gebhart/patrepeval huggingface dataset:
Selective enhancement of thrombopoietic activity of PEGylated interleukin 6 by a simple procedure using a reversible amino‐protective reagent (2001)

We developed a novel method for the chemical modification of cytokines with synthetic polymers to increase the therapeutic efficacy of the former in vivo. A pH-reversible amino-protective reagent, dimethylmaleic anhydride (DMMAn), was used for modification of interleukin-6 (IL-6) with polyethylene glycol (PEG). The novel PEG-conjugated IL-6 (DmPEG-IL-6), which had been pretreated with DMMAn before PEGylation, showed up to a 140% increase in in vitro specific activity compared with PEG-IL-6 that had been synthesized by the previous method. Moreover, DmPEG-IL-6 caused thrombopoiesis more potently in mice than PEG-IL-6. The DmPEG-IL-6 Fr.1, having 3-4 PEG chains attached to the cytokine, showed the strongest thrombopoietic effect among the DmPEG-IL-6s with different molecular sizes that were tested. PEG-IL-6 Fr.1 had a 500-fold higher potency in stimulating thrombopoiesis than native IL-6 and DmPEG-IL-6 Fr.1 achieved a threefold higher thrombopoietic effect than PEG-IL-6 Fr.1. In addition, side-effects, such as an increase in the plasma fibrinogen level, were not observed after injection of either PEG-IL-6s or DmPEG-IL-6s. These results suggest that PEGylation with DMMAn pretreatment may become a useful means for clinical cytokine delivery.
Genetic, Biochemical, and Clinical Features of Chronic Granulomatous Disease (2000)

The reduced nicotinamide dinucleotide phosphate (NADPH) oxidase complex allows phagocytes to rapidly convert O2 to superoxide anion which then generates other antimicrobial reactive oxygen intermediates, such as H2O2, hydroxyl anion, and peroxynitrite anion. Chronic granulomatous disease (CGD) results from a defect in any of the 4 subunits of the NADPH oxidase and is characterized by recurrent life-threatening bacterial and fungal infections and abnormal tissue granuloma formation. Activation of the NADPH oxidase requires translocation of the cytosolic subunits p47phox (phagocyte oxidase), p67phox, and the low molecular weight GT-Pase Rac, to the membrane-bound flavocytochrome, a heterodimer composed of the heavy chain gp91phox and the light chain p22phox. This complex transfers electrons from NADPH on the cytoplasmic side to O2 on the vacuolar or extracellular side, thereby generating superoxide anion. Activation of the NADPH oxidase requires complex rearrangements between the protein subunits, which are in part mediated by noncovalent binding between src-homology 3 domains (SH3 domains) and proline-rich motifs. Outpatient management of CGD patients relies on the use of prophylactic antibiotics and interferon-gamma. When infection is suspected, aggressive effort to obtain culture material is required. Treatment of infections involves prolonged use of systemic antibiotics, surgical debridement when feasible, and, in severe infections, use of granulocyte transfusions. Mouse knockout models of CGD have been created in which to examine aspects of pathophysiology and therapy. Gene therapy and bone marrow transplantation trials in CGD patients are ongoing and show great promise.
Secure Remote Access to an Internal Web Server. (1999)

We address the problem of secureremote access to a site&amp;apos;s internal web server from outside the #rewall. The goal is to give authorized users access to sensitive information, while protecting the information from others. We implemented our solution using a one-time password scheme for client authentication and SSL for con#dentiality. Our main design considerations weresecurity, performance, ease of use, availability, and scale. We were further constrained by the desiretoleave our #rewall and local infrastructure unchanged. 1 Introduction Most large organizations todayhave to resort to using #rewalls to protect themselves from would-be hostile attackers on the Internet. While #rewalls are an inconvenience, when well administered, they do a reasonable job of isolating an organization from the rest of the world. The security policy usually amounts to total trust of all insiders and total mistrust of outsiders, where the #rewall de#nes the boundary #2#. As a result of classifying users a...
Nonphotolithographic Nanoscale Memory Density Prospects (2005)

