gebhart/patrepeval huggingface dataset:
Rational Design of Interleukin-21 Antagonist through Selective Elimination of the γC Binding Epitope (2010)

The cytokine interleukin (IL)-21 exerts pleiotropic effects acting through innate as well as adaptive immune responses. The activities of IL-21 are mediated through binding to its cognate receptor complex composed of the IL-21 receptor private chain (IL-21Ralpha) and the common gamma-chain (gammaC), the latter being shared by IL-2, IL-4, IL-7, IL-9, and IL-15. The binding energy of the IL-21 ternary complex is predominantly provided by the high affinity interaction between IL-21 and IL-21Ralpha, whereas the interaction between IL-21 and gammaC, albeit essential for signaling, is rather weak. The design of IL-21 analogues, which have lost most or all affinity toward the signaling gammaC chain, while simultaneously maintaining a tight interaction with the private chain, would in theory represent candidates for IL-21 antagonists. We predicted the IL-21 residues, which compose the gammaC binding epitope using homology modeling and alignment with the related cytokines, IL-2 and IL-4. Next we systematically analyzed the predicted binding epitope by a mutagenesis study. Indeed two mutants, which have significantly impaired gammaC affinity with undiminished IL-21Ralpha affinity, were successfully identified. Functional studies confirmed that these two novel hIL-21 double mutants do act as hIL-21 antagonists.
Oncolytic and Immunotherapeutic Vaccinia Induces Antibody-Mediated Complement-Dependent Cancer Cell Lysis in Humans (2013)

Oncolytic viruses cause direct cytolysis and cancer-specific immunity in preclinical models. The goal of this study was to demonstrate induction of functional anticancer immunity that can lyse target cancer cells in humans. Pexa-Vec (pexastimogene devacirepvec; JX-594) is a targeted oncolytic and immunotherapeutic vaccinia virus engineered to express human granulocyte-macrophage colony-stimulating factor (GM-CSF). Pexa-Vec demonstrated replication, GM-CSF expression, and tumor responses in previous phase 1 trials. We now evaluated whether Pexa-Vec induced functional anticancer immunity both in the rabbit VX2 tumor model and in patients with diverse solid tumor types in phase 1. Antibody-mediated complement-dependent cancer cell cytotoxicity (CDC) was induced by intravenous Pexa-Vec in rabbits; transfer of serum from Pexa-Vec-treated animals to tumor-bearing animals resulted in tumor necrosis and improved survival. In patients with diverse tumor types treated on a phase 1 trial, CDC developed within 4 to 8 weeks in most patients; normal cells were resistant to the cytotoxic effects. T lymphocyte activation in patients was evidenced by antibody class switching. We determined that patients with the longest survival duration had the highest CDC activity, and identified candidate target tumor cell antigens. Thus, we demonstrated that Pexa-Vec induced polyclonal antibody-mediated CDC against multiple tumor antigens both in rabbits and in patients with diverse solid tumor types.
Do etiologies of premature ovarian aging (POA) mimic those of premature ovarian failure (POF)? (2009)

Presumed underlying etiologies with POA follow a similar distribution pattern as reported for POF. POA and POF may, therefore, represent a continuum in phenotypical expression of different etiologies of premature ovarian senescence. Like POF, POA should be considered reason to investigate underlying etiologies.
Adhesion of Memory Lymphocytes to Vascular Cell Adhesion Molecule-1–Transduced Human Vascular Endothelial Cells Under Simulated Physiological Flow Conditions In Vitro (1996)

The accumulation of mononuclear leukocytes is an early and persistent finding in atherosclerotic plaques. These mononuclear leukocytes are mostly monocyte-derived, but up to 20% are lymphocytes, predominantly CD4+ CD45RO+ (memory) T cells. To evaluate the potential of adenovirus vectors for studies of mononuclear leukocyte recruitment in vitro, we studied the effects of adenovirus vectors per se on human umbilical vein endothelial cells (HUVECs), a well-characterized in vitro model of vascular endothelium. A recombinant adenovirus containing the seven-domain isoform of rabbit vascular cell adhesion molecule-1 (rVCAM-1) was constructed and used to study lymphocyte adhesion under defined laminar flow conditions in transduced HUVEC monolayers. No increase in basal HUVEC surface expression of the inducible endothelial adhesion molecules and markers of activation, E-selectin and VCAM-1, was noted across a broad range of multiplicity of infection. A modest dose-dependent increase in surface intercellular adhesion molecule-1 expression was detectable by flow cytometry at an MOI of > 30 plaque-forming units per cell. Under defined laminar flow from 1.5 to 0.5 dyne/cm2, the adenovirus vector carrying rVCAM-1 mediated stable adhesion of both a Jurkat T-cell line and primary human CD4+ CD45RO+ (memory) T cells. Monoclonal antibodies to alpha 4-integrin or rVCAM-1 abolished adhesion, whereas monoclonal antibodies to CD18 or P-selectin had no effect. We conclude that adenoviral gene transfer in useful for studies of VCAM-1-dependent leukocyte adhesion in vitro and that endothelial expression of VCAM-1 alone, in the absence of over endothelial cell activation, is sufficient under simulated physiological flow conditions to support adhesion of memory T cells, the predominant lymphocyte subset in atherosclerotic plaque.
Emergent Human Pathogen Simian Virus 40 and Its Role in Cancer (2004)

