gebhart/patrepeval huggingface dataset:
Mechanism-based inhibition of human cytochrome P450 1A1 by rhapontigenin. (2001)

Recently we reported that resveratrol (trans-3,4',5-trihydroxystilbene) showed selective inhibition of recombinant human cytochrome P450 (P450) 1A1 in a concentration-dependent manner. The inhibition of recombinant human P450 1A1, 1A2, or 1B1 by various hydroxystilbene compounds having a similar structure to resveratrol was investigated using bacterial membranes from a human P450/NADPH-P450 reductase bicistronic expression system to find new candidates for cancer chemopreventive agents. Of seven compounds tested, rhapontigenin (3,3',5-trihydroxy-4'-methoxystilbene) exhibited a potent and selective inhibition of human P450 1A1 with an IC50 value of 0.4 microM. Rhapontigenin showed 400-fold selectivity for P450 1A1 over P450 1A2 and 23-fold selectivity for P450 1A1 over P450 1B1. Rhapontigenin did not show any significant inhibition of ethoxyresorufin O-deethylation (EROD) activity in human liver microsomes, the other human P450s such as P450 2E1, P450 3A4, P450 2D6, P450 2C8, and P450 2C9, or human NADPH-P450 reductase. We have further investigated the inhibition kinetics of P450 1A1 by rhapontigenin. Rhapontigenin inhibited EROD activity of expressed human P450 1A1 in a competitive manner. The loss of EROD activity was time- and concentration-dependent. The values for K(i) and k(inactivation) were 0.09 microM and 0.06 min(-1), respectively. The loss was not blocked by the trapping agents glutathione, N-acetylcysteine, or dithiothreitol. These results suggest that rhapontigenin is a potent mechanism-based inactivator of human P450 1A1 and may be considered as a good candidate for a cancer chemopreventive agent in humans.
Production of antineutrophil cytoplasm antibodies derived from circulating B cells in patients with systemic vasculitis (2003)

The pathogenesis of systemic vasculitis is complex and is likely to involve many mechanisms. In certain systemic vasculitides, autoimmunity plays an important role with autoantibodies developing towards neutrophils, which are termed antineutrophil cytoplasm antibodies (ANCA). There is a growing body of evidence that T cells may contribute to the pathogenesis of ANCA-associated vasculitides. A system was set up to determine whether B cells require T cell help to produce antibodies in a peripheral blood lymphocyte (PBL) culture system enriched for B cells and dendritic cells (DC). As a control, tetanus toxoid (TT) antibody production was detected from individuals not recently immunized with tetanus vaccine when stimulated with TT antigen. Proteinase 3 (PR3) and myeloperoxidase (MPO) antibodies were produced from B cell and DC enriched cultures prior to the addition of antigen in some ANCA-positive patients with high ANCA titres, but not from patients with low ANCA titres or controls. PBMC from individuals recently immunized with tetanus vaccine were also maximally stimulated in that addition of antibody did not enhance antibody production. We conclude that this system supports a role for T cell help in the production of TT antibodies in individuals not immunized recently with tetanus vaccine. However, in patients with ANCA-associated vasculitis and controls recently immunized with tetanus vaccine, circulating B cells are apparently spontaneously producing autoantibody, possibly reflecting a system already maximally driven in vivo, and therefore masking underlying potential T cell-B cell collaboration. Such B cells may be less responsive to regulatory stimuli in vivo.
Regulation of Cyclooxygenase-2 by Hypoxia and Peroxisome Proliferators in the Corneal Epithelium (2000)

Hypoxic injury provokes inflammation of many tissues including the ocular surface. In rabbit corneal epithelial cells, both peroxisome proliferator-activated receptor (PPAR)-inducible cytochrome P450 4B1 and cyclooxygenase-2 (COX-2) mRNAs were increased by hypoxia. PPAR alpha and beta but not gamma mRNAs were detected in these cells. The PPAR activator, WY-14,643 increased COX-2 expression. Similarly, non-steroidal anti-inflammatory drugs with the ability to activate PPARs induced COX-2 independently of prostaglandin synthesis inhibition. COX-2 protein overexpression by hypoxia and PPAR activation was not associated with a parallel increase in prostaglandin E(2) accumulation. However, the enzyme regained full catalytic activity when: 1) hypoxic cells were re-exposed to normoxic conditions in the presence of heme and arachidonic acid, and 2) WY-14,643-treated cells were depleted of intracellular GSH. Consistent with previous observations showing that the corneal production of cytochrome P450-derived inflammatory eicosanoids is elevated by hypoxia and inflammation, the current data suggest that hypoxic injury is a model of inflammation in which molecules other than COX-derived arachidonic acid metabolites play a major proinflammatory role. This study also suggests that increased cellular GSH may be the mechanism responsible for the characteristic dissociation of PPAR-induced COX-2 expression and activity. Moreover, we provide new insights into the commonly observed lack of efficacy of classical non-steroidal anti-inflammatory drugs in the treatment of hypoxia-related ocular surface inflammation.
Architectural patterns in branching morphogenesis in the kidney (1998)

During kidney development, several discrete steps generate its three-dimensional pattern including specific branch types, regional differential growth of stems, the specific axes of growth and temporal progression of the pattern. The ureteric bud undergoes three different types of branching. In the first, terminal bifid type, a lateral branch arises and immediately bifurcates to form two terminal branches whose tips induce the formation of nephrons. After 15 such divisions (in humans) of this specifically renal type of branching, several nephrons are induced whose connecting tubules fuse and elongate to form the arcades. Finally, the last generations undergo strictly lateral branching to form the cortical system. The stems of these branches elongate in a highly regulated pattern. The molecular basis of these processes is unknown and we briefly review their potential mediators. Differential growth in three different axes of the kidney (cortico-medullary, dorsoventral and rostro-caudal) generate the characteristic shape of the kidney. Rapid advances in molecular genetics highlight the need for development of specific assays for each of these discrete steps, a prerequisite for identification of the involved pathways. The identification of molecules that control branching (the ultimate determinant of the number of nephrons) has acquired new urgency with the recent suggestion that a reduced nephron number predisposes humans to hypertension and to progression of renal failure.
The Neurophysiological Basis of Bladder Inhibition in Response to Intravaginal Electrical Stimulation (1983)

Intravaginal electrical stimulation (IVS) induces a profound bladder inhibition and is successful in the treatment of incontinence due to detrusor instability. In this experimental study in cats, direct recordings of the efferent activity in thin hypogastric and pelvic nerve filaments to the bladder were used to analyze the neuronal mechanisms underlying this bladder inhibition. A longlasting reflex discharge, with a latency of 35 to 50 msec., was evoked in the hypogastric nerve by IVS. The reflex discharge was unaffected by imposed changes in intravesical pressure or by micturition contractions, but the response was very frequency-sensitive with an optimal transmission at about 5 Hz of stimulation. A "spontaneous" efferent activity could be recorded in the pelvic nerve filaments when the bladder pressure was elevated above 5 to 7 cm. H2O. The pelvic activity occurred in 10 to 20-second bursts, each followed by an abortive detrusor contraction. IVS of 5 to 10 Hz completely abolished this efferent pelvic activity by central inhibition. The findings are discussed in relation to the normal neuronal control of the bladder and to the clinical application of IVS.
Control and command of a six degrees of freedom active electrical orthosis for paraplegic patient (2002)

Describes the walking machine developed as part of the European project CALIES (Computer Aided Locomotion by Implanted Electrical stimulation) with the collaboration of the robotic team of the CEA. The version is an 'active electrical orthosis' mostly conceived to train the paraplegic patients to deambulate and to simulate the different control strategies.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Failure at the Effector Phase: Immune Barriers at the Level of the Melanoma Tumor Microenvironment (2007)

The clinical investigation of numerous therapeutic cancer vaccine strategies has resulted in relative disappointment. Whereas a minority of patients have indeed experienced clinical benefit, the majority of patients show disease progression even in cases in which induction of functional tumor antigen-specific T-cell responses as measured in the blood is easily detected. This observation has led to interrogation of the tumor microenvironment for potential mechanisms of tumor resistance to the effector phase of the antitumor T-cell response. Poor chemokine-mediated trafficking of effector cells and the action of negative regulatory pathways that inhibit T-cell function have been identified as key limiting factors. Important negative regulatory pathways include T-cell anergy from insufficient B7 costimulation, extrinsic suppression by regulatory T-cell populations, direct inhibition through inhibitory ligands such as PD-L1, and metabolic dysregulation such as through the activity of indoleamine 2,3-dioxygenase. Recognition of these evasion mechanisms has pointed toward new therapeutic approaches for cancer immunotherapy.
Effects of 5-HT1A-Receptor Agonist, 8-OH-DPAT, and GABAB-Receptor Agonist, Baclofen, on Lordosis in Female Rats With Lesions in Either the Dorsal Raphe Nucleus or Septum (2005)

The inhibitory effects of 8-OH-DPAT, a 5-HT1A-receptor agonist, and baclofen, a GABAB-receptor agonist, on lordosis were examined in estrogen and progesterone-treated ovariectomized rats with lesions in either the dorsal raphe nucleus (DRN) or septum and in rats with either sham lesions or no lesions. The first behavior test series was carried out 6 days after implantation of the rats with silicon tubes containing estradiol. Four hours after injection with 0.5 mg progesterone, behavioral tests were performed before and 30 min after an injection with 1 mg/kg body weight 8-OH-DPAT. As a result, the mean lordosis quotient (LQ)s were changed from 100 to less than 20 before and after the injection in all groups. These results suggest that 8-OH-DPAT acts on areas other than the DRN and the septum, leading to a decrease in lordosis. Two weeks after implantation with estradiol, the next behavioral test series was carried out after injection with progesterone. Behavioral tests were performed before and after an injection with 10 mg baclofen. The results showed that the mean LQs decreased after the injection in all groups, but the mean LQ in the DRN lesion group was higher than that in the sham groups. These results indicate that baclofen may act partially on the DRN in inhibiting lordosis in female rats.
Reduction of aryl diethyl phosphates with titanium metal: a method for deoxygenation of phenols (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReduction of aryl diethyl phosphates with titanium metal: a method for deoxygenation of phenolsSteven C. Welch and Marlin E. WaltersCite this: J. Org. Chem. 1978, 43, 25, 4797–4799Publication Date (Print):December 1, 1978Publication History Published online1 May 2002Published inissue 1 December 1978https://pubs.acs.org/doi/10.1021/jo00419a018https://doi.org/10.1021/jo00419a018research-articleACS PublicationsRequest reuse permissionsArticle Views450Altmetric-Citations23LEARN 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
Signaling through G Proteins and G Protein-coupled Receptors during Platelet Activation (1993)

Recent studies have helped to define the early events of signal transduction in platelets. The best-described of these events are those in which heterotrimeric guanine nucleotide binding regulatory proteins (G proteins) mediate the interaction between cell surface receptors for agonists and intracellular second messenger generating enzymes. To date nine different G proteins have been identified in platelets. Their targets include phospholipases C and A2, and adenylyl cyclase. Efforts to clone the receptors that can couple to these G proteins have been successful for epinephrine, thrombin, TxA2 and platelet activating factor. Each of these is comprised of a single polypeptide with seven transmembrane domains and an extracellular N-terminus. In the case of the thrombin receptor, activation occurs by a novel mechanism in which thrombin cleaves its receptor, creating a new N-terminus that can serve as a tethered ligand. Shortly after activation, thrombin receptors become resistant to re-activation by thrombin. This desensitization, which appears to involve receptor phosphorylation and internalization, provides a potent mechanism for limiting the duration of thrombin-initiated events in platelets and other thrombin-responsive vascular cells.
The effects of internal primer-template mismatches on RT-PCR: HIV-1 model studies (1997)

We investigated the effects of internal primer-template mismatches on the efficiency of reverse transcription and PCR amplification. As models, RNA transcripts representative of different HIV-1 group M subtypes were evaluated with a previously described gag primer pair system. We observed that the presence of two to four mismatches in the primer-template duplexes did not have a significant effect on RT-PCR. However, the presence of five and six mismatches with the 28 and 30 base primers reduced PCR product yield by approximately 22- and 100-fold respectively, relative to the homologous template. The amount of reduction was reproducible from experiment to experiment and was independent of the initial copy number input. Under the conditions used, viral RNA measurements of the more divergent HIV-1 subtypes (A and E) would be underestimated, while isolates of subtypes B, C, D and F-H are expected to be efficiently amplified and accurately measured. The reduced amplification efficiency for targets similar to HIV subtypes A and E can be improved 4- to 10-fold by lowering the annealing temperature and implementing a reverse transcription step that gradually increases in temperature. The additional substitution of either 5-methylcytosine for cytosine throughout or the substitution of inosine at positions of variable bases resulted in a <4-fold difference in product yield between the homologous and most divergent templates.
Real-Time Volume Graphics (2006)

Based on course notes of SIGGRAPH course teaching techniques for real-time rendering of volumetric data and effects; covers both applications in scientific visualization and real-time rendering. Starts with the basics (texture-based ray casting) and then improves and expands the algorithms incrementally. Book includes source code, algorithms, diagr
Abstract 491: NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy. (2013)

Abstract The IDO pathway mediates immunosuppressive effects through the metabolization of tryptophan (Trp) to kynurenine (Kyn), triggering downstream signaling through GCN2, mTOR and AHR that can affect differentiation and proliferation of T cells. Expression of the IDO1 gene by tumor cells or host APCs can inhibit tumor-specific effector CD8+ T cells and enhance the suppressor activity of Tregs, and high expression of IDO correlates with worse clinical prognosis in patients with a variety of malignancies. Therefore, targeting the IDO pathway via inhibition of the IDO enzyme or blocking its downstream signaling effects is a prime target for small-molecule immunomodulatory drugs in cancer. Here we describe the pharmacological and biological properties of NLG919, a novel small-molecule IDO-pathway inhibitor. NLG919 potently inhibits this pathway in vitro and in cell based assays (Ki=7 nM; EC50 =75 nM). It is orally bioavailable (F&amp;gt;70%); and has a favorable pharmacokinetic and toxicity profile. In mice, a single oral administration of NLG919 reduces the concentration of plasma and tissue Kyn by ∼ 50%. Using IDO-expressing human monocyte-derived DCs in allogeneic MLR reactions, NLG919 potently blocked IDO-induced T cell suppression and restored robust T cell responses with an ED50=80 nM. Similarly, using IDO-expressing mouse DCs from tumor-draining lymph nodes, NLG919 abrogated IDO-induced suppression of antigen-specific T cells (OT-I) in vitro, with ED50=120 nM. In vivo, in mice bearing large established B16F10 tumors, administration of NLG919 markedly enhanced the anti-tumor responses of naïve, resting pmel-1 cells to vaccination with cognate hgp100 peptide plus CpG-1826 in IFA. In this stringent established-tumor model, NLG919 plus pmel 1/vaccine produced a dramatic collapse of tumor size within 4 days of vaccination (∼95% reduction in tumor volume compared to control animals receiving pmel-1/vaccine alone without NLG919). In conclusion, NLG919 is a potent IDO pathway inhibitor with desirable pharmacological properties, suitable for the treatment of immunosuppression associated with cancer. Citation Format: Mario R. Mautino, Firoz A. Jaipuri, Jesse Waldo, Sanjeev Kumar, James Adams, Clarissa Van Allen, Agnieszka Marcinowicz-Flick, David Munn, Nicholas Vahanian, Charles J. Link. NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 491. doi:10.1158/1538-7445.AM2013-491
Heterogeneous expression of GAGE, NY‐ESO‐1, MAGE‐A and SSX proteins in esophageal cancer: Implications for immunotherapy (2005)

Cancer/testis antigens (CTAs) elicit immune response in cancer patients and are therefore targets of immunotherapy. Current information on CTA expression is primarily based on mRNA assays and little is known about their expression at the protein level. The objectives of our study are to analyze GAGE, NY-ESO-1, MAGE-A and SSX protein expression in esophageal cancer and to correlate their expression patterns with clinicopathologic parameters and survival. We examined CTA protein expression in 213 patients with esophageal cancer by immunohistochemistry. Antigen-positive tumors were evaluated once and antigen-negative tumors were evaluated 3 times by examining different parts of the cancer specimen. GAGE, NY-ESO-1 and MAGE-A were heterogeneously expressed in 42 (20%), 44 (21%) and 111 (52%) tumors, respectively, whereas SSX expression was not detected. Of the 126 (59%) patients expressing CTAs, 70 (33%) expressed 1, 41 (19%) expressed 2 and 15 (7%) expressed 3 antigens. The expression of MAGE-A was correlated with those of GAGE (p = 0.001) and NY-ESO-1 (p = 0.002), and the expression of GAGE was correlated with that of NY-ESO-1 (p = 0.002). One hundred fifty-six (79%) sections were positively stained in the first evaluation, whereas 37 (19%) and 4 (2%) positive sections were identified in the second and third evaluations, respectively. Particularly, MAGE and GAGE expression showed overlaps. GAGE, NY-ESO-1 and MAGE-A protein expression was not correlated with the disease progression, TNM factors or survival. The detection of immunonegative cells in every specimen suggests addition of other drugs such as 5-aza-2'-deoxycytidine to increase the therapeutic effect of CTA-specific cancer vaccines.
Effect of Valency on Binding Properties of the Antihuman IgM Monoclonal Antibody 202 (1995)

A murine monoclonal IgG2a antibody, 202, specific for human IgM, was produced and immunochemically characterized. Binding features of MAb 202, epitope localization, and its accessibility at the quaternary structure of polymeric IgM were investigated. Direct and competitive ELISA with fragments of IgM molecule demonstrated that the epitope recognized by MAb 202 lies on the Fc3 portion of IgM. Sandwich ELISA with MAb 202, which could be used simultaneously to capture and to detect bound IgM, indicated that more than one 202 epitope is present on the IgM molecule. MAb 202 did not precipitate IgM in solution, whereas good precipitation lines were obtained in agarose gel. Binding of MAb 202 to the J chain, C-terminal tailpiece and C mu 2 peptide, which remain attached to the C mu 3 domain of the Fc5 fragment, was excluded by a number of experimental results and structural reasons. Therefore a potential candidate for epitope 202 expression was the C mu 3 domain. MAb 202 did not react with isolated mu chain, which is expected since epitope 202 is of a conformational type. Furthermore, the reaction with monomeric IgM was almost undetectable as was demonstrated by a number of methods (ELISA, immunofluorescence, Western blotting). Since monovalent Fab portions of MAb 202 weakly reacted with polymeric IgM, we concluded that intrinsic affinity of their interaction is low but greatly enhanced by bivalent binding. Antipolymeric IgM binding specificity of MAb 202 was demonstrated only in the case of bivalent binding with a functional affinity constant of Kd = 2.14 x 10(-9) M-1. This implied up to a 10(4) difference between intrinsic and functional affinity, as in the range of concentration used in this study MAb 202 did not react with monomeric IgM.
The Effect of Gasoline Aromatics Content on Exhaust Emissions: A Cooperative Test Program (1990)

&lt;div class="htmlview paragraph"&gt;A cooperative vehicle exhaust emissions test program was conducted by the California Air Resources Board and Chevron Research and Technology Company. The focus of the program was to determine the effect of aromatics content on nitrogen oxides (NO&lt;sub&gt;x&lt;/sub&gt;) emissions. The program consisted of testing nine vehicles on three different fuels. The fuels ranged in aromatics content from 10% to 30%.&lt;span class="xref"&gt;*&lt;/span&gt; Other fuel properties were held as constant as possible.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The tests were conducted in two different laboratories. In addition to the measurement of criteria emissions (hydrocarbons, carbon monoxide, and NO&lt;sub&gt;x&lt;/sub&gt;), some of the hydrocarbon emissions were speciated and a reactivity of the exhaust was calculated. Only slight changes in the exhaust emissions and reactivity were observed for a change in aromatics content from 30% to 10%.&lt;/div&gt;