gebhart/patrepeval huggingface dataset:
Synthesis and Biological Evaluation of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) Inhibitors Based on a Thieno[2,3-<i>d</i>]pyrimidin-4(3<i>H</i>)-one Core (2009)

Many breast tumors are hormone-dependent, and estrogens, especially estradiol (E2), have a pivotal role in their growth and development. 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a key enzyme in the biosynthesis of female sex steroids, catalyzing the NADPH-dependent reduction of estrone into biologically active estradiol. In this study, a library of fused (di)cycloalkeno thieno[2,3-d]pyrimidin-4(3H)-one based compounds was synthesized, and the biological activities against 17beta-HSD1 in a cell-free and in a cell-based assay were evaluated. Several thieno[2,3-d]pyrimidin-4(3H)-one based compounds, at 0.1 and 1 muM test concentrations, were found to be potent 17beta-HSD1 inhibitors. For example, 4-(3-hydroxyphenylthio)-1,2,7,8,9,10,11,13-octahydro-13-oxo-[1]benzothieno[2',3':4,5]-pyrimido[1,2-a]azepine-3-carboxaldehyde (7f) is one of the most potent nonsteroidal 17beta-HSD1 inhibitors reported to date with 94% inhibition of the recombinant enzyme at 0.1 muM test concentration. Importantly, the majority of these compounds exhibited excellent selectivity over the oxidative isoform 17beta-HSD2 and lacked estrogenic effects in an estrogen receptor (ER) binding assay.
Changes in Protein Prenylation and Prenyltransferase Activity in the Rat Seminiferous Epithelium during Early Stages of Spermatogenesis1 (1995)

Changes in protein prenyltransferase activity, levels of prenylated protein, and the type of isoprenoid modification was described in cells of rat seminifereous epithelium and correlated with differentiative events of spermatogenesis. The activity of protein farnesyltransferase (PFT) was at least 10-fold higher than that for protein geranylgeranyltransferase-I (PGGT-I) in seminiferous epithelium and spermatogenic cells of prepubertal rats of different ages. Both activities increased during the meiotic stages of differentiation and peaked at 23 days of age. The activity of farnesyltransferase in seminiferous epithelium was the same as that in mixed spermatogenic cell populations from animals aged 9 and 23 days, indicating that the activity of this enzyme in somatic cells and germ cells was similar at these ages. Farnesyltransferase activities were similar and low in both pachytene spermatocytes and round spermatids from adult rats; however, the activity in pachytene spermatocytes from 23-day old animals was 2-fold higher than in adults. The highest activity was associated with intermediate-sized spermatocytes appearing late during meiosis. PGGT-I activity was at least 10-fold lower than farnesyltransferase activity and was not significantly different among all cell populations. Differentiation-dependent in vivo protein prenylation was demonstrated by labeling of seminiferous epithelium with [3H]mevalonic acid at different prepubertal ages. Total protein prenylation and the ratio of geranylgeranylated to farnesylated protein, in contrast to prenyltransferase activity, decreased with increasing age. Although 20-30-kDa proteins were the most highly labeled at all ages, [3H]-proteins from different-aged prepubertal rats showed age-dependent changes in the level of prenylation of at least 14 proteins as determined by two-dimensional (2D) electrophoresis. Prenylated proteins of round spermatids were distinguished from those of the spermatocytes by the lack of many 20-30-kDa proteins and by low geranylgeranyl/farnesyl (GG/F) ratios. These results show that independent changes in prenyltransferase activity and protein prenylation accompany the differentiation events during the premeiotic and meiotic stages of spermatogenesis. This suggests that prenylation in the seminiferous epithelium may be more dependent on available protein substrate than on protein prenyltransferase activity.
Prolonged release of rifampicin from multiple W/O/W emulsion systems (1995)

