gebhart/patrepeval huggingface dataset:
In vivo antiviral activity and pharmacokinetics of (-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in woodchuck hepatitis virus-infected woodchucks (1997)

The (-) enantiomer of cis-5-fluoro-1l-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine [(-)-FTC)], a substituted oxathiolane compound with anti-hepatitis B virus activity in vitro, was assessed for its efficacy in woodchucks with naturally acquired woodchuck hepatitis virus (WHV) infection. Pharmacokinetics and in vitro anabolism were also determined. (-)-FTC was anabolized to the 5'-triphosphate in a dose-related fashion, reaching a maximum concentration at about 24 h in cultured woodchuck hepatocytes. Following administration of a dose of 10 mg/kg of body weight intraperitoneally (i.p.), the clearance of (-)-FTC from plasma was monoexponential, the terminal half-life was 3.76 +/- 1.4 h, and the systemic clearance was 0.12 +/- 0.06 liters/h/kg. The antiviral efficacy of (-)-FTC in the woodchuck model was assessed by quantitation of serum WHV DNA levels and by WHV particle-associated DNA polymerase activity at two dosages, 30 and 20 mg/kg given i.p. twice daily (b.i.d.), respectively. The level of WHV DNA in serum was reduced 20- to 150-fold (average, 56-fold) in the 30-mg/kg-b.i.d. treatment group and 6- to 49-fold (average, 27-fold) in the 20-mg/kg-b.i.d. treatment group. Viral DNA polymerase levels diminished accordingly. One week after treatment was discontinued, WHV levels returned to pretreatment levels in both studies. These animals were biopsied before and following treatment with 30 mg of (-)-FTC per kg. Their livers were characterized by a mild increase in cytoplasmic lipid levels, but this change was not associated with altered liver enzyme levels. Serum chemistry and hematology results were within the normal ranges for all treated animals. We conclude that (-)-FTC is a potent antihepadnaviral agent and that it has no detectable toxic effects in woodchucks when given for up to 25 days. Further development of (-)-FTC as an anti-hepatitis B virus therapy for patients is warranted.
Intel® Turbo Memory (2008)

Hard-disk drives are a significant bottleneck to system performance and are also responsible for a significant fraction of total system power consumption. Intel Turbo Memory addresses these problems by adding a new layer to the storage hierarchy: a platform-based and nonvolatile, disk cache. In this article, we describe the hardware and software elements of the Intel Turbo Memory architecture. We show how it supports the new ReadyBoost and ReadyDrive features in Microsoft Vista and describe its key caching algorithms. We present performance, power savings, and wear-leveling results achieved by Intel Turbo Memory.
Differential Culture Medium for Pseudomonas species Causing Sheath Rot (ShR) and Grain Discoloration (GLD) of Rice (1989)

This article 'Differential Culture Medium for Pseudomonas species Causing Sheath Rot (ShR) and Grain Discoloration (GLD) of Rice' appeared in the International Rice Research Newsletter series, created by the International Rice Research Institute (IRRI). The primary objective of this publication was to expedite communication among scientists concerned with the development of improved technology for rice and for rice based cropping systems. This publication will report what scientists are doing to increase the production of rice in as much as this crop feeds the most densely populated and land scarce nations in the world.
Abbau der Chinasäure nach Hunsdiecker (1965)

Abstract Das Silbersalz der Tetraacetylchinasäure läßt sich unter bestimmten Bedingungen glatt nach H UNSDIECKER abbauen. Das Reaktionsprodukt II wird auf einem unabhängigen Wege synthetisiert. Es geht bei der Cyanhydrin‐Synthese in stereospezifischer Reaktion wieder in Chinasäure über.
Analysis and Optimal Design Considerations for an Improved Full Bridge ZVS DC–DC Converter With High Efficiency (2006)

This paper proposes an improved full bridge dc-dc converter, which can achieve zero-voltage-switching (ZVS) with wide input voltage range and load range. The operation principle of the converter and the optimal design considerations for high efficiency and ZVS range are analyzed. By adding two clamp diodes and two small coupled inductors at the primary side of the transformer, the voltage ringing across rectifier diodes is reduced. Therefore, Schottky diodes can be employed to reduce conduction loss, and high efficiency is achieved. A 1.2-kW/105-kHz prototype was made with an efficiency higher than 95% at full load to verify the theoretical analysis
Why Have Recent Trials of Neuroprotective Agents in Head Injury Failed to Show Convincing Efficacy? A Pragmatic Analysis and Theoretical Considerations (1999)

An overview of the results of recent trials of neuroprotective agents in head injury is presented. None of the trials showed efficacy in the general population of patients with a severe head injury. A critical analysis of the possible reasons for this failure is given. Specific attention is focused on the heterogeneity of the patient population, the importance of baseline prognostic indicators, and the problems caused by the distribution of outcome and the dichotomization of these outcomes in the Glasgow Outcome Scale. Recommendations are presented for consideration in the design and analysis of future trials in head injury.
Estimation of Total-Body Skeletal Muscle Mass in Children and Adolescents (2005)

Besides DEXA technique, the determination of total-body skeletal muscle mass in children and adolescents can be highly validated with satisfactory confidence by simple anthropometric measurements or 24-h urine creatinine excretion.
Practical algorithms for a family of waterfilling solutions (2005)