Technologies are now emerging to construct molecular-scale electronic wires and switches using bottom-up self-assembly. This opens the possibility of constructing nanoscale circuits and memories where active devices are just a few nanometers square and wire pitches may be on the order of ten nanometers. The features can be defined at this scale without using photolithography. The available assembly techniques have relatively high defect rates compared to conventional lithographic integrated circuits and can only produce very regular structures. Nonetheless, with proper memory organization, it is reasonable to expect these technologies to provide memory densities in excess of 10/sup 11/ b/cm/sup 2/ with modest active power requirements under 0.6 W/Tb/s for random read operations.
Detection of Epstein–Barr virus nucleic acid sequences and protein in nodal T‐cell lymphomas: relation between latent membrane protein‐1 positivity and clinical course (1993)

Forty-six nodal T-cell lymphomas, classified according to the updated Kiel classification, were investigated for the presence of Epstein-Barr virus (EBV) DNA by polymerase chain reaction (PCR), EBER 1 and 2 (EBER 1/2) and latent membrane protein-1 (LMP-1) expression. A combination of RNA in situ hybridization and immunohistochemistry was used to establish the phenotype of the Epstein-Barr virus harbouring cells. In 21 of 45 cases Epstein-Barr virus DNA sequences could be detected with the polymerase chain reaction. In 15 cases (14 of 21 EBV PCR positive cases), EBER 1/2 positive cells could be demonstrated. As judged by morphology, EBER 1/2 expression was found in nonneoplastic and neoplastic lymphoid cells. Double staining revealed that more than 80% of the EBER 1/2 harbouring cells, lacked B-, T- or histiocytic markers, suggesting down regulation of T- and B-cell markers by Epstein-Barr virus. In eight of 15 cases some EBER 1/2 positive T-cells (CD3, CD45RO, CD43) morphologically resembling tumour cells were found. In nine of 14 cases tested EBER 1/2 positive non-neoplastic B-cells (CD20) were seen. Based on in situ hybridization results, four patterns of EBER 1/2 positive cells were found, i.e. single cells (< 1 per medium power field (mpf), n = 3), scattered (1-25/mpf, n = 4), clustered (26-100/mpf, n = 5) and diffuse (> 100/mpf, n = 3). In eight of 15 cases a clustered or diffuse pattern of EBER 1/2 positive cells was found and these lymphomas were therefore considered to be strongly associated with Epstein-Barr virus. In these lymphomas LMP-1 expression was found to be associated with an aggressive clinical course and hepatosplenomegaly.
Fecal microbiota transplantation as therapy for inflammatory bowel disease: A systematic review and meta-analysis (2014)

This analysis suggests that FMT is a safe, but variably efficacious treatment for IBD. More randomized controlled trials are needed and should investigate frequency of FMT administration, donor selection and standardization of microbiome analysis.
Perspective/navigation-The Global Positioning System (1993)

A brief history of navigation is given, highlighting the needs that led ultimately to the development of 3-D satellite based navigation. The evolution of Navstar, commonly known as GPS (Global Positioning System), is traced from its initial conception in 1960. The use of bandwidth compression to overcome the SNR problem is discussed. An explanation of how the GPS works is provided. Civilian as well as military applications are examined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase [see comments] (1989)

