gebhart/patrepeval huggingface dataset:
Extravascular fibrin formation and dissolution in synovial tissue of patients with osteoarthritis and rheumatoid arthritis (1991)

Fibrin deposition is a prominent finding in the synovium of patients with rheumatoid arthritis (RA). Macrophages are found in increased numbers in RA synovium, and these cells are known to produce a variety of procoagulant and anticoagulant molecules. Using immunohistologic techniques, the content and distribution of several important components of the coagulation system in the synovium of patients with RA, osteoarthritis (OA), or traumatic joint abnormalities requiring surgery were investigated. Samples from 3 patients from each category were examined in detail. RA synovium (compared with that of patients with OA or joint trauma) had increased numbers of macrophages and increased expression/content of fibrinogen, tissue factor, factor XIII, tissue transglutaminase, cross-linked fibrin (fibrin D dimer), urokinase-type plasminogen activator, and alpha 2-plasmin inhibitor. Macrophage content in RA synovium was increased in both the lining cell areas and the interstitial cell areas. Fibrinogen was distributed throughout the tissue in all samples and was greater in RA synovium. In trauma and OA synovia, tissue factor was seen only in association with vessels (endothelial cells), but in RA synovium, it was markedly increased throughout the tissues. While fibrin D dimer was seen in small amounts in synovial lining cell areas of trauma and OA synovia, it was present in increased amounts in the lining cell and interstitial cell areas of RA synovium. Factor XIII and tissue transglutaminase were present in scant amounts in trauma and OA synovia, but there were increased amounts of both (especially tissue transglutaminase) in RA synovium in the vessel, lining cell, and interstitial cell areas. Urokinase and alpha 2-plasmin inhibitor were also markedly increased in RA synovium. These results suggest that in inflamed synovium, there is ongoing extravascular tissue fibrin formation and dissolution that correlates with the degree of inflammation and macrophage content. Extravascular coagulation/fibrinolysis in RA represents a potential target for therapeutic intervention in this disease.
Timewarp rigid body simulation (2000)

The traditional high-level algorithms for rigid body simulation work well for moderate numbers of bodies but scale poorly to systems of hundreds or more moving, interacting bodies. The problem is unnecessary synchronization implicit in these methods. Jefferson's timewarp algorithm [22] is a technique for alleviating this problem in parallel discrete event simulation. Rigid body dynamics, though a continuous process, exhibits many aspects of a discrete one. With modification, the timewarp algorithm can be used in a uniprocessor rigid body simulator to give substantial performance improvements for simulations with large numbers of bodies. This paper describes the limitations of the traditional high-level simulation algorithms, introduces Jefferson's algorithm, and extends and optimizes it for the rigid body case. It addresses issues particular to rigid body simulation, such as collision detection and contact group management, and describes how to incorporate these into the timewarp framework. Quantitative experimental results indicate that the timewarp algorithm offers significant performance improvements over traditional high-level rigid body simulation algorithms, when applied to systems with hundreds of bodies. It also helps pave the way to parallel implementations, as the paper discusses.
Determination of Nanogram Levels of Peptide Drug in Rabbit and Human Plasma Using High-Performance Liquid Chromatography Coupled with Electrospray Ionization Mass Spectrometry (1994)

High-performance liquid chromatography (HPLC) coupled to mass spectrometry (MS) using an electrospray ionization (ESI) interface provides a sensitive method for the quantitative analysis of peptide drugs in complex biological matrixes. ESI HPLC-MS was applied to the analysis of a pentapeptide drug (IRI-514) in rabbit and human plasma. Prior to analysis, the plasma samples were prepared using protein precipitation followed by solid-phase extraction. The lower limit of quantitation using selected ion monitoring was determined to be 2 ng/mL, when 8 mL of human plasma spiked with 1-40 ng/mL was extracted. Rabbit plasma (1 mL) samples spiked with 10-40,000 ng of authentic drug/mL gave a linear response when a deuterated peptide analog was employed as an internal standard. A commercial ESI interface was modified to permit higher flow rates (10-20 microL/min) to enter the mass spectrometer source. The revised interface provided a 10-fold increase in sensitivities and permitted the use of standard HPLC columns (2.0-mm i.d.) and HPLC instrumentation. ESI HPLC-MS analysis was automated to provide unattended, precise, and sensitive detection of small peptides in both human and rabbit plasma. Using this methodology, a toxicokinetic study of intravenously administered IRI-514 at three dose levels indicated that the area under the curve values were dose proportional.
Improving a circularly permuted TEM-1 β-lactamase by directed evolution (2002)

