gebhart/patrepeval huggingface dataset:
Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin‐like growth factor‐1 (1995)

Autocrine activation of the epidermal growth factor (EGF) receptor on keratinocytes has been recognized as an important growth regulatory mechanism involved in epithelial homeostasis, and, possibly, hyperproliferative diseases. Insulin-like growth factor (IGF)-1 and insulin have been shown to be paracrine keratinocyte mitogens that bind to the type I IGF receptor which is expressed on actively proliferating keratinocytes in situ. In this report, we demonstrate that IGF-1/insulin induced production of keratinocyte-derived autocrine growth factors that bind to the EGF receptor. Increased steady-state mRNA levels for transforming growth factor alpha (TGF-alpha) and for amphiregulin (AR) were observed upon incubation of keratinocytes with mitogenic concentrations of IGF-1. IGF-1 also induced production and secretion of TGF-alpha and AR proteins as detected by immunoassays. An EGF receptor antagonistic monoclonal antibody abolished the mitogenic effect of IGF-1 on cultured keratinocytes. These results suggest that stimulation of keratinocyte growth of IGF-1 requires activation of an EGF receptor-mediated autocrine loop.
Integrative molecular characterization of malignant pleural mesothelioma (2021)

Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. SIGNIFICANCE: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expresssion of the immune-checkpoint gene VISTA in epithelioid MPM.
[Characteristics of tuberculosis running with HIV infection]. (2004)

Four clinical models of TB/HIV onset and course are suggested.
Dehydropolymerization of bis- and tris(silyl)arenes to highly crosslinked disilanylenearylene polymers, catalyzed by [(.eta.5-C5H5)(.eta.5-C5Me5)ZrH2]2 (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDehydropolymerization of bis- and tris(silyl)arenes to highly crosslinked disilanylenearylene polymers, catalyzed by [(.eta.5-C5H5)(.eta.5-C5Me5)ZrH2]2Hee Gweon Woo, John F. Walzer, and T. Don TilleyCite this: Macromolecules 1991, 24, 26, 6863–6866Publication Date (Print):December 1, 1991Publication History Published online1 May 2002Published inissue 1 December 1991https://pubs.acs.org/doi/10.1021/ma00026a013https://doi.org/10.1021/ma00026a013research-articleACS PublicationsRequest reuse permissionsArticle Views266Altmetric-Citations45LEARN 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-Alertsclose Get e-Alerts
High Throughput Kinetic Profiling Approach for Covalent Binding to Peptides: Application to Skin Sensitization Potency of Michael Acceptor Electrophiles (2009)

Research aimed at nonanimal approaches to provide the relevant information needed for the effective assessment of skin sensitization, for both hazard characterization and risk assessment purposes, is currently an area of high activity, stimulated by regulatory initiatives related to chemicals used in consumer products. The ability of a chemical to react covalently with protein or peptide nucleophiles in the skin is recognized as the key determinant in determining sensitization potency, and initiatives to develop peptide reactivity assays to replace animal testing have been undertaken recently. This paper describes a high throughput kinetic profiling (HTKP) approach, developed as an extension of a published standard assay, with the aim of providing a quantitatively robust end point in the form of a kinetic profile from which reactivity to a model peptide can be quantified in the form of second order rate constants. The approach allows solubility issues to be identified and overcome; these are frequently encountered, but can often go undetected, in aqueous reactivity assays with organic compounds of interest in the skin sensitization context. Using rate constants determined by the HTKP approach we have obtained a quantitative mechanistic model for the Michael acceptor reaction mechanistic domain, relating the sensitization potency in the murine local lymph node assay to the rate constant. The observation that the correlation is not improved by incorporation of a hydrophobicity term has implications regarding the nature and location of the skin nucleophile whose reaction leads to sensitization by Michael acceptor electrophiles.
A Strategic Planning Approach to Tourism Development in Rural Communities (1992)

Rural tourism planners have called for more consideration to be given to potential social and environmental costs associated with tourism development. This paper demonstrates a process of developing a tourism strategic plan with goals consistent with the limitations imposed by the social and environmental conditions of the destination area. It outlines the seven sequential steps of a rural tourism planning approach. A strategic planning process of inventorying attractions, competitive analysis, assimilating resident, business leader and natural resource advocate input, using a Delphi approach to work toward consensus, testing ideas with potential or existing tourists and monitoring quality of life and visitor satisfaction is summarized. Although most of· the individual steps of this approach have been applied in different tourism planning settings, the full strategic planning approach where this information is integrated into an applied development plan has yet to be implemented.
Plasmonic resonance energy transfer-based nanospectroscopy for sensitive and selective detection of 2,4,6-trinitrotoluene (TNT) (2010)

