gebhart/patrepeval huggingface dataset:
Kinetic Analysis of Pausing and Fidelity of Human Immunodeficiency Virus Type 1 Reverse Transcription (1996)

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase catalyzes DNA synthesis from RNA and DNA templates by a sequential mechanism. This enzyme is neither processive nor distributive but has a rather intermediate behavior; at any template position, there is a certain probability that the replica strand will be extended, which we define as extensibility. The extensibility depends on the substrate concentration, i.e. on the concentration of the cognate (and to a smaller extent of the noncognate) deoxynucleoside triphosphates, in a typical Michaelis-Menten mode. The extensibility varies from position to position in a sequence-dependent manner, being particularly low at certain sites, accordingly called pause sites. The rate and fidelity of successive incorporation of nucleotides were measured and then compared with numerical integrations of the pertinent rate equations, which were composed to describe a suitable reaction mechanism and parameterized starting starting with rate constants reported in the literature. We found that agreement between stimulation and experiment requires two-step binding of enzyme to the template-primer. In an initial second-order step, an "outer" binary complex is rapidly formed; this is followed by a slower conformational change into an "inner" complex. During multiple rounds of nucleotide incorporation, the complex remains in the inner form; the rate-determining step for enzyme release is the reversion from the inner to the outer complex, with a standard rate constant of 0.2s-1. This rate constant may be significantly increased at pause sites. In order to match the experimental results, the standard rate constants had to be modified for pause sites. At low concentrations or in the absence of the cognate nucleotide, the site-specific misinsertion frequency, a function of the nucleotide pool is bias and of the efficiency to discriminate against a noncognate nucleotide, can be determined from the dependence of extensibility on concentration of cognate and noncognate substrates. The error frequency was found to be somewhat smaller than the misinsertion frequency, because mismatches are extended less efficiently than matched pairs.
The role of histone acetylation in SMN gene expression (2005)

Increasing survival motor neuron 2 (SMN2) gene expression may be an effective strategy for the treatment of spinal muscular atrophy (SMA). Histone deacetylase (HDAC) inhibitors have been shown to increase SMN transcript and protein levels, but the specific role of histone acetylation in regulating SMN gene expression has not been explored. Using chromatin immunopreciptation, we investigated the levels of acetylated H3 and H4 histones and HDACs associated with different regions of the human and mouse SMN genes in both cultured cells and tissues. We show that the SMN gene has a reproducible pattern of histone acetylation that is largely conserved among different tissues and species. A limited region of the promoter surrounding the transcriptional start site has relatively high levels of histone acetylation, whereas regions further upstream or downstream have lower levels. After HDAC inhibitor treatment, acetylated histone levels increased, particularly at upstream regions, correlating with a 2-fold increase in promoter activity. During development in mouse tissues, histone acetylation levels decreased and associated HDAC2 levels increased at the region closest to the transcriptional start site, correlating with a 40-60% decrease in SMN transcript and protein levels. These data indicate that histone acetylation modulates SMN gene expression and that pharmacological manipulation of this epigenetic determinant is feasible. HDAC2, in particular, may be a future therapeutic target for SMA.
An Expanded Eukaryotic Genetic Code (2003)

We describe a general and rapid route for the addition of unnatural amino acids to the genetic code of Saccharomyces cerevisiae. Five amino acids have been incorporated into proteins efficiently and with high fidelity in response to the nonsense codon TAG. The side chains of these amino acids contain a keto group, which can be uniquely modified in vitro and in vivo with a wide range of chemical probes and reagents; a heavy atom-containing amino acid for structural studies; and photocrosslinkers for cellular studies of protein interactions. This methodology not only removes the constraints imposed by the genetic code on our ability to manipulate protein structure and function in yeast, it provides a gateway to the systematic expansion of the genetic codes of multicellular eukaryotes.
Neoteric optical media for refractive index determination of gems and minerals (2006)