Circular permutation of proteins is a powerful technique to explore the importance of the polypeptide secondary structure order for attaining the final three-dimensional structure. Here, we designed a circular permutation of the TEM beta-lactamase in order to produce a new domain-forming amino acid arrangement in the polypeptide sequence. Closing the normal N- and C-termini with the connecting peptide GGS and creating new N- and C-termini at position 216, produces a severely impaired permuted protein. Introduction of a connector with random components allows the isolation of enzymes with better activities and indicates a selection for a potential helix-stop signal at the new super-secondary motif. We applied several directed-evolution cycles, starting from permuted enzymes with each of the two different connecting peptides, and selecting for antibiotic resistance and isolated several mutants with resistance levels close to those of the wild-type enzyme. We also analyze some of the data collected on the outcomes and paths of these evolutionary experiments. A purified sixth cycle variant with connector peptide GGS showed catalytic efficiency values approximately 8% of the natural enzyme.
Method for evaluating compatibility of commercial electromagnetic (EM) microsensor tracking systems with surgical and imaging tables (2008)

Electromagnetic (EM) tracking systems have been successfully used for Surgical Navigation in ENT, cranial, and spine applications for several years. Catheter sized micro EM sensors have also been used in tightly controlled cardiac mapping and pulmonary applications. EM systems have the benefit over optical navigation systems of not requiring a line-of-sight between devices. Ferrous metals or conductive materials that are transient within the EM working volume may impact tracking performance. Effective methods for detecting and reporting EM field distortions are generally well known. Distortion compensation can be achieved for objects that have a static spatial relationship to a tracking sensor. New commercially available micro EM tracking systems offer opportunities for expanded image-guided navigation procedures. It is important to know and understand how well these systems perform with different surgical tables and ancillary equipment. By their design and intended use, micro EM sensors will be located at the distal tip of tracked devices and therefore be in closer proximity to the tables. Our goal was to define a simple and portable process that could be used to estimate the EM tracker accuracy, and to vet a large number of popular general surgery and imaging tables that are used in the United States and abroad.
Suppression and Regression of Choroidal Neovascularization by Polyamine Analogues (2005)

Periocular delivery of the polyamine analogues may be a useful approach for the treatment of CNV.
Units, Symbols, and Terminology for Plant Physiology: A Reference for Presentation of Research Results in the Plant Sciences (1997)

SECTION I: THE BASICS 1. Summary of the International System of Units (SI Units) 2. Rules for Botanical Nomenclature 3. Statistics SECTION II: PLANT BIOPHYSICS 4. Basic Thermodynamic Quantities 5. Solutions (Ionic Relations) 6. Water Relations 7. Energy Transfer 8. Phloem Transport 9. Electromagnetic Radiation SECTION III: PLANT BIOCHEMISTRY AND MOLECULAR BIOLOGY 10. Plant Biochemistry 11. Plant Molecular Biology and Gene Designations SECTION IV: PLANT GROWTH AND DEVELOPMENT 12. Morphogenesis and the Kinetics of Plant Growth 13. Growth Analysis and Yield Components 14. Plant Movements 15. Growth Substances 16. Biological Timing 17. Dormancy, Photoperiodism, and Vernalization 18. Stress Physiology Appendices: Presenting Scientific Data A. Some Suggestions About Scientific Writing B. Standards for Effective Presetnations C. Guidelines for Measuring and Reporting Environmental Parameters for Plant Experiments in Growth Chambers
Inhibition of specific binding of okadaic acid to protein phosphatase 2A by microcystin-LR, calyculin-A and tautomycin: method of analysis of interactions of tight-binding ligands with target protein (1995)