Here we report sensitive and selective detection of TNT based on plasmonic resonance energy transfer from a gold nanoplasmonic probe to conjugated target TNT molecules, leading to quenching on the Rayleigh scattering spectrum of the probe.
A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies (2019)

Immunotherapy that targets <i>N</i>-linked glycans has not yet been developed due in large part to the lack of specificity of <i>N</i>-linked glycans between normal and malignant cells. <i>N</i>-Glycan chains are synthesized by the sequential action of glycosyl transferases in the Golgi apparatus. It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively. It has long been known that <i>N</i>-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate <i>N</i>-acetylglucosaminephosphotransferase 1 (DPAGT1). Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of <i>N</i>-linked glycans in their growth progressions. Recently, we discovered that an anti-<i>Clostridium difficile</i> molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC<sub>50</sub> value of 0.25 μM. It was confirmed that APPB inhibits <i>N</i>-glycosylation of β-catenin at 2.5 nM concentration. A sharp difference between APPB and tunicamycin was that the hemolytic activity of APPB is significantly attenuated (IC<sub>50</sub> > 200 μM RBC). Water solubility of APPB is >350-times greater than that of tunicamycin (78.8 mg/mL for APPB, <0.2 mg/mL for tunicamycin). A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (<i>e.g</i>. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations. <i>In vitro</i> metabolic stability using rat liver microsomes indicated that a half-life (<i>t</i> <sub>1/2</sub>) of APPB is sufficiently long (>60 min) for <i>in vivo</i> studies (PK/PD, safety profiles, and <i>in vivo</i> efficacy) using animal models. We have refined all steps in the previously reported synthesis for APPB for larger-scale. This article summarizes protocols of gram-scale synthesis of APPB and its physicochemical data, and a convenient DPAGT1 assay. •Remember that the abstract is what readers see first in electronic abstracting & indexing services.•This is the advertisement of your article. Make it interesting, and easy to be understood.•Be accurate and specific, keep it as brief as possible.
Representing control in the presence of first-class continuations (1990)

Languages such as Scheme and Smalltalk that provide continuations as first-class data objects present a challenge to efficient implementation. Allocating activation records in a heap has proven unsatisfactory because of increased frame linkage costs, increased garbage collection overhead, and decreased locality of reference. However, simply allocating activation records on a stack and copying them when a continuation is created results in unbounded copying overhead. This paper describes a new approach based on stack allocation that does not require the stack to be copied when a continuation is created and that allows us to place a small upper bound on the amount copied when a continuation is reinstated. This new approach is faster than the naive stack allocation approach, and it does not suffer from the problems associated with unbounded copying. For continuation-intensive programs, our approach is at worst a constant factor slower than the heap allocation approach, and for typical programs, it is significantly faster. An important additional benefit is that recovery from stack overflow is handled gracefully and efficiently.
Comparison between Two Methods in the Determination of Circulating Chromogranin A in Neuroendocrine Tumors (NETs): Results of a Prospective Multicenter Observational Study (2005)

Several methods for analyzing CgA using either monoclonal or polyclonal antibodies have been developed, which differ in their diagnostic performance. The present paper describes the results of a prospective multicenter study aimed at comparing the clinical value of the two most widely used commercially available CgA assay kits in patients affected by neuroendocrine tumors (NETs). Two hundred sixty-one patients from 40 different centers and 99 healthy subjects were evaluated. CgA levels were measured with two different methods, a two-step immunoradiometric assay (IRMA) and an enzyme-linked immunosorbent assay (ELISA). CgA was measured centrally by two reference laboratories, one of which used IRMA and the other ELISA, and it was measured by the participating institutions with the method routinely used by each of them. The major findings of the present study were: (i) the two assays for the determination of CgA present good diagnostic performance; (ii) both assays are robust and guarantee comparable results when applied in different settings (central vs local laboratory); (iii) the negative/positive cutoff points (87 ng/mL for IRMA and 21.3 U/L for ELISA) were established according to standardized criteria; (iv) the results obtained with the two assays in basal clinical samples of patients affected by NETs show an apparently satisfactory correlation (rs = 0.843, p < 0.0001). However, a possibly clinically meaningful 36% discordance rate was found. These findings support the hypothesis that the two CgA kits might provide partially different information.
Quality characteristics in rice by near-infrared reflectance analysis of whole-grain milled samples (1996)