Refractive index determination of minerals and gems often requires their immersion in fluids with the same refractive index. However, these natural materials frequently have refractive indices above the ranges of common organic solvents. Most available high refractive index immersion materials are solid at room temperature, toxic, noxious, corrosive, carcinogenic, or any combination thereof. Since the physical properties of ionic liquids can be tuned by varying the cation and/or anion, we have developed immersion fluids for mineralogical studies which are relatively benign. We report here the syntheses of a range of ionic liquids (many novel) based on the 1-alkyl-3-methylimidazolium cation, which all have refractive indices greater than 1.4, and can be used as immersion fluids for optical mineralogy studies. We further show that for a series of ionic liquids with the same anion, the refractive indices can be adjusted by systematic changes in the cation.
Redirecting Mouse CTL Against Colon Carcinoma: Superior Signaling Efficacy of Single-Chain Variable Domain Chimeras Containing TCR-ζ vs FcεRI-γ (2001)

The structurally related TCR-zeta and Fc receptor for IgE (Fc epsilon RI)-gamma are critical signaling components of the TCR and Fc epsilon RI, respectively. Although chimeric Ab receptors containing zeta and gamma signaling chains have been used to redirect CTL to tumors, a direct comparison of their relative efficacy has not previously been undertaken. Here, in naive T lymphocytes, we compare the signaling capacities of the zeta and gamma subunits within single-chain variable domain (scFv) chimeric receptors recognizing the carcinoembryonic Ag (CEA). Using a very efficient retroviral gene delivery system, high and equivalent levels of scFv-zeta and scFv-gamma receptors were expressed in T cells. Despite similar levels of expression and Ag-specific binding to colon carcinoma target cells, ligation of scFv-anti-CEA-zeta chimeric receptors on T cells resulted in greater cytokine production and direct cytotoxicity than activation via scFv-anti-CEA-gamma receptors. T cells expressing scFv-zeta chimeric receptors had a greater capacity to control the growth of human colon carcinoma in scid/scid mice or mouse colon adenocarcinoma in syngeneic C57BL/6 mice. Overall, these data are the first to directly compare and definitively demonstrate the enhanced potency of T cells activated via the zeta signaling pathway.
ICAM‐1 costimulation induces IL‐2 but inhibits IL‐10 production in superantigen‐activated human CD4+ T cells (1998)

We have previously reported that costimulatory pathways including B7-CD28 and lymphocyte function-associated antigen-3 (LFA-3)-CD2 shape distinct activation profiles in human CD4+ T cells. We now show that superantigen (SAg), in combination with intracellular adhesion molecule-1 (ICAM-1) costimulation drives a proliferative response accompanied by high levels of interleukin-2 (IL-2) and moderate levels of interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF). This response profile differs from that observed in B7 or LFA-3 costimulated T cells because our previous results showed that B7-CD28 costimulation was accompanied by high levels of IL-2, IFN-gamma and TNF, whereas LFA-3 was a potent inducer of IFN-gamma and TNF, but had little influence on IL-2 production. The ICAM-1-induced IL-2 production could efficiently be abrogated with monoclonal antibody (mAb) against ICAM-1 or LFA-1, showing that the activation is dependent of a functional ICAM-1-LFA-1 pathway. SAg-induced IL-2, IFN-gamma and TNF were detected in both CD4+ and CD8+ T cells, whereas production of IL-10 was restricted to CD4+ T cells. A major finding in the present study was that ICAM-1 costimulation strongly inhibits IL-10 production in CD4+ T cells. Our data demonstrate that ICAM-1 costimulation is sufficient to induce large amounts of IL-2. The presence of ICAM-1 results in suppression of IL-10 production in T helper (Th) cells, which may favour the development of Th1 and not Th2 T cells.
Retroviral-Mediated Gene Transduction of c-kit Into Single Hematopoietic Progenitor Cells From Cord Blood Enhances Erythroid Colony Formation and Decreases Sensitivity to Inhibition by Tumor Necrosis Factor- and Transforming Growth Factor-β1 (1999)

