gebhart/patrepeval huggingface dataset:
Identification of the Cyclosporin-Binding Site in P-Glycoprotein (1998)

The binding site of cyclosporin A to P-glycoprotein was characterized by using a multidrug-resistant Chinese hamster ovary cell line. P-glycoprotein photolabeled with diazirine-cyclosporin A analogue was purified by a two-step process involving continuous elution electrophoresis followed by wheat germ agglutinin-agarose precipitation. The cyclosporin A covalently bound to P-glycoprotein and to subsequent proteolytic fragments was detected by Western blot analysis using a monoclonal antibody against cyclosporin A. Proteolytic digestion of purified P-glycoprotein by V8 generated a major fragment of 15 kDa photolabeled by cyclosporin A, while proteolysis of P-glycoprotein photolabeled by [125I]-iodoaryl azidoprazosin generated a major fragment of 7 kDa. Limited proteolysis of cyclosporin A-photolabeled P-glycoprotein with trypsin indicated that the major binding site for cyclosporin A was in the C-terminal half of the protein. This cyclosporin A binding site was further characterized with chemical agents (N-chlorosuccinimide, cyanogen bromide, and 2-nitro-5-thiocyanobenzoate). These three chemical agents established a proteolytic profile of P-glycoprotein for fragments photolabeled with cyclosporin A and for fragments that contained the C494 and C219 epitopes. The smallest fragments generated by these chemical agents include the transmembrane domains (TMs) 10, 11, and 12 of P-glycoprotein. When the fragments generated by these chemical agents are aligned, the region that binds cyclosporin A is reduced to the 953-1007 residues. These combined results suggest that the major binding site of cyclosporin A occurs between the end of TM 11 and the end of TM 12.
Reporting application usage in a LAN environment (1990)

The University of Wisconsin-Stevens Point (UW-SP) has developed a unique system of logging and reporting computing resource usage. Our environment consists of an 800 node AT&T Starlan local area network which uses a consistent menu interface to access all computing hosts and applications. One particular function, which is independent of the menu system, is to automatically record each time an application has been selected and the duration the application was used. Below is an example of a single transaction record: minitab;S01LRC;SGILE;08 00 6a e5 4b;01-20-90; 09:12:38;10:10:13;2991
Single cell Ca2+/cAMP cross-talk monitored by simultaneous Ca2+/cAMP fluorescence ratio imaging. (1996)

The spatial and temporal dynamics of two intracellular second messengers, cAMP and Ca2+, were simultaneously monitored in living cells by digital fluorescence ratio imaging using FlCRhR, a single-excitation dual-emission cAMP indicator, and fura-2, a dual-excitation single-emission Ca2+ probe. In single C6-2B glioma cells, isoproterenol- or forskolin-evoked cAMP accumulation (measured in vivo as an increased FlCRhR emission ratio) was reduced when cytosolic free Ca2+ concentration was elevated before, simultaneously with, or after cAMP activation. However, in REF-52 fibroblasts, Ca2+ neither prevented nor reduced forskolin-stimulated cAMP production. These results provide novel in vivo evidence for the Ca2+ modulation of the cAMP transduction pathway in C6-2B cells. The simultaneous microscopic measurement of cAMP and Ca2+ kinetics in single cells makes it now possible to study the regulatory interactions between these second messengers at the cellular and even the subcellular level.
Structured data and inference in DeepQA (2012)

Although the majority of evidence analysis in DeepQA is focused on unstructured information (e.g., natural-language documents), several components in the DeepQA system use structured data (e.g., databases, knowledge bases, and ontologies) to generate potential candidate answers or find additional evidence. Structured data analytics are a natural complement to unstructured methods in that they typically cover a narrower range of questions but are more precise within that range. Moreover, structured data that has formal semantics is amenable to logical reasoning techniques that can be used to provide implicit evidence. The DeepQA system does not contain a single monolithic structured data module; instead, it allows for different components to use and integrate structured and semistructured data, with varying degrees of expressivity and formal specificity. This paper is a survey of DeepQA components that use structured data. Areas in which evidence from structured sources has the most impact include typing of answers, application of geospatial and temporal constraints, and the use of formally encoded a priori knowledge of commonly appearing entity types such as countries and U.S. presidents. We present details of appropriate components and demonstrate their end-to-end impact on the IBM Watson™ system.
Efficacy of huperzine in preventing soman‐induced seizures, neuropathological changes and lethality (1997)

