gebhart/patrepeval huggingface dataset:
SELECTIVE REVERSIBLE INHIBITION OF MICROBIAL GROWTH WITH PYRITHIAMINE (1943)

Growth of many microbial species was inhibited by pyrithiamine, the pyridine analog of thiamine. Growth of many other species was not influenced. In a series of bacteria, yeasts, and molds, it was found that inhibition of growth occurred only in those in which growth was stimulated by thiamine or its component pyrimidine and thiazole portions. The amount of pyrithiamine required for inhibition was correlated with the type of thiamine requirements of various species. The least amount was needed to inhibit organisms which required intact thiamine. Those which could use the pyrimidine and thiazole portions were not so readily inhibited. In the case of the former organisms, half maximal inhibition was produced by as little as 0.03 gamma per cc. In all instances, the inhibition was overcome by sufficient amounts of thiamine. The synthesis of thiamine by insusceptible species was studied, and it was concluded that formation of thiamine or other antagonistic substance did not provide an adequate explanation of the resistance of these species to the action of pyrithiamine.
The anti-inflammatory effect of exercise (2005)

Regular exercise offers protection against all-cause mortality, primarily by protection against cardiovascular disease and Type 2 diabetes mellitus. The latter disorders have been associated with chronic low-grade systemic inflammation reflected by a two- to threefold elevated level of several cytokines. Adipose tissue contributes to the production of TNF-α, which is reflected by elevated levels of soluble TNF-α receptors, IL-6, IL-1 receptor antagonist, and C-reactive protein. We suggest that TNF-α rather than IL-6 is the driver behind insulin resistance and dyslipidemia and that IL-6 is a marker of the metabolic syndrome, rather than a cause. During exercise, IL-6 is produced by muscle fibers via a TNF-independent pathway. IL-6 stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra and IL-10 and inhibits the production of the proinflammatory cytokine TNF-α. In addition, IL-6 enhances lipid turnover, stimulating lipolysis as well as fat oxidation. We suggest that regular exercise induces suppression of TNF-α and thereby offers protection against TNF-α-induced insulin resistance. Recently, IL-6 was introduced as the first myokine, defined as a cytokine that is produced and released by contracting skeletal muscle fibers, exerting its effects in other organs of the body. Here we suggest that myokines may be involved in mediating the health-beneficial effects of exercise and that these in particular are involved in the protection against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.
Overexpression of Histone Deacetylase 6 Enhances Resistance to Porcine Reproductive and Respiratory Syndrome Virus in Pigs (2017)

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically relevant viral pathogens in pigs and causes substantial losses in the pig industry worldwide each year. At present, PRRSV vaccines do not effectively prevent and control this disease. Consequently, it is necessary to develop new antiviral strategies to compensate for the inefficacy of the available vaccines. Histone deacetylase 6 (HDAC6) is an important member of the histone deacetylase family that is responsible for regulating many important biological processes. Studies have shown that HDAC6 has anti-viral activities during the viral life cycle. However, whether HDAC6 overexpression enhances resistance to PRRSV in pigs remains unknown. In this study, we used a somatic cell cloning method to produce transgenic (TG) pigs that constitutively overexpress porcine HDAC6. These TG pigs showed germ line transmission with continued overexpression of HDAC6. In vitro, virus-challenged porcine alveolar macrophages (PAMs) overexpressed HDAC6, which suppressed viral gene expression and PRRSV production. In vivo, resistance to PRRSV in TG pigs was evaluated by direct or cohabitation mediated infection with a highly pathogenic PRRSV (HP-PRRSV) strain. Compared with non-TG (NTG) siblings, TG pigs showed a significantly lower viral load in the lungs and an extended survival time after infection with HP-PRRSV via intramuscular injection. In the cohabitation study, NTG pigs housed with challenged NTG pigs exhibited significantly worse clinical symptoms than the other three in-contact groups. These results collectively suggest that HDAC6 overexpression enhances resistance to PRRSV infection both in vitro and in vivo. Our findings suggest the potential involvement of HDAC6 in the response to PRRSV, which will facilitate the development of novel therapies for PRRSV.
Polymer-Supported Synthesis of Pyridone-Focused Libraries as Inhibitors of Anaplastic Lymphoma Kinase (2006)

