gebhart/patrepeval huggingface dataset:
Reward Processing by the Opioid System in the Brain (2009)

The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides processed from three protein precursors, proopiomelanocortin, proenkephalin, and prodynorphin. Opioid receptors are recruited in response to natural rewarding stimuli and drugs of abuse, and both endogenous opioids and their receptors are modified as addiction develops. Mechanisms whereby aberrant activation and modifications of the opioid system contribute to drug craving and relapse remain to be clarified. This review summarizes our present knowledge on brain sites where the endogenous opioid system controls hedonic responses and is modified in response to drugs of abuse in the rodent brain. We review 1) the latest data on the anatomy of the opioid system, 2) the consequences of local intracerebral pharmacological manipulation of the opioid system on reinforced behaviors, 3) the consequences of gene knockout on reinforced behaviors and drug dependence, and 4) the consequences of chronic exposure to drugs of abuse on expression levels of opioid system genes. Future studies will establish key molecular actors of the system and neural sites where opioid peptides and receptors contribute to the onset of addictive disorders. Combined with data from human and nonhuman primate (not reviewed here), research in this extremely active field has implications both for our understanding of the biology of addiction and for therapeutic interventions to treat the disorder.
Expanding CRISPR/Cas9 Genome Editing Capacity in Zebrafish Using SaCas9 (2016)

The type II CRISPR/Cas9 system has been used widely for genome editing in zebrafish. However, the requirement for the 5'-NGG-3' protospacer-adjacent motif (PAM) of Cas9 from Streptococcus pyogenes (SpCas9) limits its targeting sequences. Here, we report that a Cas9 ortholog from Staphylococcus aureus (SaCas9), and its KKH variant, successfully induced targeted mutagenesis with high frequency in zebrafish. Confirming previous findings, the SpCas9 variant, VQR, can also induce targeted mutations in zebrafish. Bioinformatics analysis of these new Cas targets suggests that the number of available target sites in the zebrafish genome can be greatly expanded. Collectively, the expanded target repertoire of Cas9 in zebrafish should further facilitate the utility of this organism for genetic studies of vertebrate biology.
Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy (2009)

The aim of adoptive T-cell therapy of cancer is to selectively confer immunity against tumor cells. Autoimmune side effects, however, remain a risk, emphasizing the relevance of a suicide mechanism allowing in vivo elimination of infused T cells. We investigated the use of human CD20 as suicide gene in T-lymphocytes. Potential effects of forced CD20 expression on T-cell function were investigated by comparing CD20- and mock-transduced cytomegalovirus (CMV) specific T cells for cytolysis, cytokine release and proliferation. The use of CD20 as suicide gene was investigated in CMV specific T cells and in T cells genetically modified with an antigen specific T-cell receptor. No effect of CD20 on T-cell function was observed. CD20-transduced T cells with and without co-transferred T-cell receptor were efficiently eliminated by complement dependent cytotoxicity induced by therapeutic anti-CD20 antibody rituximab. The data support the broad value of CD20 as safety switch in adoptive T-cell therapy.
Saponins from aerial parts of alfalfa (Medicago sativa) (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSaponins from aerial parts of alfalfa (Medicago sativa)Georges Massiot, Catherine Lavaud, Veronique Besson, Louisette Le Men-Olivier, and Georges Van BinstCite this: J. Agric. Food Chem. 1991, 39, 1, 78–82Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://pubs.acs.org/doi/10.1021/jf00001a014https://doi.org/10.1021/jf00001a014research-articleACS PublicationsRequest reuse permissionsArticle Views201Altmetric-Citations31LEARN 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
Caveolin-1 Null Mice Are Viable but Show Evidence of Hyperproliferative and Vascular Abnormalities (2001)

