gebhart/patrepeval huggingface dataset:
CD95 (APO-1/Fas)-associating signalling proteins. (1996)

The CD95 (APO-1/Fas) receptor has attracted great interest in recent years because it transduces an apoptotic signal in a variety of different tissues. CD95 belongs to the NGF/TNF-receptor superfamily, members of which need to be trimerized by specific protein ligands in order to generate a signal. This review focuses on recent advances in the understanding of the proximal signal transduction mechanism of CD95. The cloning of numerous proteins that interact with CD95 and other members of this receptor family and the in vivo identification of several proteins that associate with CD95 in a ligand-dependent fashion opens the way to delineate the death pathway and to explain crosstalk among these receptors on a molecular basis.
Research on the IDSS of High-speed Railway Based on Multi-agent (2007)

According to "Medium and long-term railway network plan" and railway "11 five-year plan", China will build 7,000 kilometers high-speed passenger transport special railway line. So railway ministry of China decided to develop High-speed Railway Decision Support System for helping high-speed railway construct and develop of China. On the basis of sufficiently analyzing the necessity and feasibility for using the multi-agent technology to develop the distributed high-speed railway intelligence decision support system, this paper proposes a three-layer structure of the IDSS for high-speed railway decision support (HSR-IDSS) based on multi-agent. HSR-IDSS has three-layer system structure, which includes client layer, decision logic layer and data service layer with distributed database, model base, knowledge base. The prototype application is implemented using Eclipse technology, and the agents are deployed on the FIPA-OS (Foundation for Intelligent Physical Agents-Open-Source) environment, we used J2EE (Java 2 Enterprise Edition) to develop the knowledge based of the agents' reasoning.
Involvement of distinct murine T-cell receptors in the autoimmune encephalitogenic response to nested epitopes of myelin basic protein. (1988)

The peptide p89-101 (Val-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro) of myelin basic protein is encephalitogenic in mice expressing H-2q and H-2s antigens. Six of 13 encephalitogen-specific T-cell clones were shown to express the variable beta-chain (V beta) 17a gene product (KJ23a+), whereas seven clones were KJ23a-. Both KJ23a+ and KJ23a- subpopulations were encephalitogenic in SJL/J mice when adoptively transferred. Depletion of KJ23a+ cells in vivo with the administration of the antibody KJ23a suppresses experimental allergic encephalomyelitis induced with KJ23a+ T-cell lines. However, experimental allergic encephalomyelitis induced with either (i) encephalitogenic peptide p89-101, (ii) intact myelin basic protein, or (iii) KJ23a- T cells reactive to p89-101 cannot be prevented with monoclonal antibody KJ23a. These data indicate that in spite of the V beta 17a gene expression in a relatively large proportion of p89-101-specific T cells, such V beta gene use is not essential for the induction of experimental allergic encephalomyelitis in SJL/J mice. These results contrast with the predominance of V beta gene use (V beta 8.2) in T cells reactive to the encephalitogenic fragment (pR1-11) in PL/J mice. One reason for this lack of dominant use of a particular T-cell receptor V beta gene family in the autoimmune response to myelin basic protein in SJL/J mice stems from the observation that two encephalitogenic epitopes exist in p89-101. KJ23a- T cells are stimulated by the deleted peptide p89-100, whereas KJ23a+ T cells are not. Thus, in the response to an encephalitogenic fragment of myelin basic protein containing two nested epitopes, at least two distinct T-cell receptor V beta genes are expressed. These distinct T-cell subpopulations can each trigger experimental allergic encephalomyelitis. These findings have implications for therapy of autoimmune disease with antibodies to the T-cell receptor gene products.
Studies on the mechanism of skin tumor promotion: Evidence for several stages in promotion (1980)