Huperzine A (HUP) is a potent reversible inhibitor of acetylcholinesterase (AChE) that crosses the blood-brain barrier. Its ability to prevent seizures and subsequent hippocampal neuropathological changes induced by the organophosphate soman was studied in guinea pigs. Results were compared to guinea pigs treated with pyridostigmine (PYR, 0.2 mg/kg, subcutaneously). HUP pretreatment at 0.5 mg/kg, intraperitoneally, totally prevented seizures and ensured the survival of all animals for 24 h after intoxication. Hippocampal tissue was then free of any neuronal damage. Comparatively, all animals pretreated with PYR exhibited epileptic activity after soman poisoning and five of six animals died. Examination of the hippocampus of the only surviving guinea pig pretreated with PYR showed extensive neuropathological changes. Although HUP or PYR induced similar inhibitions of blood AChE activity, only HUP pretreatment led to a decrease in central AChE activity. In binding studies on guinea-pig brain homogenates, HUP had no affinity for muscarinic, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and gamma-aminobutyric acid (GABA)A receptors and only a very low one for N-methyl-D-aspartate (NMDA) receptors. In conclusion, HUP, unlike PYR, protects against soman-induced convulsions and neuropathological changes in the hippocampus. This efficacy seems to be related to a protection by HUP of both peripheral and central stores of AChE.
Allergen Drives Class Switching to IgE in the Nasal Mucosa in Allergic Rhinitis (2005)

IgE-expressing B cells are over 1000 times more frequent in the nasal B cell than the peripheral blood B cell population. We have investigated the provenance of these B cells in the nasal mucosa in allergic rhinitis. It is generally accepted that expression of activation-induced cytidine deaminase and class switch recombination (CSR) occur in lymphoid tissue, implying that IgE-committed B cells must migrate through the circulation to the nasal mucosa. Our detection of mRNA for activation-induced cytidine, multiple germline gene transcripts, and epsilon circle transcripts in the nasal mucosa of allergic, in contrast to nonallergic control subjects, however, indicates that local CSR occurs in allergic rhinitis. The germline gene transcripts and epsilon circle transcripts in grass pollen-allergic subjects are up-regulated during the season and also when biopsies from allergic subjects are incubated with the allergen ex vivo. These results demonstrate that allergen stimulates local CSR to IgE, revealing a potential target for topical therapies in allergic rhinitis.
Cyclopiamines A and B, novel oxindole metabolites of Penicillium cyclopium westling (1979)

The isolation of two new oxindole alkaloids, cyclopiamine A and B, from Penicillium cyclopium is described. The chemical and spectral properties of cyclopiamine B are interpreted in terms of the constitution and relative stereochemistry (2a) of the compound as determined by X-ray structure analysis. The enantiomeric relationship between cyclopiamine A(1) and B(2a) at C(22) is established on the basis of chemical studies.
Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients. (2010)

In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.
<title>Text-based search of TV news stories</title> (1996)