Several groups have reported that okadaic acid (OA) and some other tight-binding protein phosphatase inhibitors including microcystin-LR (MCLR), calyculin-A and tautomycin prevent each other from binding to protein phosphatase 2A (PP2A). In this paper, we have introduced an improved procedure for examining to what extent the affinity of an enzyme for a labelled tight-binding ligand is reduced by binding of an unlabelled tight-binding, ligand to the enzyme. Using this procedure, we have analysed the dose-dependent reduction of PP2A binding of [24-3H]OA by addition of OA, MCLR, calyculin-A and tautomycin. The results indicate that the binding of the unlabelled inhibitors to the PP2A molecule causes a dramatic (10(6)-10(8)-fold) increase in the dissociation constant associated with the interaction of [24-3H]OA and PP2A. This suggests that OA and the other inhibitors bind to PP2A in a mutually exclusive manner. The protein phosphatase inhibitors may share the same binding site on the PP2A molecule. We have also measured values of the dissociation constant (Ki) for the interaction of these toxins with protein phosphatase 1 (PP1). For MCLR and calyculin-A, the ratio of the Ki value obtained for PP1 to that for PP2A was in the range 4-9, whereas it was 0.01-0.02 for tautomycin. The value of tautomycin is considerably smaller than that (0.4) calculated from previously reported Ki values.
Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses (2017)

Emerging viral infections are difficult to control because heterogeneous members periodically cycle in and out of humans and zoonotic hosts, complicating the development of specific antiviral therapies and vaccines. Coronaviruses (CoVs) have a proclivity to spread rapidly into new host species causing severe disease. Severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) successively emerged, causing severe epidemic respiratory disease in immunologically naïve human populations throughout the globe. Broad-spectrum therapies capable of inhibiting CoV infections would address an immediate unmet medical need and could be invaluable in the treatment of emerging and endemic CoV infections. We show that a nucleotide prodrug, GS-5734, currently in clinical development for treatment of Ebola virus disease, can inhibit SARS-CoV and MERS-CoV replication in multiple in vitro systems, including primary human airway epithelial cell cultures with submicromolar IC<sub>50</sub> values. GS-5734 was also effective against bat CoVs, prepandemic bat CoVs, and circulating contemporary human CoV in primary human lung cells, thus demonstrating broad-spectrum anti-CoV activity. In a mouse model of SARS-CoV pathogenesis, prophylactic and early therapeutic administration of GS-5734 significantly reduced lung viral load and improved clinical signs of disease as well as respiratory function. These data provide substantive evidence that GS-5734 may prove effective against endemic MERS-CoV in the Middle East, circulating human CoV, and, possibly most importantly, emerging CoV of the future.
Analysis of Borna disease virus-specific RNAs in infected cells and tissues (1991)

Borna disease virus (BDV) is an infectious agent that causes profound disturbances in motor function and behaviour in a wide range of animal species and possibly humans. The infectious nature of BDV has long been established, but the aetiological agent has not been isolated or classified. Recently, we have reported the isolation of BDV-specific cDNA clones using subtractive libraries constructed from mRNA from infected material. Here we describe studies on one of these cDNA clones, B8, and confirm its specificity by in situ hybridization on sections of BDV-infected brain. The complete nucleotide sequence of BDV-specific clone B8 was determined. Oligonucleotides of positive and negative polarity synthesized from sequences from the 5' and 3' ends, as well as the central part, of clone B8 identified both positive- and negative-strand BDV-specific RNAs in infected rat brain. All B8 sequences used as oligonucleotide probes were found to be contained in the larger positive- and negative-strand RNAs. Thus, the structure of the BDV-specific RNAs appears to be a nested set of multiple, overlapping subgenomic positive- and negative-strand RNA transcripts.
Continuous, clonal, insulin- and somatostatin-secreting cell lines established from a transplantable rat islet cell tumor. (1980)

