gebhart/patrepeval huggingface dataset:
Induction of Fibrinogen Binding and Platelet Aggregation as a Potential Intrinsic Property of Various Glycoprotein IIb/IIIa (IIbβ3) Inhibitors (1998)

Abstract The blockade of platelet integrin glycoprotein (GP) IIb/IIIa is a promising new antiplatelet strategy. The binding of ligands or of the ligand-mimetic peptide RGD causes a conformational change of GP IIb/IIIa from the nonactivated to the activated state. Because several blocking agents/inhibitors are ligand-mimetics, the current study evaluates whether these agents have the intrinsic property to activate GP IIb/IIIa. Fibrinogen binding to GP IIb/IIIa on platelets or on CHO cells expressing recombinant GP IIb/IIIa was evaluated by flow cytometry or 125I-labeled fibrinogen. Incubation with the monoclonal antibody (MoAb) fragment c7E3 (abciximab) results in fibrinogen binding to GP IIb/IIIa and in the access of ligand-induced binding sites. At low concentrations (0.01 to 0.1 μg/mL), this intrinsic activating property of c7E3 can result in platelet aggregation. The disintegrin flavorodin and the RGD analogue fradafiban also induce fibrinogen binding, whereas the blocking MoAbs 2G12 and P2 and the activation-specific MoAb PAC-1 do not. Aspirin and indomethacin cannot block c7E3-induced fibrinogen binding to GP IIb/IIIa, but can inhibit c7E3-induced platelet aggregation. Thus, we conclude that GP IIb/IIIa inhibitors can demonstrate an intrinsic activating property, which can result in fibrinogen binding to GP IIb/IIIa and consequently in platelet aggregation. Cyclooxygenase inhibitors can inhibit platelet aggregation caused by GP IIb/IIIa inhibitors. Further studies will have to evaluate the clinical relevance of the potential intrinsic activating property of GP IIb/IIIa inhibitors and define consequences for the future drug development and evaluation of these potent antiplatelet agents. © 1998 by The American Society of Hematology.
Synthesis of 2,4-Diaminoquinazolines and Tricyclic Quinazolines by Cascade Reductive Cyclization of Methyl N-Cyano-2-nitrobenzimidates (2012)

An efficient route to N(4)-substituted 2,4-diaminoquinazolines has been developed by employing tandem condensation of cyanoimidate-amine and reductive cyclization in iron-HCl system. This method is tolerant of a following intramolecular N-alkylation and produces two fused heterocycles in a one-pot procedure. This protocol is a facile two-step synthesis of tricyclic quinazolines, which is effected by potent cyanoimidation and tandem reductive cyclization from 2-nitrobenzaldehydes. Moreover, the forming process of tricyclic quinazolines has been investigated from the ring-opening/ring-closing cascade point of view. It is found that the preparation of tricyclic quinazolinones in good yields relies on the selective hydrolysis of tricyclic quinazolines in base or acid system.
Carbonyl Odorants Contributing to the In-Oven Roast Beef Top Note (2005)

Among the few papers related to the gas chromatography (GC)-olfactometric determination of important odorants in cooked beef aroma, only one uses roasting conditions, but none of them investigates the appealing aroma during the cooking of the piece of meat. The present paper investigates this top note as perceived from the oven, by analyzing the oven headspace using GC-"SNIF", a GC-olfactometric technique. From the different functional classes of odorants participating in overall in-oven aroma, this first paper focuses only on the role of aldehydes and ketones, as they represent the majority of aroma compounds formed during cooking. To ascertain the identification of these odorants, a microderivatization technique was used, based on (2,3,4,5,6-pentafluorophenyl)hydrazine. The resulting hydrazones exhibit very specific mass spectrometric fragments, leading to a sensitive and specific detection. A total of 23 carbonyl compounds were shown to contribute to the roast beef top note.
Presbyopia: The First Stage of Nuclear Cataract? (2006)

