gebhart/patrepeval huggingface dataset:
Adenosine inhibits the adhesion of anti-CD3-activated killer lymphocytes to adenocarcinoma cells through an A3 receptor. (1994)

We have investigated the hypothesis that adenosine, a purine nucleoside produced within hypoxic regions of solid tumors, may interfere with the recognition of tumor cells by cytolytic effector cells of the immune system. We measured the adhesion of murine spleen-derived anti-CD3-activated killer (AK) lymphocytes to syngeneic MCA-38 colon adenocarcinoma cells in a model system. Adenosine, in the presence of the adenosine deaminase inhibitor coformycin to prevent the breakdown of adenosine, inhibited adhesion by up to 60%. The inhibitory effect of adenosine was exerted on the AK cells and not on the MCA-38 targets. The response to adenosine was generated at the cell surface, since the inhibition of adhesion was not abrogated by S-(4-nitrobenzyl)-6-thioinosine or dipyridamole, which block adenosine uptake. The inhibition of adhesion due to adenosine was not blocked by either the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine or the A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine. This suggested that a non-A1, A2 receptor might be involved. The relative order of potencies of adenosine and common analogues was: 5'-N-ethylcarboxamidoadenosine = adenosine = (R)-phenylisopropyladenosine > N6-cyclopentyladenosine > 2-chloro-N6-cyclopentyladenosine = 2-p-(2- carboxyethyl)phenethylamino-5'-N-ethyl-carboxamidoadenosine. This agonist potency profile was again inconsistent with either the A1 or the A2 receptor subtype but indicated that the recently described A3 receptor subtype might be responsible for the inhibition of adhesion. Consistent with this suggestion, aminophenylethyladenosine, an adenosine analogue that binds with high affinity to A3 receptors, inhibited the adhesion of AK cells to MCA-38 tumor cells with high potency (50% inhibitory concentration approximately 1 nM). Adenosine, therefore, interferes with the AK cell recognition of colorectal tumor targets by acting through an A3 receptor on the effector cells. We suggest that this mechanism of immunosuppression, secondary to tissue hypoxia, may be important in the resistance of colorectal and other solid cancers to immunotherapy.
CD73: A potential biomarker for anti-PD-1 therapy (2015)

In our recent study, we show that tumoral CD73 expression limits the efficacy of anti-PD-1 therapy, and this is rescued by concomitant A2A blockade. Since CD73 is known to be overexpressed in several human cancers and A2A antagonists have undergone clinical trials for Parkinson's Disease, this combination warrants further investigation.
N-Mono- and N,N-Dialkyl-N'-1-naphthylalkylenediamines (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTN-Mono- and N,N-Dialkyl-N'-1-naphthylalkylenediaminesLeslie M. Werbel, David B. Capps, Edward F. Elslager, William Pearlman, Franklin W. Short, Enta A. Weinstein, and Donald F. WorthCite this: J. Med. Chem. 1963, 6, 6, 637–646Publication Date (Print):November 1, 1963Publication History Published online1 May 2002Published inissue 1 November 1963https://doi.org/10.1021/jm00342a005RIGHTS & PERMISSIONSArticle Views250Altmetric-Citations8LEARN 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 (1 MB) Get e-Alertsclose Get e-Alerts
The weight of nations: an estimation of adult human biomass (2012)

Increasing population fatness could have the same implications for world food energy demands as an extra half a billion people living on the earth.
Effect of the pressure drop rate on cell nucleation in continuous processing of microcellular polymers (1995)

Abstract Microllular plastics are cellular polymers characterized by cell densities greater than 10 9 cells/cm 3 and cells smaller than 10 μm. One of the critical steps in the continuous production of microcellular plastics is the promotion of high cell nucleation rates in a flowing polymer matrix. These high nucleation rates can be achieved by first forming a polymer/gas solution followed by rapidly decreasing the solubility of gas in the polymer. Since, in the processing range of interest, the gas solubility in the polymer decreases as the pressure decreases, a rapid pressure drop element, consisting of a nozzle, has been employed as a continuous microcellular nucleation device. In this paper, the effects of the pressure drop rate on the nucleation of cells and the cell density are discussed. The experimental results indicate that both the magnitude and the cell density are discussed. The experimental results indicate that both the magnitude and the rate of pressure drop play a strong role in microcellular processing. The pressure phenomenon affects the thermodynamic instability induced in the polymer/gas solution and the competition between cell nucleation and growth.
Out‐of‐Autoclave Prepreg Processing (2012)

