gebhart/patrepeval huggingface dataset:
Early infancy microbial and metabolic alterations affect risk of childhood asthma (2015)

Asthma is the most prevalent pediatric chronic disease and affects more than 300 million people worldwide. Recent evidence in mice has identified a "critical window" early in life where gut microbial changes (dysbiosis) are most influential in experimental asthma. However, current research has yet to establish whether these changes precede or are involved in human asthma. We compared the gut microbiota of 319 subjects enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, and show that infants at risk of asthma exhibited transient gut microbial dysbiosis during the first 100 days of life. The relative abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia was significantly decreased in children at risk of asthma. This reduction in bacterial taxa was accompanied by reduced levels of fecal acetate and dysregulation of enterohepatic metabolites. Inoculation of germ-free mice with these four bacterial taxa ameliorated airway inflammation in their adult progeny, demonstrating a causal role of these bacterial taxa in averting asthma development. These results enhance the potential for future microbe-based diagnostics and therapies, potentially in the form of probiotics, to prevent the development of asthma and other related allergic diseases in children.
Angiogenesis: A Paradigm for BalancedExtracellular Proteolysis during Cell Migrationand Morphogenesis (1996)

Extracellular proteolysis is required for matrix degradation and the regulation of cytokine activity during angiogenesis, and this is dependent on a cohort of proteases and protease inhibitors produced by endothelial and nonendothelial cells. The plasminogen activator (PA)/plasmin system has been extensively investigated in these processes, and descriptive studies have demonstrated that urokinase-type PA (uPA), uPA receptor (uPAR) and PA inhibitor-1 (PAI-1) are expressed by endothelial cells during angiogenesis in vivo. In vitro studies have led to the notion that normal capillary morphogenesis is dependent on a protease-antiprotease equilibrium. These findings are discussed in the context of recent observations on uPA-, uPAR-, PAI-1 and plaminogen-deficient mice, in which developmental and physiological angiogenesis appear to occur normally. This has led to a reevaluation of the role of the PA/plasmin system during angiogenesis. In particular, these observations raise the possibility that the role of this system may be limited to situations in which endothelial cells encounter and must degrade fibrin in order to form new capillary sprouts.
High efficiency, high repetition-rate Nd:YVO4 laser with TEM00 end-pumped by 887 nm (2010)

Thermal effect of laser crystal is a very important factor for solid lasers. The most of heat is generated from the quantum loss between pump light and lasing light. If a longer wavelength of pump light is adopted, quantum loss and quantum loss efficiency can be reduced and improved, respectively. In this paper, a Nd:YVO4 laser end-pumped by 887 nm LD is reported. Output power of 25 W is obtained from a single Nd:YVO4, when the crystal absorbs pump light power of 38 W. The corresponding opto-optic conversion efficiency is up to 65.7%. When 30.7 W pump light is absorbed in the crystal, 19.4 W TEM00 is obtained with M 2 = 1.30, M 2 = 1.26 and opto-optic conversion efficiency of 63.2%. The laser can work at the Q-switched mode. The uniform pulses are generated at high repetition of 100 kHz. And the conditions of pulse stability are analyzed in this paper.
p38 Mitogen–activated Protein Kinase Activation by Nerve Growth Factor in Primary Sensory Neurons Upregulates μ-Opioid Receptors to Enhance Opioid Responsiveness Toward Better Pain Control (2010)

Local NGF through activation of the p38-MAPK pathway leads to adaptive changes in sensory neuron MOR toward enhanced susceptibility to local opioids. This effect may act as a counter-regulatory response to p38-MAPK-induced pain (e.g., inflammatory pain) to facilitate opioid-mediated antinociception.
On the source of oscillatory behaviour during switching of power enhancement mode GaN HEMTs (2017)