Circulating IgG autoantibodies that produce cytoplasmic immunofluorescence staining of ethanol-fixed normal neutrophils have recently been found in a large percentage of patients with active Wegener's granulomatosis. Such autoantibodies are rarely found in other diseases and are therefore virtually diagnostic of Wegener's granulomatosis. The nature of the neutrophil antigen defined by these autoantibodies is controversial and the roles of the antigen and/or autoantibodies in the pathogenesis of Wegener's granulomatosis are unknown. We studied serum samples that produce the cytoplasmic pattern of staining from 10 patients with a diagnosis of Wegener's granulomatosis. By Western blot analysis, all 10 sera reacted with a 29-Kd neutrophil protein (p29). We generated a mouse monoclonal antibody directed against this antigen. The monoclonal antibody produced the same immunofluorescence staining pattern as the serum autoantibodies and was used to affinity-purify p29. The purified antigen had a novel N-terminal sequence homologous to members of the serine proteinase family and bound to radiolabeled diisopropyl fluorophosphate (DFP). We conclude that the neutrophil antigen responsible for the cytoplasmic staining pattern produced by autoantibodies in patients with active Wegener's granulomatosis is a distinctive serine proteinase.
Nuclear localization signals: a driving force for nuclear transport of plasmid DNA in zebrafish (1997)

Nuclear localization signals (NLSs) are short peptides required for nuclear transport of karyophilic proteins. We review in this paper how the nuclear targeting property of NLS peptides has been taken advantage of to enhance the efficiency of nuclear uptake of transgene DNA in zebrafish and how it may improve the efficiency of transgenesis in this species. Synthetic NLS peptides can bind to plasmid DNA by ionic interactions. Cytoplasmic injection of DNA-NLS complexes in zebrafish eggs enhances the rate and the amount of plasmid DNA taken up by embryonic nuclei. Nuclear import of DNA-NLS complexes has been duplicated in vitro and exhibits energetic and cytosolic requirements similar to those for nuclear protein import. Furthermore, binding NLSs to DNA increases expression frequency of the transgene. We suggest that NLS peptides may constitute a valuable tool to improve the efficiency of transgenesis in zebrafish and other species.
Site-specific glycosylation of human recombinant erythropoietin: analysis of glycopeptides or peptides at each glycosylation site by fast atom bombardment-mass spectrometry (1988)

We have previously determined the carbohydrate structure of human recombinant erythropoietin [Sasaki, H., Bothner, B., Dell, A., & Fukuda, M. (1987) J. Biol. Chem. 262, 12059-12076]. The carbohydrate chains are distributed in three N-glycosylation sites and one O-glycosylation site. In order to examine the extent to which protein structure influences glycosylation, we have analyzed the saccharide structures at each glycosylation site (Asn24, Asn38, Asn83, and Ser126) of human recombinant erythropoietin. By high-performance liquid chromatography, we have succeeded in separation of glycopeptides containing different O-linked saccharides to the same peptide backbone. Fast atom bombardment mass spectrometry of the isolated glycopeptides combined with Edman degradation allowed us to elucidate the composition of glycopeptides and the amino acid attachment site. The analysis of glycopeptides and saccharides by fast atom bombardment mass spectrometry and high-performance liquid chromatography provided the following conclusions on N-glycans: (1) saccharides at Asn24 are heterogeneous and consist of biantennary, triantennary, and tetraantennary saccharides with or without N-acetyllactosaminyl repeats; (2) saccharides at Asn38 mainly consist of well-processed saccharides such as tetraantennary saccharides with or without N-acetyllactosaminyl repeats; (3) saccharides at Asn83, on the other hand, are homogeneous in the backbone structure and are composed mainly of tetraantennary without N-acetyllactosaminyl repeats. It was also noted that saccharides at Asn24 are much less sialylated than those at Asn38, although these two glycosylation sites are close to each other. These results clearly indicate that the protein structure and, possibly, the carbohydrate chain at the neighboring site greatly influence glycosylation of a given glycosylation site.
Integrated flight/thrust vectoring control for jet-powered unmanned aerial vehicles with ACHEON propulsion (2014)

