gebhart/patrepeval huggingface dataset:
Targeting IgE production in mice and humans (2014)

Immunoglobulin E (IgE) is pathogenic in allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy. Recent studies using genetically modified IgE reporter mice indicate that the majority of serum IgE in mice is produced by short-lived IgE plasma cells, with minor contributions from long-lived IgE plasma cells, and implicate IgG1 and IgE memory B cells as potential sources of IgE memory. Clinical studies using antibodies against IL-13 or the IL-4 and IL-13 receptor subunit IL-4Rα, as well as an antibody against the M1 prime domain of human membrane IgE, indicate that, similar to mice, a proportion of IgE in humans is derived from ongoing IgE immune responses and short-lived plasma cells. Targeting IgE production may lead to new therapies for the treatment of allergic diseases.
Localized stimulation of neural tissues in the brain by means of a paired configuration of time-varying magnetic fields (1988)

A method of localized stimulation of the human brain is proposed. The basic idea is to concentrate induced eddy currents locally in the vicinity of a target in the cortex by a pair of coils which are positioned outside the head so that time-varying magnetic fields pass through the head in the opposite directions around a target. The eddy currents induced at the target are expected to flow together, which results in an increased current flow at the target. Spatial distributions of induced eddy currents are calculated in cubical and spherical volume conductor models by a finite element method. The results show that the current vectors make themselves two vortexes which flow together at the target. The current density at the target makes a peak which is higher by 2–3 times than current densities at nontarget regions. The validity of the proposed method is demonstrated by experiments using frog nerve-muscle preparations.
Increased inflammation and lethality of Dusp1−/− mice in polymicrobial peritonitis models (2010)

The mitogen-activated protein kinase phosphatase Dusp1 (also known as MKP-1) is essential for control of the inflammatory response to systemic challenge with the lipopolysaccharide of Gram-negative bacteria. Here, we have investigated the consequences of Dusp1-deficiency in colon ascendens stent peritonitis (CASP) and caecal ligation and puncture (CLP), two mouse models of septic peritonitis. Following CASP, Dusp1(-/-) mice had increased serum levels of CCL4, interleukin-10 (IL-10) and IL-6, with differences from wild-type mice being dependent on severity of sepsis. These cytokines, along with inducible nitric oxide synthase messenger RNA, were also expressed at higher levels in spleen and liver. Similar over-production of these cytokines was detected in the CLP model, with even larger differences from wild-type mice. Despite the increased inflammatory response, bacterial clearance was impaired in Dusp1(-/-) mice subjected to CASP and CLP. Dusp1(-/-) mice suffered increased lethality in both peritonitis models. Together our data indicate that exaggerated inflammatory responses to gut bacteria introduced into the peritoneum in the absence of Dusp1 do not help to control bacterial replication but are detrimental for the host.
Retinoic acid-inducible gene-I is induced by double-stranded RNA and regulates the expression of CC chemokine ligand (CCL) 5 in human mesangial cells (2010)

The TLR3/IFN-β/RIG-I/CCL5 signalling pathway may mediate immune and inflammatory responses against viral infection in mesangial cells, suggesting the role of this pathway in the aggravation of glomerulonephritis due to viral infection.
Sensing the environment through SpiderSense (2013)

Recent scientific advances allow the use of technology to expand the number of forms of energy that can be perceived by humans. Smart sensors can detect hazards that human sensors are unable to perceive, for example radiation. This fusing of technology to human s forms of perception enables exciting new ways of perceiving the world around us. In this paper we describe the design of SpiderSense, a wearable device that projects the wearer s near environment on the skin and allows for directional awareness of objects around him. The millions of sensory receptors that cover the skin presents opportunities for conveying alerts and messages. We discuss the challenges and considerations of designing similar wearable devices.
Transactivation of RAGE mediates angiotensin-induced inflammation and atherogenesis (2018)