Caveolin-1 is the principal structural protein of caveolae membranes in fibroblasts and endothelia. Recently, we have shown that the human CAV-1 gene is localized to a suspected tumor suppressor locus, and mutations in Cav-1 have been implicated in human cancer. Here, we created a caveolin-1 null (CAV-1 -/-) mouse model, using standard homologous recombination techniques, to assess the role of caveolin-1 in caveolae biogenesis, endocytosis, cell proliferation, and endothelial nitric-oxide synthase (eNOS) signaling. Surprisingly, Cav-1 null mice are viable. We show that these mice lack caveolin-1 protein expression and plasmalemmal caveolae. In addition, analysis of cultured fibroblasts from Cav-1 null embryos reveals the following: (i) a loss of caveolin-2 protein expression; (ii) defects in the endocytosis of a known caveolar ligand, i.e. fluorescein isothiocyanate-albumin; and (iii) a hyperproliferative phenotype. Importantly, these phenotypic changes are reversed by recombinant expression of the caveolin-1 cDNA. Furthermore, examination of the lung parenchyma (an endothelial-rich tissue) shows hypercellularity with thickened alveolar septa and an increase in the number of vascular endothelial growth factor receptor (Flk-1)-positive endothelial cells. As predicted, endothelial cells from Cav-1 null mice lack caveolae membranes. Finally, we examined eNOS signaling by measuring the physiological response of aortic rings to various stimuli. Our results indicate that eNOS activity is up-regulated in Cav-1 null animals, and this activity can be blunted by using a specific NOS inhibitor, nitro-l-arginine methyl ester. These findings are in accordance with previous in vitro studies showing that caveolin-1 is an endogenous inhibitor of eNOS. Thus, caveolin-1 expression is required to stabilize the caveolin-2 protein product, to mediate the caveolar endocytosis of specific ligands, to negatively regulate the proliferation of certain cell types, and to provide tonic inhibition of eNOS activity in endothelial cells.
The Nucleoside Derivative 5′-O-Trityl-inosine (KIN59) Suppresses Thymidine Phosphorylase-triggered Angiogenesis via a Noncompetitive Mechanism of Action (2004)

Thymidine phosphorylase (TPase) catalyzes the reversible phosphorolysis of pyrimidine deoxynucleosides to 2-deoxy-d-ribose-1-phosphate and their respective pyrimidine bases. The enzymatic activity of TPase was found to be essential for its angiogenesis-stimulating properties. All of the previously described TPase inhibitors are either pyrimidine analogues that interact with the nucleoside-binding site of the enzyme or modified purine derivatives that mimic the pyrimidine structure and either compete with thymidine or act as a multisubstrate (competitive) inhibitor. We now describe the inhibitory activity of the purine riboside derivative KIN59 (5'-O-tritylinosine) against human and bacterial recombinant TPase and TPase-induced angiogenesis. In contrast to previously described TPase inhibitors, KIN59 does not compete with the pyrimidine nucleoside or the phosphate-binding site of the enzyme but noncompetitively inhibits TPase when thymidine or phosphate is used as the variable substrate. In addition, KIN59 was far more active than other TPase inhibitors, previously tested by us, against TPase-induced angiogenesis in the chorioallantoic membrane assay. The observed anti-angiogenic effect of KIN59 was not accompanied by inflammation or any visible toxicity. Inosine did not inhibit the enzymatic or angiogenic activity of the enzyme, indicating that the 5'-O-trityl group in KIN59 is essential for the observed effects. In contrast with current concepts, our data indicate that the angiogenic activity of TPase is not solely directed through its functional nucleoside and phosphate-binding sites. Other regulatory (allosteric) site(s) in TPase may play an important role in the mechanism of TPase-triggered angiogenesis stimulation and apoptosis inhibition. Identification of these site(s) is important to obtain a better insight into the molecular role of TPase in the progression of cancer and angiogenic diseases.
In‐situ alcoholysis of soybean oil (1996)

