gebhart/patrepeval huggingface dataset:
Differential Activation of Target Cellular Promoters by p53 Mutants with Impaired Apoptotic Function (1996)

The p53 tumor suppressor protein is a sequence-specific transcriptional activator, a function which contributes to cell cycle arrest and apoptosis induced by p53 in appropriate cell types. Analysis of a series of p53 point mutants has revealed the potential for selective loss of the ability to transactivate some, but not all, cellular p53-responsive promoters. p53 175P and p53 181L are tumor-derived p53 point mutants which were previously characterized as transcriptionally active. Both mutants retained the ability to activate expression of the cyclin-dependent kinase inhibitor p2lcip1/waf1, and this activity correlated with the ability to induce a G1 cell cycle arrest. However, an extension of this survey to include other p53 targets showed that p53 175P was defective in the activation of p53-responsive sequences derived from the bax promoter and the insulin-like growth factor-binding protein 3 gene (IGF-BP3) promoter, while p53 181L showed loss of the ability to activate a promoter containing IGF-BP3 box B sequences. Failure to activate transcription was also reflected in the reduced ability of the mutants to bind the p53-responsive DNA sequences present in these promoters. These specific defects in transcriptional activation correlated with the impaired apoptotic function displayed by these mutants, and the results suggest that activation of cell cycle arrest genes by p53 can be separated from activation of genes with a role in mediating the p53 apoptotic response. The cellular response to p53 activation may therefore depend, at least in part, on which group of p53-responsive genes become transcriptionally activated.
Chemoenzymatic Synthesis of Classical and Non-classical Anticoagulant Heparan Sulfate Polysaccharides (2003)

Heparan sulfate (HS) polysaccharides interact with numerous proteins at the cell surface and orchestrate many different biological functions. Though many functions of HS are well established, only a few specific structures can be attributed to HS functions. The extreme diversity of HS makes chemical synthesis of specific bioactive HS structures a cumbersome and tedious undertaking that requires laborious and careful functional group manipulations. Now that many of the enzymes involved in HS biosynthesis are characterized, we show in this study how one can rapidly and easily assemble bioactive HS structures with a set of cloned enzymes. We have demonstrated the feasibility of this new approach to rapidly assemble antithrombin III-binding classical and non-classical anticoagulant polysaccharide structures for the first time.
Classifier Swarms for Human Detection in Infrared Imagery (2005)

In this paper, we describe a new method for visual recognition of objects in an image that combines feature-based object classification with efficient search mechanisms based on swarm intelligence. Our approach utilizes the particle swarm optimization algorithm (PSO), a population based evolutionary algorithm, which is effective for optimization of a wide range of functions. PSO searches a multi-dimensional solution space for a global optimum using a population of "particles" in which each particle has its own velocity vector. In our approach, we extend PSO using sequential niching methods to handle multiple minima. Also, in our approach, each particle in the swarm is actually a self-contained classifier that "flys" through the solution space seeking the most "object-like" regions. By performing this optimization, the classifier swarm simultaneously finds objects in the scene, determines their size, and optimizes the classifier parameters.
Fast atom bombardment mass spectrometry: a powerful technique for the study of polar molecules (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFast atom bombardment mass spectrometry: a powerful technique for the study of polar moleculesDudley H. Williams, Carol Bradley, Gustav Bojesen, Sitthivet Santikarn, and Lester C. E. TaylorCite this: J. Am. Chem. Soc. 1981, 103, 19, 5700–5704Publication Date (Print):September 1, 1981Publication History Published online1 May 2002Published inissue 1 September 1981https://pubs.acs.org/doi/10.1021/ja00409a013https://doi.org/10.1021/ja00409a013research-articleACS PublicationsRequest reuse permissionsArticle Views253Altmetric-Citations210LEARN 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
Structured Analysis and the Data Flow Diagram: Tools for Library Analysis (1986)

Les termes «systeme» et «analyse systeme» recouvrent des sens differents suivant le domaine ou ils sont employes. Cet article definit l'analyse systeme comme «l'examen d'une acitivite, d'une procedure, d'une methode, d'une technique ou d'une occupation pour determiner ce qui doit etre fait et la meilleure methode pour accomplir les operations necessaires». L'analyse systeme est liee dans l'esprit de beaucoup a une application informatique. De nombreux outils peuvent etre developpes pour ce type d'analyse dont les caracteristiques sont: l'aide a la decision, et un dispositif efficace de communication. Diverses methodes, utilisant les graphiques, sont presentees. Un nouvel outil est decrit: le Data Flow Diagram (DFD) specialement adapte aux besoins des bibliotheques et dont l'approche est celle de l'analyse structuree. (INTD)
Exploring Splunk (2012)