As a new alternative to tilting rotors or turbojet vector mechanical oriented nozzles, ACHEON (Aerial Coanda High Efficiency Orienting-jet Nozzle) has enormous advantages because it is free of moving elements and highly effective for vertical/short-take-off and landing (V/STOL) aircraft. In this article, an integrated flight/thrust vectoring (TV) control scheme for a jet-powered unmanned aerial vehicle (UAV) with an ACHEON nozzle is proposed to assess its suitability in jet aircraft flight applications. First, a simplified TV population model is built based on CFD simulation data and parameter identification. Second, this TV propulsion model is embedded as a jet actuator for a benchmark fixed-wing ‘Aerosonde’ UAV, and then a four ‘cascaded-loop’ controller, based on nonlinear dynamic inversion (NDI), is designed to individually control the angular rates (in the body frame), attitude angles (in the wind frame), track angles (in the navigation frame), and position (in the earth-centred frame) . Unlike previous research on fixed-wing UAV flight controls or TV controls, our proposed four-cascaded NDI control law can not only coordinate surface control and TV control as well as an optimization controller, but can also implement an absolute self-position control for the autopilot flight control. Finally, flight simulations in a high-fidelity aerodynamic environment are performed to demonstrate the effectiveness and superiority of our proposed control scheme.
A scalable architecture of a structured LDPC decoder (2004)

We present a scalable decoding architecture for a certain class of structured LDPC codes. The codes are designed using a small (n, r) protograph that is replicated Z times to produce a decoding graph for a (Z/spl times/n, Z/spl times/r) code. Using this architecture, we have implemented a decoder for a (4096, 2048) LDPC code on a Xilinx Virtex-II 2000 FPGA, and achieved decoding speeds of 31 Mbps with 10 fixed iterations. The implemented message-passing algorithm uses an optimized 3-bit nonuniform quantizer that allows near floating point performance in the waterfall region, with drastically smaller hardware implementation requirements.
Enhancing the enantioselectivity of Candida lipase-catalyzed ester hydrolysis via noncovalent enzyme modification (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnhancing the enantioselectivity of Candida lipase-catalyzed ester hydrolysis via noncovalent enzyme modificationShih Hsiung Wu, Zhi Wei Guo, and Charles J. SihCite this: J. Am. Chem. Soc. 1990, 112, 5, 1990–1995Publication Date (Print):February 1, 1990Publication History Published online1 May 2002Published inissue 1 February 1990https://pubs.acs.org/doi/10.1021/ja00161a052https://doi.org/10.1021/ja00161a052research-articleACS PublicationsRequest reuse permissionsArticle Views857Altmetric-Citations150LEARN 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
Inhibition of trypsin by cowpea thionin: Characterization, molecular modeling, and docking (2002)

Abstract Higher plants produce several families of proteins with toxic properties, which act as defense compounds against pests and pathogens. The thionin family represents one family and comprises low molecular mass cysteine‐rich proteins, usually basic and distributed in different plant tissues. Here, we report the purification and characterization of a new thionin from cowpea ( Vigna unguiculata ) with proteinase inhibitory activity. Cowpea thionin inhibits trypsin, but not chymotrypsin, binding with a stoichiometry of 1:1 as shown with the use of mass spectrometry. Previous annotations of thionins as proteinase inhibitors were based on their erroneous identification as homologues of Bowman‐Birk family inhibitors. Molecular modeling experiments were used to propose a mode of docking of cowpea thionin with trypsin. Consideration of the dynamic properties of the cowpea thionin was essential to arrive at a model with favorable interface characteristics comparable with structures of trypsin‐inhibitor complexes determined by X‐ray crystallography. In the final model, Lys11 occupies the S1 specificity pocket of trypsin as part of a canonical style interaction. Proteins 2002;48:311–319. © 2002 Wiley‐Liss, Inc.
Tissue printing : tools for the study of anatomy, histochemistry, and gene expression (1992)

Physical tissue prints, P.D. Reid localization of cell wall proteins, G.I. Cassab induction, accumulation, localization, and transport studies by tissue printing, E. del Campillo visualization of enzyme activity, J.E. Varner lectin and glycan recognition, R.F. Pont-Lezica gene expression in plants, Z. -H. Ye et al detection and localization of plant pathogens, C.A. Holt tissue prints on animal tissues, P.D. Reid miscellaneous applications of tissue prints, R.F. Pont-Lezica.
Induction of Purkinje fiber differentiation by coronary arterialization (1999)