Presbyopia, the inability to accommodate, affects almost everyone at middle age. Recently, it has been shown that there is a massive increase in the stiffness(1) of the lens with age and, since the shape of the lens must change during accommodation, this could provide an explanation for presbyopia. In this review, we propose that presbyopia may be the earliest observable symptom of age-related nuclear (ARN) cataract. ARN cataract is a major cause of world blindness. The genesis of ARN cataract can be traced to the onset of a barrier within the lens at middle age. This barrier restricts the ability of small molecules, such as antioxidants, to penetrate into the centre of the lens leaving the proteins in this region susceptible to oxidation and post-translational modification. Major protein oxidation and colouration are the hallmarks of ARN cataract. We postulate that the onset of the barrier, and the hardening of the nucleus, are intimately linked. Specifically, we propose that progressive age-dependent hardening of the lens nucleus may be responsible for both presbyopia and ARN cataract.
Logarithmic arithmetic for real data types and support for Matlab/Simulink based rapid-FPGA-prototyping (2004)

The paper is focused on the rapid prototyping for FPGA using the high-level environment of MATLAB/Simulink. An approach using the Xilinx system generator (XSG) is reviewed on an example of the high-speed logarithmic arithmetic (HSLA) unit. An alternative approach using the combination of the real time workshop (RTW) with the Handle-C compiler for automatized generation of the HDL code is presented. Finally, the possibilities to extend this solution in order to support the run-time reconfigurations are outlined.
The Host Cell Chaperone Hsp90 Is Necessary for Cytotoxic Action of the Binary Iota-Like Toxins (2004)

The heat shock protein Hsp90 is essential for uptake of the binary actin ADP-ribosylating toxins Clostridium perfringens iota-toxin and Clostridium difficile transferase into eukaryotic cells. Inhibition of Hsp90 by its specific inhibitor radicicol delayed intoxication of Vero cells by these toxins. A common Hsp90-dependent mechanism for their translocation is discussed.
Reliable non-zero skew clock trees using wire width optimization (1993)

that routing constraints and process variations make non-zero skew inevitable, this paper describes a novel methodology for constructing reliable low-skew clock trees. The algorithm efficiently calculates clock-tree delay sensitivities to achieve a target delay and a target skew. Moreover, the sensitivities also show that wires should be widened as opposed to lengthened to reduce skew since the former improves reliability while the latter reduces it. This paper introduces the concept of designing reliable clock nets with process-insensitive skew.
Por uma semiologia das mídias (2012)

This paper discuss the complex relations adopted by Semiology and media theory, to propose a televisual communication oriented semiotics, capable to embrace the specificities of this kind of media process. Thus, after to point the inadequacy of the elements enforcement of a immanent Semiology, or apllied to cinema, to the television analysis, it endorses the notion of gender promise as a replacement to the notion of contract or pact, as subjacent to the media communication
Henry Hulton and the American Revolution: an outsider's inside view (2011)

Henry Hulton was an Englishman who moved to Boston in 1767 as a member of the new American Board of Customs Commissioners. The board was supposed to curtail smuggling and bring greater efficiency to the administration of empire. It failed, and Hulton fled Massachusetts in 1776, joining an exodus of the politically displaced. Hulton eventually wrote a never-published history of the American rebellion as he experienced it. Although his complaints about the 'demagogues' who dominated Massachusetts politics echo those made by other Loyalists. Hulton adds another dimension to our understanding. As an Englishman, he could be more detached from the problems of empire than Loyalists who had been driven from their native land. For those interested in the complexities of historical causation, this interpretation provides a telling case study of how an author can combine individual action with deeper forces to explain events. Though not a historical determinist, Hulton did see rebellion as the logical result of American attitudes and behaviors that London allowed to go unchecked for too long. Hulton's history, his letters, and the letters of his sister, Ann, who lived with him outside Boston - all of which are reproduced here - provide an unusual glimpse into the onset of the Revolution in Massachusetts. Hulton was himself an intriguing figure, an Englishman seeking to secure fame and fortune abroad, first in Germany, then on the island of Antigua, then again in Germany, with a stop in London before ambition took him back across the Atlantic, this time to Massachusetts. He would end his days a retired gentleman living in the English countryside, frustrated by his experiences on both sides of the Atlantic but determined to teach his five sons the lessons about life that he learned and recorded in this history.
Functional analysis of regulatory elements in a plant embryo-specific gene. (1986)