Activation of the type 1 angiotensin II receptor (AT1) triggers proinflammatory signaling through pathways independent of classical Gq signaling that regulate vascular homeostasis. Here, we report that the AT1 receptor preformed a heteromeric complex with the receptor for advanced glycation endproducts (RAGE). Activation of the AT1 receptor by angiotensin II (Ang II) triggered transactivation of the cytosolic tail of RAGE and NF-κB-driven proinflammatory gene expression independently of the liberation of RAGE ligands or the ligand-binding ectodomain of RAGE. The importance of this transactivation pathway was demonstrated by our finding that adverse proinflammatory signaling events induced by AT1 receptor activation were attenuated when RAGE was deleted or transactivation of its cytosolic tail was inhibited. At the same time, classical homeostatic Gq signaling pathways were unaffected by RAGE deletion or inhibition. These data position RAGE transactivation by the AT1 receptor as a target for vasculoprotective interventions. As proof of concept, we showed that treatment with the mutant RAGE peptide S391A-RAGE362-404 was able to inhibit transactivation of RAGE and attenuate Ang II-dependent inflammation and atherogenesis. Furthermore, treatment with WT RAGE362-404 restored Ang II-dependent atherogenesis in Ager/Apoe-KO mice, without restoring ligand-mediated signaling via RAGE, suggesting that the major effector of RAGE activation was its transactivation.
Long short-term memory recurrent neural network architectures for large scale acoustic modeling (2014)

Long Short-Term Memory (LSTM) is a specific recurrent neural network (RNN) architecture that was designed to model temporal sequences and their long-range dependencies more accurately than conventional RNNs. In this paper, we explore LSTM RNN architectures for large scale acoustic modeling in speech recognition. We recently showed that LSTM RNNs are more effective than DNNs and conventional RNNs for acoustic modeling, considering moderately-sized models trained on a single machine. Here, we introduce the first distributed training of LSTM RNNs using asynchronous stochastic gradient descent optimization on a large cluster of machines. We show that a two-layer deep LSTM RNN where each LSTM layer has a linear recurrent projection layer can exceed state-of-the-art speech recognition performance. This architecture makes more effective use of model parameters than the others considered, converges quickly, and outperforms a deep feed forward neural network having an order of magnitude more parameters. Index Terms: Long Short-Term Memory, LSTM, recurrent neural network, RNN, speech recognition, acoustic modeling.
Characterization of Temperature-Sensitive Strains of Neospora caninum in Mice (1999)

Temperature-sensitive (ts) strains of the Neospora caninum tachyzoites were selected by chemical mutagenesis and selection for growth at 32 C. Three ts strains and the parental, N. caninum wild-type strain, NC-1, were examined in the present study for their ability to cause disease in inbred BALB/c mice, outbred ICR mice, and chemically immunosuppressed ICR mice. In BALB/c mice, all 3 strains failed to induce clinical disease, whereas infection with the NC-1 strain caused central nervous system disease and death in some mice. No disease was observed in ICR mice inoculated with the 3 ts strains or the NC-1 strain. All immunosuppressed ICR mice inoculated with the NC-1 strain died, whereas no immunosuppressed mice inoculated with the NCts-4 strain and only 1 of 5 mice inoculated with the NCts-8 and NCts-12 strains died. The NCts-4 and NCts-12 strains reverted to a wild-type phenotype when grown at 37 C. Vaccination of BALB/c mice with live, but not frozen NCts-8 strain tachyzoites induced significant (P < 0.05) protection following NC-1 strain challenge.
Small molecule αv integrin antagonists: novel anticancer agents (2000)

The members of the integrin family are targets that potentially provide both therapeutic and diagnostic opportunities. Advances in the understanding of the signalling pathways, transcriptional regulation and the structure/function relationships of the adhesion molecules to extracellular matrix proteins have all contributed to these opportunities. The role of the integrins in pathological processes in both acute and chronic diseases, include ocular, cancer (solid tumours and metastasis), cardiovascular (stroke and heart failure) and inflammatory (rheumatoid arthritis) conditions. Various therapeutic candidates, including antibodies, cyclic peptides and peptidomimetics, have been identified. This review will focus on the key role of the alpha(v) integrin (alpha(v)beta(3) and alpha(v)beta(5)) in angiogenic processes in tumours, including its potential use in cancer diagnostics and therapy.
Synthesis of some substituted pyridylsydnones (1970)