The polyomavirus simian virus 40 (SV40) is a known oncogenic DNA virus which induces primary brain and bone cancers, malignant mesothelioma, and lymphomas in laboratory animals. Persuasive evidence now indicates that SV40 is causing infections in humans today and represents an emerging pathogen. A meta-analysis of molecular, pathological, and clinical data from 1,793 cancer patients indicates that there is a significant excess risk of SV40 associated with human primary brain cancers, primary bone cancers, malignant mesothelioma, and non-Hodgkin's lymphoma. Experimental data strongly suggest that SV40 may be functionally important in the development of some of those human malignancies. Therefore, the major types of tumors induced by SV40 in laboratory animals are the same as those human malignancies found to contain SV40 markers. The Institute of Medicine recently concluded that "the biological evidence is of moderate strength that SV40 exposure could lead to cancer in humans under natural conditions." This review analyzes the accumulating data that indicate that SV40 is a pathogen which has a possible etiologic role in human malignancies. Future research directions are considered.
Genetic analysis of the promoter region of the Bacillus subtilis alpha-amylase gene (1989)

The amyR2 allele of the Bacillus subtilis alpha-amylase cis-regulatory region enhances production of amylase and transcription of amyE, the structural gene, by two- to threefold over amyR1. The amylase gene bearing each of these alleles was cloned on plasmids of about 10 to 15 copies per chromosome. Transcription of the cloned amylase gene by each amyR allele was activated at the end of exponential growth and was subject to catabolite repression by glucose. The amount of amylase produced was roughly proportional to the copy number of the plasmid, and cells containing the amyR2-bearing plasmid, pAR2, produced two- to threefold more amylase than cells with the amyR1 plasmid, pAMY10. Deletion of DNA 5' to the alpha-amylase promoter, including deletion of the A + T-rich inverted repeat found in amyR1 and amyR2, had no effect on expression or transcription of alpha-amylase. Deletion of DNA 3' to the amyR1 promoter did not impair temporal activation of chloramphenicol acetyltransferase in amyR1-cat-86 transcriptional fusions, but catabolite repression was abolished. When an 8-base-pair linker was inserted in pAMY10 at the same site from which the 3' deletion was made, amylase expression doubled and was repressed less by glucose. Both the deletion and the insertion disrupted four bases at the 3' end of the putative amylase operator region. Site-directed mutagenesis was used to change bases in the promoter-operator region of amyR1 to their amyR2 counterparts. Either change alone increased amylase production twofold, but only the change at +7, next to the linker insertion of 3' deletion site, yielded the increased amylase activity in the presence of glucose that is characteristic of the amyR2 strain. The double mutant behaved most like strains carrying the amyR2 allele.
Error bounds for convolutional codes and an asymptotically optimum decoding algorithm (1967)

The probability of error in decoding an optimal convolutional code transmitted over a memoryless channel is bounded from above and below as a function of the constraint length of the code. For all but pathological channels the bounds are asymptotically (exponentially) tight for rates above <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R_{0}</tex> , the computational cutoff rate of sequential decoding. As a function of constraint length the performance of optimal convolutional codes is shown to be superior to that of block codes of the same length, the relative improvement increasing with rate. The upper bound is obtained for a specific probabilistic nonsequential decoding algorithm which is shown to be asymptotically optimum for rates above <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R_{0}</tex> and whose performance bears certain similarities to that of sequential decoding algorithms.
Effects of Lipid Lowering by Pravastatin on Progression and Regression of Coronary Artery Disease in Symptomatic Men With Normal to Moderately Elevated Serum Cholesterol Levels (1995)

In symptomatic men with significant coronary atherosclerosis and normal to moderately elevated serum cholesterol, less progression of coronary atherosclerosis and fewer new cardiovascular events were observed in the group of patients treated with pravastatin than in the placebo group.
Safety of fluralaner oral solution, a novel systemic antiparasitic treatment for chickens, in laying hens after oral administration via drinking water (2017)