The effects of nonpromoting and weakly promoting diterpenes on skin tumor promotion by 12-O-tetradecanoylphorbol 13-acetate (TPA) were investigated. When phorbol and phorbol 12,13-diacetate (both nonpromoting) were given simultaneously with TPA after 7,12-dimethylbenz[a]-anthracene (DMBA) initiation in female mice, they had no effect on TPA promotion. However, the nonpromoter 4-O-methyl-TPA and the weak promoter mezerein were found to inhibit TPA promotion in a dose-dependent manner when given simultaneously with TPA. Because mezerein was found to be an effective inhibitor of TPA promotion when given simultaneously and because it induces many biological responses similar to those to TPA, the capacity of mezerein to act as an incomplete promoter in a two-stage promotion protocol was also investigated. Twice-weekly applications of 1,2, or 5 mug of TPA for 2 weeks after DMBA initiation produced 0, 0, and 0.5 papilloma per mouse, respectively, at 20 weeks. When the twice-weekly applications of TPA for 2 weeks were followed by twice-weekly treatments with 2 mug of mezerein for 18 weeks, the number of papillomas per mouse was 2.2, 3.5, and 9.0, respectively. Twice-weekly applications of 2 mug of TPA for 2 weeks followed by twice-weekly treatments with 1, 2, or 4 mug of mezerein for 18 weeks produced 2.1, 3.5, and 6.8 papillomas per mouse, respectively, in DMBA-treated mice. Twice-weekly doses as high as 40 mug of 4-O-methyl-TPA were not effective in producing tumors when given after a limited treatment with TPA; however, 4-O-methyl-TPA had weak activity as a first-stage promoter. The results suggest that although mezerein by itself is a weak promoter and mimics TPA in many biochemical and morphological effects it is a potent second-stage promoter in a two-stage promotion regimen.
Inhibition of cyclin D1 gene transcription by Brg-1 (2008)

The evolutionarily conserved SWI-SNF chromatin remodeling complex regulates cellular proliferation. A catalytic subunit, BRG-1, is frequently down regulated, silenced or mutated in malignant cells, however, the mechanism by which BRG-1 may function as a tumor suppressor or block breast cancer cellular proliferation is not understood. The cyclin D1 gene is a collaborative oncogene overexpressed in greater than 50% of human breast cancers. Herein, BRG-1 inhibited DNA synthesis and cyclin D1 expression in human MCF-7 breast cancer epithelial cells. The cyclin D1 promoter AP-1 and CRE sites were required for repression by BRG-1 in promoter assays. BRG-1 deficient cells abolished and siRNA to BRG-1 reduced, formation of the BRG-1 chromatin complex. The endogenous cyclin D1 promoter AP-1 site bound BRG-1. Estradiol treatment of MCF7 cells induced recruitment of BRG-1 to the endogenous hpS2 gene promoter. Estradiol, which induced cyclin D1 abundance, was associated with a reduction in recruitment of the co-repressors HP1α/HDAC1 to the endogenous cyclin D1 promoter AP-1/BRG-1 binding sites. These studies suggest the endogenous cyclin D1 promoter BRG-1 binding site functions as a molecular scaffold in the context of local chromatin upon which coactivators and corepressors are recruited to regulate cyclin D1.
Mouse β-galactoside α2,3-sialyltransferases: comparison of in vitro substrate specificities and tissue specific expression (1997)

Four types of beta-galactoside alpha 2,3-sialyltransferase (ST3Gal I-IV) have been cloned from several animals, but some contradictory observations regarding their substrate specificities and expression have been reported. Therefore, it is necessary to concurrently analyze the substrate specificities of the four enzymes, of which the source should be one animal. Accordingly, the acceptor substrate specificities and gene expression of mST3Gal I-IV were analyzed. Since we had already cloned ST3Gal I and II, as previously reported (Lee, Y.-C. et al., Eur. J. Biochem., 216, 377-385 (1993); J. Biol. Chem., 269, 10028-10033 (1994)), the cDNAs of ST3Gal III and IV were cloned from mouse cDNA libraries. Each of the four enzymes was expressed in COS-7 cells as a recombinant enzyme fused with protein A, and applied on an IgG-Sepharose gel to eliminate endogenous sialyltransferase activity. ST3Gal I and II showed the highest activity toward Gal beta 1, 3 GalNAc (type III), very low activity toward Gal beta 1,3GlcNAc (type I), but none toward Gal beta 1,4GlcNAc (type II). ST3Gal III and IV exhibited high activity toward the type I and II disaccharides, but very low activity toward the type III one. On the other hand, asialo-GM1 (Gg4Cer) was as good a substrate for ST3Gal I and II as the type III disaccharide, though ST3Gal III and IV hardly utilized glycolipids as substrates, as indicated by in vitro experiments. Northern blot analysis revealed that enzymes of the ST3Gal-family are expressed mainly in a tissue-specific manner. The ST3Gal I gene was strongly expressed in spleen and salivary gland, and weakly in brain, liver, heart, kidney, and thymus. The ST3Gal II gene was strongly expressed in brain, and weakly in colon, thymus, salivary gland, and testis, and developmentally expressed in liver, heart, kidney, and spleen. The ST3Gal III and IV genes were expressed in a wide variety of tissues. These differences in tissue specific expression suggest the expression of each ST3Gal influences the distribution of sialyl-glycoconjugates in vivo.
Myeloperoxidase and Cardiovascular Disease (2005)