Our goal is to enable viewers to access TV programs based on their content. Towards this end, we present a system that automatically captures and processes TV news programs into a database that can be searched over the internet. Users browse this database by submitting simple English queries. The results of the query is a hyperlinked list of matching news stories. Clicking on any item in the list immediately launches a video of the pertinent part of the news broadcast. We segment TV news broadcasts into distinct news stories. We then index each story as a separate entity. In reply to a query, videos for these news stories are displayed rather than the whole TV program. News program s ar usually accompanied by a transcript in closed caption text. The closed caption text contains markers for story boundaries. Due to the live nature of TV news programs, the closed caption lags the actual audio/video by varying amounts of time up to a few seconds. The closed caption text, thus, has to be shifted to be aligned in time to the video. We use video and audio events to do this synchronization. The closed caption for each story is entered into a database. In response to a query, the database retrieves and ranks the matching closed caption stores. An HTML document is returned to the user which lists: 1) the name and time of the news program that this story belongs to, 2) thumbnails providing a visual summary of the story, 3) closed caption text. To view a news story, the user simply clicks on an item form the list and the video for that story is streamed onto a media player at the user side. This system maintains the manner of presentation of the media, namely video for TV programs, while allowing the common search and selection techniques used on the web.
2,2‘-Bipyridine Ligandoside:  A Novel Building Block for Modifying DNA with Intra-Duplex Metal Complexes (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXT2,2'-Bipyridine Ligandoside: A Novel Building Block for Modifying DNA with Intra-Duplex Metal ComplexesHaim Weizman and Yitzhak TorView Author Information Department of Chemistry and Biochemistry University of California, San Diego La Jolla, California 92093-0358 Cite this: J. Am. Chem. Soc. 2001, 123, 14, 3375–3376Publication Date (Web):April 4, 2001Publication History Received14 November 2000Published online4 April 2001Published inissue 1 April 2001https://pubs.acs.org/doi/10.1021/ja005785nhttps://doi.org/10.1021/ja005785nrapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1598Altmetric-Citations214LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Biopolymers,Genetics,Ligands,Melting,Metals Get e-Alerts
Darstellung neuartiger monomerer, oligomerer und polymerer Silyltriflate (1992)

Preparation of New Monomeric, Oligomeric, and Polymeric Silyl Triflates The highly reactive silyl triflates R 3 SiOSO 2 CF 3 are valuable reagents in organosilicon chemistry. New triflate derivatives of mono‐ and oligosilanes have been prepared by substitution of phenyl groups or hydrogen atoms for the trifluoromethanesulfonyl group. The presence of the electron‐withdrawing triflate group leads to a strong deactivation of the other substituents at the silicon atom, and the displacement of a second phenyl group at the same silicon atom is much slower than the first step. For this reason in the case of phenylated oligosilanes stepwise monosubstitution of the silicon atoms has been found. Other new oligomeric silyl triflates are obtained by reaction of silanediyl(triyl) bis(tris)(trifluoromethanesulfonates) with lithium derivatives of organosilicon compounds. Finally, the cleavage of silicon–phenyl bonds of poly[methyl(phenyl)silanes] by CF 3 SO 3 H leads to triflate derivatives of polysilanes.
A custom 148 gene-based resequencing chip and the SNP explorer software: new tools to study antibody deficiency (2010)

Hyper-IgM syndrome and Common Variable Immunodeficiency are heterogeneous disorders characterized by a predisposition to serious infection and impaired or absent neutralizing antibody responses. Although a number of single gene defects have been associated with these immune deficiency disorders, the genetic basis of many cases is not known. To facilitate mutation screening in patients with these syndromes, we have developed a custom 300-kb resequencing array, the Hyper-IgM/CVID chip, which interrogates 1,576 coding exons and intron-exon junction regions from 148 genes implicated in B-cell development and immunoglobulin isotype switching. Genomic DNAs extracted from patients were hybridized to the array using a high-throughput protocol for target sequence amplification, pooling, and hybridization. A Web-based application, SNP Explorer, was developed to directly analyze and visualize the single nucleotide polymorphism (SNP) annotation and for quality filtering. Several mutations in known disease-susceptibility genes such as CD40LG, TNFRSF13B, IKBKG, AICDA, as well as rare nucleotide changes in other genes such as TRAF3IP2, were identified in patient DNA samples and validated by direct sequencing. We conclude that the Hyper-IgM/CVID chip combined with SNP Explorer may provide a cost-effective tool for high-throughput discovery of novel mutations among hundreds of disease-relevant genes in patients with inherited antibody deficiency.
Catalytic Steam Gasification of Biomass: Catalysts, Thermodynamics and Kinetics (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTCatalytic Steam Gasification of Biomass: Catalysts, Thermodynamics and KineticsHugo de Lasa*, Enrique Salaices, Jahirul Mazumder, and Rahima LuckyView Author Information Chemical Reactor Engineering Centre, The University of Western Ontario, London, Ontario, Canada N6A5B8E-mail: [email protected]. Phone: (519) 661-2144. Fax: (519) 850-2931.Cite this: Chem. Rev. 2011, 111, 9, 5404–5433Publication Date (Web):June 8, 2011Publication History Received12 January 2011Published online8 June 2011Published inissue 14 September 2011https://pubs.acs.org/doi/10.1021/cr200024whttps://doi.org/10.1021/cr200024wreview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views9478Altmetric-Citations353LEARN 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 SUBJECTS:Biomass,Catalysts,Equilibrium,Gasification,Water Get e-Alerts
The design and realization of a wearable embedded device for dietary and physical activity monitoring (2010)

