gebhart/patrepeval huggingface dataset:
Chondroitin sulfate proteoglycans as novel drivers of leucocyte infiltration in multiple sclerosis (2018)

Multiple sclerosis presents with profound changes in the network of molecules involved in maintaining central nervous system architecture, the extracellular matrix. The extracellular matrix components, particularly the chondroitin sulfate proteoglycans, have functions beyond structural support including their potential interaction with, and regulation of, inflammatory molecules. To investigate the roles of chondroitin sulfate proteoglycans in multiple sclerosis, we used the experimental autoimmune encephalomyelitis model in a time course study. We found that the 4-sulfated glycosaminoglycan side chains of chondroitin sulfate proteoglycans, and the core protein of a particular family member, versican V1, were upregulated in the spinal cord of mice at peak clinical severity, correspondent with areas of inflammation. Versican V1 expression in the spinal cord rose progressively over the course of experimental autoimmune encephalomyelitis. A particular structure in the spinal cord and cerebellum that presented with intense upregulation of chondroitin sulfate proteoglycans is the leucocyte-containing perivascular cuff, an important portal of entry of immune cells into the central nervous system parenchyma. In these inflammatory perivascular cuffs, versican V1 and the glycosaminoglycan side chains of chondroitin sulfate proteoglycans were observed by immunohistochemistry within and in proximity to lymphocytes and macrophages as they migrated across the basement membrane into the central nervous system. Expression of versican V1 transcript was also documented in infiltrating CD45+ leucocytes and F4/80+ macrophages by in situ hybridization. To test the hypothesis that the chondroitin sulfate proteoglycans regulate leucocyte mobility, we used macrophages in tissue culture studies. Chondroitin sulfate proteoglycans significantly upregulated pro-inflammatory cytokines and chemokines in macrophages. Strikingly, and more potently than the toll-like receptor-4 ligand lipopolysaccharide, chondroitin sulfate proteoglycans increased the levels of several members of the matrix metalloproteinase family, which are implicated in the capacity of leucocytes to cross barriers. In support, the migratory capacity of macrophages in vitro in a Boyden chamber transwell assay was enhanced by chondroitin sulfate proteoglycans. Finally, using brain specimens from four subjects with multiple sclerosis with active lesions, we found chondroitin sulfate proteoglycans to be associated with leucocytes in inflammatory perivascular cuffs in all four patients. We conclude that the accumulation of chondroitin sulfate proteoglycans in the perivascular cuff in multiple sclerosis and experimental autoimmune encephalomyelitis boosts the activity and migration of leucocytes across the glia limitans into the central nervous system parenchyma. Thus, chondroitin sulfate proteoglycans represent a new class of molecules to overcome in order to reduce the inflammatory cascades and clinical severity of multiple sclerosis.
Structure–activity relationships in β‐defensin peptides (2007)

The beta-defensins comprise a large family of small cationic antimicrobial peptides widely distributed in plants, mammals and insects. These cysteine rich peptides display multifunctional properties with implications as potential therapeutic agents. Recent research has highlighted their role in both the innate and adaptive immune systems as well as being novel melanocortin ligands. Studies investigating structure and function provide an insight into the molecular basis of their immunological properties.
Organic Pesticides. Part VIII. Synthesis of Halo-aryl Esters of Phosphoric and Thiophosphoric Acids and Certain Related Com.pounds (1962)

Seven substituted fluorophenols have been condensed with \(O:O\)-diethyl chlorothiophosphate to give esters of thiophosphoric acid, with phosphorous oxychloride to give phosphoric acid esters, and finally with ethylene chlorohydrin to yield the corresponding ethers. All these compounds are expected to possess insecti­cidal activity.
Specific Interactions between Retrovirus Env and Gag Proteins in Rat Neurons (1998)

In this work we have studied the intracellular localization properties of the Gag and Env proteins of Moloney murine leukemia virus (MLV) and human immunodeficiency virus (HIV) in dorsal root ganglion (DRG) neurons of rat. These neurons form thick bundles of axons, which facilitates protein localization studies by immunofluorescence analyses. When such neuron cultures were infected with recombinant Semliki Forest virus particles carrying the gag genes of either retrovirus, the expressed Gag proteins were localized to both the somatic and the axonal regions of the DRG neurons. In contrast, the Env proteins were confined only to the somatic region. When the Gag and Env proteins were coexpressed, the Gag proteins were also excluded from the axons. This effect of the Env proteins was shown to be dependent on the concentration of the Gag proteins in the neuron and also to be specific for homologous pairs of retrovirus proteins. Therefore, the results suggest that there are specific interactions between the Env and the Gag proteins of MLV and HIV in the DRG neurons.
Enhanced crossover SCRATCHY: construction and high-throughput screening of a combinatorial library containing multiple non-homologous crossovers (2003)