© 2017 by the author. With Gallium Nitride (GaN) device technology for power electronics applications being ramped up for volume production, an increasing amount of research is now focused on the performance of GaN power devices in circuits. In this study, an enhancement mode GaN high electron mobility transistor (HEMT) is switched in a clamped inductive switching configuration with the aim of investigating the source of oscillatory effects observed. These arise as a result of the increased switching speed capability of GaN devices compared to their silicon counterparts. The study identifies the two major mechanisms (Miller capacitance charge and parasitic common source inductance) that can lead to ringing behaviour during turn-off and considers the effect of temperature on the latter. Furthermore, the experimental results are backed by SPICE modelling to evaluate the contribution of different circuit components to oscillations. The study concludes with good design techniques that can suppress the effects discussed.
A Length-Flexible Threshold Cryptosystem with Applications (2003)

We propose a public-key cryptosystem which is derived from the Paillier cryptosystem. The scheme inherits the attractive homomorphic properties of Paillier encryption. In addition, we achieve two new properties: First, all users can use the same modulus when generating key pairs, this allows more efficient proofs of relations between different encryptions. Second, we can construct a threshold decryption protocol for our scheme that is length flexible, i.e., it can handle efficiently messages of arbitrary length, even though the public key and the secret key shares held by decryption servers are of fixed size. We show how to apply this cryptosystem to build:&lt;br /&gt; &lt;br /&gt;1) a self-tallying election scheme with perfect ballot secrecy. This is a small voting system where the result can be computed from the submitted votes without the need for decryption servers. The votes are kept secret unless the cryptosystem can be broken, regardless of the number of cheating parties. This is in contrast to other known schemes that usually require a number of decryption servers, the majority of which must be honest.&lt;br /&gt; &lt;br /&gt;2) a length-flexible mix-net which is universally verifiable, where the size of keys and ciphertexts do not depend on the number of mix servers, and is robust against a corrupt minority. Mix-nets can provide anonymity by shuffling messages to provide a random permutation of input ciphertexts to the output plaintexts such that no one knows which plaintexts relate to which ciphertexts. The mix-net inherits several nice properties from the underlying cryptosystem, thus making it useful for a setting with small messages or high computational power, low-band width and that anyone can verify that the mix have been done correctly.
Role of protein kinases in regulating sheep erythrocyte K-Cl cotransport (1996)

K-Cl cotransport in sheep erythrocytes can be activated by treatment either with A-23187 and EDTA to reduce concentration of internal ionized Mg [Mg]i) to submicromolar levels, with staurosporine, a potent kinase inhibitor, or with N-ethylmaleimide (NEM). Activation by these maneuvers is prevented and reversed by genistein [inhibition constant (Ki) of 15 microM], which inhibits tyrosine kinases (TK). The related glycosidated compound genistin, which does not inhibit TK, does not inhibit transport, whereas another TK inhibitor, tyrphostin B46, inhibits both basal and stimulated transport (Ki of 28 microM). Cotransport activation by NEM is prevented and reversed by the phosphatase inhibitor, calyculin A, and activation by staurosporine occurs only if cells contain ATP. Increasing [Mg]i inhibits cotransport in the presence of calyculin A whether or not staurosporine is present as well. Our work suggests that genistein inhibits cotransport through a TK and that staurosporine and NEM activate cotransport, probably through inhibition of other kinases, causing stimulation through dephosphorylation of a protein (possibly the transporter itself) be a serine/threonine phosphatase. [Mg]i inhibits cotransport by activating a kinase (concentration for half-maximal activation of 10 microM) that phosphorylates this protein.
The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain (2004)

Several novel interleukin (IL)-10-related cytokines have recently been discovered. These include IL-22, IL-26, and the interferon-lambda (IFN-lambda) proteins IFN-lambda1 (IL-29), IFN-lambda2 (IL-28A), and IFN-lambda3 (IL-28B). The ligand-binding chains for IL-22, IL-26, and IFN-lambda are distinct from that used by IL-10; however, all of these cytokines use a common second chain, IL-10 receptor-2 (IL-10R2; CRF2-4), to assemble their active receptor complexes. Thus, IL-10R2 is a shared component in at least four distinct class II cytokine-receptor complexes. IL-10 binds to IL-10R1; IL-22 binds to IL-22R1; IL-26 binds to IL-20R1; and IFN-lambda binds to IFN-lambdaR1 (also known as IL-28R). The binding of these ligands to their respective R1 chains induces a conformational change that enables IL-10R2 to interact with the newly formed ligand-receptor complexes. This in turn activates a signal-transduction cascade that results in rapid activation of several transcription factors, particularly signal transducer and activator of transcription (STAT)3 and to a lesser degree, STAT1. Activation by IL-10, IL-22, IL-26, or IFN-lambda can be blocked with neutralizing antibodies to the IL-10R2 chain. Although IL-10R2 is broadly expressed on a wide variety of tissues, only a subset of these tissues expresses the ligand-binding R1 chains. The receptors for these cytokines are often present on cell lines derived from various tumors, including liver, colorectal, and pancreatic carcinomas. Consequently, the receptors for these cytokines may provide novel targets for inhibiting the growth of certain types of cancer.
Expression of connective tissue growth factor in tumor tissues is an independent predictor of poor prognosis in patients with gastric cancer (2008)