The c-kit receptor and its ligand, steel factor (SLF), are critical for optimal hematopoiesis. We evaluated effects of transducing cord blood (CB) progenitor cells with a retrovirus encoding human c-kit cDNA. CD34(+) cells were sorted as a population or as 1 cell/well for cells expressing high levels of CD34 and different levels of c-kit (++,+,Lo/-), transduced and then cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), IL-6, erythropoietin (Epo) +/- SLF in the absence of serum. At a single-cell level, transduction with c-kit, but not with control (neo only), virus significantly increased colony formation, especially by erythroid and multipotential progenitors. The enhancing effect of c-kit transduction was inversely correlated with expression of c-kit protein before transduction. The greatest enhancing effects were noted in CD34KitLo+/- cells transduced with c-kit. The stimulating effect was apparent even in the absence of exogenously added SLF, but in the presence of GM-CSF, IL-3, IL-6, and Epo. Enzyme-linked immunosorbent assay (ELISA) of SLF protein, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of SLF mRNA expression in CD34+ cells, and use of neutralizing antibodies to SLF and/or c-kit suggested the presence of endogenous, although probably very low level, expression of SLF by these progenitor cells. Transduction of c-kit significantly decreased sensitivity of progenitor cells to the inhibitory effects of transforming growth factor-beta1 and tumor necrosis factor-alpha. c-kit-transduced cells had increased expression of c-kit protein and decreased spontaneous or cytokine-induced apoptosis. Our results suggest that transduced c-kit into selected progenitor cells can enhance proliferation and decrease apoptosis and that endogenous SLF may mediate this effect.
Fluorescence from the 11Bu state of diphenylhexatriene: inversion of the 11Bu and 21Ag levels in carbon disulfide (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluorescence from the 11Bu state of diphenylhexatriene: inversion of the 11Bu and 21Ag levels in carbon disulfideBryan E. Kohler and Takao ItohCite this: J. Phys. Chem. 1988, 92, 18, 5120–5122Publication Date (Print):September 1, 1988Publication History Published online1 May 2002Published inissue 1 September 1988https://doi.org/10.1021/j100329a013RIGHTS & PERMISSIONSArticle Views90Altmetric-Citations37LEARN 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 InReddit PDF (352 KB) Get e-Alerts
Induction of an antiviral response by interferon requires thymidine kinase. (1983)

Mouse fibroblastoid cells (Ltk-) that lack thymidine kinase (tk) activity are unable to respond to murine beta-interferon by establishing antiviral activity or inducing the double-stranded RNA-dependent enzymes, oligo[(2'-5')A] polymerase and Mr 68,000 protein kinase. In contrast, the parental L-929 cell line or clonal derivatives of Ltk- cells into which the herpes virus tk gene was introduced by DNA-mediated gene transfer respond normally to interferon in developing resistance to viral infection and in inducing double-stranded RNA-dependent enzymes. Further evidence for a role of tk in the response to interferon was obtained by isolating revertants of tk+ clones that lost the herpes virus tk gene during growth in BrdUrd-containing medium. In such revertant sublines both tk enzyme activity and viral tk genes were undetectable and treatment with interferon failed to produce an antiviral effect or induce synthesis of the double-stranded RNA-dependent enzymes. Our results indicate that the ability of mouse L cells to respond to beta-interferon is dependent upon the presence of a functional tk gene. We propose that the induction of antiviral responses by interferon stringently requires a metabolite, the level of which is determined by tk activity. The system described may provide a means for elucidating the mechanisms by which responses to interferon are induced.
Wife Assault Treatment and Criminal Recidivism: An 11-Year Follow-Up (1997)

The impact of court-ordered treatment for wife assault was assessed by monitoring 156 men who had completed such treatment for up to 11 years (mean = 5.2 years) after treatment completion. Recidivist assault and wife assault was assessed through access to Canadian Police Information Centre data that record crimes committed anywhere in Canada. Comparisons were drawn between this group and a group of 167 dropouts from treatment (noncompleters), 32 men rejected for treatment because of resistance or denial (rejects), and 91 men who never appeared for their treatment assessment (no shows). Whereas time-to-failure failed to reveal significant between-group differences, a recidivism ratio (total repeat offenses per man-in-group) revealed significantly lower recidivism rates for treatment completers (.23 versus .50). No shows recidivated at an equal rate to completers. Some inferences are drawn about spiral models of behavioral change.
Cysteine-rich fibroblast growth factor receptor 1, a new marker for precancerous epithelial lesions defined by the human monoclonal antibody PAM-1. (2003)

