gebhart/patrepeval huggingface dataset:
Nonpeptide angiotensin II antagonists derived from 4H-1,2,4-triazoles and 3H-imidazo[1,2-b][1,2,4]triazoles (1993)

By a variety of synthetic routes, we have synthesized a series of 3,4,5-trisubstituted 4H-1,2,4-triazoles and a related series of 3H-imidazo[1,2-b][1,2,4]triazoles and evaluated them in vitro and in vivo as angiotensin II (AII) antagonists. Principal efforts focused on triazoles bearing an n-alkyl substitutent at C3 and a 4-[(2-carboxybenzoyl)amino]benzyl, (2'-carboxybiphenyl-4-yl)methyl, or [2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl side chain at N4. Among numerous variations at C5, benzylthio groups gave the best potency. Particularly noteworthy was 3-n-butyl-5-[(2-carboxybenzyl)thio]-4-[[2'-(1H-tetrazol-5-yl )biphenyl-4 - yl]methyl]-4H-1,2,4-triazole (71, IC50 1.4 nM), which blocked the AII pressor response in conscious rats at 0.3 mg/kg iv with a duration of action of approximately 6 h, similar to that of DuP 753. Although 71 was active orally only at a 10-fold higher dose level, good oral bioavailability was demonstrated for a monoacidic analogue 62. Most potent among the bicyclic derivatives was 2-n-butyl-5,6-dimethyl-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]meth yl]- 3H-imidazo[1,2-b][1,2,4]triazole (93, IC50 7.8 nM). The effects of hydrophobic, hydrogen-bonding, and ionic interactions with the AT1 receptor are considered.
Diversity of thermophilic and non-thermophilic crenarchaeota at 80 Â°C (2005)

A hot spring in the solfataric field of Pisciarelli (Naples-Italy) was analysed for Archaeal diversity. Total DNA was extracted from the environment, archaeal 16S rRNA genes were amplified with Archaea specific primers, and a clone library consisting of 201 clones was established. The clones were grouped in 10 different groups each representing a specific band pattern using restriction fragment length polymorphism (RFLP). Members of all 10 groups were sequenced and phylogenetically analyzed. Surprisingly, a high abundance of clones belonging to non-thermophilic Crenarchaeal clusters were detected together with the thermophilic archaeon Acidianus infernus in this thermophilic environment. Neither Sulfolobus species nor other hyperthermophilic Crenarchaeota were detected in the clone library. The relative abundance of the sequenced clones was confirmed by terminal restriction fragment analyses. Amplification of 16S rRNA genes from Archaea transferred from the surrounding environment was considered negligible because DNA from non-thermophilic Crenarchaeota incubated under conditions similar to the solfatara could not be PCR amplified after 5 min.
Interleukin‐12 Regulates the Response to Chemotherapy in Experimental Visceral Leishmaniasis (2000)

In experimental visceral leishmaniasis, interleukin (IL)-12 initiates control over Leishmania donovani via Th1 cell activation, interferon (IFN)-gamma secretion, and granuloma formation. Because the leishmanicidal effect of conventional therapy, pentavalent antimony (Sb), also requires T cells and endogenous IFN-gamma, we tested IL-12 as a determinant of host responsiveness to chemotherapy. L. donovani-challenged IL-12p35 gene knockout (KO) mice permitted uncontrolled hepatic infection and failed to respond to Sb. In contrast, 96% of liver parasites in KO mice were killed by amphotericin B, which acts independently of immune responses. Exogenous IL-12 combined with Sb was tested in normal mice: low-dose Sb was converted from weakly to strongly leishmanicidal, and a no-effect Sb dose was converted to approximately 100% leishmanistatic. IL-12 plus Sb synergism in normal mice was IFN-gamma dependent; however, IL-12 also increased responsiveness to Sb in IFN-gamma KO mice. Thus, IL-12 regulates host IFN-gamma-dependent and -independent responses that permit and/or enhance the leishmanicidal activity of Sb.
L’importance macroéconomique du système de protection sociale et ses enjeux pour la politique sociale en Allemagne (2013)

L’auteur a présenté le rôle du système de protection sociale en Allemagne à court et à long terme. En ce qui concerne son rôle à court terme, il a évoqué sa fonction stabilisatrice pendant les crises conjoncturelles ; concernant le long terme, il a étudié l’impact sur son fonctionnement des modifications démographiques prévisibles. L’évaluation des performances diffère, en effet, selon que l’on étudie des chocs transitoires ou des variations démographiques à long terme. Ceci est très important, dans la mesure où le financement du système de protection sociale en Allemagne, tout comme en France, repose largement sur les cotisations sociales prélevées sur les salariés.
Efficacy of Imiquimod as an Adjunct to Cryotherapy for Actinic Keratoses (2007)

Imiquimod postcryotherapy may increase clearance of subclinical and total AKs and proportions of subjects clear at 3 months. These findings require confirmation in larger controlled trials powered for statistical significance.
Transmission lines for digital and communication networks : an introduction to transmission lines, high-frequency and high-speed pulse characteristics and applications (1995)

Electrical Engineering/Circuits and Systems Transmission Lines for Digital and Communication Networks An IEEE Press Classic Reissue In the recent past, knowledge of transmission line behavior was not essential to understanding digital logic design. Slow signals, relatively short wires, logic probes and the treatment of wave forms as sequences of ones and zeros made it possible to design logic without a solid understanding of fields. That has changed dramatically. Today, with edge rates and gate delays moving into the picosecond realm, innovative product designers must be able to understand and model the essential distributed element nature of electrical circuits. Those who don't will lag far behind the competition. Keeping pace with these developments, IEEE Press is pleased to bring back into print this definitive reference on high-speed transmission line behavior.
Effect of Alpha Interferon on the Hepatitis C Virus Replicon (2001)

Chronic hepatitis C virus (HCV) infections can be cured only in a fraction of patients treated with alpha interferon (IFN-alpha) and ribavirin combination therapy. The mechanism of the IFN-alpha response against HCV is not understood, but evidence for a role for viral nonstructural protein 5A (NS5A) in IFN resistance has been provided. To elucidate the mechanism by which NS5A and possibly other viral proteins inhibit the cellular antiviral program, we have constructed a subgenomic replicon from a known infectious HCV clone and demonstrated that it has an approximately 1,000-fold-higher transduction efficiency than previously used subgenomes. We found that IFN-alpha reduced replication of HCV subgenomic replicons approximately 10-fold. The estimated half-life of viral RNA in the presence of the cytokine was about 12 h. HCV replication was sensitive to IFN-alpha independently of whether the replicon expressed an NS5A protein associated with sensitivity or resistance to the cytokine. Furthermore, our results indicated that HCV replicons can persist in Huh7 cells in the presence of high concentrations of IFN-alpha. Finally, under our conditions, selection for IFN-alpha-resistant variants did not occur.
Transforming growth factor beta 2 (TGF-beta 2) levels in plasma of patients with metastatic breast cancer treated with tamoxifen. (1995)

Blood levels of transforming growth factor beta 2 (TGF-beta 2) were measured in 20 patients with metastatic breast cancer before and during treatment with the antiestrogen tamoxifen, and in a control group of 7 patients with primary breast cancer before and during adjuvant tamoxifen treatment. The results of this study reveal typical time patterns for TGF-beta 2 in relation to the clinical outcome. Patients in remission showed a significant increase of TGF-beta 2 in the first 4-6 weeks of therapy, followed by a subsequent decrease. Patients who did not respond showed unchanged or diminished TGF-beta 2 values after start of therapy, followed by a later increase preceding the clinical manifestation of tumor progression. Thus, TGF-beta 2 blood levels after 4 weeks of tamoxifen treatment can be used as an early marker for prediction of response.
Spin coating: One-dimensional model (1989)

The model of the spin-coating process presented here accounts for variations of concentration, viscosity, and diffusivity across the thickness of the spin-coated film. The flow of the liquid is governed by a balance between centrifugal driving force and viscous resisting force. Radial variations in film thickness and concentration are neglected. The Galerkin/finite-element method is employed to solve the equation set. Film thinning slows initially due to decreasing film thickness and ceases finally due to dramatically increasing viscosity of the coating liquid as solvents evaporate. The formation of a region of extremely low solvent concentration and correspondingly high viscosity and low binary diffusivity at the free surface, i.e., a solid ‘‘skin,’’ is predicted. Coating defects can occur if convective flow has not completely ceased when this skin forms. Skin formation can be eliminated or delayed by partially saturating the overlying gas with solvent or by using mixed solvents (having both high and low volatilities) in the coating liquid. The temperature variation in the film during coating varies negligibly from the ambient.
Low-dose lidocaine reduces secondary hyperalgesia by a central mode of action (2000)

Sodium channel blockers are approved for intravenous administration in the treatment of neuropathic pain states. Preclinical studies have suggested antihyperalgesic effects on the peripheral as well as the central nervous system. The objective of this study was to determine mechanisms of action of low-dose lidocaine in experimental induced, secondary hyperalgesia. In a first experimental trial, participants (n=12) received lidocaine systemically (a bolus injection of 2 mg/kg in 10 min followed by an intravenous infusion of 2 mg kg(-1)h(-1) for another 50 min). In a second trial, a modified intravenous regional anesthesia (IVRA) was administered to exclude possible central analgesic effects. In one arm, patients received an infusion of 40 ml lidocaine, 0.05%; in the other arm 40 ml NaCl, 0.9%, served as a control. In both trials capsaicin, 20 microgram, was injected intradermally and time course of capsaicin-induced pain, allodynia and hyperalgesia as well as axon reflex flare was determined. The capsaicin-induced pain was slightly reduced after systemic and regional application of the anesthetic. The area of pin-prick hyperalgesia was significantly reduced by systemic lidocaine, whereas the inhibition of hyperalgesia was absent during regional administration of lidocaine. In contrast, capsaicin-induced flare was significantly decreased after both treatments. We conclude that systemic lidocaine reduces pin-prick hyperalgesia by a central mode of action, which could involve blockade of terminal branches of nociceptors. A possible role for tetrodotoxin resistant sodium channels in the antihyperalgesic effect of low-dose lidocaine is discussed.
Resiquimod 3M. (2003)

3M Pharmaceuticals is developing a topical formulation of resiquimod as an immunomodulator for the potential treatment of herpes simplex virus (HSV) infections. As of September 2001, resiquimod was to be commercialized worldwide in association with Eli Lilly. Phase III trials for the treatment of HSV infection were initiated in November 2000 and were ongoing in September 2001. In October 2001, US and European filings were scheduled for 2004, and by February 2002, Lilly was anticipating launch in either 2004 or 2005. The compound has also been investigated for the potential treatment of various other diseases, including other viral infections and eczema and as a vaccine adjuvant.
Big Vein: Hits Quality, Quantity of Lettuce (1962)

This item is part of the Arizona Land and People (formerly Progressive Agriculture in Arizona) archive. It was digitized from a physical copy provided by the College of Agriculture and Life Sciences at The University of Arizona. For more information about this periodical, please email CALS Publications at pubs@ag.arizona.edu.
Functional food science and gastrointestinal physiology and function (1998)

The gut is an obvious target for the development of functional foods, acting as it does as the interface between diet and the metabolic events which sustain life. The key processes in digestive physiology which can be regulated by modifying diet are satiety, the rate and extent of macronutrient breakdown and absorption from the small bowel, sterol metabolism, the colonic microflora, fermentation, mucosal function and bowel habit, and the gut immune system. The intestinal microflora is the main focus of many current functional foods. Probiotics are foods which contain live bacteria which are beneficial to health whilst prebiotics, such as certain non-digestible oligosaccharides which selectively stimulate the growth of bifidobacteria in the colon, are already on the market. Their claimed benefits are to alleviate lactose maldigestion, increase resistance to invasion by pathogenic species of bacteria in the gut, stimulate the immune system and possibly protect against cancer. There are very few reports of well-designed human intervention studies with prebiotics as yet. Certain probiotic species have been shown to shorten the duration of rotavirus diarrhoea in children but much more work is needed on the mechanism of immunomodulation and of competitive exclusion and microflora modification. The development of functional foods for the gut is in its infancy and will be successful only if more fundamental research is done on digestive physiology, the gut microflora, immune system and mucosal function.
Modified bagging of maximal information coefficient for genome-wide identification (2016)

A new method, modified Bagging (mBagging) of Maximal Information Coefficient (mBoMIC), was developed for genome-wide identification. Traditional Bagging is inadequate to meet some requirements of genome-wide identification, in terms of statistical performance and time cost. To improve statistical performance and reduce time cost, an mBagging was developed to introduce Maximal Information Coefficient (MIC) into genome-wide identification. The mBoMIC overcame the weakness of original MIC, i.e., the statistical power is inadequate and MIC values are volatile. The three incompatible measures of Bagging, i.e. time cost, statistical power and false positive rate, were significantly improved simultaneously. Compared with traditional Bagging, mBagging reduced time cost by 80%, improved statistical power by 15%, and decreased false positive rate by 31%. The mBoMIC has sensitivity and university in genome-wide identification. The SNPs identified only by mBoMIC have been reported as SNPs associated with cardiac disease.
Formation of gas bubbles in supersaturated solutions of gases in water (1985)

Abstract The objective of this study is to develop a model and correlate it with experimental measurements for predicting the tolerable degree of supersaturation of gas‐water solutions. This model is also capable of predicting quite accurately the cavitation phenomenon in water.
Modeling of Rifampicin-Induced CYP3A4 Activation Dynamics for the Prediction of Clinical Drug-Drug Interactions from In Vitro Data (2013)

Induction of cytochrome P450 3A4 (CYP3A4) expression is often implicated in clinically relevant drug-drug interactions (DDI), as metabolism catalyzed by this enzyme is the dominant route of elimination for many drugs. Although several DDI models have been proposed, none have comprehensively considered the effects of enzyme transcription/translation dynamics on induction-based DDI. Rifampicin is a well-known CYP3A4 inducer, and is commonly used as a positive control for evaluating the CYP3A4 induction potential of test compounds. Herein, we report the compilation of in vitro induction data for CYP3A4 by rifampicin in human hepatocytes, and the transcription/translation model developed for this enzyme using an extended least squares method that can account for inherent inter-individual variability. We also developed physiologically based pharmacokinetic (PBPK) models for the CYP3A4 inducer and CYP3A4 substrates. Finally, we demonstrated that rifampicin-induced DDI can be predicted with reasonable accuracy, and that a static model can be used to simulate DDI once the blood concentration of the inducer reaches a steady state following repeated dosing. This dynamic PBPK-based DDI model was implemented on a new multi-hierarchical physiology simulation platform named PhysioDesigner.
The complex mechanistic aspects of redox-active compounds, commonly regarded as SOD mimics (2013)

Abstract This review aims to clarify (1) what is a true mimic of superoxide dismutase family of enzymes, SOD; and (2) whether such compound could act as SOD mimic in a complex biological milieu. Several groups of compounds (metalloporphyrins, metallocorroles, Mn biliverdins, Mn cyclic polyamines, Mn salens, and metal oxides and salts) have been described. Their ability to catalyze the dismutation of O 2 ·– , [ k cat (O 2 ·– )], thermodynamic property that supports high catalytic ability ( E 1/2 ), kinetic factors that facilitate the catalysis, and the stability of compounds, which assures the integrity of metal coordination sphere where reactions of interest occur have been discussed. The other possible in vivo actions of those compounds, such as peroxynitrite and hypochlorite reduction, peroxidase-like activity, thiol oxidase activity etc., have been described as well. Based on in vivo studies it appears that k cat (O 2 ·– ) for Mn(III) N-substituted pyridylporphyrins parallels their therapeutic ability. The reason for that lies in their electrophilic nature which favors reactions with nucleophilic (anionic) reactive species (O 2 ·– , ONOO – , ClO – , HO 2 – , CO 3 ·– ) and simple or protein thiolates. Their in vivo multiple rather than single modes of actions, would be determined by: (a) their redox properties; (b) localization at targeted cellular site; and (c) redox environment of diseased or mutated/cancer cell. Quality of any drug preparation and the knowledge of researchers on its properties are essential when its mechanistic aspects are explored.
Phase II trial of pulse dactinomycin as salvage therapy for failed low‐risk gestational trophoblastic neoplasia (2006)

Pulse dactinomycin is an active regimen for patients with low-risk GTN who fail previous methotrexate therapy.
Nijmegen breakage syndrome. (1996)

Nijmegen breakage syndrome (NBS), a rare autosomal recessive condition also known as ataxia telangiectasia (AT) variants V1 and V2, is characterised by microcephaly, typical facies, short stature, immunodeficiency, and chromosomal instability. We report the clinical, immunological, chromosomal, and cell biological findings in 42 patients who are included in the NBS Registry in Nijmegen. The immunological, chromosomal, and cell biological findings resemble those in AT, but the clinical findings are quite different. NBS appears to be a separate entity not allelic with AT.
Interaction between 18-crown-6-tetracarboxylic acid and positional substituents of enantiomers and simultaneous separation of positional enantiomers of methyl-DL-tryptophans by capillary electrophoresis (2001)

18-Crown-6-tetracarboxylic acid (18C6H4) is a chiral selector with high selectivity for the enantioseparation of solutes bearing the primary amine function. This work presents the simultaneous separation of positional enantiomers of methyl-DL-tryptophans by using 18C6H4 as an additive to the background electrolyte. Separation conditions such as pH, the concentration of 18C6H4, and the applied voltages have critical inference on the simultaneous separation. The addition of cyclodextrins as anionic surfactants to the background electrolyte did not improve the separation. The selector-selectand interactions between 18C6H4 and the positional enantiomers have been investigated. It was observed that both the position and type of substituents contribute to the enantioselectivity. The migration order and resolution depended on the distance from the substituents to the asymmetric carbon of the enantiomers.
Wnt11 stimulation induces polarized accumulation of Dishevelled at apical adherens junctions through Frizzled7 (2007)

Dishevelled, an essential mediator of Wnt signaling, is shown to regulate vertebrate gastrulation movements by controlling cell polarity, but how cell polarization is regulated during gastrulation has remained unclear. Here, we show that Dishevelled accumulates in the apical region at cell-cell contacts in involuting mesodermal cells, and that Wnt11 stimulation induces the accumulation of Dishevelled at apical adherens junctions in Xenopus ectodermal explants. We also show that the accumulation of Dishevelled is suppressed by the depletion of the Wnt receptor Frizzeld7 with a morpholino antisense oligonucleotide, and Frizzled7 itself also accumulates at apical adherens junctions in response to Wnt11. These results indicate that Wnt11 stimulation induces the accumulation of Dishevelled via the accumulation of Frizzled7. Our subsequent analysis shows that the DIX domain of Dishevelled is necessary for its translocation and accumulation in response to Wnt11. Our results suggest that Wnt11-induced polarized accumulation of Frizzled7 and Dishevelled at adherens junctions underlies the formation and maintenance of apicobasal cell polarity.
The Role of Alanine and Glutamine in Steroid-Induced Nitrogen Wasting in Man (1977)

1. Administration of dexamethasone, 8 mg/day (0·02 mmol/day), for 5 days to normal subjects produced negative nitrogen balance, due to early and sustained increases in urinary urea nitrogen excretion. 2. In eight subjects ingesting 0·9–1·6 g of protein day−1 kg−1 body weight the cumulative increment in urea nitrogen excretion averaged + 12·5 g (sem 2·8, P &lt; 0·01) over the 5 days of glucocorticoid administration. 3. Increases in urinary urea nitrogen excretion could be related to both plasma alanine and blood glutamine changes by using a multiple regression equation. 4. These results suggest that corticosteroids induce increased release of alanine and glutamine by peripheral tissues, which may augment urea formation and negative nitrogen balance. 5. The correlation between increments in urea nitrogen excretion and increases in plasma arginine remains unexplained.
ChemInform Abstract: 1,3‐Dipolar Cycloadditions with Methyl 4‐Oxo‐ and 4‐Hydroxy‐2‐butynoates (II). Synthesis of Functionalized Pyrazoles (III), (IV), (VI), (VII) and Triazoles (IX), (X). (1989)

Abstract 1,3‐Dipolar Cycloadditions with Methyl 4‐Oxo‐ and 4‐Hydroxy‐2‐butynoates (II).
Potentiation of Taxol Efficacy by Discodermolide in Ovarian Carcinoma Xenograft-Bearing Mice (2006)

The synergistic activity of Taxol and discodermolide in cells is most potent at drug concentrations that result in drug-induced aneuploidy rather than mitotic arrest. Moreover, in an animal model of ovarian carcinoma, this is a well-tolerated combination that induces tumor regressions and suppresses angiogenesis. These data confirm the potency of this combination and support the use of concurrent low doses of Taxol and discodermolide for potential use in cancer therapeutics.
Enzyme‐Responsive Nanoparticle Systems (2008)

Abstract Inorganic nanoparticles and their accompanying diverse physical properties are now virtually in routine use as imaging tools in cell‐biology. In addition to serving as excellent contrast agents, their size‐ and environment‐dependent optical and magnetic properties can be harnessed to create enzyme biosensor devices of extremely high sensitivity, whilst circumventing the numerous technical limitations associated with traditional enzyme assays. In this Research News article we discuss recent advances in field of enzyme‐responsive nanoparticle systems, where the activity of an enzyme elicits a specific response in the nanoparticle assembly to produce a signal relating to enzyme activity, focusing on three important systems: DNA‐structured nanoparticles, protein kinases and proteases.