) mouse lines of the AXB-BXA RI set to map a gene for autotomy. Autotomy levels following unilateral sciatic and saphenous nerve section were scored daily for 36 days, using a standardized scale, in all 23 RI lines available for this set. We used a genetic map of 395 marker loci and a permutation-based statistical method for categorical data to assess the statistical significance of mapping results. We identified a marker on chromosome 15 with statistical support (P=0.0003) in the range considered significant for genome-wide scans in the mouse. Several genes located in this chromosomal region encode for neural functions related to neuropathic pain and may indicate targets for development of novel analgesics.
The Message of God's People in the Old Testament (2010)

The principal task of God's people in the Old Testament 1 was to worship and serve the Lord (Exod 4:22
Tetra-Substituted Ethylenes (1976)

Abstract As part of our studies into certain aspects of organosulphur chemistry we published recently a short communication concerning a new synthesis of tetra-substituted ethylenes. We have extended the scope of this reaction and have more closely defined the optimum experimental conditions. It appears that substituted alkyl acetates, and probably other alkyl esters, containing a further electron-with-drawing group and with a low enol content (approx. < 1%) or similar compounds having a methylene group activated by two electron-with-drawing groups, e.g. malononitrile, will react with thionyl chloride generally under reflux conditions to give the corresponding alkene, eq. 1. We have also found that similar compounds with a rather higher enol content will generally react with thionyl chloride in the cold to give a sulphinyl chloride or a sulphide or polysulphide, eq. 2.
Pharmacokinetic Mapping of the Breast: A New Method for Dynamic MR Mammography (1995)

A dynamic contrast-enhanced MRI technique for whole breast examinations is presented. The fast kinetics of tissue response during and after constant-rate intravenous infusion of gadolinium diethylenetriaminopentaacetic acid was resolved using a strongly T1-weighted saturation recovery TurboFLASH sequence that makes it possible to acquire signal-time courses sequentially from 15 adjacent slices with a temporal sampling rate of 21 s. On the basis of the mathematically established and experimentally verified linear relationship between the measured saturation recovery TurboFLASH signal variation and the gadolinium diethylenetriaminopentaacetic acid concentration in the tissue, the signal-time courses were analyzed within the framework of pharmacokinetic modeling. In our study, the tissue response was parameterized adequately using an open linear two-compartment model. With this approach, the tissue specific information contained in the signal-time course can be described using only two parameters: an amplitude A, reflecting the degree of MR signal enhancement, and an exchange parameter k21, characterizing vascular permeability and perfusion of the tissue. A clearly arranged representation of the large amount of data (480 saturation recovery TurboFLASH breast images/examination) was accomplished by means of color coding of the computed parameters, resulting in one color-coded pharmacokinetic parameter map/cross-section.
Combined gemcitabine and radioimmunotherapy for the treatment of pancreatic cancer (2001)

MAb-PAM4 is an anti-MUC1 antibody that has been shown to be reactive with 85% of pancreatic adenocarcinomas with no reactivity with normal pancreas or other tissues. Initial clinical studies have shown excellent targeting with high tumor/nontumor ratios. Gemcitabine, an analog of deoxycytidine, is currently a frontline treatment for pancreatic cancer. Acting via a number of metabolic pathways, gemcitabine is also a powerful radiosensitizer. Combined-modality, chemo/radiosensitization with gemcitabine and low dose (131)I-PAM4 radioimmunotherapy was performed to determine if a more effective treatment procedure could be developed. Athymic nude mice bearing large (1 cm(3)) CaPan1 human pancreatic tumors were given a single treatment cycle consisting of gemcitabine, 333 mg/m(2) administered on Days 0, 3, 6, 9 and 12 by intraperitoneal injection, along with either 100 or 200 microCi, (131)I-PAM4 administered on Day 0 by intravenous injection. Gemcitabine did not interfere with the biodistribution of radiolabeled antibody. Specific tumor targeting was observed for (131)I-PAM4, with a tumor/blood radiation dose ratio of 2.6 over the first 14 days. Gemcitabine alone and low dose radioimmunotherapy alone, each had no affect upon tumor growth; no statistical differences were noted in comparison to the untreated group. When combined, however, a statistically significant (p = 0.0324), synergistic anti-tumor effect was observed. Median survival time doubled for the combined treatment regimen compared to single modality treatment groups. The combined treatment modality was well tolerated by the mice. Our data show that combined gemcitabine with radioimmunotherapy may provide an improved alternative for the treatment of pancreatic cancer, achieving successful anti-tumor effects with low toxicity.
Rechargeable Lithium Battery Cathodes. Nonaqueous Synthesis, Characterization, and Electrochemical Properties of LiCoO2 (1998)