Abstract In‐situ alcoholysis of soybean oil with methanol, ethanol, n ‐propanol, and n ‐butanol was investigated, as well as the extraction of the oil with these solvents, to explain the progress of in‐situ alcoholysis and to determine the parameters that affect this reaction. Because methanol is a poor solvent for soybean oil, the amount of oil dissolved in methanol and converted to methyl esters was low after in‐situ alcoholysis. Ethyl, propyl, and butyl esters of soybean fatty acids could be obtained in high yields from in‐situ alcoholysis of soybean oil with these alcohols. In‐situ alcoholysis proceeded through dissolution and alcoholysis of triglycerides successively, and the overall reaction rate was determined by the extraction and alcoholysis rates. The parameters, affecting yield and purity of the product esters, were mainly those that favor extraction rate.
The protein interactions of the immunoglobulin receptor family tyrosine‐based activation motifs present in the T cell receptor ζ subunits and the CD3 γ,δ and ϵ chains (1996)

Immunoglobulin family tyrosine-based activation motifs (ITAM), which define the conserved signaling sequence EX2YX2L/IX7YX2L/I, couple the T cell antigen receptor (TCR) to cellular proteins including protein tyrosine kinases (PTK) and adapter molecules. The TCR is a multichain complex with four invariant chains CD3 gamma, delta and epsilon that each contain a single ITAM and the TCR zeta chain that contains three ITAM. The present study explores the protein interactions of the doubly phosphorylated CD3 gamma, delta, epsilon ITAM to determine whether they have common or unique biochemical properties. The data show that the doubly phosphorylated ITAM all bind the PTK ZAP-70, but the ITAM also variably bind the PTK p59fyn and the adapters Shc, Grb-2 and the p85 regulatory subunit of phosphoinositol 3' kinase. The CD3 and zeta ITAM display a hierarchy of ZAP-70 binding: zeta 1 = gamma = delta > zeta 3 > zeta 2 = epsilon. Shc, Grb-2 and p85 could bind the zeta ITAM and the CD3 gamma and delta ITAM, but not the CD3 epsilon ITAM. There were also subtle differences in the hierarchy of reactivity of these adapters for the CD3 gamma, delta and zeta ITAM that show that the zeta, CD3 gamma, delta and epsilon ITAM have different binding properties. The present study thus shows that the different ITAM of the TCR/CD3 complex can interact with different cytosolic effectors, indicating that differential ITAM phosphorylation during T cell activation could be a mechanism to generate signaling diversity by the TCR complex.
IgA-specific proteins of pathogenic bacteria (2009)

Data on structure and specificity of bacterial IgA receptors (IgA-binding M-like proteins Arp4 and Sir22 from hemolytic streptococci of serogroup A, beta-antigen from hemolytic streptococci of serogroup B, and SSL family proteins from Staphylococcus aureus) are surveyed in this review. The principal conclusion derived from comparison is the fact that all bacterial receptors bind the same site in the IgA molecule overlapping with the binding site of endogenous human IgA receptor CD89. We assume that this site, consisting of spatially close amino acid strands Leu257-Gly259 in domain Calpha2 and Pro440-Phe443 in domain Calpha3, is subject to conformational rearrangement induced by the binding of antigen in the IgA active site.
IT Web Services: A Roadmap for the Enterprise (with CD-ROM) (2002)

From the Publisher:
Architectures, platforms, roles, business models, and deployment realities.

Joe Sisto, Vice President, North Highland Company

The complete Web Services briefing for every strategist, architect, CIO, and CTO.

Web Services offer immense potential for reducing integration costs and accelerating the delivery of new products and services. But Web Services technologies are evolving at breakneck speed, making it extremely difficult to define strategies and make choices. In IT Web Services, Alex Nghiem offers a comprehensive, up-to-the-minute roadmap for every IT decision-maker. This book's unique 360 degree view of the marketplace will help you objectively assess architectures, platforms, and business models alikeand its early-adopter interviews offer powerful insights into the realities of deployment. 