SCRATCHY is a methodology for the construction of libraries of chimeras between genes that display low sequence homology. We have developed a strategy for library creation termed enhanced crossover SCRATCHY, that significantly increases the number of clones containing multiple crossovers. Complementary chimeric gene libraries generated by incremental truncation (ITCHY) of two distinct parental sequences are created, and are then divided into arbitrarily defined sections. The respective sections are amplified by skewed sets of primers (i.e. a combination of gene A specific forward primer and gene B specific reverse primer, etc.) allowing DNA fragments containing non-homologous crossover points to be amplified. The amplified chimeric sections are then subjected to a DNA shuffling process generating an enhanced crossover SCRATCHY library. We have constructed such a library using the rat theta 2 glutathione transferase (rGSTT2) and the human theta 1 glutathione transferase (hGSTT1) genes (63% DNA sequence identity). DNA sequencing analysis of unselected library members revealed a greater diversity than that obtained by canonical family shuffling or with conventional SCRATCHY. Expression and high-throughput flow cytometric screening of the chimeric GST library identified several chimeric progeny that retained rat-like parental substrate specificity.
A review of the pathology and treatment of canine respiratory infections (2012)

Numerous infectious agents are responsible for causing primary or secondary respiratory disease in dogs. These agents can cause upper or lower respiratory infections commonly observed in veterinary practices. Clinical signs might vary from mild dyspnea, sneezing, and coughing to severe pneumonia with systemic manifestations. Depending on the etiologic agent, the gross and microscopic changes observed during these infections can be rather unspecific or have highly characteristic patterns. While histopathology and cytology are not always required for diagnosis of respiratory infections, they are often useful for establishing a definitive diagnosis and identifying specific etiologic agents. Research regarding epidemiology, pathogenesis, diagnostics, and clinical manifestations related to these infectious pathogens provides valuable information that has improved treatments and management of the diseases they cause. This review discusses the epidemiology, general clinical characteristics, and pathologic lesions for some of the important viral, bacterial, fungal, and parasitic etiologies of canine respiratory disease.
Compilation ofE.colimRNA promoter sequences (1993)

An updated compilation of 300 E. coli mRNA promoter sequences is presented. For each sequence the most recent relevant paper was checked, to verify the location of the transcriptional start position as identified experimentally. We comment on the reliability of the sequence databanks and analyze the conservation of known promoter features in the current compilation. This database is available by E-mail.
The effect of alloy scattering on the mobility of holes in a quantum well (1998)

The effect of alloy scattering on the mobility of holes in a quantum well is considered from a theoretical perspective. Issues relating to the definition and value of the alloy potential are discussed, and results are presented showing how the alloy scattering component of the overall mobility varies with temperature, carrier density and alloy concentration. Screening is allowed for and found to be important at low temperatures. By considering other scattering mechanisms such as interface impurities, surface roughness and acoustic phonons, we argue that alloy scattering is not a significant limiting factor as regards device applications, contrary to recent claims.
Total syntheses of (.+-.)-cephalotaxine and (.+-.)-8-oxocephalotaxine (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal syntheses of (.+-.)-cephalotaxine and (.+-.)-8-oxocephalotaxineMartin E. Kuehne, William G. Bornmann, William H. Parsons, Timothy D. Spitzer, J. F. Blount, and J. ZubietaCite this: J. Org. Chem. 1988, 53, 15, 3439–3450Publication Date (Print):July 1, 1988Publication History Published online1 May 2002Published inissue 1 July 1988https://pubs.acs.org/doi/10.1021/jo00250a008https://doi.org/10.1021/jo00250a008research-articleACS PublicationsRequest reuse permissionsArticle Views1723Altmetric-Citations65LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Expression of the human beta-amyloid protein of Alzheimer's disease specifically in the brains of transgenic mice. (1991)

The human beta-amyloid protein is deposited in senile plaques and in the cerebro-vasculature of people with Alzheimer's disease and Down's syndrome. The precise role of beta-amyloid in Alzheimer's disease pathology is presently unknown. To study the properties of beta-amyloid in vivo, we generated transgenic mice that harbor the gene for the carboxyl-terminal 100 amino acids of the human amyloid precursor protein, beginning with the beta-amyloid region, under control of the JC viral early region promoter. The mRNA is expressed exclusively in brain tissue. Further, we demonstrate increased levels of beta-amyloid immunoreactivity on fixed brain tissue. These animals will be useful as a model to study beta-amyloid deposition and its consequences.
Stat3: a STAT Family Member Activated by Tyrosine Phosphorylation in Response to Epidermal Growth Factor and Interleukin-6 (1994)