A nonaqueous coprecipitation process has been developed to prepare controlled stoichiometry lithium cobalt oxide precipitates. The process involved mixing a methanolic “LiCo(NO3)3” solution with a methanolic solution containing tetramethylammonium oxalate as a precipitating agent. The resulting oxalates were readily converted to phase-pure lithium cobalt oxide at 800 °C under an oxygen atmosphere. The various starting solutions, oxalate precipitates, and the resulting oxides have been extensively characterized using a variety of techniques, including multinuclear NMR, TGA/DTA, EPR, and XRD analyses. Results indicate that the strong interaction between the metals (Li and Co) that occurred in solution was maintained during precipitation. The calcined precipitate revealed that the desired LiCoO2 phase was formed at 800 °C under an O2 atmosphere. When electrochemically cycled, the material exhibited an initial capacity of ∼133 (mA h)/g with a fade of 0.02% in capacity per cycle.
"Panning" for lymphocytes: a method for cell selection. (1978)

We have developed a simple method for the fractionation of T and B lymphocytes. Plastic dishes coated with antibodies specific for mouse Ig selectively bind splenic B lymphocytes. The adherent cells are easily removed by gentle pipetting; both adherent and nonadherent populations retain immunologic function. In a typical experiment, when 3 X 10(7) splenic lymphocytes were added to a 100 X 15 mm plastic dish coated with microgram quantities of anti-Ig, 98 % of the nonadherent cells were Ig negative and 97% of the adherent cells were Ig positive. The method is sufficiently sensitive to allow detection and separation of cell types comprising as little as 2% of the total population and can be modified to allow the selection of cells by a double-antibody procedure. We believe that the plastic dish method will be generally useful for fractionating cells on the basis of their cell surface antigens.
Mechanism of Immunoglobulin G4 Fab-arm Exchange (2011)

Immunoglobulin G (IgG) antibodies are symmetrical molecules that may be regarded as covalent dimers of 2 half-molecules, each consisting of a light chain and a heavy chain. Human IgG4 is an unusually dynamic antibody, with half-molecule exchange ("Fab-arm exchange") resulting in asymmetrical, bispecific antibodies with two different antigen binding sites, which contributes to its anti-inflammatory activity. The mechanism of this process is unknown. To elucidate the elementary steps of this intermolecular antibody rearrangement, we developed a quantitative real-time FRET assay to monitor the kinetics of this process. We found that an intrinsic barrier is the relatively slow dissociation of the CH3 domains that noncovalently connect the heavy chains, which becomes rate determining in case disulfide bonds between the heavy chains are reduced or absent. Under redox conditions that mimic the previously estimated in vivo reaction rate, i.e., 1 mM of reduced glutathione, the overall rate is ca. 20 times lower because only a fraction of noncovalent isomers is present (with intra- rather than interheavy chain disulfide bonds), formed in a relatively fast pre-equilibrium from covalent isomers. Interestingly, Fab arms stabilize the covalent isomer: the amount of noncovalent isomers is ca. 3 times higher for Fc fragments of IgG4 (lacking Fab domains) compared to intact IgG4, and the observed rate of exchange is 3 times higher accordingly. Thus, kinetic data obtained from a sensitive and quantitative real-time FRET assay as described here yield accurate data about interdomain interactions such as those between Fab and/or Fc domains. The results imply that in vivo, the reaction is under control of local redox conditions.
Tagged mutations at the Tox1 locus of Cochliobolus heterostrophus by restriction enzyme-mediated integration. (1994)