Precancerous epithelial lesions are sites of uncontrolled cellular proliferation, generated by irreversible genetic changes. Not all of these lesions progress to invasive cancer, some may even regress, but early detection of abnormal cells can be crucial for survival of the patient. Diagnosis is mainly performed by using morphological parameters. Proliferation markers can facilitate the analysis, if they show a consistent expression, and distinguish between healthy and malignant cells. The fully human monoclonal IgM antibody PAM-1 was isolated from a patient with stomach carcinoma and binds to a new variant of cysteine-rich fibroblast growth factor receptor 1 (CFR-1). This CFR-1/PAM-1 receptor is expressed on nearly all of the epithelial cancers of every type and origin, but not on healthy tissue. It is also present on precursor lesions found in: Helicobacter pylori-induced gastritis, intestinal metaplasia and dysplasia of the stomach, ulcerative colitis-related dysplasia and adenomas of the colon, Barrett's metaplasia and dysplasia of the esophagus, squamous cell metaplasia and dysplasia of the lung, and cervical intraepithelial neoplasia. The unique, growth-dependent expression of this new CFR-1 isoform makes the PAM-1 antibody an ideal diagnostic tool for the detection of precancerous and cancerous lesions.
Monolithic InP Optical Crossconnects: 4×4 and Beyond (1999)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text G. A. Fish, B. Mason, L. A. Coldren, and S. P. DenBaars, "Monolithic InP Optical Crossconnects: 4×4 and Beyond," in Integrated Photonics Research, OSA Technical Digest Series (Optical Society of America, 1999), paper JWB2. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Redirecting the substrate specificity of heparan sulfate 2- O -sulfotransferase by structurally guided mutagenesis (2008)

Heparan sulfate (HS) is a polysaccharide involved in essential physiological functions from regulating cell growth to blood coagulation. HS biosynthesis involves multiple specialized sulfotransferases such as 2-O-sulfotransferase (2OST) that transfers the sulfo group to the 2-OH position of iduronic acid (IdoA) or glucuronic acid (GlcA) within HS. Here, we report the homotrimeric crystal structure of 2OST from chicken, in complex with 3'-phosphoadenosine 5'-phosphate. Structural based mutational analysis has identified amino acid residues that are responsible for substrate specificity. The mutant R189A only transferred sulfates to GlcA moieties within the polysaccharide whereas mutants Y94A and H106A preferentially transferred sulfates to IdoA units. Our results demonstrate the feasibility for manipulating the substrate specificity of 2OST to synthesize HS with unique sulfation patterns. This work will aid the development of an enzymatic approach to synthesize heparin-based therapeutics.
Large depth-of-focus time-multiplexed three-dimensional integral imaging by use of lenslets with nonuniform focal lengths and aperturesizes (2003)

Conventional integral-imaging systems utilize lenslet arrays with fixed focal lengths and aperture sizes. We propose a time-multiplexed integral-imaging method that enhances both the depth of focus and the resolution of a three-dimensional image by displaying it with an array of lenslets with different focal lengths and aperture sizes. The nonuniform lenslet parameters (focal lengths and aperture sizes) for our method are calculated. Our theoretical analysis indicates that significant improvements in both depth of focus and resolution can be obtained with the proposed technique.
Pulmonary Rehabilitation in Patients With COPD (1995)

The available evidence indicates that pulmonary rehabilitation benefits patients with symptomatic COPD. The effect of pulmonary rehabilitation programs on health care utilization is promising but requires further investigation. In contrast, aerobic lower extremity training is of benefit in several areas of importance to patients with COPD. These areas include exercise endurance, perception of dyspnea, quality of life, and self-efficacy. The exact role of upper extremity exercise and ventilatory muscle training in the exercise training programs requires further studies. Education and psychological support improve the awareness of the patient and increase their understanding of the disease, but when used alone they are of limited value. Pulmonary rehabilitation, when coupled with smoking cessation, optimization of blood gases, and medications, offers the best treatment option for patients with symptomatic airflow obstruction.
Neuroprotective Effects of Thymosin β4 in Experimental Models of Excitotoxicity (2007)