Previously we demonstrated the expression of a plant embryo-specific gene encoding the alpha' subunit of beta-conglycinin, a seed storage protein of soybean (Glycine max), in transgenic petunia plants. To examine the regulatory elements that control the expression of this embryo-specific gene (Gmg17.1), a series of deletion mutants was made that contain the alpha'-subunit gene flanked in the 5' direction from +14 nucleotides to -8.5 kilobases (kb) relative to the site of transcription initiation. Each of these deletion mutants was introduced into the genome of petunia cells with the help of Ti-plasmid-derived vectors. Petunia plants were regenerated from transformed cells and expression of the introduced soybean gene was examined. When the alpha'-subunit gene was flanked by 159 nucleotides upstream (Gmg17.1 delta-159), the gene was expressed at a low level in immature embryos. When the gene was flanked by 257 nucleotides upstream of the site of transcription initiation (Gmg17.1 delta-257), a high level of expression was obtained. An additional 8 kb of DNA sequence (which includes the sequence GTGGATAG at -560, which is identical to the core enhancer sequence of simian virus 40 and some animal genes) did not significantly increase the level of expression. The increase in expression level between the delta-159 and delta-257 mutants was at least 20-fold. Analysis of the nucleotides between delta-159 and delta-257 reveals four repeats of a 6-base-pair (G + C)-rich sequence (see formula in text). The deletion Gmg17.1 delta-159 contains a single AACCCA sequence. We suggest that the (G + C)-rich repeats play a critical role in determining the level of expression of the transgenic plants.
A Critical Role for the RelA Subunit of Nuclear Factor κB in Regulation of Multiple Immune-response Genes and in Fas-induced Cell Death (1999)

Binding sites for the nuclear factor (NF)-kappaB transcription factor have been identified within control regions of many genes involved in inflammatory and immune responses. Such kappaB sites are often found adjacent to those of interferon (IFN)-gamma-inducible transcription factors, suggesting a requirement for multiple signaling pathways for gene regulation. Using fibroblasts from RelA (p65)-deficient mice generated by gene targeting, we have investigated the role of this subunit of NF-kappaB in gene activation by microbial lipopolysaccharide, tumor necrosis factor alpha, and in possible synergism with the IFN-gamma-signaling pathway. Our results indicate not only that RelA is required for activation of key genes involved in adaptive (acquired) immune responses, including major histocompatibility complex class I, CD40, and the Fas death receptor, but also that both NF-kappaB-inducing signals and IFN-gamma are necessary for maximal activation. In contrast, neutrophil-specific chemokine genes KC and MIP-2, which can function as nonspecific mediators in innate immune responses, were strongly induced by RelA in the absence of IFN-gamma. Our results show that RelA plays a critical role in activation of immune system genes in response to nonspecific stimuli and demonstrate a novel proapoptotic function for this protein in Fas-induced cell death.
Microstructure of the mist zone on glass fracture surfaces (1968)

Abstract The mist zone, the arc of stippled surface surrounding the mirror-smooth area at the origin of fracture, was examined in detail using an optical microscope and progressive etching. The results show that the stippled area can be regarded as a collection of large numbers of individual local elements of but two basic types, and that microscopic cracks exist below the fracture surface which are related to the structure on the exposed surface.
Pulse shaping for high -harmonic generation. (2000)