Myeloperoxidase (MPO) is a leukocyte-derived enzyme that catalyzes the formation of a number of reactive oxidant species. In addition to being an integral component of the innate immune response, evidence has emerged that MPO-derived oxidants contribute to tissue damage during inflammation. MPO-catalyzed reactions have been attributed to potentially proatherogenic biological activities throughout the evolution of cardiovascular disease, including during initiation, propagation, and acute complication phases of the atherosclerotic process. As a result, MPO and its downstream inflammatory pathways represent attractive targets for both prognostication and therapeutic intervention in the prophylaxis of atherosclerotic cardiovascular disease.
PEPTIDES DERIVED FROM ICAM-1 AND LFA-1 MODULATE T CELL ADHESION AND IMMUNE FUNCTION IN A MIXED LYMPHOCYTE CULTURE1 (1999)

Our data suggest that these peptides or their derivatives may be useful as therapeutic modulators of LFA-1/ICAM-1 interaction during organ transplants.
Switching-mode DC-DC converter with switched-capacitor-based resonant circuit (1996)

A soft-switching dc-dc converter, in which the resonant capacitor is replaced by a switched-capacitor circuit, is presented. The new system incorporates a switching technique at zero-current or zero-voltage for each switch and an operation at constant switching frequency. The first feature is due to the presence of a resonant circuit, which shapes the switches' current and voltage waveforms in a sinusoidal form. It assures minimal switching losses. The switched-capacitor circuit determines a simple, discrete control, extends the region in which the soft-switching condition is fulfilled to large values of the load or small values of the input voltage, and prevents the current stress on the electronic devices from increasing with the input voltage. An original design approach allows for choosing the element values so as to get both soft-switching and regulation over a large range of input voltage and load values. Analysis, computer simulation and experiments indicate the operation principles of the new structure and render evident its performances, such as high efficiency and good regulation capability.
Dynamic spectral equalization using micro-opto-mechanics (2002)

Power equalization in WDM systems can be achieved by a variety of means including signal pre-emphasis, fixed fiber gratings, and individual attenuators placed between two wavelength routers. Each of these approaches represents a tradeoff in network operator flexibility. In this paper, we demonstrate a dynamic WDM equalizer using a voltage-controlled variable reflectivity strip mirror and free-space wavelength multiplexing to provide dynamic control over wavelength power levels across a continuous transmission spectrum.
U.S. Trends In CABG Hospital Volume: The Effect Of Adding Cardiac Surgery Programs (2007)

Hospital coronary artery bypass graft (CABG) volume is inversely related to mortality--with low-volume hospitals having the highest mortality. Medicare data (1992-2003) show that the number of CABG procedures increased from 158,000 in 1992 to a peak of 190,000 in 1996 and then fell to 152,000 in 2003, while the number of hospitals performing CABG increased steadily. Predictably, the proportion of CABG procedures performed at low-volume hospitals increased, and the proportion in high-volume hospitals declined. An unintended consequence of starting new cardiac surgery programs is declining CABG hospital volume--a side effect that might increase mortality.
Transforming Growth Factor-β/Smad3 Signaling Regulates Insulin Gene Transcription and Pancreatic Islet β-Cell Function (2009)