Big data has incredible business value, and Splunk is the best tool for unlocking that value. Exploring Splunk shows you how to pinpoint answers and find patterns obscured by the flood of machinegenerated data. This book uses an engaging, visual presentation style that quickly familiarizes you with how to use Splunk. You'll move from mastering Splunk basics to creatively solving real-world problems, finding the gems hidden in big data. Part I: Exploring Splunk Chapter 1 tells you what Splunk is and how it can help you. Chapter 2 discusses how to download Splunk and get started. Chapter 3 discusses the search user interface and searching with Splunk. Chapter 4 covers the most commonly used search commands. Chapter 5 explains how to visualize and enrich your data with knowledge. Part II: Solution Recipes Chapter 6 covers the most common monitoring and alerting solutions. Chapter 7 covers the most common transaction solutions. Chapter 8 covers the most common lookup table solutions.
Anthracycline-associated cardiac and renal damage in rabbits. Evidence for mediation by vasoactive substances. (1981)

We tested the hypothesis that anthracycline-induced cardiac and renal damage is mediated by vasoactive substances. A 1-minute exposure to 5 micrograms per ml. of doxorubicin (DXR, Adriamycin) produced cardiac histamine release in isolated rabbit hearts. Under conditions in which histamine uptake and metabolism were impaired, the administration of DXR, 2 mg. per kg., over 1 minute was associated with elevations in arterial histamine and catecholamines. The chronic weekly administration of DXR produced severe cardiac and renal damage. The administration of combined histaminic and adrenergic blockade with diphenhydramine, cimetidine, phentolamine, and propranolol (DCPP) pre- and immediately post-DXR resulted in near total protection against DXR-mediated cardiac damage and prevented the majority of the renal lesions. The combined administration of diphenhydramine, cimetidine, phentolamine, and propranolol did not appear to be acting by mechanisms other than blockade of vasoactive amine receptors as cardiac uptake of DXR and the DXR antitumor response were not altered by diphenhydramine, cimetidine, phentolamine, and propranolol. This study demonstrates that anthracycline-associated cardiac and renal toxicity may be mediated by vasoactive substances and that anthracycline cardiomyopathy is potentially preventable.
Arterial to end-tidal CO2 tension difference after bilateral lung transplantation (1993)

Our data suggest marked alveolar deadspace ventilation immediately after bilateral lung transplantation. The presence and rapid improvement of this ventilation/perfusion mismatch may reflect the presence of ischemia-reperfusion lung injury and its improvement in the first hours of reperfusion. In five of seven patients, capnography was not a good measure of PaCO2 during the first hours after bilateral lung transplantation.
Modulation of megakaryocytopoiesis by thrombopoietin: the c-Mpl ligand (1995)

We have further characterized the biological activities, mechanism of action, and target cell populations of recombinant human and murine thrombopoietin (rhTPO and rmTPO) in in vitro human and murine model systems. Alone, hTPO or mTPO stimulated the maturation of immature murine megakaryoblasts as measured in a single cell assay. The combination of hTPO or mTPO and interleukin-6 (IL-6) resulted in a further increase in megakaryocyte differentiation in this system. Murine TPO stimulated mouse megakaryocyte progenitor development. Human megakaryocyte progenitor development was potentiated by hTPO alone and further augmented in the presence of the early-acting cytokines (IL-3) or kit ligand/stem cell factor (KL/SCF). To further define the mechanism of action of TPO, neutralization studies were performed with antisera to IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 beta, and IL-11. No diminution in TPO activity was observed in the presence of these antisera. Moreover, because adhesive interactions are known to modulate hematopoiesis, we studied whether hTPO might alter such interactions between human bone marrow (BM) megakaryocytes and human BM stromal fibroblasts. No changes were observed in either megakaryocyte expression of the surface molecules lymphocyte function-associated antigen-1, very late activation antigen-4, or intercellular adhesion molecule-1 or the adhesion of megakaryocytes to stromal fibroblasts after treatment with the growth factor. Furthermore, no induction of secretion of the cytokines IL-1 alpha, IL-1 beta, GM-CSF, IL-6, granulocyte-CSF, tumor necrosis factor-alpha, transforming growth factor-beta 1, or transforming growth factor-beta 2 by primary human BM megakaryocytes was noted after treatment of the cells with hTPO. To address whether TPO affects very primitive hematopoietic progenitors, we studied the residual cells from the BMs of mice treated with high doses of 5-fluorouracil. Although no effect of mTPO alone was noted on the viability or replication of such primitive murine progenitor populations, the triple combination of IL-3 + KL/SCF + TPO stimulated growth of megakaryocyte progenitors. These results indicate that TPO is a highly lineage-specific growth factor whose primary biological effects are likely to be direct modulation of the growth and maturation of committed megakaryocyte precursors and immature megakaryoblasts.
Identification of A2-restricted hepatitis C virus-specific cytotoxic T lymphocyte epitopes from conserved regions of the viral genome (1996)