The optimization of screening hits on a promising new target for therapy of certain cancers involving anaplastic lymphoma kinase (ALK) inspired the development of this efficient solid-phase chemistry. A series of novel pyridones have been recently discovered as inhibitors of ALK, which led to the design of focused libraries around the pyridone scaffold. A stepwise process involving iterative template modification based on both medicinal chemistry insights and computational ranking of virtual libraries was employed in the design. The unique solid-phase chemistry has addressed the need for rapid optimization of this "early lead" series. Herein the methodology and scope of the chemistry, as well as its application for library synthesis, are discussed.
Image demosaicing: a systematic survey (2007)

Image demosaicing is a problem of interpolating full-resolution color images from so-called color-filter-array (CFA) samples. Among various CFA patterns, Bayer pattern has been the most popular choice and demosaicing of Bayer pattern has attracted renewed interest in recent years partially due to the increased availability of source codes/executables in response to the principle of "reproducible research". In this article, we provide a systematic survey of over seventy published works in this field since 1999 (complementary to previous reviews<sup>22, 67</sup>). Our review attempts to address important issues to demosaicing and identify fundamental differences among competing approaches. Our findings suggest most existing works belong to the class of sequential demosaicing - i.e., luminance channel is interpolated first and then chrominance channels are reconstructed based on recovered luminance information. We report our comparative study results with a collection of eleven competing algorithms whose source codes or executables are provided by the authors. Our comparison is performed on two data sets: Kodak PhotoCD (popular choice) and IMAX high-quality images (more challenging). While most existing demosaicing algorithms achieve good performance on the Kodak data set, their performance on the IMAX one (images with varying-hue and high-saturation edges) degrades significantly. Such observation suggests the importance of properly addressing the issue of mismatch between assumed model and observation data in demosaicing, which calls for further investigation on issues such as model validation, test data selection and performance evaluation.
Cinnamamide analogs as inhibitors of protein tyrosine kinases. (1993)

Protein tyrosine kinases (PTK) are important signal transducing enzymes involved in the modulation of normal cellular growth and differentiation and have been associated with the etiology of various human cancers. The development of properly designed inhibitors, which block their function by interfering with the substrate binding, may therefore offer an unique target for selective anticancer chemotherapy. Here we describe synthesis and biochemical testing of a novel series of non-peptide PTK inhibitors which have as characteristic active pharmacophore the cinnamamide moiety. For testing we used an exogenous substrate kinase assay based on the phosphorylation of (Val5)-angiotensin II with radiolabelled ATP by the catalytic domain of the PTK encoded by the v-abl oncogene (p45 v-abl). The most potent compounds were found in the class of 3-arylidene-2-oxindoles (II) with IC50 values in the 1 microM range. Among these the 2-tetralylmethylene-, 4-quinolylmethylene-, 5-quinolylmethylene- and 3-indolylmethylene-2-oxindole compounds of formulae 16, 20, 21 and 24 respectively were selected for further investigation.
Iterative sentence-pair extraction from quasi-parallel corpora for machine translation (2009)

This paper addresses parallel data extraction from the quasi–parallel corpora generated in a crowd-sourcing project where ordinary people watch tv shows and movies and transcribe/translate what they hear, creating document pools in different languages. Since they do not have guidelines for naming and performing translations, it is often not clear which documents are the translations of the same show/movie and which sentences are the translations of the each other in a given document pair. We introduce a method for automatically pairing documents in two languages and extracting parallel sentences from the paired documents. The method consists of three steps: i) document pairing, ii) sentence pair alignment of the paired documents, and iii) context extrapolation to boost the sentence pair coverage. Human evaluation of the extracted data shows that 95% of the extracted sentences carry useful information for translation. Experimental results also show that using the extracted data provides significant gains over the baseline statistical machine translation system built with manually annotated data. Index Terms: data extraction, comparable data, machine translation
Seizure 6-Like ( SEZ6L ) Gene and Risk for Lung Cancer (2007)