This paper introduces the design and realization of a wearable device for dietary and physical activity monitoring. This design is based on technological advances in microelectronics and our previous prototypes which have verified the system concept. From our results, it is shown that the device meets all functional requirements as well as size and power consumption constraints essential to participants' use. With further technological development, we believe that the size of the system can be reduced and accurate and objective dietary assessments will become possible.
An Inherited Disorder of Lymphocyte Apoptosis: The Autoimmune Lymphoproliferative Syndrome (1999)

The autoimmune lymphoproliferative syndrome (ALPS) affords novel insights into the mechanisms that regulate lymphocyte homeostasis and underlie the development of autoimmunity. This syndrome arises early in childhood in persons who inherit mutations in genes that mediate apoptosis, or programmed cell death. The timely deletion of lymphocytes is a way to prevent their accumulation and the persistence of cells that can react against the body's own antigens. In ALPS, defective lymphocyte apoptosis permits chronic, nonmalignant adenopathy and splenomegaly; the survival of normally uncommon "double-negative" CD3+ CD4- CD8- T cells; and the development of autoimmune disease. Most cases of ALPS involve heterozygous mutations in the lymphocyte surface protein Fas that impair a major apoptotic pathway. Detailed immunologic investigations of the cellular and cytokine profiles in ALPS show a prominent skewing toward a T-helper 2 phenotype; this provides a rational explanation for the humoral autoimmunity typical of patients with ALPS. Prospective evaluations of 26 patients and their families show an ever-expanding spectrum of ALPS and its major complications: hypersplenism, autoimmune hemolytic anemia, thrombocytopenia, and neutropenia. Defective apoptosis may also contribute to a heightened risk for lymphoma.
Transmembrane signaling by a chimera of the Escherichia coli aspartate receptor and the human insulin receptor. (1989)

Since many receptors apparently contain only one or two membrane-spanning segments, their transmembrane topology should be similar. This feature suggests that these receptors share common mechanisms of transmembrane signaling. To test the degree of conservation of signaling properties, a chimeric receptor containing the ligand-binding extracellular domain of the Escherichia coli aspartate chemoreceptor and the cytosolic portion of the human insulin receptor was constructed. This chimeric receptor is active as a tyrosine kinase, and aspartate stimulates its activity. Some interesting differences are noted in the target proteins phosphorylated by the chimera compared to the wild-type insulin receptor. These results indicate that features of the signaling mechanisms used by these diverse receptors are conserved, but that interesting changes in the protein properties are caused by differences in the neighboring domains.
A composite FKBP12-FK506 surface that contacts calcineurin (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA composite FKBP12-FK506 surface that contacts calcineurinDan Yang, Michael K. Rosen, and Stuart L. SchreiberCite this: J. Am. Chem. Soc. 1993, 115, 2, 819–820Publication Date (Print):January 1, 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://pubs.acs.org/doi/10.1021/ja00055a081https://doi.org/10.1021/ja00055a081research-articleACS PublicationsRequest reuse permissionsArticle Views275Altmetric-Citations74LEARN 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
Conjugated aromatic asymmetrical terpyridine analogues via step-wise photocyclization and their ruthenium complexes (2015)

Asymmetrical conjugated terpyridines were acquired by the UV irradiation. Step oxidative cyclodehydrogenation along with the aromatic conjugation expansion was proved with the intermediates isolations. The terpyridine Ru<sup>2+</sup> dimerizations were successfully introduced.