Continuous cell lines that secrete both insulin and somatostatin were established by two cooperating groups of investiagtors from a serially transplantable, radiation-induced, rat islet cell tumor. The cell lines, named RIN-r and RIN-m, were initiated from tumors maintained in inbred rats or in athymic nude mice, respectively. The cultured cells are epithelioid, free of fibroblast contamination, and can be cloned. They have a hypodiploid chromosome number, are tumorigenic, and posses amine-handling properties, including high levels of L-dopa decarboxylase and formaldehyde-induced fluorescence. Preliminary analysis of clones revealed a spectrum of insulin secretion from undetectable to relatively high. These clonal cell lines provide important systems to study the biology of insulin and somatostatin.
Music Retrieval: A Tutorial and Review (2006)

The increasing availability of music in digital format needs to be matched by the development of tools for music accessing, filtering, classification, and retrieval. The research area of Music Information Retrieval (MIR) covers many of these aspects. The aim of this paper is to present an overview of this vast and new field. A number of issues, which are peculiar to the music language, are described--including forms, formats, and dimensions of music--together with the typologies of users and their information needs. To fulfil these needs a number of approaches are discussed, from direct search to information filtering and clustering of music documents. An overview of the techniques for music processing, which are commonly exploited in many approaches, is also presented. Evaluation and comparisons of the approaches on a common benchmark are other important issues. To this end, a description of the initial efforts and evaluation campaigns for MIR is provided.
Intestinal Stem Cell Organoid Transplantation Generates Neomucosa in Dogs (2009)

Intestinal stem cell organoid transplantation can be used to generate neomucosa in dogs. This is the first report of successful generation of intestinal neomucosa using intestinal stem cell organoid transplantation in a large animal model.
The protein kinase C-β inhibitor, ruboxistaurin, for the treatment of diabetic microvascular complications (2005)

The potential for addressing the underlying biological abnormalities in diabetes has eluded most investigators because of the complex mechanisms underlying the effects of diabetes on the pathogenesis of the complications. Although macrovascular complications, such as myocardial infarction, stroke and gangrene, are only partially attributable to hyperglycaemia and its attendant effects, the microvascular complications including retinopathy, nephropathy and neuropathy are directly related to the degree of hyperglycaemia. In controlled trials, a 22-34% reduction in one of these side effects was achieved for every 1% reduction in glycosylated haemoglobin. Theoretically, it should be feasible to eliminate these complications in a perfect world. However, achieving euglycaemia is nearly impossible and there is increasing data to suggest that it may be an elusive target with ever lower levels being implicated in the pathogenesis of microvascular disease and there is a price to be paid of hypoglycaemia if further intensification is pursued. A logical argument would be to block pathways that are activated by hyperglycaemia. A major pathway implicated is the activation of protein kinase C-beta in all of the targeted tissues, and there is animal data to support the notion that blocking this pathway can reverse or abrogate the untoward effects of diabetes. The possible role of the protein kinase C-beta inhibitor, ruboxistaurin, in animal studies and the recently reported clinical studies to place in perspective a possible addition to the therapeutic armamentarium of the imperfect world of diabetes control will be reviewed.
Magnaporthe grisea genes for pathogenicity and virulence identified through a series of backcrosses. (1991)