DNA pooling in combination with high-throughput sequencing was done as a part of the Sequenom-Genefinder project. In the pilot study, we tested 83,715 single nucleotide polymorphisms (SNP), located primarily in gene-based regions, to identify polymorphic susceptibility variants for lung cancer. For this pilot study, 369 male cases and 287 controls of both sexes (white Europeans of Southern German origin) were analyzed. The study identified a candidate region in 22q12.2 that contained numerous SNPs showing significant case-control differences and that coincides with a region that was shown previously to be frequently deleted in lung cancer cell lines. The candidate region overlies the seizure 6-like (SEZ6L) gene. The pilot study identified a polymorphic Met430Ile substitution in the SEZ6L gene (SNP rs663048) as the top candidate for a variant modulating risk of lung cancer. Two replication studies were conducted to assess the association of SNP rs663048 with lung cancer risk. The M. D. Anderson Cancer Center study included 289 cases and 291 controls matched for gender, age, and smoking status. The Liverpool Lung Project (a United Kingdom study) included 248 cases and 233 controls. Both replication studies showed an association of the rs663048 with lung cancer risk. The homozygotes for the variant allele had more than a 3-fold risk compared with the wild-type homozygotes [combined odds ratio (OR), 3.32; 95% confidence interval (95% CI), 1.81-7.21]. Heterozygotes also had a significantly elevated risk of lung cancer from the combined replication studies with an OR of 1.15 (95% CI, 1.04-1.59). The effect remained significant after adjusting for age, gender, and pack-years of tobacco smoke. We also compared expression of SEZ6L in normal human bronchial epithelial cells (n = 7), non-small cell lung cancer (NSCLC; n = 52), and small cell lung cancer (SCLC; n = 22) cell lines by using Affymetrix HG-U133A and HG-U133B GeneChips. We found that the average expression level of SEZ6L in NSCLC cell lines was almost two times higher and in SCLC cell lines more than six times higher when compared with normal lung epithelial cell lines. Using the National Center for Biotechnology Information Gene Expression Omnibus database, we found a approximately 2-fold elevated and statistically significant (P = 0.004) level of SEZ6L expression in tumor samples compared with normal lung tissues. In conclusion, the results of these studies representing 906 cases compared with 811 controls indicate a role of the SEZ6L Met430Ile polymorphic variant in increasing lung cancer risk.
Initial Trial of Bispecific Antibody-Mediated Immunotherapy of CD15-Bearing Tumors: Cytotoxicity of Human Tumor Cells Using a Bispecific Antibody Comprised of Anti-CD15 (MoAb PM81) and Anti-CD64/FcγRI (MoAb 32) (1992)

The high-affinity receptor for IgG, Fc gamma RI, expressed on monocytes and interferon-gamma (IFN-gamma)-stimulated neutrophils, is a trigger molecule for cell-mediated cytotoxicity. We have prepared murine monoclonal antibodies (MoAb 22 and MoAb 32) that bind to Fc gamma RI outside the ligand binding site and thus bind to and trigger cytotoxicity that is not competed by other immunoglobulins. Because of these properties, it seemed that these MoAbs would be very useful for the development of bispecific antibodies (BsAb) for targeting normal cellular immune defense mechanisms as a new form of immunotherapy for treatment of cancer. BsAbs incorporate into a single molecule the binding specifities of two different antibodies, and, thus, can be used to target myeloid cells to tumors, ensure activation of cellular cytotoxic mechanisms, and target cell lysis and/or phagocytosis. BsAbs were prepared using anti-Fc gamma RI MoAb and an anti-myeloid cell MoAb, PM81, reactive with the CD15 antigen, for studies of antibody-dependent cellular cytotoxicity. Conjugates were made by cross-linking sulfhydryl groups of Fab fragments of MoAb 32 or 22 (both IgG1) and sulfhydryl groups added to intact PM81 (an IgM) using N-succinimdyl-acetyl-S-thioacetate (SATA). The resulting product was purified by high-performance size-exclusion chromatography. The ability of the BsAbs to mediate attachment of human monocytes to tumor target cells was confirmed in a microtiter well assay of binding of MTT-labeled U937 cells (a human Fc gamma RI-bearing cell line) to SKBR-3 (PM81-reactive breast carcinoma) target cells. The ability of the BsAbs to mediate killing of HL-60 promyelocytic leukemia cells was studied using a 6-hour Chromium-51 release assay. Effector cells were monocytes obtained by cytopheresis and cultured for 18 hours with IFN-gamma. Monocytes alone caused minimal killing (5-20%), monocytes plus BsAb caused moderate killing (20-50%), and monocytes plus BsAb plus human serum resulted in maximal killing (50-80%). Experiments were performed to test the ability of the BsAb to purge bone marrow of small numbers of leukemia cells using bone marrow mononuclear phagocytes treated for 18 hours with IFN-gamma prior to adding target cells. Without the addition of human serum as a source of complement, a 90% depletion of clonogenic HL-60 cells could be demonstrated. With human complement, up to 95% depletion was seen. Thus, this BsAb possessed the ability to lyse tumor cell targets by two different mechanisms, complement and cell-mediated lysis.(ABSTRACT TRUNCATED AT 400 WORDS)
Channel Equalization Using Partial Likelihood Estimation And Recurrent Canonical Piecewise Linear Network (1996)