GC patients with an elevated CTGF expression have more lymph node metastases and a shorter survival time. CTGF seems to be an independent prognostic factor for the successful differentiation of high-risk GC patients staging I + II + III. Over-expression of CTGF in human GC cells results in an increased aggressive ability.
Synthesis of the aziridino[1,2-a]pyrrolidine substructure of the antitumor agents azinomycin A and B (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of the aziridino[1,2-a]pyrrolidine substructure of the antitumor agents azinomycin A and BRobert S. Coleman and Andrew J. CarpenterCite this: J. Org. Chem. 1992, 57, 22, 5813–5815Publication Date (Print):October 1, 1992Publication History Published online1 May 2002Published inissue 1 October 1992https://pubs.acs.org/doi/10.1021/jo00048a006https://doi.org/10.1021/jo00048a006research-articleACS PublicationsRequest reuse permissionsArticle Views1094Altmetric-Citations55LEARN 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
Antibodies specific for the carboxy- and amino-terminal regions of simian virus 40 large tumor antigen. (1980)

Antibodies specific for the amino- and carboxy-terminal portions of simian virus 40 large tumor (T) antigen were obtained by immunization of rabbits with synthetic peptides corresponding to these regions. The amino-terminal synthetic peptide has the sequence Ac-Met-Asp-Lys-Val-Leu-Asn-Arg-(Tyr). The tyrosine residue was introduced in order to couple the peptide to bovine serum albumin with bis-diazotized benzidine. The carboxy-terminal peptide has the sequence Lys-Pro-Pro-Thr-Pro-Pro-Pro-Glu-Pro-Glu-Thr. It was coupled to bovine serum albumin with glutaraldehyde. The antisera against both peptides reacted with large T antigen. The specificity of the immune reaction was demonstrated by inhibition experiments using excess synthetic peptides. Furthermore, fragments of T antigen encoded by the nondefective adenovirus 2-simian virus 40 hybrid viruses Ad2+ND2 and Ad2+ND4, which contain the carboxy terminus and lack the amino terminus of large T antigen, were precipitated only with antiserum to the carboxy-terminal peptide. Small T antigen was not precipitated with either serum, suggesting that the amino terminus of small T antigen has a conformation different from that of large T antigen or that it is sterically hindered by a host protein. The procedures used here are of general importance for identification and characterization of gene product.
Inhibitors of HIV‐1 Protease by Using In Situ Click Chemistry (2006)

Twice poor equals potent: HIV-1 Protease assembles its own potent inhibitor through formation of the triazole linkage from azide- and alkyne-containing fragments that are themselves poor binders. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z502161_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Enhancement of the antiproliferative effect of cis‐diamminedichloroplatinum(II) and nitrogen mustard by inhibitors of protein kinase C (1988)

Quercetin (3,3',4',5,7-pentahydroxyflavone) has been shown to inhibit a variety of enzymes including the calcium- and phospholipid-dependent protein kinase (protein kinase C) in vivo and in vitro. We show that this compound synergistically enhances the antiproliferative activity of cis-diamminedichloroplatinum(II) (cis-DDP) and nitrogen mustard. Quercetin does not affect the repair of DNA interstrand cross-links introduced by cis-DDP. Long-term exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA), which reduces total protein kinase C activity, also amplifies the growth-inhibitory effect of cis-DDP and acts synergistically with quercetin. A synergism is also observed if tamoxifen or staurosporine are combined with cis-DDP. For both drugs the dose-effect curves for the inhibition of protein kinase C closely resemble the dose-effect curves for the antiproliferative activities. Although alternative mechanisms cannot be definitively excluded, the effects of quercetin, TPA, tamoxifen and staurosporine may result from the inhibition of protein kinase C.
An <i>in vitro</i> investigation of immunomodulatory properties of <i>Lactobacillus plantarum</i> and <i>L. delbrueckii</i> cells and their extracellular polysaccharides (2017)