Abstract Out‐of‐autoclave (OOA) preimpregnated (prepreg) materials are a prospective alternative to traditional autoclave (AC) processing, with the potential to reduce processing costs and build structures without size limitations imposed by the AC. OOA prepregs differ from AC‐processed prepregs in that they are designed to be processed only with a vacuum bag and oven curing. This article details the state‐of‐the‐art carbon/epoxy OOA prepreg systems. These systems are able to achieve void levels and mechanical properties similar to that of carbon/epoxy AC‐processed prepregs. In this article, a brief insight into the processing of OOA prepregs is given for the following topics: laminate gas transport, vacuum bagging, tooling, and debulking.
Learning sculpts the spontaneous activity of the resting human brain (2009)

The brain is not a passive sensory-motor analyzer driven by environmental stimuli, but actively maintains ongoing representations that may be involved in the coding of expected sensory stimuli, prospective motor responses, and prior experience. Spontaneous cortical activity has been proposed to play an important part in maintaining these ongoing, internal representations, although its functional role is not well understood. One spontaneous signal being intensely investigated in the human brain is the interregional temporal correlation of the blood-oxygen level-dependent (BOLD) signal recorded at rest by functional MRI (functional connectivity-by-MRI, fcMRI, or BOLD connectivity). This signal is intrinsic and coherent within a number of distributed networks whose topography closely resembles that of functional networks recruited during tasks. While it is apparent that fcMRI networks reflect anatomical connectivity, it is less clear whether they have any dynamic functional importance. Here, we demonstrate that visual perceptual learning, an example of adult neural plasticity, modifies the resting covariance structure of spontaneous activity between networks engaged by the task. Specifically, after intense training on a shape-identification task constrained to one visual quadrant, resting BOLD functional connectivity and directed mutual interaction between trained visual cortex and frontal-parietal areas involved in the control of spatial attention were significantly modified. Critically, these changes correlated with the degree of perceptual learning. We conclude that functional connectivity serves a dynamic role in brain function, supporting the consolidation of previous experience.
The Effect of Capital Structure, Profitability and Dividend Policy on Intrinsic Value of Firm (2017)

Objectives : To investigate the effect of capital structure, profitability and dividend policy to intrinsic value of firm on property and real estate companies listed in Indonesia Stock Exchange. Method/Analysis : The data of this study are analyzed using path analysis at alpha 5%. The population of this study are the property and real estate sector companies listed on Indonesia Stock Exchange from period 2013 to 2015 and the sample are 51 companies. Capital structure and profitability as independent variable, dividend policy as intervening variable and intrinsic value of firm as dependent variable which is the present value of projected free cash flow to firm. Findings : The result of the study finds that capital structure and profitability have significant effect on intrinsic value of firm. Dividend policy have no significant effect on intrinsic value of firm. The results also show that dividend policy is not a mediating variable between capital structure and profitability to intrinsic value of firm. Keywords: Capital Structure, Profitability, Dividend Policy, Intrinsic Value of Firm, Free Cash Flow to Firm
Process parameter Optimization of CNC Turning for Titanium Wrought Alloy (2015)