Oral administration of fluralaner via drinking water at the recommended treatment dose (0.5 mg/kg body weight twice at 1-week interval), is well tolerated and has a high safety margin up to an overall dose of 15 times the recommended one (5 times the daily dose given 3 times the number of days) in healthy adult laying hens. Based on the present results, the use of the new mite treatment based on fluralaner administered via drinking water is expected to be safe for laying hens under industrial conditions, and to have no negative impact on their egg quality and production.
Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma (2004)

Pathogenetic mechanisms of hepatocellular carcinoma (HCC) are still unclear and new tools for diagnostic and therapeutic purposes are ongoing. We have assessed whether squamous cell carcinoma antigen (SCCA), a serpin overexpressed in neoplastic cells of epithelial origin, is also expressed in liver cancer. Squamous cell carcinoma antigen was evaluated by immunohistochemistry in 65 HCCs of different aetiology and in 20 normal livers. Proliferative activity was assessed using MIB-1 antibody. In 18 surgical samples, tumour and nontumour liver tissue was available for SCCA cDNA amplification and sequencing. Squamous cell carcinoma antigen was detected in 55 out of 65 (85%) tumour specimens, but in none of the 20 controls. In the majority of the cases, the positive signal was found in the cytoplasm of more than 50% of the hepatocytes. Low or undetectable SCCA (score<or=1) was associated to lower MIB-1 labelling index, compared to cases with SCCA score >or=2 (mean+/-s.d.: 2%+/-2.4 vs 7.5%+/-10.3, P<0.05). Squamous cell carcinoma antigen mRNA could be directly sequenced in 14 out of 18 liver tumours but in none of the corresponding nontumour samples. From sequence alignment, a novel SCCA1 variant (G(351) to A) was identified in five cases, while SCCA1 was revealed in six cases and SCCA2 in three cases. In conclusion, SCCA variants are overexpressed in HCC, independently of tumour aetiology. A novel SCCA1 variant has been identified in one third of liver tumours.
Cytotoxicity of lymphocytes from patients with cancer of the urinary bladder: Detection by A 3H‐proline microcytotoxicity test (1974)

Abstract Human lymphocytes (purified from defibrinated venous blood using gelatin sedimentation, nylon column incubation, and Tris NH 4 Cl lysis of contaminating erythrocytes) were tested for cytotoxicity (CTX) against T24 cells derived from a carcinoma of the bladder and against cell cultures derived from other tissues. The CTX was assessed in a modified microcytotoxicity test (MCT) where loss of 3 H‐proline prelabelled monolayer target cells from the surface of micro‐wells indicates destruction of these cells. The number of target cells that remained attached after incubation with lymphocytes (measured as residual 3 H‐counts) was compared to the number that remained attached after incubation with control lymphocytes. The results were classified into three categories: (1) specific CTX (destruction only of T24 cells); (2) non‐specific CTX (destruction ofT24 cells as well as other target cells); and (3) negative (no destruction of any type of target cell). Specific CTX for T24 cells was seen more often with lymphocytes from bladder cancer patients (10/27) than from other patients and normal individuals (2/49) (p &lt;0.001) which suggests that this is a disease‐related phenomenon. By contrast, non‐specific CTX occurred with equal frequency amopg bladder patients (6/27) and other patients (9/36), although less frequently among normal individuals (0/13). In addition, lymphocytes that showed specific CTX for T24 cells were found more often in patients with early or superficial bladder cancer (8/15) and less often in patients with advanced bladder cancer (2/12). These results are in agreement with those obtained by others who used the standard MCT that measures target‐cell destruction and influences on target‐cell proliferation.
Syngeneic monoclonal internal image anti-idiotopes as prophylactic vaccines. (1986)

A syngeneic monoclonal anti-idiotope that behaves as an internal image of the mammalian reovirus type 3 cellular attachment protein (viral hemagglutinin) was used in the syngeneic host for the induction of a prophylactic anti-viral antibody response. These studies were performed without the aid of co-stimulation by viral antigens. The high stringency of this system enables us to define the maximum constraints on the use of anti-idiotopes as anti-viral vaccines. We have used the murine BALB/c monoclonal IgM anti-idiotope 87.92.6 to study the idiotope and antigen specificity, kinetics, dose dependence, adjuvant, carrier, and valency requirements of anti-idiotope-induced anti-viral antibody responses. These studies show that the production of high titer neutralizing antibody requires a lengthy (60 day) immunization protocol, which includes the use of adjuvant and multivalent anti-idiotope, and is dependent on anti-idiotope concentrations of greater than 50 micrograms. When administered in this manner anti-idiotope can stimulate serotype-specific antibody responses across species barriers at levels comparable with those obtained after inoculation with virus. The practical efficacy of these reagents and procedures is documented by the ability of maternal immunization with anti-idiotope to confer complete protection in neonates from a potentially lethal reovirus type 3 viral infection.
T-bet Regulates Metastasis Rate in a Murine Model of Primary Prostate Cancer (2004)