The formation of multiple w/o/w emulsions with improved stability by using interfacial complex films between polyvinyl alcohol, acacia, polyvinylpyrrolidone and sorbitan monooleate (Span 80) is described. The long term stability of the emulsions, as assessed by microscopy and particle size analysis, showed no changes in the w/o/w emulsion systems prepared using these macromolecules in the internal phase. It has also been observed that the release rate of rifampicin, contained in the internal phase, increased significantly on addition of calcium stearate and/or soya lecithin to the organic phase.
General pharmacological properties of dapiprazole, a potential psychotropic agent. (1982)

A study of the general pharmacology of 3-[2-[4-(2-methylphenyl)-1-piperazinyl]ethyl]-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-alpyridine HCl (dapiprazole), a new psychotropic agent, is reported. The predominant feature of this compound appears to be alpha-adrenergic blockade. This action has been observed both in vitro and in vivo. Dapiprazole also possesses antihistaminic and antiserotonin activities, although at relatively high doses. The antihistaminic action appears to be restricted to H1 receptors as suggested by the lack of activity on the guinea-pig atrium. Dapiprazole appears to be devoid of anticholinergic, local anaesthetic, antimicrobial and diuretic effects.
Atlantic Hurricanes (2001)

Click to increase image sizeClick to decrease image size Additional informationNotes on contributorsLixion AvilaJames Franklin and Lixion Avila are hurricane specialists at the National Hurricane Center in Miami, Florida.
The effectiveness of realistic replication strategies on quality of availability for peer-to-peer systems (2004)

We take an availability-centric view on quality of service (QoS) and propose a model and mechanisms for studying the effectiveness of realistic replication schemes on availability QoS for peer-to-peer (P2P) systems. We especially tackle the dynamic replica placement (RP) problem where our focus is on choosing dynamically the number and location of replicas while (1) meeting different availability QoS requirements for all individual peers and (2) taking the intermittent connectivity of peers explicitly into account. We model P2P systems as a dynamic stochastic graph in which the nodes go up and down depending on their assigned up probability. We develop some simple heuristic algorithms for solving the RP problem, which are fully distributed and adaptive. Through an event-driven simulation study we compare and evaluate the achieved availability QoS of the proposed RP algorithms. Simulation results show that (1) even simple heuristics can achieve reasonably high availability QoS, and (2) satisfying availability QoS requires more replicas than for only increasing the hit rate.
Space charge distribution limitation on scale down of MNOS memory devices (1979)

The space charge distribution due to the trapped charge in the nitride of a MNOS memory device, produces a significant modulation of the nitride field outside the space charge region, that can appreciably effect the limit to which these devices can be scaled. Trapped hole and electron space charge distribution in silicon nitride have been derived from steady-state measurements of the change in flat-band voltage vs the maximum field in the nitride. Here, the steady-state density of trapped charge near the nitride-oxide interface n <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</inf> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">st</sup> (0), trapping length, X <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">o</inf> , and capture cross section, σ <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</inf> , were determined for nitrides deposited with a LPCVD system and an APCVD system. It was observed that the hole and electron trapped charge density increased and the trappings length decreased as the NH <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> to SiH <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</inf> ratio is decreased. The trapping length for holes, however, is much greater than for electrons and thus the hole distribution limits the extent to which the nitride can be reduced in thickness. As temperature was increased, the trapping length of electrons increased more rapidly and approached the hole trapping length at 125°C. An approximate scaling limit is defined as the nitride thickness which is twice the charge centroid for a stored charge of 1µC/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . By changing the NH <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> to SiH <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</inf> ratio from 450:1 to 28:1, the nitride thickness scaling limit at 25°C was decreased from 320Å to 190Å. Both the threshold shift and voltage decay rate of the MNOS memory device scale linearly with the reduced nitride thickness over a limited range of stored charge.
Antiphospholipid antibodies and antiphospholipid syndrome (1995)