Optimization of machining parameters is valuable to maintain the accuracy of the components and to minimize the cost of machining. Tool wear and Surface finish are important measure for machining cost and the quality of the machined parts respectively. The present work is an experimental investigation to study the effect of machining parameters on tool wear and surface roughness for turning of VT-20 (titanium wrought alloy). The experiments were conducted as per Taguchi's L9 Orthogonal Array on CNC lathe. Cutting parameters of speed, feed and depth of cut were taken as inputs and machining was done by CNMG 120408 insert. Regression models for the responses were prepared by using MINITAB-16 software. It was found that speed has high influence followed by feed and depth of cut has very low influence in achieving the optimum values for tool wear and surface roughness. Finally, experimental and Regression values of responses were compared, it was found that both values are close to each other hence, the regression models prepared were more accurate and adequate. Keywords—CNC Turning, Titanium wrought alloy, Grey Relational Analysis
Clinical experience with minimally invasive reoperative coronary bypass surgery (1996)

In selected patients reoperative coronary artery bypass grafting can be performed with this minimally invasive approach with a low perioperative morbidity and mortality rate and satisfactory early graft patency rate with good symptomatic improvement.
Cloning and regulation of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis. (1990)

The rate-limiting step in bile acid biosynthesis is catalyzed by the microsomal cytochrome P-450 cholesterol 7 alpha-hydroxylase (7 alpha-hydroxylase). The expression of this enzyme is subject to feedback regulation by sterols and is thought to be coordinately regulated with enzymes in the cholesterol supply pathways, including the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase and synthase. Here we report the purification of rat 7 alpha-hydroxylase and the determination of a partial amino acid sequence. Oligonucleotides derived from peptide sequence were used to clone a full-length cDNA encoding 7 alpha-hydroxylase. DNA sequence analysis of the cDNA revealed a 7 alpha-hydroxylase protein of 503 amino acids with a predicted molecular weight of 56,890 which represents a novel family of cytochrome P-450 enzymes. Transfection of a 7 alpha-hydroxylase cDNA into simian COS cells resulted in the synthesis of a functional enzyme whose activity was stimulated in vitro by the addition of rat microsomal cytochrome P-450 reductase protein. RNA blot hybridization experiments indicated that the mRNA for 7 alpha-hydroxylase is found only in the liver. The levels of this mRNA increased when bile acids were depleted by dietary cholestyramine and decreased when bile acids were consumed. Dietary cholesterol led to an increase in 7 alpha-hydroxylase mRNA levels. The enzymatic activity of 7 alpha-hydroxylase paralleled the observed changes in mRNA levels. These results suggest that bile acids and sterols are able to alter the transcription of the 7 alpha-hydroxylase gene and that this control explains the previously observed feedback regulation of bile acid synthesis.
Virulence and immunity of Staphylococcus aureus BB and certain deficient mutants (1978)

Coagulase-negative and deoxyribonuclease-negative mutants were isolated from Staphylococcus aureus BB by treatment with N-methyl-N'-nitro-N-nitrosoguanidine. Comparison of virulence (50% lethal dose) to mice of these six mutant strains and S. aureus BB was determined by both intravenous and intraperitoneal routes. The ratios of the 50% lethal dose of coagulase-negative mutants to that of the parental strain S. aureus BB ranged from 201 to 403 for intravenous infection and 30.7 to 52.7 for intraperitoneal infection. The virulence of deoxyribonuclease-negative mutants was essentially the same as that of S. aureus BB. When mice were immunized subcutaneously with live S. aureus BB or its deoxyribonuclease-negative mutants, the resulting protection against the intravenous challenge of S. aureus BB was remarkable. The ratios of the 50% lethal dose for the mice that were immunized by these strains to that for the untreated mice extended from 40.1 to 60.6 for intravenous infection and 6.61 to 11.5 for the intraperitoneal route. However, no effect against S. aureus BB challenge was shown in the mice that were immunized with coagulase-negative mutants.
Nucleotide Regulation of Goblet Cells in Human Airway Epithelial Explants: Normal Exocytosis in Cystic Fibrosis (1993)