The aim of this study was to evaluate the possible neuroprotective effects of thymosin beta(4) in different models of excitotoxicity. The application of thymosin beta(4) significantly attenuated glutamate-induced toxicity both in primary cultures of cortical neurons and in rat hippocampal slices. In in vivo experiments, the intracerebroventricular administration of thymosin beta(4) significantly reduced hippocampal neuronal loss induced by kainic acid. These results show that thymosin beta(4) induced a protective effect in models of excitotoxicity. The mechanisms underlying such an effect, as well as the real neuroprotective potential of thymosin beta(4), are worthy of further investigations.
L'économie des passerelles technologiques et l'évolution des réseaux. Leçons apprises de l'histoire de la distribution de l'électricité. 2ème partie (1991)

Paul A. DAVID &amp; Julie A. BUNN, L'Economie des passerelles-tecbnologiques et l'évolution des réseaux. Leçons apprises de l'histoire de la distribution d'électricité. 2ème partie. Cet article est consacré au rôle des passerelles technologiques dans les processus de développement des réseaux techniques. Les auteurs appuient leur thèse sur une étude de cas : l'influence du convertisseur rotatif dans le développement du courant alternatif (et sa victoire sur le courant continu) aux Etats-Unis à la charnière du siècle (1890-1910). Dans la première partie de cet article, publiée dans FLUX 4, à partir d'exemples dans des domaines techniques divers, les auteurs revenaient sur la définition de concepts largement employés dans la littérature (innovation, norme, compatibilité) et introduisaient la notion de passerelle technologique ("gateway technology") entre sous-systèmes incompatibles. Puis ils retraçaient l'histoire de la 'Bataille des Courants' qui a défrayé la chronique aux Etats-Unis à la fin des années 1880, en discutant les analyses qu'elle a déjà suscitées dans la littérature. Dans la seconde partie de l'article, publiée ici, les auteurs proposent leur interprétation de ces événements, en mettant l'accent sur le convertisseur rotatif, considéré comme passerelle technologique.
Isolation of Multipotent Cells from Human Term Placenta (2005)

Current sources of stem cells include embryonic stem cells (ESCs) and adult stem cells (ASCs). However, concerns exist with either source: ESCs, with their significant ethical considerations, tumorigenicity, and paucity of cell lines; and ASCs, which are possibly more limited in potential. Thus, the search continues for an ethically conducive, easily accessible, and high-yielding source of stem cells. We have isolated a population of multipotent cells from the human term placenta, a temporary organ with fetal contributions that is discarded postpartum. These placenta-derived multipotent cells (PDMCs) exhibit many markers common to mesenchymal stem cells--including CD105/endoglin/SH-2, SH-3, and SH-4--and they lack hematopoietic-, endothelial-, and trophoblastic-specific cell markers. In addition, PDMCs exhibit ESC surface markers of SSEA-4, TRA-1-61, and TRA-1-80. Adipogenic, osteogenic, and neurogenic differentiation were achieved after culturing under the appropriate conditions. PDMCs could provide an ethically uncontroversial and easily accessible source of multipotent cells for future experimental and clinical applications.
Magnetic bearing turbomachinery case histories and applications for space related equipment (1993)

The concept of magnetic levitation is not a new one and can be easily traced back to the 1800's. It is only recently, however, that the congruous technologies of electronic control systems, power electronics, and magnetic materials have begun to merge to make the magnetic suspension device a viable product. A brief overview of an active magnetic bearing technology is provided. Case histories of various turbomachinery in North America presently operating on magnetic bearings are reviewed. Finally, projections are made as to the space related machinery that may be benefited by incorporating magnetic bearings into the equipment design.