More than a decade has gone by since the detailed clinical description of antiphospholipid syndrome (APS). Thrombosis, the main complication of the syndrome, can affect vessels of all sizes; the consistent histopathologic lesion is a bland thrombus without inflammation. Animal models are providing important new data on clinical and pathogenic aspects of APS. New data on the biology of the so-called cofactor beta 2-glycoprotein I is now available. Clearly, the mode of presentation of the phospholipid antigen appears significant, and beta 2-glycoprotein I may play an important part. Regarding treatment, there is further confirmation that long-term anticoagulation therapy with maintenance of a high international normalized ratio is needed in patients with antiphospholipid antibody-associated thrombosis to prevent recurrences.
Excitonic transitions and exciton damping processes in InGaAs/InP (1986)

Detailed absorption measurements and the analysis of the absorption spectra of In1−xGaxAs lattice matched to InP are reported. The lattice matching parameter Δa/a covered a range from +4×10−3 to −1×10−3. From the absorption data of material with small matching parameter we obtain the value of the interband matrix element ( P2=20.7 eV), the excitonic Rydberg (Ex =2.5 meV), and damping constant (Γ0=5.1 meV) in the temperature range from 1.5 to 340 K. From the temperature dependent band-gap shrinkage and exciton damping constant Γ, information on the carrier-phonon interaction is obtained. The effect of the biaxial stress in the epitaxial layers caused by the mismatch with the substrate is demonstrated by absorption spectra which directly reveal the valence band splitting due to stress. Absorption measurements on samples with and without substrate indicate that the strained expitaxial layers do not relax completely if the substrate is etched away. The remaining strain field is probably caused by misfit dislocations generated during the epitaxial growth. Taking into account these stress effects, a precise value of the band gap as a function of temperature is derived. At zero temperature, we obtain a value of Eg(0) =821.5±0.2 meV for the band gap of In0.53Ga0.47As. From the absorption spectra we further determine the value of the bimolecular recombination coefficient (B=0.96×10−10 cm3/s at room temperature). The comparison of material grown by molecular-beam epitaxy (MBE) and liquid-phase epitaxy (LPE) shows that there is no difference between significant optical data of LPE and MBE high-quality layers.
Disturbance-free BIST for loop characterization of DC-DC buck converters (2015)

Complex electronic systems include multiple power domains and drastically varying dynamic power consumption patterns, requiring the use of multiple power conversion and regulation units. High frequency switching converters have been gaining prominence in the DC-DC converter market due to their high efficiency. Unfortunately, they are also subject to higher process variations jeopardizing stable operation of the power supply. This paper presents a technique to track changes in the dynamic loop characteristics of the DC-DC converters without disturbing the normal mode of operation using a white noise based excitation and correlation. White noise excitation is generated via pseudo random disturbance at reference and PWM input of the converter with the test signal energy being spread over a wide bandwidth, below the converter noise and ripple floor. Test signal analysis is achieved by correlating the pseudo random input sequence with the output response and thereby accumulating the desired behavior over time and pulling it above the noise floor of the measurement set-up. An off-the-shelf power converter, LM27402 is used as the DUT for the experimental verification. Experimental results show that the proposed technique can estimate converter's natural frequency and Q-factor within ±2.5% and ±0.7% error margin respectively, over changes in load inductance and capacitance.
Fast, High Flux, Photovoltaic Cdte Detector (1981)

A recently invented CdTe radiation detector designed for high flux applications has been improved to give excellent response over a wide range of x-ray and gamma-ray fluxes. This device operates without an externally applied bias and has no dark current, which makes it very sensitive even at low flux. Measurements over a range of 10-1R/hr to 106 R/hr (Flux of ~ 104 to 1011 photons/cm2-sec) show both nearly linear response and high signal-to-noise. Afterglow has been reduced dramatically so that 1 ms time response can be achieved. This advance opens the possibility of using this semiconductor in the "current mode" of operation for both medical and industrial applications.
N-[3-(1-alkylpiperidyl)]acetamides and N,N-dimethyl-N'-[3-(1-alkyl-piperidyl)]ureas as cholinesterase inhibitors. I (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTN-[3-(1-alkylpiperidyl)]acetamides and N,N-dimethyl-N'-[3-(1-alkyl-piperidyl)]ureas as cholinesterase inhibitors. IIan W. Mathison, James G. Beasley, Kathleen C. Fowler, and Elizabeth R. PetersCite this: J. Med. Chem. 1969, 12, 5, 928–931Publication Date (Print):September 1, 1969Publication History Published online1 May 2002Published inissue 1 September 1969https://pubs.acs.org/doi/10.1021/jm00305a058https://doi.org/10.1021/jm00305a058research-articleACS PublicationsRequest reuse permissionsArticle Views37Altmetric-Citations3LEARN 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
Hyperactivation of the NLRP3 Inflammasome in Myeloid Cells Leads to Severe Organ Damage in Experimental Lupus (2016)