We have used the restriction enzyme-mediated integration insertional mutagenesis procedure to tag the Tox1 locus in the filamentous Ascomycete Cochliobolus heterostrophus. Mutations at other, unselected, loci were also identified and a high proportion (30-50%) of them were tagged. This procedure may be of general utility for simultaneously mutating and tagging genes in fungi and in other eukaryotes. The Tox1 locus of C. heterostrophus has been defined by Mendelian analysis as a single genetic element that controls production of T toxin, a linear polyketide involved in virulence of the fungus to its host plant, corn. To tag Tox1, protoplasts of a Tox1+ (T-toxin producing) strain were transformed with a linearized, nonhomologous plasmid along with an excess of the restriction enzyme used to linearize the plasmid. Of 1310 transformants recovered, two produced no detectable T toxin in culture or on corn plants. In each of these transformants, the Tox- mutation mapped at Tox1, was tagged with the selectable marker (hygB) on the transforming plasmid, and was tightly linked to the other tagged Tox- mutation. The two mutations, however, represent two different points of plasmid insertion at the Tox1 locus.
A Desktop Image Processing System for Computer-Assisted Orthopedic Surgery (DISOS) (1996)

Within the framework of our research activities in orthopedic surgery a PC-based imageprocessing system for the processing of x-ray computer-tomographic data has been developed. The system is used as a work platform for the investigations concerning interaction modalities, strategies and techniques for an efficient planning and execution of surgical interventions in orthopedic surgery by means of individual templates. The method of individual templates has been presented in /1,2/ and will not be subject of this paper.
Statistical Analysis of Weak Reliability Links in Power Generation Equipment (2001)

The paper introduces the basic concept of weak reliability links in power generating equipment and presents calculation formulae for their statistical evaluation, together with some practical examples of large fossil firing sets. Such statistical analyses point out the track to improving the reliability of power generating equipment and are therefore significant for effective promotion of reliability. Tables 2
Local Surface Charges Direct the Deposition of Carbon Nanotubes and Fullerenes into Nanoscale Patterns (2007)

This article reports on the directed deposition of carbon nanotubes (CNTs) and fullerenes onto solid surfaces using local electrostatic fields. Arbitrary patterns of local surface charges are created by charge writing with an atomic force microscope. During the subsequent development of the sample in an aqueous suspension containing surfactant-stabilized CNTs or fullerenes, Coulomb attraction guides the positioning and alignment of these particles onto the charge patterns. The surface potential of the charge patterns provides a direct control over the particle attachment. CNTs and fullerenes precisely reproduce the charge patterns, yielding structures with a lateral resolution down to the particle diameter.
Discovery of small molecule inhibitors of the Wnt/β-catenin signaling pathway by targeting β-catenin/Tcf4 interactions (2017)

The Wnt/β-catenin signaling pathway typically shows aberrant activation in various cancer cells, especially colorectal cancer cells. This signaling pathway regulates the expression of a variety of tumor-related proteins, including c-myc and cyclin D1, and plays essential roles in tumorigenesis and in the development of many cancers. Small molecules that block the interactions between β-catenin and Tcf4, a downstream stage of activation of the Wnt/β-catenin signaling pathway, could efficiently cut off this signal transduction and thereby act as a novel class of anticancer drugs. This paper reviews the currently reported inhibitors that target β-catenin/Tcf4 interactions, focusing on the discovery approaches taken in the design of these inhibitors and their bioactivities. A brief perspective is then shared on the future discovery and development of this class of inhibitors. Impact statement This mini-review summarized the current knowledge of inhibitors of interactions of beta-catenin/Tcf4 published to date according to their discovery approaches, and discussed their in vitro and in vivo activities, selectivities, and pharmacokinetic properties. Several reviews presently available now in this field describe modulators of the Wnt/beta-catenin pathway, but are generally focused on the bioactivities of these inhibitors. By contrast, this review focused on the drug discovery approaches taken in identifying these types of inhibitors and provided our perspective on further strategies for future drug discoveries. This review also integrated many recently published and important works on highly selective inhibitors as well as rational drug design. We believe that the findings and strategies summarized in this review have broad implications and will be of interest throughout the biochemical and pharmaceutical research community.
Peptide Catalyzed Asymmetric Conjugate Addition Reactions of Aldehydes to Nitroethylene—A Convenient Entry into γ2-Amino Acids (2008)