Various physical and chemical tests exist to assess the cooking and processing characteristics of rice. As new lines of rice are developed in the United States and elsewhere, plant breeders routinely test for amylose content, alkali spreading value (an indicator of gelatinization temperature), protein content, viscosity properties of the flour-water paste, and the appearance of milled grains (whiteness, transparency, and degree of milling). A study was undertaken to determine the extent to which near-infrared reflectance (NIR) spectroscopy on whole-grain milled rice could be used to measure such characteristics. Samples of U.S. rices (n = 196) from advanced breeders' lines and commercial releases, representing conventional and specialty short-, medium-, and long-grain classes, were milled and scanned in the visible and near-IR regions (400-2,498 nm). Reference chemical and physical analyses were also performed on each sample. Results of partial least squares modeling indicated that reasonably accurate models were attained for apparent amylose content (standard error of prediction [SEP] = 1.3 percentage units ; coefficient of determination on the validation set [r 2 ] = 0.89), protein content (SEP = 0.13 percentage units, r 2 = 0.97), whiteness (SEP = 0.60 percent reflectance, r 2 = 0.97), transparency (SEP = 0.15 percent transmittance, r 2 = 0.93), and milling degree (SEP = 2.7 dimensionless units on a 0-199 scale, r 2 = 0.97). To a lesser extent, alkali spreading value could be modeled by NIR (SEP = 0.43 units on a 2-7 scale, r 2 = 0.82), however, this accuracy is probably sufficient for initial screening in breeding programs. Conversely, models for the five flour paste viscosity properties recorded by a rapid visco analyzer (RVA) were not sufficiently accurate (r 2 < 0.75) to warrant replacement of the RVA procedure with an NIR model. Reducing the sample size for NIR scanning from approximately 100 to approximately 8 g did not significantly affect the model performance of any constituent.
A homogeneous method to quantify mRNA levels: a hybridization of RNase protection and scintillation proximity assay technologies (1997)

A novel method to measure mRNA levels has been developed by combining the detection capabilities of RNase protection (RPA) with the quantification advantages of scintillation proximity assay (SPA) technology. Sample processing is reduced to the addition of a single reagent post RNase digestion. As a model system, the inducible expression of rat apolipoprotein-A1 mRNA has been measured by both traditional gel-based RPAs and the SPA-based RPA assay. Results demonstrate that the ribonuclease protection proximity assay (RiPPA) faithfully reproduces the gel-based results and is at least as sensitive as many existing methods.
Amyloid Beta Resistance in Nerve Cell Lines Is Mediated by the Warburg Effect (2011)

Amyloid beta (Aβ) peptide accumulation in the brains of patients with Alzheimer's disease (AD) is closely associated with increased nerve cell death. However, many cells survive and it is important to understand the mechanisms involved in this survival response. Recent studies have shown that an anti-apoptotic mechanism in cancer cells is mediated by aerobic glycolysis, also known as the Warburg effect. One of the major regulators of aerobic glycolysis is pyruvate dehydrogenase kinase (PDK), an enzyme which represses mitochondrial respiration and forces the cell to rely heavily on glycolysis, even in the presence of oxygen. Recent neuroimaging studies have shown that the spatial distribution of aerobic glycolysis in the brains of AD patients strongly correlates with Aβ deposition. Interestingly, clonal nerve cell lines selected for resistance to Aβ exhibit increased glycolysis as a result of activation of the transcription factor hypoxia inducible factor 1. Here we show that Aβ resistant nerve cell lines upregulate Warburg effect enzymes in a manner reminiscent of cancer cells. In particular, Aβ resistant nerve cell lines showed elevated PDK1 expression in addition to an increase in lactate dehydrogenase A (LDHA) activity and lactate production when compared to control cells. In addition, mitochondrial derived reactive oxygen species (ROS) were markedly diminished in resistant but not sensitive cells. Chemically or genetically inhibiting LDHA or PDK1 re-sensitized resistant cells to Aβ toxicity. These findings suggest that the Warburg effect may contribute to apoptotic-resistance mechanisms in the surviving neurons of the AD brain. Loss of the adaptive advantage afforded by aerobic glycolysis may exacerbate the pathophysiological processes associated with AD.
Spectrophotometric Calibration of pH Electrodes in Seawater Using Purified m-Cresol Purple (2012)