Abstract Systemic lupus erythematosus (SLE) is an autoimmune syndrome associated with severe organ damage resulting from the activation of immune cells. Recently, a role for caspase-1 in murine lupus was described, indicating an involvement of inflammasomes in the development of SLE. Among multiple inflammasomes identified, the NLRP3 inflammasome was connected to diverse diseases, including autoimmune encephalomyelitis. However, the function of NLRP3 in SLE development remains elusive. In this study, we explored the role of NLRP3 in the development of SLE using the pristane-induced experimental lupus model. It was discovered that more severe lupus-like syndrome developed in Nlrp3-R258W mice carrying the gain-of-function mutation. Nlrp3-R258W mutant mice exhibited significantly higher mortality upon pristane challenge. Moreover, prominent hypercellularity and interstitial nephritis were evident in the glomeruli of Nlrp3-R258W mice. In addition, hyperactivation of the NLRP3 inflammasome in this mouse line resulted in proteinuria and mesangial destruction. Importantly, all of these phenotypes were largely attributed to the Nlrp3-R258W mutation expressed in myeloid cells, because Cre recombinase–mediated depletion of this mutant from such cells rescued mice from experimental lupus. Taken together, our study demonstrates a critical role for NLRP3 in the development of SLE and suggests that modulating the inflammasome signal may help to control the inflammatory damage in autoimmune diseases, including lupus.
New Frontiers in Educational Research (1973)

Philip H. Taylor, New Frontiers in Educational Research, Paedagogica Europaea, Vol. 8, Guidance and Assessment in European Education / Orientation et Evaluation Continue en Europe / Schülerberatung und Schülerbeurteilung im europäischen Erziehungswesen (1973), pp. 17-33
Low-dose bisoprolol/hydrochlorothiazide: an option in first-line, antihypertensive treatment. (1993)

Two recent, multicenter, double-blind, placebo-controlled studies established the efficacy and safety of low-dose bisoprolol/hydrochlorothiazide (HCTZ) in patients with mild to moderate essential hypertension. Bisoprolol, a cardioselective beta-blocker, was used in a dose of 2.5 mg, 5 mg, or 10 mg. HCTZ was used at a dose of 6.25 mg. This low-dose compound was developed to minimize dose-related adverse effects. The addition of HCTZ to each of the doses of bisoprolol was compared with monotherapy and placebo. Results of both studies demonstrated that this once-a-day, low-dose option effectively reduced sitting diastolic and systolic blood pressure measured at the end of the 24-hour dosing period. Drug-related adverse effects, including those generally associated with traditional beta-blocker therapy, were infrequent in individuals who received the low-dose bisoprolol/HCTZ regimen. Dose-related side effects were minimized because of the low doses of the two agents used together. There were no significant changes in mean total cholesterol, triglycerides, or serum glucose with bisoprolol/HCTZ 6.25 mg therapy versus placebo (analysis of variance statistical methods). The incidence of treatment-induced hypokalemia with bisoprolol/HCTZ 6.25 mg was not significant; uric acid elevations were minimized, and the incidence of hyperuricemia was significantly (P < 0.01) less with bisoprolol/HCTZ 6.25 mg than with 25 mg of HCTZ. Once-a-day dosing with the low-dose agent controlled (defined as a sitting diastolic blood pressure < or = 90 mmHg and/or a decrease from baseline > or = 10 mmHg) blood pressure in up to 80% of patients for a full 24 hours after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)
Biological agent detection technologies (2009)