Pancreatic islet beta-cell dysfunction is a signature feature of Type 2 diabetes pathogenesis. Consequently, knowledge of signals that regulate beta-cell function is of immense clinical relevance. Transforming growth factor (TGF)-beta signaling plays a critical role in pancreatic development although the role of this pathway in the adult pancreas is obscure. Here, we define an important role of the TGF-beta pathway in regulation of insulin gene transcription and beta-cell function. We identify insulin as a TGF-beta target gene and show that the TGF-beta signaling effector Smad3 occupies the insulin gene promoter and represses insulin gene transcription. In contrast, Smad3 small interfering RNAs relieve insulin transcriptional repression and enhance insulin levels. Transduction of adenoviral Smad3 into primary human and non-human primate islets suppresses insulin content, whereas, dominant-negative Smad3 enhances insulin levels. Consistent with this, Smad3-deficient mice exhibit moderate hyperinsulinemia and mild hypoglycemia. Moreover, Smad3 deficiency results in improved glucose tolerance and enhanced glucose-stimulated insulin secretion in vivo. In ex vivo perifusion assays, Smad3-deficient islets exhibit improved glucose-stimulated insulin release. Interestingly, Smad3-deficient islets harbor an activated insulin-receptor signaling pathway and TGF-beta signaling regulates expression of genes involved in beta-cell function. Together, these studies emphasize TGF-beta/Smad3 signaling as an important regulator of insulin gene transcription and beta-cell function and suggest that components of the TGF-beta signaling pathway may be dysregulated in diabetes.
Ectopic expression of platelet integrin αIIbβ3 in tumor cells from various species and histological origin (1997)

The integrin alphaIIb beta3 is a membrane receptor which was considered to be expressed only in cells of megakaryocytic lineage. We have shown that alphaIIb beta3 is expressed in mouse melanoma B16a cells, and in human prostate adenocarcinoma cells. The purpose of this study was to determine whether the megakaryocytic product alphaIIb beta3 was functionally expressed in other non-megakaryocyte lineage tumor cells. By using the reverse transcription polymerase chain reaction (RT-PCR), we have obtained data demonstrating that alphaIIb beta3 is expressed in a variety of tumor cell lines (17) derived from different species (human, rat and mouse) and of different histological origins (skin, blood, lung, liver, kidney, cervix, colon, bladder, breast and prostate). Immunostaining of tumor cells with a monoclonal antibody (MAb) to alphaIIb beta3 demonstrates that alphaIIb beta3 protein is also expressed in tumor cells. A protein kinase C activator PMA stimulates adhesion of tumor cells to fibronectin and fibrinogen, and this stimulated adhesion is blocked by a function-blocking MAb directed to alphaIIb beta3. Our results indicate that the megakaryocytic gene product alphaIIb beta3 integrin is widely expressed among tumor cells of non-megakaryocytic lineage, suggesting that ectopic expression of this integrin may play an important role in tumor progression.
Synthesis of 7-carboxytricyclo[3.3.1.03,7]nonan-3-ol (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 7-carboxytricyclo[3.3.1.03,7]nonan-3-olGeorge E. Renzoni and Weston Thatcher BordenCite this: J. Org. Chem. 1983, 48, 26, 5231–5236Publication Date (Print):December 1, 1983Publication History Published online1 May 2002Published inissue 1 December 1983https://pubs.acs.org/doi/10.1021/jo00174a015https://doi.org/10.1021/jo00174a015research-articleACS PublicationsRequest reuse permissionsArticle Views152Altmetric-Citations16LEARN 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
CHO Quasispecies—Implications for Manufacturing Processes (2013)

Chinese hamster ovary (CHO) cells are a source of multi-ton quantities of protein pharmaceuticals. They are, however, immortalized cells, characterized by a high degree of genetic and phenotypic diversity. As is known for any biological system, this diversity is enhanced by selective forces when laboratories (no sharing of gene pools) grow cells under (diverse) conditions that are practical and useful. CHO cells have been used in culture for more than 50 years, and various lines of cells are available and have been used in manufacturing. This article tries to represent, in a cursory way, the history of CHO cells, particularly the origin and subsequent fate of key cell lines. It is proposed that the name CHO represents many different cell types, based on their inherent genetic diversity and their dynamic rate of genetic change. The continuing remodeling of genomic structure in clonal or non-clonal cell populations, particularly due to the non-standardized culture conditions in hundreds of different labs renders CHO cells a typical case for “quasispecies”. This term was coined for families of related (genomic) sequences exposed to high mutation rate environments where a large fraction of offspring is expected to carry one or more mutations. The implications of the quasispecies concept for CHO cells used in protein manufacturing processes are significant. CHO genomics/transcriptomics may provide only limited insights when done on one or two “old” and poorly characterized CHO strains. In contrast, screening of clonal cell lines, derived from a well-defined starting material, possibly within a given academic or industrial environment, may reveal a more narrow diversity of phenotypes with respect to physiological/metabolic activities and, thus, allow more precise and reliable predictions of the potential of a clone for high-yielding manufacturing processes.
Cloning of the Alcaligenes eutrophus genes for synthesis of poly-beta-hydroxybutyric acid (PHB) and synthesis of PHB in Escherichia coli (1988)