Publication in the conference proceedings of EUSIPCO, Trieste, Italy, 1996
Vero cell platform in vaccine production: moving towards cell culture-based viral vaccines (2009)

The development of cell culture systems for virus propagation has led to major advances in virus vaccine development. Primary and diploid cell culture systems are now being replaced by the use of continuous cell lines (CCLs). These substrates are gaining increasing acceptance from regulatory authorities as improved screening technologies remove fears regarding their potential oncogenic properties. The Vero cell line is the most widely accepted CCL by regulatory authorities and has been used for over 30 years for the production of polio and rabies virus vaccines. The recent licensure of a Vero cell-derived live virus vaccine (ACAM2000, smallpox vaccine) has coincided with an explosion in the development of a range of new viral vaccines, ranging from live-attenuated pediatric vaccines against rotavirus infections to inactivated whole-virus vaccines against H5N1 pandemic influenza. These developments have illustrated the value of this cell culture platform in the rapid development of vaccines against a range of virus diseases.
Clinical and microbiological features of refractory periodontitis subjects (1998)

The purpose of this investigation was to compare the clinical parameters and the site prevalence and levels of 40 subgingival species in successfully treated and refractory periodontitis subjects. 94 subjects received scaling and root planing and if needed, periodontal surgery and systemically administered tetracycline. 28 refractory subjects showed mean full mouth attachment loss and/or > 3 sites showing attachment loss > 2.5 mm within 1 year post-therapy. 66 successfully treated subjects showed mean attachment level gain and no sites with attachment loss > 2.5 mm. Baseline subgingival plaque samples were taken from the mesial aspect of each tooth and the presence and levels of 40 subgingival taxa were determined using whole genomic DNA probes and checkerboard DNA-DNA hybridization. The mean levels and % of sites colonized by each species (prevalence) was computed for each subject and differences between groups sought using the Mann-Whitney test. Most of the 40 species tested, including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola and Bacteroides forsythus, were equally or less prevalent in the refractory group. Prevotella nigrescens was significantly more prevalent in successfully treated subjects, while refractory subjects harbored a larger proportion of Streptococcus species, particularly Streptococcus constellatus. The odds of a subject being refractory was 8.6 (p < 0.001) if S. constellatus constituted > or = 3.5% of the total DNA probe count. Since few microbiological differences existed between treatment outcome groups using DNA probes to known species, the predominant cultivable microbiota of 33 subgingival samples from 14 refractory subjects was examined. 85% of the 1649 isolates were identified using probes to 69 recognized subgingival species. The remaining unidentified strains were classified by analyzing 16S rRNA gene sequences. Many sequenced isolates were of taxa not considered a common part of the oral microbiota such as Acinetobacter baumanni, Gemella haemolysans, Enterococcus faecalis, Staphylococcus warneri, Pseudomonas aeruginosa and novel species in the genera Bartonella, Ralstonia, Neisseria, Eubacterium, Rothia, Gordona, Gemella, Corynebacterium, Leptotrichia, and Actinomyces. Refractory subjects constituted a heterogeneous group based on their subgingival microbiota. As a group, they did not harbor more of the "classic" periodontopathogens, although elevated proportions of S. constellatus were found.
A long‐term prospective study of the use of methotrexate in rheumatoid arthritis (1988)