Abstract Synthesis of the I‐oxide ( 2 ) of the photochromic N ‐(3‐pyridyl) sydnone ( 1 ), of N ‐(5‐bromo‐3‐pyridyl) sydnone ( 3 ), and the I‐oxide ( 4 ) of 3 were undertaken in order to study the effect on photochromism exerted by substituents on the pyridine ring. Compounds 2 and 3 were prepared via the corresponding aminopyridines and N ‐pyridylglycines by the general procedure used earlier to prepare 1 . The required amines, 3‐aminopyridine I‐oxide and 3‐amino‐5‐bromopyridine, were obtained by Hofmann rearrangement of the corresponding amides. An excellent preparation of 5‐bromonicotinamide was developed involving bromination in thionyl chloride followed by reaction of the bromoacid chloride with ammonia in chloroform. Proof of structure for 2 and 3 was accomplished by acid hydrolysis to the corresponding hydrazines, which were isolated, respectively, as acetophenone 3‐pyridylhydrazone I‐oxide and as 5‐bromo‐3‐pyridylhydrazine hydrochloride. These products were identical with samples prepared by reduction of the respective diazotized amines. Sydnone 4 eluded preparation by this general procedure. 3‐Amino‐5‐bromopyridine I‐oxide was prepared conveniently from 5‐bromonicotinamide but attempts to prepare the corresponding glycine by catalytic hydrogenation of a mixture of the amine and butyl glyoxylate afforded, in acid solution, N ‐(3‐pyridyl)glycine and, in neutral or alkaline solution, the I‐oxide of N ‐(3‐pyridyl)glycine. Both products resulted from the reductive cleavage of the bromine atom. Neither 2 nor 3 was photochromic.
Update on immune checkpoint inhibitors in gynecological cancers (2016)

In recent years, progress in our understanding of immune-modulatory signaling pathways in immune cells and the tumor microenvironment (TME) has led to rejuvenated interest in cancer immunotherapy. In particular, immunotherapy targeting the immune checkpoint receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell-death 1 (PD-1), and programmed cell-death ligand 1 (PD-L1) have demonstrated clinical activity in a wide variety of tumors, including gynecological cancers. This review will focus on the emerging clinical data on the therapeutic role of immune checkpoint inhibitors, and potential strategies to enhance the efficacy of this class of compounds, in the context of gynecological cancers. It is anticipated that future biomarker-directed clinical trials will provide further insights into the mechanisms underlying response and resistance to immunotherapy, and help guide our approach to designing therapeutic combinations that have the potential to enhance the benefit of immunotherapy in patients with gynecologic cancers.
Complementary circuits with organic transistors (1996)

The operating characteristics of complementary inverters with n-channel napthalenetetracarboxylic dianhydride thin-film transistors (TFTs) and p-channel transistors with hole transporting organic active materials are described. The n-channel TFTs have been used as the load in one circuit configuration and as the driver in the second configuration.
JL1, a novel differentiation antigen of human cortical thymocyte. (1993)

Expression of a novel thymocyte differentiation antigen, JL1, defined by a monoclonal antibody (mAb) developed against human thymocytes showed a specificity for stage II double positive (CD4+CD8+) human cortical thymocytes. This antigen was not expressed at detectable levels on medullary thymocytes, mature peripheral leukocytes, bone marrow cells or on other types of tissues elsewhere in the human body. Immunohistologic analysis revealed that JL1 had a clear pattern of distribution on cortical thymocytes. Immunoprecipitation of 125I-labeled cell lysates from human thymocytes and Molt-4 leukemic cell line with anti-JL1 mAb yielded a 120-130-kD single chain glycoprotein. When immunoprecipitation of cell lysate was done after endoglycosidase F treatment, JL1 antigen was still detected by antibody but the band showed a reduction in apparent molecular mass of approximately 5 kD. This suggests that, although JL1 molecule contains carbohydrate group, this does not form a critical part of the antigenic determinant for anti-JL1 antibody. JL1 antigen appears to be the first double positive, stage-specific differentiation antigen of human thymocyte reported so far. This antigen would be a useful marker for lymphoblastic malignancy of stage II thymocyte origin and it may be involved in the thymocyte education process.
Identification of the Site-Specific DNA Invertase Responsible for the Phase Variation of SusC/SusD Family Outer Membrane Proteins in Bacteroides fragilis (2009)