Eight mutants of Alcaligenes eutrophus defective in the intracellular accumulation of poly-beta-hydroxybutyric acid (PHB) were isolated after transposon Tn5 mutagenesis with the suicide vector pSUP5011. EcoRI fragments which harbor Tn5-mob were isolated from pHC79 cosmid gene banks. One of them, PPT1, was used as a probe to detect the intact 12.5-kilobase-pair EcoRI fragment PP1 in a lambda L47 gene bank of A. eutrophus genomic DNA. In six of these mutants (PSI, API, GPI, GPIV, GPV, and GPVI) the insertion of Tn5-mob was physically mapped within a region of approximately 1.2 kilobase pairs in PP1; in mutant API, cointegration of vector DNA has occurred. In two other mutants (GPII and GPIII), most probably only the insertion element had inserted into PP1. All PHB-negative mutants were completely impaired in the formation of active PHB synthase, which was measured by a radiometric assay. In addition, activities of beta-ketothiolase and of NADPH-dependent acetoacetyl coenzyme A (acetoacetyl-CoA) reductase were diminished, whereas the activity of NADPH-dependent acetoacetyl-CoA reductase was unaffected. In all PHB-negative mutants the ability to accumulate PHB was restored upon complementation in trans with PP1. The PHB-synthetic pathway of A. eutrophus was heterologously expressed in Escherichia coli. Recombinant strains of E. coli JM83 and K-12, which harbor pUC9-1::PP1, pSUP202::PP1, or pVK101::PP1, accumulated PHB up to 30% of the cellular dry weight. Crude extracts of these cells had significant activities of the enzymes PHB synthase, beta-ketothiolase, and NADPH-dependent acetoacetyl-CoA reductase. Therefore, PP1 most probably encodes all three genes of the PHB-synthetic pathway in A. eutrophus. In addition to PHB-negative mutants, we isolated mutants which accumulate PHB at a much lower rate than the wild type does. These PHB-leaky mutants exhibited activities of all three PHB-synthetic enzymes; Tn5-mob had not inserted into PP1, and the phenotype of the wild type could not be restored with fragment PP1. The rationale for this mutant type remains unknown.
A Long-Acting, Mono-PEGylated Human Growth Hormone Analog Is a Potent Stimulator of Weight Gain and Bone Growth in Hypophysectomized Rats (2007)

Recombinant human GH is used to treat GH deficiency in children and adults and wasting in AIDS patients. GH has a circulating half-life of only a few hours in humans and must be administered to patients by daily injection for maximum effectiveness. Previous studies showed that longer-acting forms of GH could be created by modification of GH with multiple 5-kDa amine-reactive polyethylene glycols (PEGs). Eight of nine lysine residues and the N-terminal amino acid were modified to varying extents by amine PEGylation of GH. The amine-PEGylated GH product comprised a complex mixture of multiple PEGylated species that differed from one another in mass, in vitro bioactivity, and in vivo potency. In vitro bioactivity of GH was reduced 100- to 1000-fold by extensive amine PEGylation of the protein. Here we describe a homogeneously modified, mono-PEGylated GH protein that possesses near complete in vitro bioactivity, a long half-life, and increased potency in vivo. The mono-PEGylated GH was created by substituting cysteine for threonine-3 (T3C) of GH, followed by modification of the added cysteine residue with a single 20-kDa cysteine-reactive PEG. The PEG-T3C protein has an approximate 8-fold longer half-life than GH after sc administration to rats. Every other day or every third day administration of PEG-T3C stimulates increases in body weight and tibial epiphysis growth comparable with that produced by daily administration of GH in hypophysectomized rats. Long-acting, mono-PEGylated GH analogs such as PEG-T3C are promising candidates for future testing in humans.