Twenty-five patients have completed a mean of 53 months of treatment with methotrexate (MTX) as part of a prospective study of the long-term safety and efficacy of the drug. Since the time of the last report (at a mean of 29 months), the mean dosage of MTX has increased from 12.4 mg/week to 14.6 mg/week, whereas the mean prednisone dosage has decreased from a baseline of 7.1 mg/day to 1.9 mg/day. A significant improvement from baseline in all clinical parameters tested was maintained, and response to therapy did not vary significantly between the assessment at 29 months and that at 53 months. Toxic reactions were as common during months 30-53 as during the first 29 months of the study, with patterns of toxic reactions remaining consistent within each patient. Radiologic evidence of disease progression was not seen before 24 months of MTX treatment, but after this time, it was observed in some patients. We conclude that many clinical features of long-term MTX therapy are distinctly different from what might have been expected after the short-term trials.
Agent-based software configuration and deployment (1999)

ions 76 9.1.1.1 Consumer Abstraction 76 9.1.1.2 Software System Abstraction 77 ix 9.1.1.3 Process Abstraction 78 9.1.2 Process Coverage 78 9.1.3 Coordination 79 9.1.4 General Requirements 79 9.2 Mapping the Software Dock to Requirements 82 9.3 Critical Analysis Of Related Technologies 86 9.3.1 Traditional Configuration Management 86 9.3.2 Software System Install, Update, and Remove 87 9.3.3 Software System and Site Description 89 9.3.3.1 The Open Software Description (OSD) Format 89 9.3.3.2 The Software Management Information Format (MIF) 92 9.3.3.3 Other Software System and Site Description Technologies 94 9.3.4 Network Management and System Administration 95 9.3.5 Content Delivery 98 9.3.6 Configurable Distributed Systems 98 9.3.7 Component Models 100 9.4 Usage Experiments 102 9.4.1 Online Learning Academy 102 9.4.1.1 Existing Deployment Solution 103 9.4.1.2 Software Dock Deployment Solution 104 9.4.2 The Chimera Open Hypermedia System 106 9.4.2.1 Existing Deployment Solution 107 9....
The Arabidopsis dwarf1 Mutant Is Defective in the Conversion of 24-Methylenecholesterol to Campesterol in Brassinosteroid Biosynthesis1 (1999)

Since the isolation and characterization of dwarf1-1 (dwf1-1) from a T-DNA insertion mutant population, phenotypically similar mutants, including deetiolated2 (det2), constitutive photomorphogenesis and dwarfism (cpd), brassinosteroid insensitive1 (bri1), and dwf4, have been reported to be defective in either the biosynthesis or the perception of brassinosteroids. We present further characterization of dwf1-1 and additional dwf1 alleles. Feeding tests with brassinosteroid-biosynthetic intermediates revealed that dwf1 can be rescued by 22alpha-hydroxycampesterol and downstream intermediates in the brassinosteroid pathway. Analysis of the endogenous levels of brassinosteroid intermediates showed that 24-methylenecholesterol in dwf1 accumulates to 12 times the level of the wild type, whereas the level of campesterol is greatly diminished, indicating that the defective step is in C-24 reduction. Furthermore, the deduced amino acid sequence of DWF1 shows significant similarity to a flavin adenine dinucleotide-binding domain conserved in various oxidoreductases, suggesting an enzymatic role for DWF1. In support of this, 7 of 10 dwf1 mutations directly affected the flavin adenine dinucleotide-binding domain. Our molecular characterization of dwf1 alleles, together with our biochemical data, suggest that the biosynthetic defect in dwf1 results in reduced synthesis of bioactive brassinosteroids, causing dwarfism.
Control of immune responses by gene immunization (1998)

The use of plasmid DNA to elicit immune responses has greatly increased our ability to skew the desired immune response to a particular antigen. DNA immunization elicits potent cell-mediated responses including humoral immunity as well as cytolytic T-lymphocyte immunity. This review will first discuss the overall immune response induced by naked DNA vaccination and will then summarize recent advances in basic research on DNA immunization, which have furthered our understanding of the role of DNA as an adjuvant as well as a carrier of genetic material. Subsequently, we will consider the possible mechanisms by which DNA immunization is able to induce such immune responses and how DNA immunization may be useful in both basic science research and also in future vaccine development in various disease processes. Finally, we will examine the advantages and disadvantages of DNA vaccines as well as safety issues. In conclusion, DNA vaccination shows promise in a number of areas including infectious diseases, allergy and cancer immunotherapies.