The regulation of mucin secretion by airway goblet cells is poorly understood and the receptor-based regulatory mechanisms have not been described in human airways. In the present study, we report that extracellular triphosphate nucleotides regulate the rate of granule release from goblet cells in both normal and cystic fibrosis (CF) airway epithelial explants. Explants isolated from nasal and tracheobronchial tissues were mounted in perfusion chambers and the secretory activity was assessed by videomicroscopic determination of degranulation in single goblet cells and by ELISA determination of mucins secreted into the mucosal perfusate. Baseline degranulation was measured at 0.05 degranulation events (DE)/min. In normal goblet cells, mucosal ATP (10(-4) M, n = 17) induced a biphasic secretory response comprising 29.1 +/- 4.9 DE during the first 5 min, with an initial rate of 118.2 +/- 10.2 DE/min. Mucosal UTP (10(-4) M, n = 9) induced a similar response to ATP (initial rate: 89.2 +/- 23.9 DE/min, 17.9 +/- 5.1 DE in 5 min), but mucosal 2-MeSATP was not an effective agonist (initial rate: 1.5 +/- 1.4 DE/min, 2.3 +/- 0.5 DE in 5 min). Determination of mucins by ELISA confirmed that both ATP and UTP induced similar secretory responses but that 2-MeSATP was not effective. In CF explants, mucosal UTP (10(-4) M, n = 6) induced similar responses to those observed in normal tissues (initial rate: 82.5 +/- 27.5 DE/min, 18.8 +/- 4.1 DE in 5 min). We conclude that human nasal and tracheobronchial goblet cells are stimulated by mucosal nucleotides, probably via a 5'-nucleotide receptor, and that this response is unaffected by CF.
Tumor-Induced Immune Suppression ofIn vivoEffector T-Cell Priming Is Mediated by the B7-H1/PD-1 Axis and Transforming Growth Factor β (2008)

We have generated effector T cells from tumor-draining lymph nodes (TDLN) that are efficacious in adoptive immunotherapy. We now examine the effect of concomitant tumors on the generation of effector T cells. We inoculated methylcholanthrene (MCA) 205 in the flanks of normal mice and mice bearing MCA 205 lung metastases. TDLN cells from these mice were activated and expanded in vitro, and adoptively transferred to mice bearing lung metastases. Effector T cells generated from TDLN in mice with only flank tumor mediated potent antitumor activity. However, antitumor efficacy of the effector T cells generated from TDLN in mice with pre-existent lung tumor (cTDLN) was reduced. Phenotyping studies showed that dendritic cells in cTDLN expressed higher levels of B7-H1, whereas cTDLN T cells expressed higher levels of PD-1. The levels of IFNgamma were reduced, and the levels of CD4(+)Foxp3(+) regulatory T cells were increased in cTDLN versus TDLN. The in vitro activation of cTDLN was increased by blocking B7-H1 or transforming growth factor (TGF)-beta. Importantly, we found a synergistic up-regulation of IFNgamma with simultaneous blockade of B7-H1 and TGF-beta that was much greater than observed with TDLN. In vitro activation of cTDLN with anti-B7-H1 and anti-TGF-beta and in vivo administration of these antibodies after adoptive transfer resulted in the abrogation of the suppression associated with cTDLN. These results show a major role for the B7-H1/PD-1 axis and TGF-beta as synergistic suppressive mechanisms in cTDLN. Our data have clinical relevance in the generation of effector T cells in the tumor-bearing host.
Expression of human macrophage metalloelastase gene in hepatocellular carcinoma: Correlation with angiostatin generation and its clinical significance (1998)

Macrophage metalloelastase, a member of the human matrix metalloproteinase family, is believed to play an important role in angiostatin generation, which, in experimental studies, has an antiangiogenic function and is a key molecule in tumor dormancy. However, no clinical studies have been reported regarding the correlation between human macrophage metalloelastase (HME) gene expression and angiostatin production. Therefore, the present study was designed to evaluate the HME messenger RNA (mRNA) expression and angiostatin generation in hepatocellular carcinoma (HCC). Tumorous and contiguous nontumorous tissues were obtained from 40 HCC patients who underwent curative partial hepatectomy. By using Northern blot hybridization, HME mRNA was detected in 25 of the 40 HCC samples and, in all of these cases, the expression in tumorous tissues was stronger than in the nontumorous tissues. In situ hybridization identified the HCC cells as mainly responsible for the signals shown in Northern blot. Angiostatin was detected by Western blot mainly in tumors and showed significant association with HME mRNA expression in tumorous tissues (P = .0008). The patients whose tumors did not express HME mRNA and, thus, did not produce angiostatin, demonstrated poorer survival than those whose tumors showed high expression of HME mRNA and angiostatin generation (P = . 002). The univariate and multivariate analyses revealed that HME mRNA expression is a new and independent variable affecting overall survival (P = .001 and P = .03, respectively). These findings show that the HME gene is expressed in HCC being significantly associated with angiostatin generation by such tumors and that HME mRNA expression may serve as a new molecular prognostic marker in HCC patients after partial hepatectomy.
The role of performance factors in the active avoidance-conditioning deficit in autoimmune mice. (1996)