Many probiotic lactobacilli and their extracellular polysaccharides (EPS) have beneficial immunological properties. However, it is unclear how they elicit the host immune response. We thus investigated the immunological properties of UV-killed <i>Lactobacillus delbrueckii</i> TU-1 and <i>L. plantarum</i> KM-9 cells as well as their extracellular polysaccharides (EPSs). High-performance liquid chromatography and ion exchange chromatography analyses showed that their EPSs differ in sugar composition and sugar fractionation. The immunological properties were evaluated in a semi-intestinal model using a Transwell co-culture system that employed human intestinal epithelial (Caco-2) cells on the apical side and murine macrophage (RAW264.7) cells on the basolateral side. The UV-killed cells and EPSs were added to the apical side to allow direct contact with Caco-2 cells and incubated for 6 hr. After incubation, the amounts of tumor necrosis factor-α and several cytokines released by RAW264.7 or Caco-2 cells were quantified by cytotoxic activity on L929 cells (murine fibrosarcoma cell line) and quantitative reverse-transcriptase PCR. We found that the UV-killed cells and their EPSs had immunological effects on RAW264.7 cells via Caco-2 cells. The RAW264.7 cells showed different cytokine production profiles when treated with UV-killed cells and EPSs. The UV-killed cells and EPSs promoted a Th1-type cellular response. Furthermore, we found that the UV-killed cells sent positive signals through Toll-like receptor (TLR) 2. Meanwhile, neither EPS sent a positive signal through TLR4 and TLR2. This evidence suggests that both UV-killed cells of the lactobacillus strains and their EPSs trigger a Th1-type immune response in a human host, with the former triggering the response via the TLRs expressed on its epithelium and the latter employing a mechanism yet to be determined, possibly involving a novel receptor that is designed to recognize specific patterns of repeating sugar in the EPSs.
Lipid-dependent Recruitment of Neuronal Src to Lipid Rafts in the Brain (2003)

Although most Src family tyrosine kinases are modified by palmitoylation as well as myristoylation, Src itself is only myristoylated. Dual acylation is important for attachment to liquid-ordered microdomains or lipid rafts. Accordingly, Src is excluded from lipid rafts in fibroblasts. Evidence of partial genetic redundancy between Src and Fyn for brain-specific targets suggests that these two kinases may occupy overlapping subcellular locations. Neuronal Src (NSrc), an alternative isoform of Src with a 6-amino acid insert in the Src homology 3 domain, is highly expressed in neurons. We investigated whether this structural difference in NSrc allows it to associate with lipid rafts. We found that perinatal mouse brains express predominantly NSrc, which is partly (10-20%) in a lipid raft fraction from brain but not fibroblasts. The association of Src with brain lipid rafts does not depend on the NSrc insert but depends on the amino-terminal myristoylation signal. A crude lipid fraction from brain promotes NSrc entry into rafts in vitro. Moreover, lipid raft-localized NSrc is more catalytically active than NSrc from the soluble fraction, possibly because raft localization alters access to other tyrosine kinases and phosphatases. These findings suggest that NSrc may be involved in signaling from lipid rafts in mouse brain.
Facile Synthesis of Trialkoxymolybdenum(VI) Alkylidyne Complexes for Alkyne Metathesis (2000)

New molybdenum(VI) alkylidyne complexes (Ar[iPr]N)3MoCCH2SiMe3 (Ar = 3,5-C6H3Me2) and (1AdO)3MoCR (R = Me, Et, CH2SiMe3) were obtained in high yield and in multigram quantities starting from a known metallaaziridine−hydride complex. The synthetic protocol involves treatment with Me3SiCCH, heating, and ligand exchange via alcoholysis; (1AdO)3MoCCH2SiMe3 is an active catalyst for alkyne metathesis at room temperature.
Mini-plasminogen: a mechanism for leukocyte modulation of plasminogen activation by urokinase (1981)