We have identified genes for pathogenicity toward rice (Oryza sativa) and genes for virulence toward specific rice cultivars in the plant pathogenic fungus Magnaporthe grisea. A genetic cross was conducted between the weeping lovegrass (Eragrostis curvula) pathogen 4091-5-8, a highly fertile, hermaphroditic laboratory strain, and the rice pathogen O-135, a poorly fertile, female-sterile field isolate that infects weeping lovegrass as well as rice. A six-generation backcrossing scheme was then undertaken with the rice pathogen as the recurrent parent. One goal of these crosses was to generate rice pathogenic progeny with the high fertility characteristic of strain 4091-5-8, which would permit rigorous genetic analysis of rice pathogens. Therefore, progeny strains to be used as parents for backcross generations were chosen only on the basis of fertility. The ratios of pathogenic to nonpathogenic (and virulent to avirulent) progeny through the backcross generations suggested that the starting parent strains differ in two types of genes that control the ability to infect rice. First, they differ by polygenic factors that determine the extent of lesion development achieved by those progeny that infect rice. These genes do not appear to play a role in infection of weeping lovegrass because both parents and all progeny infect weeping lovegrass. Second, the parents differ by simple Mendelian determinants, "avirulence genes," that govern virulence toward specific rice cultivars in all-or-none fashion. Several crosses confirm the segregation of three unlinked avirulence genes, Avr 1-CO39, Avr 1-M201 and Avr1-YAMO, alleles of which determine avirulence on rice cultivars CO39, M201, and Yashiro-mochi, respectively. Interestingly, avirulence alleles of Avr1-CO39, Avr1-M201 and Avr1-YAMO were inherited from the parent strain 4091-5-8, which is a nonpathogen of rice. Middle repetitive DNA sequences ("MGR sequences"), present in approximately 40-50 copies in the genome of the rice pathogen parent, and in very low copy number in the genome of the nonpathogen of rice, were used as physical markers to monitor restoration of the rice pathogen genetic background during introgression of fertility. The introgression of highest levels of fertility into the most successful rice pathogen progeny was incomplete by the sixth generation, perhaps a consequence of genetic linkage between genes for fertility and genes for rice pathogenicity. One chromosomal DNA segment with MGR sequence homology appeared to be linked to the gene Avr1-CO39. Finally, many of the crosses described in this paper exhibited a characteristic common to many crosses involving M. grisea rice pathogen field isolates.(ABSTRACT TRUNCATED AT 400 WORDS)
Activation of the contact system in lethal hypotensive bacteremia in a baboon model. (1992)

The hypotension in septicemia is believed to be mediated by the combined action of many mediators including cytokines, prostaglandins, and complement components. To evaluate the contribution of the contact/kinin-forming system to hypotension, the authors used an established experimental baboon model of bacteremia in which two concentrations of Escherichia Coli (E. coli) were used to produce lethal and nonlethal hypotension. The lethal group (n = 5) developed irreversible hypotension that significantly correlated with the decline in levels of high molecular weight kininogen (HK) and an increase in alpha 2 macroglobulin-kallikrein complexes (alpha 2M-kal). The nonlethal group (n = 9) experienced reversible hypotension, a less striking decline in HK, and only slight elevation in alpha 2M-kal. No significant changes were found in levels of factor XII, prekallikrein, and factor XI in either group. A significant change in the contact system, which reflects the fatal outcome, is the rise in alpha 2M-kal. This study suggests that irreversible hypotension correlates with prolonged activation of the contact system.
Expression Levels Influence Ribosomal Frameshifting at the Tandem Rare Arginine Codons AGG_AGG and AGA_AGA in Escherichia coli (2005)

The rare codons AGG and AGA comprise 2% and 4%, respectively, of the arginine codons of Escherichia coli K-12, and their cognate tRNAs are sparse. At tandem occurrences of either rare codon, the paucity of cognate aminoacyl tRNAs for the second codon of the pair facilitates peptidyl-tRNA shifting to the +1 frame. However, AGG_AGG and AGA_AGA are not underrepresented and occur 4 and 42 times, respectively, in E. coli genes. Searches for corresponding occurrences in other bacteria provide no strong support for the functional utilization of frameshifting at these sequences. All sequences tested in their native context showed 1.5 to 11% frameshifting when expressed from multicopy plasmids. A cassette with one of these sequences singly integrated into the chromosome in stringent cells gave 0.9% frameshifting in contrast to two- to four-times-higher values obtained from multicopy plasmids in stringent cells and eight-times-higher values in relaxed cells. Thus, +1 frameshifting efficiency at AGG_AGG and AGA_AGA is influenced by the mRNA expression level. These tandem rare codons do not occur in highly expressed mRNAs.