A synchronized heart beat is controlled by pacemaking impulses conducted through Purkinje fibers. In chicks, these impulse-conducting cells are recruited during embryogenesis from myocytes in direct association with developing coronary arteries. In culture, the vascular cytokine endothelin converts embryonic myocytes to Purkinje cells, implying that selection of conduction phenotype may be mediated by an instructive cue from arteries. To investigate this hypothesis, coronary arterial development in the chicken embryo was either inhibited by neural crest ablation or activated by ectopic expression of fibroblast growth factor (FGF). Ablation of cardiac neural crest resulted in approximately 70% reductions (P < 0.01) in the density of intramural coronary arteries and associated Purkinje fibers. Activation of coronary arterial branching was induced by retrovirus-mediated overexpression of FGF. At sites of FGF-induced hypervascularization, ectopic Purkinje fibers differentiated adjacent to newly induced coronary arteries. Our data indicate the necessity and sufficiency of developing arterial bed for converting a juxtaposed myocyte into a Purkinje fiber cell and provide evidence for an inductive function for arteriogenesis in heart development distinct from its role in establishing coronary blood circulation.
Pericytes of Newly Formed Vessels in Experimental Subretinal Neovascularization (1995)

Pericytes are involved in maturation of the endothelial cells that form subretinal new vessels.
Caloric Restriction Mimetics: Metabolic Interventions (2001)

Caloric restriction (CR) retards diseases and aging in laboratory rodents and is now being tested in nonhuman primates. One way to apply these findings to human health is to identify and test agents that may mimic critical actions of CR. Panel 2 focused on two outcomes of CR, reduction of oxidative stress and improved glucoregulation, for which candidate metabolic mimics exist. It was recommended that studies on oxidative stress should emphasize mitochondrial function and to test the efficacy of nitrone and other antioxidants in mimicking CR's effects. Studies should also focus on the long-term effects of compounds known to lower circulating glucose and insulin concentrations or to increase insulin sensitivity. Also, four other developing areas were identified: intermediary metabolism, response to infection, stress responses, and source of dietary fat. These areas are important because either they hold promise for the discovery of new mimetics or they need to be explored prior to initiation of CR trials in humans. Other recommendations were that transgenic approaches and adult-onset CR should be emphasized in future studies.
The Role of the 5′-Hydroxyl Group of Adenosine in Determining Substrate Specificity for Adenosine Deaminase (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Role of the 5′-Hydroxyl Group of Adenosine in Determining Substrate Specificity for Adenosine DeaminaseAlexander. Bloch, Morris J. Robins, and James R. McCarthyCite this: J. Med. Chem. 1967, 10, 5, 908–912Publication Date (Print):September 1, 1967Publication History Published online1 May 2002Published inissue 1 September 1967https://pubs.acs.org/doi/10.1021/jm00317a034https://doi.org/10.1021/jm00317a034research-articleACS PublicationsRequest reuse permissionsArticle Views202Altmetric-Citations87LEARN 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
Elements of the Yeast Pheromone Response Pathway Required for Filamentous Growth of Diploids (1993)

Transmission of an external signal from receptors to downstream targets is often mediated by a conserved set of protein kinases that act in sequence (a kinase cascade). In haploid strains of Saccharomyces cerevisiae, a signal initiated by peptide pheromones is transmitted through this kinase cascade to a transcription factor STE12, which is required for the expression of many mating-specific genes. Here it was shown that in diploids some of the same kinases and STE12 are required for filamentous growth, but the pheromone receptors and guanosine triphosphate-binding protein are not required for filament formation. Thus, a similar kinase cascade is activated by different signals in haploids and diploids and mediates different developmental outcomes in the two cell types.