In this work, I present a programmable, deformable-mirror based pulse shaper. The mirror used was a micromachined membrane deformable mirror. I used the pulse shaper to compress pulses from an ultrafast Ti:sapphire oscillator and to remove the residual phase from an ultrafast Ti:sapphire amplifier system. In both systems, I was able to obtain near transform-limited pulses. To achieve this compression I used two different methods. In one method, I calibrated the pulse shaper using frequency resolved optical gating (FROG), and calculated the settings necessary to eliminate the phase from the pulse. In the other method, I used an evolutionary strategy algorithm to optimize the second harmonic signal. I also used the pulse shaper to optimize the output of high-harmonic generation (HHG). For this I again used the evolutionary strategy algorithm to optimize the harmonic spectrum. Using this method, I was able to more than double the peak intensity of a single harmonic, and I was able to shift the cutoff of the harmonics. In subsequent work, colleagues have achieved a factor of eleven increase in the peak intensity of a single harmonic using the setup reported here.
Met and hepatocyte growth factor/scatter factor expression in human gliomas. (1997)

Using double immunofluorescence staining and quantitative confocal laser scan microscopy, we show that the intensity of hepatocyte growth factor/scatter factor (HGF/SF) and Met staining in human primary brain tumors increases with the grade of malignancy and is prevalent in both the infiltrating tumor cells and endothelial hyperplastic areas. HGF/SF and Met also are expressed in vitro in glioblastoma multiforme cell lines as well as in normal human astrocyte (NHA) cells. Moreover, HGF/SF stimulates tyrosine phosphorylation of Met in both glioma cell lines and NHA cells, but only the glioma cell lines proliferate and become motile and invasive in response to HGF/SF, whereas the NHA cells are nonresponsive. These results implicate autocrine/paracrine Met-HGF/SF signaling in glioma tumorigenesis and suggest that HGF/SF signaling through Met is negatively regulated in NHA cells.
A spatial filtering approach to robust adaptive beaming (1992)

The problem of controlling the superresolution in adaptive beamformers is treated. A straightforward method is presented that works for both narrowband and broadband arrays. The method is based on forming the blocking matrix in a general sidelobe canceller structure using a spatial FIR filter. The suppression of this spatial filter and the implicit noise of the leaky least-mean-square algorithm together determine the beamformer.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Sentinel-Node Biopsy or Nodal Observation in Melanoma (2006)

The staging of intermediate-thickness (1.2 to 3.5 mm) primary melanomas according to the results of sentinel-node biopsy provides important prognostic information and identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy. (ClinicalTrials.gov number, NCT00275496 [ClinicalTrials.gov].).
Mediation of c-Myc-Induced Apoptosis by p53 (1994)

The cellular proto-oncogene c-myc is involved in cell proliferation and transformation but is also implicated in the induction of programmed cell death (apoptosis). The same characteristics have been described for the tumor suppressor gene p53, the most commonly mutated gene in human cancer. In quiescent mouse fibroblasts expressing wild-type p53 protein, activation of c-Myc was found to induce apoptosis and cell cycle reentry, preceded by stabilization of p53. In contrast, in quiescent p53-null fibroblasts, activation of c-Myc induced cell cycle reentry but not apoptosis. These results suggest that p53 mediates apoptosis as a safeguard mechanism to prevent cell proliferation induced by oncogene activation.
Soluble P-selectin in Atherosclerosis: A Comparison with Endothelial Cell and Platelet Markers (1997)

von Willebrand factor and soluble thrombomodulin are established plasma markers of endothelial cell dysfunction, whilst beta thromboglobulin is an established plasma marker of platelet activity. Soluble P-selectin may be the product of either or both types of cell and levels of all four molecules have been previously found to be increased in atherosclerosis. To determine the relationship of soluble P-selectin to the endothelial cell and platelet products, we measured the four indices in a case control study of 55 patients with peripheral vascular disease and 55 age and sex matched controls. von Willebrand factor (p < 0.0001), beta thromboglobulin (p = 0.0006), soluble P-selectin (p = 0.0021) and soluble thrombomodulin (p = 0.021) were all raised in the patients. Soluble P-selectin correlated with beta thromboglobulin (r = 0.34, p = 0.019) but failed to correlate with either endothelial cell marker. Co-culture of endothelial cells in vitro with bovine thrombin resulted in increased levels of von Willebrand factor in the supernatants but levels of soluble thrombomodulin and soluble P-selectin were not enhanced. Exposure of endothelial cell monolayers to elastase resulted in different patterns of release of von Willebrand factor, soluble thrombomodulin and soluble P-selectin. We suggest that soluble P-selectin is unlikely to arise from the endothelium and may be a new marker of platelet activation in atherosclerosis.
Frequent gene expression of granulocyte colony-stimulating factor (G-CSF) receptor in CD7+ surface CD3- acute lymphoblastic leukaemia. (1993)

Gene expression of various cytokine receptors in CD7+ acute lymphoblastic leukemia (ALL) cells in relation to responsiveness to these cytokines was examined by reverse transcription polymerase chain reaction and Northern blot studies. Leukemic cells from all of seven CD7+ ALL patients examined fulfilled the criteria for ALL according to the FAB classification; surface CD3 was absent in all of these patients, while cytoplasmic CD3 and/or CD3 epsilon mRNA were found in all of them. Samples from six of the seven patients at initial disease expressed the granulocyte colony-stimulating factor receptor (G-CSFR) gene. Leukemic cells with G-CSFR transcripts from one patient at initial disease showed growth response to G-CSF in vitro, and those from two other patients became responsive to G-CSF at relapse. Neither in vitro nor in vivo myeloid differentiation was observed in any samples that responded to G-CSF. Interleukin 3R alpha (IL-3R alpha) gene was expressed in samples from one patient at initial disease and from two patients at relapse. GM-CSFR beta gene mRNA was detected in two patients with IL-3R alpha mRNA. Our results show that the leukemic cells in these CD7+ ALL patients frequently expressed G-CSFR as a functional property, thus calling attention to the appropriate clinical application of G-CSF for ALL patients.
Recovery of antibody activity on reoxidation of completely reduced polyalanyl heavy chain and its Fd fragment derived from anti-2,4-dinitrophenyl antibody (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRecovery of antibody activity on reoxidation of completely reduced polyalanyl heavy chain and its Fd fragment derived from anti-2,4-dinitrophenyl antibodyJean C. Jaton, Norman R. Klinman, David. Givol, and Michael. SelaCite this: Biochemistry 1968, 7, 12, 4185–4195Publication Date (Print):December 1, 1968Publication History Published online1 May 2002Published inissue 1 December 1968https://pubs.acs.org/doi/10.1021/bi00852a008https://doi.org/10.1021/bi00852a008research-articleACS PublicationsRequest reuse permissionsArticle Views71Altmetric-Citations28LEARN 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
Distinct mechanisms of suppression of murine T cell activation by the related macrolides FK-506 and rapamycin. (1990)

FK-506 and the structurally related macrolide rapamycin (RAP) were investigated in comparison with cyclosporin A (CsA) for their immunosuppressive effects on murine T cells. All three agents suppressed the proliferation of splenic T cells triggered by lectins or antibodies to CD3 and Ly-6C. FK-506 or CsA also inhibited proliferation, IL-2 production, and IL-2R expression in splenic T cells activated with ionomycin + PMA. However, RAP minimally affected IL-2 production and IL-2R expression in these cells, although it reduced proliferation. Similarly, FK-506 and CsA, but not RAP, suppressed IL-2 production by activated DO.11.10 T hybridoma cells. In such a system, as well as in normal T cells stimulated with high ionomycin concentrations, FK-506 and CsA enhanced proliferation, indicating that they both abrogate negative signals associated with T cell activation. On the contrary, RAP diminished the autonomous proliferation of hybridoma cells, whereas FK-506 and CsA had little effect. The proliferative response induced in D10.G4 cells by IL-1 + ionomycin but not that induced by IL-1 + PMA was sensitive to inhibition by FK-506 and CsA. In contrast, RAP inhibited equally well both types of stimulation. Finally, T cell proliferation driven by IL-2 or IL-4 was found to be relatively resistant to FK-506 or CsA but sensitive to RAP. Altogether, these data demonstrate that FK-506 and CsA alter similar calcium-associated events of T cell activation and block T cell proliferation primarily by suppressing lymphokine production. RAP interferes with a different set of events and inhibits T cells by impairing their response to growth-promoting lymphokines.