We have focused on conserved regions of the hepatitis C Virus (HCV) genome to identify viral peptides that contain HLA class I binding motifs and bind with high affinity to the corresponding purified HLA molecules. Accordingly, we have identified 31 candidate epitopes in the HCV that have the potential to be recognized by either HLA-A1, A2.1-, A3, A11- or A24-restricted cytotoxic T lymphocytes (CTL). Twelve conserved peptides that bind HLA-A2.1 with high or intermediate affinity were tested for immunogenicity in vitro in human primary CTL cultures and in vivo by direct immunization of HLA-A2.1/Kb transgenic mice. Six HLA-A2.1-restricted CTL epitopes were immunogenic in both systems. At least three of these peptide epitopes were endogenously processed and presented for CTL recognition. Overall, these data illustrate the value of this approach for the development of virus-specific, peptide-based vaccines.
Solid-Phase Synthesis of Heterocycles Containing an 1-Acyl-3-oxopiperazine Skeleton (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSolid-Phase Synthesis of Heterocycles Containing an 1-Acyl-3-oxopiperazine SkeletonTomáš Vojkovský, Aleksandra Weichsel, and Marcel PátekView Author Information Selectide Corporation, a subsidiary of Hoechst Marion Roussel, Inc., 1580 East Hanley Boulevard, Tucson, Arizona 85737 Cite this: J. Org. Chem. 1998, 63, 10, 3162–3163Publication Date (Web):April 23, 1998Publication History Received6 February 1998Published online23 April 1998Published inissue 1 May 1998https://doi.org/10.1021/jo980203uCopyright © 1998 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views487Altmetric-Citations54LEARN 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 Read OnlinePDF (119 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Amines,Ions,Monomers,Organic polymers,Peptides and proteins Get e-Alerts
High-temperature, short-time sulfation of calcium-based sorbents. 2. Experimental data and theoretical model predictions (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHigh-temperature, short-time sulfation of calcium-based sorbents. 2. Experimental data and theoretical model predictionsCorey R. Milne, Geoffrey D. Silcox, David W. Pershing, and David A. KirchgessnerCite this: Ind. Eng. Chem. Res. 1990, 29, 11, 2201–2214Publication Date (Print):November 1, 1990Publication History Published online1 May 2002Published inissue 1 November 1990https://pubs.acs.org/doi/10.1021/ie00107a004https://doi.org/10.1021/ie00107a004research-articleACS PublicationsRequest reuse permissionsArticle Views181Altmetric-Citations32LEARN 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
Exogenous Administration of Gangliosides Displaces GPI-anchored Proteins from Lipid Microdomains in Living Cells (1999)

Exogenous application of gangliosides to cells affects many cellular functions. We asked whether these effects could be attributed to the influence of gangliosides on the properties of sphingolipid-cholesterol microdomains on the plasma membrane, also termed rafts. The latter are envisaged as lateral assemblies of sphingolipids (including gangliosides), cholesterol, and a specific set of proteins. Rafts have been implicated in processes such as membrane trafficking, signal transduction, and cell adhesion. Recently, using a chemical cross-linking approach with Madin-Darby canine kidney (MDCK) cells permanently expressing a GPI-anchored form of growth hormone decay accelerating factor (GH-DAF) as a model system, we could show that GPI-anchored proteins are clustered in rafts in living cells. Moreover, this clustering was dependent on the level of cholesterol in the cell. Here we show that incubation of MDCK cells with gangliosides abolished subsequent chemical cross-linking of GH-DAF. Furthermore, insertion of gangliosides into the plasma membrane of MDCK GH-DAF cells renders GH-DAF soluble when subjected to extraction with Triton X-114 at 4 degrees C. Our data suggest that exogenous application of gangliosides displaces GPI-anchored proteins from sphingolipid-cholesterol microdomains in living cells.
Two factor XI mutations in a Chinese family with factor XI deficiency (2003)