The challenge for first responders, physicians in the emergency room, public health personnel, as well as for food manufacturers, distributors and retailers is accurate and reliable identification of pathogenic agents and their corresponding diseases. This is the weakest point in biological agent detection capability today. There is intense research for new molecular detection technologies that could be used for very accurate detection of pathogens that would be a concern to first responders. These include the need for sensors for multiple applications as varied as understanding the ecology of pathogenic micro-organisms, forensics, environmental sampling for detect-to-treat applications, biological sensors for 'detect to warn' in infrastructure protection, responses to reports of 'suspicious powders', and customs and borders enforcement, to cite a few examples. The benefits of accurate detection include saving millions of dollars annually by reducing disruption of the workforce and the national economy and improving delivery of correct countermeasures to those who are most in need of the information to provide protective and/or response measures.
Wounds and wound healing (1988)

Journal Article Wounds and wound healing Get access J R T Eckersley, J R T Eckersley Academic Surgical Unit, St Mary's HospitalLondon Search for other works by this author on: Oxford Academic PubMed Google Scholar H A F Dudley H A F Dudley Academic Surgical Unit, St Mary's HospitalLondon Search for other works by this author on: Oxford Academic PubMed Google Scholar British Medical Bulletin, Volume 44, Issue 2, 1988, Pages 423–436, https://doi.org/10.1093/oxfordjournals.bmb.a072259 Published: 01 June 1988
Initial clinical trial of a high-affinity retinoic acid receptor ligand (LGD1550). (2000)

Retinoids mediate their biological response by binding to specific nuclear receptors, including retinoic acid receptors and/or retinoid X receptors. LGD1550 is a high-affinity ligand for all three retinoic acid receptors (alpha, beta, and gamma isoforms) and a potent inhibitor of AP-1, a protein that is closely linked with trophic responses and malignant transformation. We conducted a dose ranging study to evaluate the pharmacokinetics, safety, clinical tolerance, and potential efficacy of this drug in patients with advanced cancer. Twenty-seven patients received oral doses of LGD1550 once per day at doses ranging from 20-400 microg/m2. Skin toxicity was the dose-limiting reaction at the 400 microg/m2 daily dose level. Less prominent reactions included nausea and headache. No major antitumor effects were observed. Pharmacokinetic studies in 15 patients at five dose levels showed that the peak plasma concentration (Cmax) and areas under the plasma concentration-time curve on day 1 were dose-proportional and were similar to values obtained on days 15, 29, and 84. Unlike other retinoids, LGD1550 did not induce its own metabolism, and there was little evidence of drug accumulation. The t1/2 was approximately 5 h after both the initial and repeated doses. We conclude that once-daily doses of LGD1550 of up to 300 microg/m2 are relatively well tolerated. Additional clinical explorations are warranted, especially in patients with cancers of the prostate, thyroid, head and neck, and cervix.
Assessment of large-scale biomass gasification systems for less-developed countries (1980)

This state-of-the-art report evaluates large-scale biomass gasification systems both economically and technically and analyses their potential applications in developing countries. After a discussion of biomass feedstock types, handling, and preparation, the authors describe various types of gasifiers available (fixed-bed updraft and downdraft, fluid-bed, and entrained-bed) and their current applications. Gasification chemistry, advanced gasification systems, and gas cleaning are also considered. Next, the use of fuel gas from biomass for steam power production, other fired equipment, internal combustion engines for power production, gas turbine cycles, synthesis of methanol and other liquid fuels, and synthesis of ammonia and other chemicals, is discussed. The environmental impacts of biomass gasification are reviewed. The authors conclude that availability of sufficient feed materials is essential for large-scale biomass gasification in developing countries. The most promising applications are: (1) rural electrification using air-blown biomass gasifiers and diesel generators; (2) retrofitting existing oil and gas fired equipment in various industries, particularly in agricultural processing plants; and (3) producing ammonia-based fertilizers from biomass-derived synthesis gas.