You'll learn how to:

Objectively assess the promised benefits of Web Services in your organization
Identify the optimal short- and long-term roles for Web Services
Understand the Web Services stack: XML, SOAP, WSDL, and UDDI
Understand the role of ebXML, WSFL, and the interoperability groups
Choose the right enterprise Web Services architectures and models
Compare Microsoft .NET and leading J2EE technology implementations
Maximize security and scalability: emerging mechanisms and best practices
Utilize value-added Web Services networks for provisioning, messaging, reporting, and resolving non-repudiation
Define your high-level Web Services implementation plan 


Leading experts and analysts agree, Alecomplexity and delivers clarity to the over-hyped Web Services topic. IT Web Services is a necessary handbook for all parties interested in Web Services. 
About the CD-ROM
CD-ROM contains a 1-year licensed developer version of Iona's Orbix E2A Web Services Integration Platform: XMLBus Edition, a high-performance, pure Web Services platform for integrating heterogeneous applications built with .NET, J2EE, J2ME, and CORBA.
Gpr40 Is Expressed in Enteroendocrine Cells and Mediates Free Fatty Acid Stimulation of Incretin Secretion (2008)

Together, our data provide evidence that Gpr40 modulates FFA-stimulated insulin secretion from beta-cells not only directly but also indirectly via regulation of incretin secretion. Moreover, our data suggest a conserved role for Ipf1/Pdx1 and Gpr40 in FFA-mediated secretion of hormones that regulate glucose and overall energy homeostasis.
Light-driven Uptake of Oxygen, Carbon Dioxide, and Bicarbonate by the Green Alga Scenedesmus (1980)

Mass spectrometric techniques were used to study several aspects of the competition between O(2) and species of inorganic carbon for photosynthetically generated reducing power in the green alga, Scenedesmus.In contrast to wild type, no appreciable light-driven O(2) uptake was observed in a mutant lacking photosystem I. It is concluded that the carbon cycle-independent reduction of O(2) occurs at the expense of photosystem I-generated reducing equivalents.The commonly observed differences between CO(2)-grown and air-grown Scenedesmus with respect to CO(2) uptake and glycolate formation cannot be ascribed to differences in their capacity for light-driven O(2) uptake. There were no intrinsic differences found in O(2) uptake capacity between the two physiological types under conditions in which CO(2) was saturating or CO(2) uptake was inhibited. It was only under CO(2)-limited conditions that pronounced differences between the two physiological types were observed. This fact suggests that differences in O(2) metabolism and sensitivity between the two types really reflect differences in their capacity to assimilate inorganic carbon; in this respect they are analogous to C(3) and C(4) plants.The hypothesis that air-grown Scenedesmus can assimilate HCO(3) (-) by directly monitoring the time course of dissolved CO(2), O(2) uptake, and O(2) evolution in illuminated algal suspensions at alkaline pH was tested. Inasmuch as the measuring technique employed was fast compared to the nonenzymic equilibration of the inorganic carbon species, it was possible to determine the degree to which the CO(2) concentration deviated from equilibrium (with the other inorganic carbon species) during the course of illumination. The observed kinetics in air-grown and CO(2)-grown algae in the presence and absence of carbonic anhydrase, and a comparison of these kinetics with theoretical (computer-generated) time courses, support the idea that air-adapted algae are able to assimilate HCO(3) (-) actively at a high rate. The data suggest that these algae preferentially assimilate CO(2) and supply the balance of their needs by taking up HCO(3) (-). Since (unlike C(4) plants) these algae have no special CO(2) pump, and thus have a relatively low affinity for CO(2), HCO(3) (-) assimilation is the major carbon uptake process at alkaline pH even when the total CO(2) is present in millimolar concentrations.
Phorbol esters increase calcitonin gene transcription and decrease c-myc mRNA levels in cultured human medullary thyroid carcinoma. (1985)