We describe a Chinese family with factor XI deficiency, the first reported to date. The proband had factor XI activity of 1% and was heterozygous for two nonsense mutations, an exon-8 C713-->T mutation resulting in Gln263-->Term, and an exon-10 C979-->A mutation resulting in Tyr351-->Term. Two daughters were heterozygous for the Gln263-->Term mutation and two for the Try351-->Term mutation. All showed a reduction of factor XI activity to about 50%. The Gln263-->Term mutation has been described in two Japanese families, and it remains to be determined whether a common founder exists between the three kindreds. The Try351-->Term mutation is novel.
Astrocytes: biology and pathology (2009)

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.
Monedas. La Plata Segoviana (2003)

In patients progressing on imatinib/sunitinib, cediranib 45 mg/day demonstrated evidence of activity by (18)FDG-PET, but did not reduce average SUVmax. Evidence of antitumor activity was seen in ASPS.
A faster algorithm for rubber-band equivalent transformation for planar VLSI layouts (1996)

In this paper we consider the problem of transforming a single-layer topological routing of n two-terminal nets into a rubber-band equivalent using rectilinear wires in the presence of rectilinear circuit modules. Given a topological planar VLSI layout sketch with |F| features and |W| noncrossing wire segments connecting n two-terminal nets, we present an O(|F|/spl middot/|W|) time algorithm to do the vertex-disjoint rubber-band equivalent transformation of these n nets if it exists. The algorithm consists of two phases, computing a loose homotopy with four spokes matrices, and computing a vertex-disjoint rubber-band equivalent of the given homotopy, each phase taking O(|F|/spl middot/|W|) time and space. Both complexities are asymptotically optimal in the worst case. From the vertex-disjoint rubber-band equivalent of the given homotopy, one can obtain the detailed routing within the same time complexity. Experimental results are also presented.
Toll-Like Receptor 8-Mediated Reversal of CD4 + Regulatory T Cell Function (2005)

CD4+ regulatory T (Treg) cells have a profound ability to suppress host immune responses, yet little is understood about how these cells are regulated. We describe a mechanism linking Toll-like receptor (TLR) 8 signaling to the control of Treg cell function, in which synthetic and natural ligands for human TLR8 can reverse Treg cell function. This effect was independent of dendritic cells but required functional TLR8-MyD88-IRAK4 signaling in Treg cells. Adoptive transfer of TLR8 ligand-stimulated Treg cells into tumor-bearing mice enhanced anti-tumor immunity. These results suggest that TLR8 signaling could play a critical role in controlling immune responses to cancer and other diseases.
A Signal Transducer and Activator of  Transcription (Stat)4-independent Pathway for the Development of  T Helper Type 1 Cells (1998)

The differentiation of T helper (Th) cells is regulated by members of the signal transducer and activator of transcription (STAT) family of signaling molecules. We have generated mice lacking both Stat4 and Stat6 to examine the ability of Th cells to develop in the absence of these two transcription factors. Stat4, Stat6(-/-) lymphocytes fail to differentiate into interleukin (IL)-4-secreting Th2 cells. However, in contrast to Stat4(-/-) lymphocytes, T cells from Stat4, Stat6(-/-) mice produce significant amounts of interferon (IFN)-gamma when activated in vitro. Although Stat4, Stat6(-/-) lymphocytes produce less IFN-gamma than IL-12-stimulated control lymphocytes, equivalent numbers of IFN-gamma-secreting cells can be generated from cultures of Stat4, Stat6(-/-) lymphocytes activated under neutral conditions and control lymphocytes activated under Th1 cell-promoting conditions. Moreover, Stat4, Stat6(-/-) mice are able to mount an in vivo Th1 cell-mediated delayed-type hypersensitivity response. These results support a model of Th cell differentiation in which the generation of Th2 cells requires Stat6, whereas a Stat4-independent pathway exists for the development of Th1 cells.