The human gut microbe Bacteroides fragilis can alter the expression of its surface molecules, such as capsular polysaccharides and SusC/SusD family outer membrane proteins, through reversible DNA inversions. We demonstrate here that DNA inversions at 12 invertible regions, including three gene clusters for SusC/SusD family proteins, were controlled by a single tyrosine site-specific recombinase (Tsr0667) encoded by BF0667 in B. fragilis strain YCH46. Genetic disruption of BF0667 diminished or attenuated shufflon-type DNA inversions at all three susC/susD genes clusters, as well as simple DNA inversions at nine other loci, most of which colocalized with susC/susD family genes. The inverted repeat sequences found within the Tsr0667-regulated invertible regions shared the consensus motif sequence AGTYYYN(4)GDACT. Tsr0667 specifically mediated the DNA inversions of 10 of the 12 regions, even under an Escherichia coli background when the invertible regions were exposed to BF0667 in E. coli cells. Thus, Tsr0667 is an additional globally acting DNA invertase in B. fragilis, which probably involves the selective expression of SusC/SusD family outer membrane proteins.
CpG‐oligodeoxynucleotides enhance T‐cell receptor‐triggered interferon‐γ production and up‐regulation of CD69 via induction of antigen‐presenting cell‐derived interferon type I and interleukin‐12 (2000)

Bacterial cytidine-phosphate-guanosine (CpG-DNA) activates antigen-presenting cells (APC) and drives T helper 1 (Th1)-polarized immune responses in the mouse. Claims have been made that CpG-DNA costimulates murine T cells. We examined the direct and indirect effects of CpG-oligodeoxynucleotides (CpG-ODN) on human T-cell activation. CpG-ODN failed to costimulate purified human T cells activated with alpha-CD3 or alpha-T-cell receptor (TCR)alphabeta antibodies. In contrast, CpG-ODN sequence-specifically caused increased expression of CD69 on CD4 and CD8 T cells when peripheral blood mononuclear cells (PBMC) were stimulated via alpha-CD3. CpG-ODN and alpha-CD3 stimulation synergized to induce interferon-gamma (IFN-gamma) in T cells and natural killer (NK) cells, as shown by intracellular fluorescence-activated cell sorter (FACS) staining. These effects of CpG-ODN on human T cells were caused by the release of IFN type I (IFN-I) and interleukin-12 (IL-12) from PBMC. Enhancement of CD69 expression on alpha-CD3-triggered T cells could be reproduced in a coculture transwell system of purified T cells and PBMC, was inhibited by neutralizing antibodies to IFN-I and could be mimicked by adding exogenous IFN-I. Furthermore, neutralization of either IFN-I or IL-12 diminished, and in combination abolished, IFN-gamma production. These findings show that CpG-ODN potentiate TCR-triggered activation of human T cells in an APC-dependent manner.
Hepatocellular carcinoma in woodchuck hepatitis virus-infected woodchucks: Presence of viral DNA in tumor tissue from chronic carriers and animals serologically recovered from acute infections (1989)