The STAT family of proteins carries out a dual function: signal transduction and activation of transcription. A new family member, Stat3, becomes activated through phosphorylation on tyrosine as a DNA binding protein in response to epidermal growth factor (EGF) and interleukin-6 (IL-6) but not interferon gamma (IFN-gamma). It is likely that this phosphoprotein forms homodimers as well as heterodimers with the first described member of the STAT family, Stat91 (renamed Stat1 alpha), which is activated by the IFNs and EGF. Differential activation of different STAT proteins in response to different ligands should help to explain specificity in nuclear signaling from the cell surface.
Type 2 antifolates in the chemotherapy of falciparum malaria (2002)

About 40% of the world population is exposed to malaria, which results in the death of over 2 million people per year in Africa, Latin America, Southern Asia and Oceania. The most severe type of malaria in humans is caused by the protozoan parasite Plasmodium falciparum. Chemotherapy is still one of the main control strategies for this parasite. Many of the antimalarials act by inhibiting the enzyme dihydrofolate reductase (DHFR), resulting in protozoan death. However, the development of drug resistance is reducing the efficiency of antifolates as antimalarials. This phenomenon has been linked to the occurrence of mutations in the dihydrofolate reductase of the parasite. This article includes a preliminary review of some of the features of falciparum malaria, followed by a more extensive review of the dihydrofolate reductase of P. falciparum and the mutations related to antifolate resistance.
Interspecies comparison of liver carcinogenesis: implications for cancer risk assessment (1997)

The morphology of hepatocellular carcinoma is similar among mice, rats and humans, and the cellular pathogenesis shows features that are both similar and divergent among these species. However, major elements of etiology, molecular pathogenesis, and natural history differ between humans and rodents. As a reflection of these species-determined differences, rodents appear to be neither highly sensitive nor highly specific surrogates for detecting agents that are potential causes of hepatocellular cancer in humans. Results of tests of chemical carcinogenicity in rodents are likely to include a significant number of both false-positive and false-negative risks for humans.
Evaluation of Alternative Technologies to Estimate Travel Time on Rural Interstates (2013)

New technologies are becoming more and more readily available to collect vehicular traffic data in a cost-effective and non-intrusive fashion. The primary objective of this paper is to present the results of an evaluation of alternative technologies to estimate travel time along a segment of Interstate 91 in Western Massachusetts where traffic volumes and corresponding sample sizes are expected to be relatively low. The first means of data collection uses global positions system technology (GPS) technology employed by INRIX, an enterprise that provides traffic-related information including travel time, directions, and other driver services. The second means uses Bluetooth technology and field data collected by another vendor, BlueTOAD, along the I-91 study site. A third means of data collection using a license plate based method was devised by the authors to provide “ground truth” travel time against which the results of the above two technologies were compared and evaluated. The data analysis showed that sufficient sample sizes were collected and that the accuracy of travel times estimated from data provided by both vendors (i.e., GPS-based INRIX and Bluetooth-based BlueTOAD) is acceptable since their mean absolute percentage errors (MAPE) were consistently less than 6 percent.
Active Microneedles with Integrated Functionality (2000)

The focus of this work is the design, fabrication, and characterization of a new class of biomedical micro systems, the active microneedle. Active microneedle systems represent an advancement over current microneedle technologies through the integration of additional functionality (e.g. biochemical sensing, mechanical, etc.). The active microneedles described in this paper include the following additional functionality: integration of multiple inlet/output ports, multiple lumens (flow channels), and bioluminescence based biosensors for monitoring metabolic levels (e.g. creatine and glucose).
Identifying and Merging Related Bibliographic Records (1996)

Bibliographic records freely available on the Internet can be used to construct a highquality, digital finding aid that provides the ability to discover paper and electronic documents. The key challenge to providing such a service is integrating mixed-quality bibliographic records, coming from multiple sources and in multiple formats. This thesis describes an algorithm that automatically identifies records that refer to the same work and clusters them together; the algorithm clusters records for which both author and title match. It tolerates errors and cataloging variations within the records by using a full-text search engine and an n-gram-based approximate string matching algorithm to build the clusters. The algorithm identifies more than 90 percent of the related records and includes incorrect records in less than 1 percent of the clusters. It has been used to construct a 250,000-record collection of the computer science literature. This thesis also presents preliminary work on aut...
Sequence and domain structure of yeast pyruvate carboxylase. (1988)