Urokinase activation of blood fibrinolysis involves polymorphonuclear leukocytes. To determine if a leukocyte proteinase can modulate plasminogen activation, plasminogen was digested with leukocyte elastase. A major product was a small, approximately 34,000 dalton fragment (mini-plasminogen), without lysine-binding function, but with fibrin-binding activity. After urokinase activation, the resulting mini- plasmin had amidolytic activity for a tripeptide plasmin substrate and fibrinolytic activity. By 125I-fibrin assay, activities of mini-plasmin and plasmin (12 nmole/liter) were 38 and 20 ng fibrin lysed/min, respectively. Lysis times of fibrin clots containing urokinase, and mini-plasminogen or plasminogen (800 nmole/liter), were 282 and 290 sec, respectively. Mini-plasmin and plasmin were inhibited similarly by epsilon-aminocaproic acid and normal plasma, but differed in responses to gel filtration fractions of plasma containing alpha 2-antiplasmin and alpha 2-macroglobulin, the primary and secondary plasmin inhibitors. With purified inhibitors, mini-plasmin required higher concentrations of, or longer preincubation with, alpha 2-antiplasmin, and lower concentrations of, or shorter preincubation with, alpha 2- macroglobulin, to produce inhibition equivalent to that observed with plasmin. Leukocyte elastase digests plasminogen to generate a mini- plasminogen which, when activated by urokinase, has a novel pattern of response to the major plasmin inhibitors in plasma.
Both CD133+ and CD133– medulloblastoma cell lines express ligands for triggering NK receptors and are susceptible to NK‐mediated cytotoxicity (2007)

Adoptive cellular immunotherapy has been proposed as an additional treatment of medulloblastoma, an intracranial tumor characterized by a particularly poor prognosis. However, little is known on the ability of the immune system to effectively attack this tumor. In this study, we show that activated human NK cells efficiently kill medulloblastoma cell lines in vitro. NK-mediated killing involved different activating receptors (including NKp46, NKp30, DNAM-1 and NKG2D) and correlated with the presence of their specific ligands on tumor cells. In contrast, the absence of major adhesion interactions, such as LFA-1/ICAM did not impair the NK-mediated cytotoxicity. Medulloblastoma expressed a number of tumor-associated molecules including CD146 and CD133, considered a marker for cancer stem cells. Remarkably, both CD133-positive and CD133-negative cell lines were susceptible to lysis. Tumor cells also expressed molecules that are currently used as diagnostic tools for neuroblastoma cell identification. In particular, B7 homolog 3 (B7-H3) was expressed by all the medulloblastoma cell lines analyzed, while the presence of GD(2) and NB84 was restricted to given cell lines and/or marked a defined tumor cell subset.
Reduced Fertility in High‐yielding Dairy Cows: Are the Oocyte and Embryo in Danger? Part I  The Importance of Negative Energy Balance and Altered Corpus Luteum Function to the Reduction of Oocyte and Embryo Quality in High‐yielding Dairy Cows* (2008)

Fertility in high yielding dairy cows is declining, and there is increasing evidence to presume that oocyte and embryo quality are major factors in the complex pathogenesis of reproductive failure. In this report we present an overview of possible mechanisms linking negative energy balance (NEB) and deficiencies in oocyte and embryo developmental competence; specifically, in the high producing dairy cow. Changes in follicular growth patterns during a period of NEB can indirectly affect oocyte quality. The endocrine and biochemical changes, which are associated with NEB, are reflected in the microenvironment of the growing and maturing female gamete, and likely result in the ovulation of a developmentally incompetent oocyte. Even after an oocyte is successfully ovulated and fertilized, a full-term pregnancy is still not guaranteed. Inadequate corpus luteum function, associated with reduced progesterone, and probably also low insulin-like growth factor concentrations, can cause a suboptimal microenvironment in the uterus that is incapable of sustaining early embryonic life. This may partly account for the low conception rates and the high incidence of early embryonic mortality in high yielding dairy cows.