The local progression of primary tumors is extrinsically controlled by type 1 immune responses, particularly via the cytokine IFN-gamma, whose secretion is highly dependent on helper T cells. The T-box transcription factor T-bet (Tbx21) plays a critical role in the development of type 1 helper T cells and is essential for the production of IFN-gamma. Here, the T-bet pathway in the autochthonous transgenic adenocarcinoma mouse prostate model is demonstrated to have only a modest effect on the characteristics of primary prostate cancers but rather exerts a significant suppressor function in the development of metastatic disease.
THE ANALYSIS OF NUCLEAR MAGNETIC RESONANCE SPECTRA: V. THE ANALYSIS OF DECEPTIVELY SIMPLE SPECTRA (1961)

The analyses of the ABX, A 2 X 2 , and ABXY types of spectra are discussed in detail under the conditions for which the observed spectra give less than the theoretical number of transitions. These conditions for which an observed spectrum is deceptively simple are derived from the general analyses, and experimental examples of such spectra are given.
Molecular basis for improved gene silencing by Dicer substrate interfering RNA compared with other siRNA variants (2013)

The canonical exogenous trigger of RNA interference (RNAi) in mammals is small interfering RNA (siRNA). One promising application of RNAi is siRNA-based therapeutics, and therefore the optimization of siRNA efficacy is an important consideration. To reduce unfavorable properties of canonical 21mer siRNAs, structural and chemical variations to canonical siRNA have been reported. Several of these siRNA variants demonstrate increased potency in downstream readout-based assays, but the molecular mechanism underlying the increased potency is not clear. Here, we tested the performance of canonical siRNAs and several sequence-matched variants in parallel in gene silencing, RNA-induced silencing complex (RISC) assembly, stability and Argonaute (Ago) loading assays. The commonly used 19mer with two deoxythymidine overhangs (19merTT) variant performed similarly to canonical 21mer siRNA. A shorter 16mer variant (16merTT) did not perform comparably in our assays. Dicer substrate interfering RNA (dsiRNA) demonstrated better gene silencing by the guide strand (target complementary strand), better RISC assembly, persistence of the guide strand and relatively more loading of the guide strand into Ago. Hence, we demonstrate the advantageous properties of dsiRNAs at upstream, intermediate and downstream molecular steps of the RNAi pathway.
Surface grammatical analysis for the extraction of terminological noun phrases (1992)

LEXTER is a software package for extracting terminology. A corpus of French language texts on any subject field is fed in, and LEXTER produces a list of likely terminological units to be submitted to an expert to be validated. To identify the terminological units, LEXTER takes their form into account and proceeds in two main stages: analysis, parsing. In the first stage, LEXTER uses a base of rules designed to indentify frontier markers in view to analysing the texts and extracting maximal-length noun phrases. In the second stage, LEXTER parses these maximal-length noun phrases to extract subgroups which by virtue of their grammatical structure and their place in the maximal-length noun phrases are likely to be terminological units. In this article, the type of analysis used (surface grammatical analysis) is highlighted, as the methodological approach adopted to adapt the rules (experimental approach).
Metal deposition from a supported metal film using an excimer laser (1986)

A method for the direct writing of metal features from a metal film supported on an optically transparent substrate using a single pulse from a high-energy excimer laser (193 nm) is presented. The technique eliminates the need for gas-phase precursors in many cases and is an inherently clean process. Results of copper depositions onto silicon substrates are shown to exemplify the technique and a mechanism for the process is proposed.
Alkylation of the dianion of .beta.-keto esters (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlkylation of the dianion of .beta.-keto estersLarry WeilerCite this: J. Am. Chem. Soc. 1970, 92, 22, 6702–6704Publication Date (Print):November 1, 1970Publication History Published online1 May 2002Published inissue 1 November 1970https://doi.org/10.1021/ja00725a088RIGHTS & PERMISSIONSArticle Views1351Altmetric-Citations93LEARN 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 (407 KB) Get e-Alerts Get e-Alerts
Expression of PD-L1 on Canine Tumor Cells and Enhancement of IFN-γ Production from Tumor-Infiltrating Cells by PD-L1 Blockade (2014)

Programmed death 1 (PD-1), an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1), its ligand, together induce the "exhausted" status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1-expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed.