gebhart/patrepeval huggingface dataset:
Forecasting the cytokine storm following systemic interleukin (IL)-2 administration (2004)

Extensive clinical experience has shown that systemic interleukin (IL)-2 administration can induce complete or partial regression of renal cell cancer (RCC) metastases in 15 to 20 % of patients. Since IL-2 has no direct anti-cancer effects, it is believed that cancer regression is mediated either by a direct modulation of immune cell effector functions or through the mediation of soluble factors released as a result of IL-2 administration.We previously observed that transcriptional and protein changes induced by systemic IL-2 administration affect predominantly mononuclear phagocytes with little effect, particularly within the tumor microenvironment, on T cell activation, localization and proliferation. It further appeared that mononuclear phagocyte activation could be best explained by the indirect mediation of a secondary release of cytokines by IL-2 responsive cells either in the circulation or in peripheral tissues.To better characterize the cytokine outburst that follows systemic IL-2 administration we followed the serum levels of 68 soluble factors in ten patients with RCC undergoing high dose (720,000 IU/kg intravenously every 8 hours) IL-2 therapy. Serum was collected before therapy, 3 hours after the 1st and 4th dose and assayed on a multiplexed protein array platform. This study demonstrated that 1) the serum concentration of more than half the soluble factors studied changed significantly during therapy; 2) changes became more dramatic with increasing doses; 3) subclasses of soluble factors displayed different kinetics and 4) cytokine patterns varied quantitatively among patients.This study shows that the cytokine storm that follows systemic IL-2 administration is complex and far-reaching inclusive of soluble factors with disparate, partly redundant and partly contrasting effects on immune function. Therefore comparing in parallel large number of soluble factors, it sets a comprehensive foundation for further elucidation of "cytokine storm" in larger patient pools. Based on this analysis, we propose a prospective collection of serum samples in a larger cohort of patients undergoing IL-2 administration with the purpose of discerning patterns predictive of clinical outcome and toxicity.
Abstracting object state (1997)

The term `state' has many different meanings, depending on the context in which it is used. In the implementation phase, it refers to the values of the instance variables of the object; during design, it refers to states used in finite state models or their derivatives. For both interpretations, problems have been identified: (1) the way clients of an object access its state is defined in an ad hoc manner, (2) the conventional object-oriented model provides no means to change the interface of an object dynamically on the basis its state or the type of client accessing it, (3) finite state machine approaches are not uniformly integrated in the object-oriented model nor do they provide sufficient complexity reduction for modelling the dynamic behaviour, and (4) no support is provided for defining active states. In this paper we introduce the concept of abstract object state as a solution to these problems. This concept provides a systematic technique to explicitly define an abstraction of the object state which is placed at the interface of the object. The abstract object state consists of static states, but also of active states which can be seen as time derivatives of static states. We show that the abstract object state provides a more uniform approach to object behaviour specification than do finite state models. The concepts discussed have been implemented in the layered object model ((LOM)-O-AY), an extended object-oriented model which is supported by a translator to C++, an execution environment and an integrated development environment.
1,3-dialkylxanthine derivatives having high potency as antagonists at human A2B adenosine receptors (1999)

The structure-activity relationships (SAR) of alkylxanthine derivatives as antagonists at the recombinant human adenosine receptors were explored in order to identify selective antagonists of A<sub>2B</sub> receptors. The effects of lengthening alkyl substituents from methyl to butyl at 1- and 3-positions and additional substitution at the 7- and 8-positions were probed. K<sub>i</sub> values, determined in competition binding in membranes of HEK-293 cells expressing A<sub>2B</sub> receptors using <sup>125</sup>I-ABOPX (<sup>125</sup>I-3-(4-amino-3-iodobenzyl)-8-(phenyl-4-oxyacetate)-1-propylxanthine), were approximately 10 to 100 nM for 8-phenylxanthine functionalized congeners. Xanthines containing 8-aryl, 8-alkyl, and 8-cycloalkyl substituents, derivatives of XCC (8-[4-[[[carboxy]methyl]oxy]phenyl]-1,3-dipropylxanthine) and XAC (8-[4-[[[[(2-aminoethyl)amino]carbonyl]methyl]-oxy]phenyl]-1,3-dipropylxanthine), containing various ester and amide groups, including L- and D-amino acid conjugates, were included. Enprofylline was 2-fold more potent than theophylline in A<sub>2B</sub> receptor binding, and the 2-thio modification was not tolerated. Among the most potent derivatives examined were XCC, its hydrazide and aminoethyl and fluoroethyl amide derivatives, XAC, N-hydroxyethyl-XAC, and the L-citrulline and D-p-aminophenylalanine conjugates of XAC. An N-hydroxysuccinimide ester of XCC (XCC-NHS, MRS 1204) bound to A<sub>2B</sub> receptors with a K<sub>i</sub> of 9.75 nM and was the most selective (at least 20-fold) in this series. In a functional assay of recombinant human A<sub>2B</sub> receptors, four of these potent xanthines were shown to fully antagonize the effects of NECA-induced stimulation of cyclic AMP accumulation.
Monoclonal antibodies to the integrin α−4 subunit inhibit the murine contact hypersensitivity response (1993)

Lymphocyte-endothelial cell recognition is an active multistep process central to the pathophysiology of inflammation. In vitro models of lymphocyte adhesion predict that the beta 1 integrin very late antigen-4 (VLA-4), an activation-dependent adhesion receptor, can mediate the firm sustained attachment required for the extravasation of memory lymphocytes. We have used murine contact hypersensitivity as an in vivo model in which to evaluate the role of alpha-4 integrins in an evolving inflammatory response. We demonstrate that the intravenous administration of 75 micrograms of the anti-alpha-4 specific monoclonal antibodies R1-2 or PS/2 4-6 h prior to challenge significantly inhibits the efferent response of 2,4 dinitrofluorobenzene, or oxazolone-sensitized mice. The disease-modifying effect of anti-alpha 4 treatment was evident as a 50-60% reduction in the ear swelling response. By histological analysis treated animals scored lower for edema, number of epidermal lesions and degree of leukocyte infiltration. Antibody-treated animals have elevated numbers of circulating mononuclear leukocytes present in the same relative ratio as untreated control animals, suggesting that the inhibitory effect was not due to antibody-dependent cellular depletion of effector lymphocytes. These data are consistent with a central role for VLA-4 in the pathophysiologic process of inflammation.
Large high-density monolithic XY-addressable arrays for flat-panel LED displays (1977)

A large-area <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">XY</tex> -addressable matrix display has been designed and fabricated. This display consists of 4 tiles, each a ½ in × ½ in array of 30 × 36 LED's, end-stacked to form a continuous dot-matrix display, ½ in × 2 in of 30 × 144 LED's. This paper discusses the design considerations, the fabrication technique used, and the yields experienced in fabricating these displays. The yield of perfect tiles was 5 percent. Using as an acceptance criteria, tiles with no more than 4 LED's either out or dim and using repair techniques described herein, yields of 54 percent have been achieved.
Über Thiobarbitursäure‐Methin‐Farbstoffe (1959)

Abstract Es wird bewiesen, daß die aus 6 verschiedenen Stoffen isolierten Farbstoffe mit dem TBS‐Farbstoff 532 identisch sind. Stoffe, die nach der Oxydation, nach Säurehydrolyse oder nach Alkali‐Einwirkung Malonaldehyd bzw. β‐Oxyacrolein ergeben, die ihrerseits den roten Farbstoff TBS 532 bilden, werden aufgeführt. Ferner werden die Reaktionsmechanismen besprochen, die zur Bildung des Aldehyds aus verschiedenen Stoffen führen. Der Autor schlägt eine Strukturformel für den Trimethinfarbstoff vor. Weitere TBS‐Methinfarbstoffe mit Absorptionsmaxima bei 452, 622, 549 und 542 mμ werden synthetisiert und ihre Konstitutionsformeln zur Diskussion gestellt.
Segmented CRC-Aided SC List Polar Decoding (2016)

Because of the existence of channel noise, channel coding serves as an indispensable part of mobile communication system and the essential guarantee for the reliable, accurate, and effective transmission of information. As one of the most competitive channel code candidates for the 5th generation (5G) mobile communication, polar codes are the first codes which can provably achieve the symmetric capacity of binary-input discrete memoryless channels (B-DMCs). In this paper, the segmented CRC- aided successive cancellation list (SCA-SCL) polar decoding scheme is proposed for better tradeoff of performance and complexity. Numerical results on binary-input additive white Gaussian noise channel (BI-AWGNC) have shown that, at SNR of 0.5 dB, this approach successfully provides as high as 41.65% complexity reduction and similar decoding performance compared to state-of-the-art ones.
A Facile Synthesis of an Oxidation Product of Terfenadine (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Facile Synthesis of an Oxidation Product of TerfenadineStephen H. Kawai, Robert J. Hambalek, and George JustCite this: J. Org. Chem. 1994, 59, 9, 2620–2622Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 May 1994https://pubs.acs.org/doi/10.1021/jo00088a056https://doi.org/10.1021/jo00088a056research-articleACS PublicationsRequest reuse permissionsArticle Views1069Altmetric-Citations19LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts
Secondary Structure, Orientation, Oligomerization, and Lipid Interactions of the Transmembrane Domain of Influenza Hemagglutinin (1999)

Influenza virus hemagglutinin (HA), the viral envelope glycoprotein that mediates fusion between the viral and cellular membranes, is a homotrimer of three subunits, each containing two disulfide-linked polypeptide chains, HA(1) and HA(2). Each HA(2) chain spans the viral membrane with a single putative transmembrane alpha-helix near its C-terminus. Fusion experiments with recombinant HAs suggest that this sequence is required for a late step of membrane fusion, as a glycosylphosphatidylinositol-anchored analogue of HA only mediates "hemifusion" of membranes, i.e., the merging of the proximal, but not distal, leaflets of the two juxtaposed lipid bilayers [Kemble et al. (1994) Cell 76, 383-391]. To find a structural explanation for the function of the transmembrane domain of HA(2) in membrane fusion, we have studied the secondary structure, orientation, oligomerization, and lipid interactions of a synthetic peptide representing the transmembrane segment of X:31 HA (TMX31) by circular dichroism and attenuated total reflection Fourier transform infrared spectroscopy and by gel electrophoresis. The peptide was predominantly alpha-helical in detergent micelles and in phospholipid bilayers. The helicity was increased in lipid bilayers composed of acidic lipids compared to pure phosphatidylcholine bilayers. In planar lipid bilayers, the helices were oriented close to the membrane normal. TMX31 aggregated into small heat-resistant oligomers composed of two to five subunits in SDS micelles. Amide hydrogen exchange experiments indicated that a large fraction of the helical residues were accessible to water, suggesting the possibility that TMX31 forms pores in lipid bilayers. Finally, the peptide increased the acyl chain order in lipid bilayers, which may be related to the preferential association of HA with lipid "rafts" in the cell surface and which may be an important prerequisite for complete membrane fusion.
Novel Action of Paclitaxel against Cancer Cells: Bystander Effect Mediated by Reactive Oxygen Species (2007)

Generation of reactive oxygen species (ROS) has been observed in cancer cells treated with paclitaxel, but the underlying mechanisms and therapeutic implications remain unclear. In the present study, we showed that paclitaxel promoted ROS generation through enhancing the activity of NADPH oxidase (NOX) associated with plasma membranes. Treatment of breast cancer cells caused an increased translocation of Rac1, a positive regulatory protein of NOX, to the membrane fraction. The paclitaxel-induced ROS generation occurred rapidly within several hours of drug exposure, with O(2)(-) and H(2)O(2) accumulation mainly outside the cells while the intracellular ROS remained unchanged. Importantly, the increase in extracellular ROS caused lethal damage to the bystander cancer cells not exposed to paclitaxel, as shown by two different methods using coculture systems where the bystander cells were differentiated from the paclitaxel-treated cells by fluorescent or radioactive labeling. This cytotoxic bystander effect was also observed with other microtubule-targeted agents vincristine and taxotere but not with 5-fluorouracil or doxorubicin. This toxic bystander effect was enhanced by CuZnSOD that converts O(2)(-) to H(2)O(2) and was abolished by a catalase that eliminates H(2)O(2). Furthermore, paclitaxel was able to induce an almost complete inhibition of proliferation of the bystander cells in the coculture system. Our study revealed a novel mechanism by which paclitaxel induces toxic bystander effect through generation of extracellular H(2)O(2) from the membrane-associated NOX. This may contribute to the potent anticancer activity of paclitaxel and provide a novel basis to improve the clinical use of this important drug.
Comparing Zinc Finger Nucleases and Transcription Activator-Like Effector Nucleases for Gene Targeting in Drosophila (2013)

Zinc-finger nucleases have proven to be successful as reagents for targeted genome manipulation in Drosophila melanogaster and many other organisms. Their utility has been limited, however, by the significant failure rate of new designs, reflecting the complexity of DNA recognition by zinc fingers. Transcription activator-like effector (TALE) DNA-binding domains depend on a simple, one-module-to-one-base-pair recognition code, and they have been very productively incorporated into nucleases (TALENs) for genome engineering. In this report we describe the design of TALENs for a number of different genes in Drosophila, and we explore several parameters of TALEN design. The rate of success with TALENs was substantially greater than for zinc-finger nucleases , and the frequency of mutagenesis was comparable. Knockout mutations were isolated in several genes in which such alleles were not previously available. TALENs are an effective tool for targeted genome manipulation in Drosophila.
Targeted brain delivery of AZT via transferrin anchored pegylated albumin nanoparticles (2006)

Hydrophilic drugs/peptides have poor cross Blood-brain permeability. Various drug delivery systems with diverse surfacial characteristics have been reported for effective translocation of drugs across Blood-brain barrier. In present investigation, the potential of engineered albumin nanoparticles was evaluated for brain specific delivery after intravenous administration. Long circulatory PEGylated albumin nanoparticles encapsulating water-soluble antiviral drug azidothymidine (AZT) were prepared by ultra-emulsification method using chemical cross-linking by glutaraldehyde. Surface of the PEGylated nanoparticles was modified by anchoring transferrin as a ligand for brain targeting. Nanoparticles were characterized for their size, polydispersity, surfacial charge, drug loading and in vitro drug release. Fluorescence studies revealed the enhanced uptake of transferrin-anchored nanoparticles in the brain tissues when compared with unmodified nanoparticles. In vivo evaluation was carried out on albino rats to evaluate tissue distribution of engineered nanoparticles after intravenous administration. A significant ((*)P < 0.01) enhancement of brain localization of AZT was observed for transferrin anchored pegylated albumin nanopariticles (Tf-PEG-NPs). Hence, the specific role of transferrin ligand on nanoparticles for brain targeting was confirmed.
Serum levels of the low molecular weight form of insulin-like growth factor binding protein in healthy subjects and patients with growth hormone deficiency, acromegaly and anorexia nervosa (1988)

The low molecular weight form of insulin-like growth factor binding protein (35 kD IGFBP), determined in serum by radioimmunoassay during non-fasting conditions, was high at birth and declined with increasing age during childhood and adolescence (N = 149). Inverse correlation was found between chronological age and 35 kD IGFBP values (r = -0.61, P less than 0.001) during childhood and adolescence, but no age dependency was found in adult subjects aged 20-66 years (N = 73). The mean and 95% confidence limits of immunoreactive 35 kD IGFBP were 34 micrograms/l and 15-79 micrograms/l, respectively, in healthy adults (N = 73) in whom the blood samples were drawn after a one-night fast. The mean level of the 35 kD IGFBP in patients with acromegaly (19 micrograms/l, N = 23) was decreased by 50% in comparison with healthy adults, whereas a 2-fold elevation of the mean levels was found in both anorexia nervosa patients (70 micrograms/l, N = 13) and adult patients with GH deficiency (69 micrograms/l, N = 22). In patients with anorexia nervosa, the 35 kD IGFBP levels were inversely related to the body mass index (r = -0.65, P less than 0.02).
Selective removal of apolipoprotein B-containing serum lipoproteins from blood plasma. (1981)

Studies were undertaken to determine the applicability and effectiveness of immunoadsorption chromatography on anti-low density lipoprotein (LDL) columns as a plasma-cholesterol-lowering procedure. Mass production and isolation of monospecific antibodies against swine LDL (rho = 1.006-1.063 g/ml) was carried out by immunization of sheep with swine LDL and selective antibody adsorption from their antisera by chromatography on LDL-Sepharose. The isolated LDL antibodies were then covalently linked to Sepharose CL-4B. Pig plasma LDL was effectively removed in vitro by the anti-LDL-Sepharose beads. In vivo studies were performed in pigs with (i) a plasma-separator membrane permeable to solutes below Mr 2,000,000 or (ii) a blood centrifuge interposed into an arteriovenous shunt to separate the corpuscular elements of blood from the plasma. In either case, the plasma was passed through the anti-LDL-Sepharose column and recirculated into the venous part of the shunt. Plasma cholesterol levels were reduced 70-80% by this procedure and rebounded 3-4 days after the extracorporeal immunoadsorption procedure. This continuous plasma separation-immunoadsorption procedure may have broad applicability for the elimination of any plasma component with antigenic properties.
The melanoma growth stimulatory activity receptor consists of two proteins. Ligand binding results in enhanced tyrosine phosphorylation (1992)

The human melanoma growth-stimulatory activities (MGSA alpha, beta, gamma/GRO) are products of immediate early genes coding for cytokines that exhibit sequence similarity to platelet factor-4 and beta-thromboglobulin. MGSA/GRO alpha has been demonstrated to partially complete for binding to the approximately 58-kDa neutrophil receptor for another beta-thromboglobulin-related chemotactic protein, IL-8. We demonstrate that when [125I]MGSA/GRO alpha was cross-linked to receptors/binding proteins from human placenta, there were two major [125I]MGSA cross-linked bands of approximately 64,000 and approximately 84,000 Mr. Because [125I]MGSA exists primarily in monomer and dimer forms at the concentrations used here, it is not clear whether the receptor/binding proteins represented by the cross-linked bands are approximately 50,000 and approximately 70,000 or approximately 58,000 and approximately 78,000 Mr. Ligand binding to the receptor proteins is associated with enhanced tyrosine phosphorylation of a number of substrates, including proteins in the same Mr range as the MGSA/GRO receptor/binding proteins.
Cryptography: Theory and Practice, Third Edition (2005)

THE LEGACYFirst introduced in 1995, Cryptography: Theory and Practice garnered enormous praise and popularity, and soon became the standard textbook for cryptography courses around the world. The second edition was equally embraced, and enjoys status as a perennial bestseller. Now in its third edition, this authoritative text continues to prov
Comparative Heat Stabilities of Some Metal Acetylacetonate Chelates (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComparative Heat Stabilities of Some Metal Acetylacetonate ChelatesRobert G. Charles and M. Arlene PawlikowskiCite this: J. Phys. Chem. 1958, 62, 4, 440–444Publication Date (Print):April 1, 1958Publication History Published online1 May 2002Published inissue 1 April 1958https://pubs.acs.org/doi/10.1021/j150562a017https://doi.org/10.1021/j150562a017research-articleACS PublicationsRequest reuse permissionsArticle Views2629Altmetric-Citations216LEARN 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 options Get e-Alerts