This work examines the use of purified meta-cresol purple (mCP) for direct spectrophotometric calibration of glass pH electrodes in seawater. The procedures used in this investigation allow for simple, inexpensive electrode calibrations over salinities of 20-40 and temperatures of 278.15-308.15 K without preparation of synthetic Tris seawater buffers. The optimal pH range is ∼7.0-8.1. Spectrophotometric calibrations enable straightforward, quantitative distinctions between Nernstian and non-Nernstian electrode behavior. For the electrodes examined in this study, both types of behavior were observed. Furthermore, calibrations performed in natural seawater allow direct determination of the influence of salinity on electrode performance. The procedures developed in this study account for salinity-induced variations in liquid junction potentials that, if not taken into account, would create pH inconsistencies of 0.028 over a 10-unit change in salinity. Spectrophotometric calibration can also be used to expeditiously determine the intercept potential (i.e., the potential corresponding to pH 0) of an electrode that has reliably demonstrated Nernstian behavior. Titrations to ascertain Nernstian behavior and salinity effects can be undertaken relatively infrequently (∼weekly to monthly). One-point determinations of intercept potential should be undertaken frequently (∼daily) to monitor for stable electrode behavior and ensure accurate potentiometric pH determinations.
Ala217 is Important for the Catalytic Function and Autoactivation of Prostate‐Specific Human Kallikrein 2 (1997)

Prostate-specific human kallikrein, hK2, is a serine protease found in prostate tissues that has 78% amino acid sequence identity with prostate-specific antigen (PSA). We have previously reported the affinity purification of hK2 heterologously expressed in a hamster cell line and demonstrated an arginine-restricted substrate specificity. Here, we describe the cloning, expression, purification, and enzymatic activity of a mutant form of hK2 containing an alanine to valine substitution at residue 217 ([Val217]hK2). This mutant form was secreted into the serum-free spent media of recombinant cells as the stable proenzyme form ([Val217]phK2). Mild trypsin treatment was used to convert [Val217]phK2 to the active form, which had reduced catalytic function compared to the wild-type hK2. Kinetic studies using the chromogenic substrate D-H-Pro-Phe-Arg-4-nitroanilide showed that [Val217]hK2 has significantly decreased substrate binding, with a K(m) of 4200 microM compared to 11 microM for wild-type hK2. The k(cat) for [Val217]hK2 was more than 100-fold lower than for hK2. hK2, but not [Val217]hK2, was able to activate [Val217]phK2. [Val217]hK2 also showed altered specificity on a synthetic peptide substrate compared to wild-type hK2, which exhibited partial hydrolysis at a PSA chymotrypsin-like cleavage site as well as the trypsin-like site cleaved by hK2. These results indicate that Ala217 is a key residue affecting the catalytic properties of hK2.
A Closed Form Solution to Multi-View Low-Rank Regression (2015)

Real life data often includes information from different channels. For example, in computer vision, we can describe an image using different image features, such as pixel intensity, color, HOG, GIST feature, SIFT features, etc.. These different aspects of the same objects are often called multi-view (or multi-modal) data. Low-rank regression model has been proved to be an effective learning mechanism by exploring the low-rank structure of real life data. But previous low-rank regression model only works on single view data. In this paper, we propose a multi-view low-rank regression model by imposing low-rank constraints on multi-view regression model. Most importantly, we provide a closed-form solution to the multi-view low-rank regression model. Extensive experiments on 4 multi-view datasets show that the multi-view low-rank regression model outperforms single-view regression model and reveals that multi-view low-rank structure is very helpful.
Copper- and Borinic Acid-catalyzed Propargylic Etherification of Propargylic Carbonates with Benzyl Alcohols (2018)

Propargylic substitution reactions have offered useful synthetic methods because further transformations based on the alkyne moiety in the propargylic substituted products was readily achieved to construct more complex organic compounds. A large number of works have been devoted to enantioselective propargylic substitution reactions with a variety of nucleophiles. However, successful examples of the use of alcohols as nucleophiles have been quite limited until now. To achieve utilization of aliphatic alcohols, herein we report the use of combined catalysis of a copper-pybox complex and a borinic acid. In this catalytic system, aliphatic alcohols such as benzyl alcohol derivatives were successfully applied to afford the corresponding propargylic etherified products in good yields with high enantioselectivities.
Cocoa butter extenders from Kokum (<i>Garcinia indica</i>) and Phulwara (<i>Madhuca butyracea</i>) butter (1994)

Abstract Cocoa butter extenders, suitable for use in chocolate and confectionery, were prepared from Kokum fat and a Phulwara butter fraction. The latter fraction was prepared from Phulwara butter by two‐stage dry fractionation and blended with Kokum fat in selected proportions to obtain a series of hard butters with different melting profiles. The blends with higher proportions of Kokum fat were harder and hence may find application in warm climates. The blends with higher proportions of Kokum fat were harder and hence may find application in warm climates. The blends had solidification properties, fatty acid and triacylglycerol compositions similar to those of cocoa butter. In addition, they had narrow melting ranges like cocoa butter, and they were compatible with cocoa butter and have tolerance toward milk fat.