The nucleotide sequence of the yeast pyruvate carboxylase gene has been determined from a cloned fragment of yeast genomic DNA. The deduced translation product codes for a polypeptide of 1178 amino acids, having a calculated molecular weight of 130,100. The protein shows strong sequence homology to specific regions of other biotin carboxylases, lipoamide transferases, and carbamyl phosphate synthetases. The homologous regions suggest the presence of three subsites in the enzyme: a biotin attachment site, a keto acid-binding site, and an ATP-binding site. Partial proteolysis with a variety of proteases under nondenaturing conditions indicates the presence of structural domains corresponding to these subsites.
Concomitant promoter methylation of multiple genes in lung adenocarcinomas from current, former and never smokers (2009)

Aberrant promoter hypermethylation is one of the major mechanisms in carcinogenesis and some critical growth regulatory genes have shown commonality in methylation across solid tumors. Twenty-six genes, 14 identified through methylation in colon and breast cancers, were evaluated using primary lung adenocarcinomas (n = 175) from current, former and never smokers. Tumor specificity of methylation was validated through comparison of 14 lung cancer cell lines to normal human bronchial epithelial cells derived from bronchoscopy of 20 cancer-free smokers. Twenty-five genes were methylated in 11-81% of primary tumors. Prevalence for methylation of TNFRSF10C, BHLHB5 and BOLL was significantly higher in adenocarcinomas from never smokers than smokers. The relation between methylation of individual genes was examined using pairwise comparisons. A significant association was seen between 138 (42%) of the possible 325 pairwise comparisons. Most notably, methylation of MMP2, BHLHB4 or p16 was significantly associated with methylation of 16-19 other genes, thus predicting for a widespread methylation phenotype. Kaplan-Meier log-rank test and proportional hazard models identified a significant association between methylation of SULF2 (a pro-growth, -angiogenesis and -migration gene) and better patient survival (hazard ratio = 0.23). These results demonstrate a high degree of commonality for targeted silencing of genes between lung and other solid tumors and suggest that promoter hypermethylation in cancer is a highly co-ordinated event.
Neuronal properties of hybrid neuroblastoma X sympathetic ganglion cells. (1975)

Clonal mouse neuroblastoma cells without tyrosine 3-monooxygenase [EC 1.14.16.2; tyrosine hydroxylase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)] activity were fused with normal cells from embryonic mouse sympathetic ganglia. One of the 37 hybrid cell lines obtained possesses high tyrosine 3-monooxygenase activity and synthesizes dopamine. These cells also have excitable membranes and generate action potentials in response to electrical stimuli. Thus hybrid cells, generated by fusion of neuroblastoma cells with normal cells from the nervous system, can acquire neural properties not found with the parental neuroblastoma cells.
Time of Day Effects on Neurobehavioral Performance During Chronic Sleep Restriction (2010)

This study provides evidence that the circadian system has a substantial modulatory effect on cumulative impairment from chronic sleep restriction and that it facilitates a period of relatively protected alertness in the late afternoon/early evening hours when nocturnal sleep is chronically restricted.
Ulcerative colitis: current pharmacotherapy and future directions (2014)

UC is a disease affecting young patients, whose quality of life may be strongly compromised by the progression of disease. Over time, the disease may lead to an impairment of the normal anatomy and physiology of the colon, and the cumulative incidence of dysplasia and colorectal cancer increases with the time. Thus, the main aims of the near future should be both a better definition of patients at risk for a poor clinical course and progression of disease, and the development of a much more aggressive treatment for patients with a poor prognosis.
Construction of unnatural heterodimeric receptors based on IL‐2 and IL‐6 receptor subunits (2013)

Cells have various receptors on their surface for responding to extracellular signals that involve intercellular communication. Although the mechanism of signal transduction by such wild-type receptors has been studied intensively, there has been minimal effort in investigating whether such receptors could signal when unnaturally coupled. In this study, we investigated whether unnatural receptor pairs comprising interleukin-2 (IL-2) and interleukin-6 (IL-6) receptor subunits could transduce a signal through forced dimerization. We replaced the extracellular domain of IL-2R and IL-6R signaling subunits (IL-2Rβ, IL-2Rγ, and gp130) with the FK506-binding protein (FKBP) or the FKBP12-rapamycin binding (FRB) domain, the protein pair known to be heterodimerized by rapamycin. When expressed in a hematopoietic cell line, unnatural heterodimers (IL-2Rβ-gp130 and IL-2Rγ-gp130 pairs) successfully transduced a signal. While the IL-2Rγ-gp130 pair maximally mimicked gp130 signaling, the IL-2Rβ-gp130 pair gave weaker gp130 signaling and no significant induction of IL-2Rβ signaling, indicating a high potential of the IL-2Rγ chain in terms of activating the coupled partners. This is the first report demonstrating that heterodimeric combinations of IL-2R and IL-6R subunits are functional for signaling. Further extension of this approach may attain a creative design of artificial receptor pairs that have distinct signaling properties when compared with natural receptors.