Medullary thyroid carcinoma is a tumor of the calcitonin-secreting thyroid C-cell, with a variable malignant potential. Virulent tumors are characterized by decreased calcitonin production, suggesting the emergence of a less differentiated medullary thyroid carcinoma cell. In order to further delineate relationships between tumor progression and status of differentiation of medullary thyroid carcinoma cells, we have sought to chemically manipulate the TT cell line, an established culture of human medullary thyroid carcinoma, derived from a patient with aggressive disease. We found that the phorbol esters, 12-O-tetradecanoyl phorbol 13-acetate and phorbol 12,13-dibutyrate 1) altered the morphology of the TT cells towards that of high-calcitonin-containing cells; 2) enhanced calcitonin secretion 7-fold; 3) increased calcitonin production at the transcriptional level by 2-fold; 4) inhibited cellular proliferation; and 5) decreased, by 80%, the levels of the c-myc gene mRNA. These data suggest that phorbol esters induce, in human medullary thyroid carcinoma cells in culture, a programmed pattern of events resulting in differentiation of these cells.
Reply: Simplified Quantification of Myocardial Flow Reserve with 18F-Flurpiridaz: Validation with Microspheres in a Pig Model (2011)

REPLY: We appreciate the thoughtful letter from Drs. Johnson and Gould expressing their concerns with an extrapolation from our study that the ratio of standardized uptake values from stress and rest studies could serve as an index of myocardial flow reserve when a physical stress test is used ([1][
Nectin-4, a New Serological Breast Cancer Marker, Is a Substrate for Tumor Necrosis Factor-α-converting Enzyme (TACE)/ADAM-17 (2005)

Serum markers are extensively used in diagnostic and follow-up of cancer patients. We recently described Nectin-4, a 66-kDa adhesion molecule of the Nectin family, which is a valuable new histological and serological marker for breast carcinoma. In vivo, Nectin-4 is re-expressed in breast carcinoma, and a circulating form of Nectin-4 is detected in the sera of patients with metastatic breast cancer. In vitro, a soluble form of Nectin-4 is produced in the supernatant of breast tumor cell lines (S. Fabre-Lafay, C. Ginestier, S. Garrido-Urbani, C. Berruyer, R. Sauvan, N. Reymond, J. Adelaide, J. Geneix, P. Dubreuil, J. Jacquemier, D. Birnbaum, and M. Lopez, manuscript in preparation). We have investigated the mechanisms that regulate the production of this soluble form. It was found that the soluble form of Nectin-4 detected in the sera of patients and the supernatant of breast tumor cell lines share similar biochemical and immunological features. The soluble Nectin-4 form (43 kDa) is formed by the entire Nectin-4 ectodomain. Nectin-4 shedding is constitutive, strongly enhanced by 12-O-tetradecanoylphorbol-13-acetate activation, and reduced tumor necrosis factor-alpha protease inhibitor TAPI-1 or by the tissue inhibitor of metalloproteinase-3 (TIMP-3). TAPI-1 and TIMP-3 are inhibitors of the endoprotease tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM-17. Overexpression or small interfering RNA-mediated silencing of TACE enhanced or reduced Nectin-4 shedding, respectively. Nectin-4 is not shed when expressed in TACE-deficient fibroblasts. Interestingly, the active form of TACE is overexpressed in breast tumors and may indicate that TACE is responsible for Nectin-4 shedding not only in vitro but also in vivo.
Simultaneous record detection and attribute labeling in web data extraction (2006)

Recent work has shown the feasibility and promise of template-independent Web data extraction. However, existing approaches use decoupled strategies - attempting to do data record detection and attribute labeling in two separate phases. In this paper, we show that separately extracting data records and attributes is highly ineffective and propose a probabilistic model to perform these two tasks simultaneously. In our approach, record detection can benefit from the availability of semantics required in attribute labeling and, at the same time, the accuracy of attribute labeling can be improved when data records are labeled in a collective manner. The proposed model is called Hierarchical Conditional Random Fields. It can efficiently integrate all useful features by learning their importance, and it can also incorporate hierarchical interactions which are very important for Web data extraction. We empirically compare the proposed model with existing decoupled approaches for product information extraction, and the results show significant improvements in both record detection and attribute labeling.