Prior studies with autoimmune mice demonstrated deficits in 2-way active avoidance conditioning that correlated with the degree of autoimmunity. In this study, autoimmune female NZB x NZW F1 hybrid (B/W) mice were tested in shock-motivated discrimination learning, 1-way avoidance conditioning, and a modified 2-way avoidance task and compared to nonautoimmune female NZW mice. The discrimination and 1-way conditioning results indicated that B/W mice can learn shock-motivated tasks that involve minimal fatigue and no conflict. B/W mice were also able to learn the 2-way avoidance task when it was made easier by increasing conditioned-stimulus cue salience, clarifying contingencies, and increasing trial spacing to decrease possible cognitive, emotional, and physical fatigue. Thus, poor performance in 2-way avoidance appears to be a consequence of altered attention, motivation, or emotionality and can be overcome by altering task parameters.
Multiseeded segmentation using fuzzy connectedness (2001)

Fuzzy connectedness has been effectively used to segment out an object in a badly corrupted image. We generalize the approach by providing a definition which is shown to always determine a simultaneous segmentation of multiple objects. For any set of seed points, the segmentation is uniquely determined by the definition. An algorithm for finding this segmentation is presented and its output is illustrated. The algorithm is fast as compared to other segmentation algorithms in current use. We also report on an evaluation of the accuracy and robustness of the algorithm based on experiments in which several users were repeatedly asked to identify the seed points for the algorithm in a number of images.
The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis. (1994)

We used the lung epithelial cell-specific surfactant protein B (SPB) gene promoter as a model with which to investigate mechanisms involved in transcriptional control of lung-specific genes. In a previous study, we showed that the SPB promoter specifically activated expression of a linked reporter gene in the continuous H441 lung cell line and that H441 nuclear proteins specifically protected a region of this promoter from bp -111 to -73. In this study, we further show that this region is a complex binding site for thyroid transcription factor 1 (TTF-1) and hepatocyte nuclear factor 3 (HNF-3). Whereas TTF-1 bound two highly degenerate and closely spaced sites, HNF-3 proteins bound a TGT3 motif (TGTTTGT) that is also found in several liver-specific gene regulatory regions, where it appears to be a weak affinity site for HNF-3. Point mutations of these binding sites eliminated factor binding and resulted in significant decreases in transfected SPB promoter activity. In addition, we developed a cotransfection assay and showed that a family of lung-specific gene promoters that included the SPB, SPC, SPA, and Clara cell secretory protein (CCSP) gene promoters were specifically activated by cotransfected TTF-1. We conclude that TTF-1 and HNF-3 are major activators of lung-specific genes and propose that these factors are involved in a general mechanism of lung-specific gene transcription. Importantly, these data also show that common factors are involved in organ-specific gene expression along the mammalian foregut axis.
Characterization of single chain antibody targets through yeast two hybrid (2010)

Our method, utilizing the yeast two-hybrid technology and scFv as bait, is a simple yet powerful approach for the detailed characterization of antibody targets. It allows precise domain mapping for linear epitopes, confirmation of non-linear epitopes for conformational sensors, and detection of secondary binding partners. This approach may thus prove to be an elegant and rapid method for the target characterization of newly obtained scFv antibodies. It may be considered prior to any research application and particularly before any use of such recombinant antibodies in clinical medicine.