The peptide H-D-Pro-Pro-Glu-NH2 is a highly effective catalyst for conjugate addition reactions between aldehydes and nitroethylene. Only 1 mol % of H-d-Pro-Pro-Glu-NH2 and a 1.5-fold excess of aldehyde with respect to nitroethylene suffice to obtain gamma-nitroaldehydes and, after reduction, monosubstituted gamma-nitroalcohols in excellent yields and optical purities. The products can be readily converted into gamma2-amino acids, thereby opening an effective direct entry into this important class of compounds.
Unique and overlapping pollutant stress proteins of Escherichia coli (1992)

Exposure of growing batch cultures of Escherichia coli to nine different "model micropollutants" (benzene, cadmium chloride, chlorpyrivos, 2,4-dichloroaniline, dioctylphtalate, hexachlorobenzene, pentachlorophenol, trichloroethylene, and tetrapropylbenzosulfonate) led to the induction of 13 to 39 proteins, as analyzed by two-dimensional gel electrophoresis. Some of these proteins overlapped with heat shock and carbon starvation proteins, but at least 50% were unique to a given chemical. The stress protein induction showed a temporal pattern, indicating sequential gene expression. Chemical stress protein synthesis occurred even at concentrations that had no effect on growth. Thus, the synthesis of these proteins can be a sensitive index of stress and the nature of environmental pollution.
PTEN expression by an oncolytic herpesvirus directs T-cell mediated tumor clearance (2018)

Engineered oncolytic viruses are used clinically to destroy cancer cells and have the ability to boost anticancer immunity. Phosphatase and tensin homolog deleted on chromosome 10 loss is common across a broad range of malignancies, and is implicated in immune escape. The N-terminally extended isoform, phosphatase and tensin homolog deleted on chromosome 10 alpha (PTENα), regulates cellular functions including protein kinase B signaling and mitochondrial adenosine triphosphate production. Here we constructed HSV-P10, a replicating, PTENα expressing oncolytic herpesvirus, and demonstrate that it inhibits PI3K/AKT signaling, increases cellular adenosine triphosphate secretion, and reduces programmed death-ligand 1 expression in infected tumor cells, thus priming an adaptive immune response and overcoming tumor immune escape. A single dose of HSV-P10 resulted in long term survivors in mice bearing intracranial tumors, priming anticancer T-cell immunity leading to tumor rejection. This implicates HSV-P10 as an oncolytic and immune stimulating therapeutic for anticancer therapy.
An Inquiry into the Mechanisms of Herpes Simplex Virus Latency (1987)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Animal Models of Diabetic Retinopathy (2015)

Diabetic retinopathy (DR) is one of today's main causes of blindness in numerous developed countries worldwide. The underlying pathogenesis of DR is complex and not well understood, thus impeding development of specific, effective treatment modalities. Consequently, the use of animal models of DR is of critical importance for investigating the pathogenesis of and treatment for DR. While rats and mice are the most commonly used animal models of DR, the zebrafish now appears to be a promising model. Nonhuman primates and humans have similar eye structures, and both can develop spontaneous diabetes mellitus (DM). Although various traditionally used animal models of DR undergo a number of pathological changes similar to those of human DR, several human variations, e.g. retinal neovascularization, cannot yet be fully mimicked in any existing animal model of DM. Since both the animal models and the methods chosen for inducing DR have great influence on experimental results, a clear understanding of available animal models is vital for planning an experimental design. In this review, we summarize the mechanisms, methodologies and pros and cons of the most commonly used animal models of DR.
Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong agonist insulin mimetope (2011)

Type 1 diabetes (T1D) results from the destruction of insulin-secreting pancreatic β cells by autoreactive T cells. Insulin is an essential target of the autoimmune attack. Insulin epitopes recognized by diabetogenic T cell clones bind poorly to the class II I-A(g7) molecules of nonobese diabetic (NOD) mice, which results in weak agonistic activity of the peptide MHC complex. Here, we describe a strongly agonistic insulin mimetope that effectively converts naive T cells into Foxp3(+) regulatory T cells in vivo, thereby completely preventing T1D in NOD mice. In contrast, natural insulin epitopes are ineffective. Subimmunogenic vaccination with strongly agonistic insulin mimetopes might represent a novel strategy to prevent T1D in humans at risk for the disease.