During long-term studies of the natural history of woodchuck hepatitis virus infection, five cases of histologically confirmed, primary hepatocellular carcinoma were observed in a total of 92 woodchucks which had recovered, by analysis of viral serologic markers (WHsAg-, anti-WHc+, anti-WHs+), from experimental acute woodchuck hepatitis virus infections 20 to 30 months prior to the detection of hepatocellular carcinoma. No hepatocellular carcinoma was observed in 167 uninfected controls at least 3 years of age and held in the same laboratory environment. Southern blot hybridization analysis of liver tissue taken from four of these recovered woodchucks revealed the presence of low levels (0.1 to 0.3 copies per cell) of integrated woodchuck hepatitis virus DNA in hepatocellular carcinoma (four of four animals) and nonneoplastic tissue (three of four animals). Similarly, hepatocellular carcinoma tissue obtained from two wild-caught, naturally infected and serologically recovered woodchucks also contained low levels of integrated woodchuck hepatitis virus DNA. Liver tissues from another 27 of these 92 recovered woodchucks (without hepatocellular carcinoma) were examined for woodchuck hepatitis virus nucleic acids 13 to 31 months following experimental woodchuck hepatitis virus infection. Nonreplicating woodchuck hepatitis virus DNA was present in the liver of eight (30%) and in the peripheral blood lymphocytes from eight (30%) of these 27 animals. These results were in marked contrast to the analysis of woodchuck hepatitis virus DNA in the liver tissue of chronic woodchuck hepatitis virus carriers (20 experimentally infected and nine naturally infected). In these animals, high levels of replicating woodchuck hepatitis virus DNA (up to 2,000 copies per cell) were observed in all hepatocellular carcinoma and nonneoplastic liver tissue. Integrated woodchuck hepatitis virus DNA was found in eight of 60 individual hepatocellular carcinomas detected in 29 chronic carriers, 15 to 40 months postinfection. Integrated woodchuck hepatitis virus DNA was present in the nonneoplastic tissue from four of these 29 chronic woodchuck hepatitis virus carriers.
Location on the Salmonella typhimurium Chromosome of the Gene Encoding Nucleoside Diphosphokinase ( ndk ) (1983)

The gene encoding nucleosidediphosphate kinase (ndk) was located at 55 units on the Salmonella typhimurium chromosome. The ndk locus was 83% cotransducible with hisS and 2% cotransducible with glyA in phage P22-mediated crosses. A nucleosidediphosphate kinase mutant that produced only 10% of the wild-type enzyme activity (ndk-1) grew normally and produced a heat-labile enzyme.
Impact of Atrial Fibrillation on Mortality, Stroke, and Medical Costs (1998)

Prevention of AF and treatment of patients with AF and associated CVD may yield benefits in reduced mortality and stroke as well as reducing health care costs.
Effect of Cutting Flute Design on Cortical Bone Screw Insertion Torque and Pullout Strength (2001)

Priorities for a cutting flute design should ideally include ease of screw insertion, minimal soft tissue irritation, and maximal screw holding power. Screws with more than two flutes were easier to insert and did not cause cortical damage during insertion. The screw with four full-length flutes showed a trend toward being the easiest to insert and having the greatest holding strength.
Virtual-channel flow control (1990)

Network throughput can be increased by dividing the buffer storage associated with each network channel into several virtual channels [DalSei]. Each physical channel is associated with several small queues, virtual channels, rather than a single deep queue. The virtual channels associated with one physical channel are allocated independently but compete with each other for physical bandwidth. Virtual channels decouple buffer resources from transmission resources. This decoupling allows active messages to pass blocked messages using network bandwidth that would otherwise be left idle. Simulation studies show that, given a fixed amount of buffer storage per link, virtual-channel flow control increases throughput by a factor of 3.5, approaching the capacity of the network.
Synthesis of a remarkably stable bicyclo[7.3.1]diynene esperamicin A1/calicheamicin .gamma. system. Structural requirements for facile formation of a 1,4-diyl (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of a remarkably stable bicyclo[7.3.1]diynene esperamicin A1/calicheamicin .gamma. system. Structural requirements for facile formation of a 1,4-diylPhilip. Magnus, Richard T. Lewis, and John C. HuffmanCite this: J. Am. Chem. Soc. 1988, 110, 20, 6921–6923Publication Date (Print):September 1, 1988Publication History Published online1 May 2002Published inissue 1 September 1988https://doi.org/10.1021/ja00228a071RIGHTS & PERMISSIONSArticle Views497Altmetric-Citations93LEARN 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 PDF (921 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Protease digestion of hepatitis A virus: disparate effects on capsid proteins, antigenicity, and infectivity (1991)

High concentrations of either trypsin or chymotrypsin caused nearly complete cleavage of capsid protein VP2 of hepatitis A virus but did not significantly reduce the infectivity, thermostability, or antigenicity of the virus. Chymotrypsin also had a lesser effect on VP1. These findings indicate the presence of a protease-accessible VP2 surface site which neither contributes significantly to the dominant antigenic site nor plays a role in the attachment of the virus to putative cell receptors.