Many engineering problems that can be formulated as constrained optimization problems result in solutions given by a waterfilling structure; the classical example is the capacity-achieving solution for a frequency-selective channel. For simple waterfilling solutions with a single waterlevel and a single constraint (typically, a power constraint), some algorithms have been proposed in the literature to compute the solutions numerically. However, some other optimization problems result in significantly more complicated waterfilling solutions that include multiple waterlevels and multiple constraints. For such cases, it may still be possible to obtain practical algorithms to evaluate the solutions numerically but only after a painstaking inspection of the specific waterfilling structure. In addition, a unified view of the different types of waterfilling solutions and the corresponding practical algorithms is missing. The purpose of this paper is twofold. On the one hand, it overviews the waterfilling results existing in the literature from a unified viewpoint. On the other hand, it bridges the gap between a wide family of waterfilling solutions and their efficient implementation in practice; to be more precise, it provides a practical algorithm to evaluate numerically a general waterfilling solution, which includes the currently existing waterfilling solutions and others that may possibly appear in future problems.
Functional specialization of calreticulin domains (2001)

Calreticulin is a Ca2+-binding chaperone in the endoplasmic reticulum (ER), and calreticulin gene knockout is embryonic lethal. Here, we used calreticulin-deficient mouse embryonic fibroblasts to examine the function of calreticulin as a regulator of Ca2+ homeostasis. In cells without calreticulin, the ER has a lower capacity for Ca2+ storage, although the free ER luminal Ca2+ concentration is unchanged. Calreticulin-deficient cells show inhibited Ca2+ release in response to bradykinin, yet they release Ca2+ upon direct activation with the inositol 1,4,5-trisphosphate (InsP3). These cells fail to produce a measurable level of InsP3 upon stimulation with bradykinin, likely because the binding of bradykinin to its cell surface receptor is impaired. Bradykinin binding and bradykinin-induced Ca2+ release are both restored by expression of full-length calreticulin and the N + P domain of the protein. Expression of the P + C domain of calreticulin does not affect bradykinin-induced Ca2+ release but restores the ER Ca2+ storage capacity. Our results indicate that calreticulin may play a role in folding of the bradykinin receptor, which affects its ability to initiate InsP3-dependent Ca2+ release in calreticulin-deficient cells. We concluded that the C domain of calreticulin plays a role in Ca2+ storage and that the N domain may participate in its chaperone functions.
Effect of N-Acetylcysteine on Lipopolysaccharide-Induced Intra-uterine Fetal Death and Intra-uterine Growth Retardation in Mice (2005)

Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including embryonic resorption, intra-uterine fetal death (IUFD), intra-uterine growth retardation (IUGR), and preterm delivery. Reactive oxygen species (ROS) have been associated with LPS-induced developmental toxicity. N-acetylcysteine (NAC) is a glutathione (GSH) precursor and direct antioxidant. The present study investigated the effects of NAC on LPS-induced IUFD and IUGR. All pregnant mice except controls were injected with LPS (75 microg/kg, ip) on gestational day (GD) 15-17. NAC was administered in two different modes. In mode A, the pregnant mice were pretreated with two doses of NAC (either 50 plus 25 mg/kg or 200 plus 100 mg/kg) before LPS, one (either 50 or 200 mg/kg) at 12 h before LPS and the other (either 25 or 100 mg/kg) at 15 min before LPS. In mode B, the pregnant mice were administered with two doses of NAC (either 50 plus 25 mg/kg or 200 plus 100 mg/kg) in 24 h, one (either 50 or 200 mg/kg) injected immediately after LPS and the other (either 25 or 100 mg/kg) injected 3 h after LPS. The number of live fetuses, dead fetuses and resorption sites was counted on GD 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were measured and skeletal development was evaluated. Results showed that pretreatment with NAC significantly alleviated LPS-induced fetal mortality and reversed LPS-induced growth and skeletal development retardation. Correspondingly, pretreatment with NAC significantly attenuated LPS-induced elevation in TNF-alpha concentration in maternal serum and amniotic fluid and lipid peroxidation in maternal and fetal livers. By contrast to pretreatment, posttreatment with NAC had no effect on LPS-induced TNF-alpha production and lipid peroxidation. When administered after LPS, NAC did not protect against LPS-induced IUFD and IUGR and in fact aggravated LPS-induced preterm labor. All these results indicate that NAC had a dual effect on LPS-induced IUFD and IUGR. Pretreatment with NAC improves fetal survival and reverses LPS-induced fetal growth and skeletal development retardation, whereas posttreatment with NAC aggravates LPS-induced preterm labor.
An Extended Conformation of Calmodulin Induces Interactions between the Structural Domains of Adenylyl Cyclase from Bacillus anthracis to Promote Catalysis (2000)

The edema factor exotoxin produced by Bacillus anthracis is an adenylyl cyclase that is activated by calmodulin (CaM) at resting state calcium concentrations in infected cells. A C-terminal 60-kDa fragment corresponding to the catalytic domain of edema factor (EF3) was cloned, overexpressed in Escherichia coli, and purified. The N-terminal 43-kDa domain (EF3-N) of EF3, the sole domain of edema factor homologous to adenylyl cyclases from Bordetella pertussis and Pseudomonas aeruginosa, is highly resistant to protease digestion. The C-terminal 160-amino acid domain (EF3-C) of EF3 is sensitive to proteolysis in the absence of CaM. The addition of CaM protects EF3-C from being digested by proteases. EF3-N and EF3-C were expressed separately, and both fragments were required to reconstitute full CaM-sensitive enzyme activity. Fluorescence resonance energy transfer experiments using a double-labeled CaM molecule were performed and indicated that CaM adopts an extended conformation upon binding to EF3. This contrasts sharply with the compact conformation adopted by CaM upon binding myosin light chain kinase and CaM-dependent protein kinase type II. Mutations in each of the four calcium binding sites of CaM were examined for their effect on EF3 activation. Sites 3 and 4 were found critical for the activation, and neither the N- nor the C-terminal domain of CaM alone was capable of activating EF3. A genetic screen probing loss-of-function mutations of EF3 and site-directed mutations based on the homology of the edema factor family revealed a conserved pair of aspartate residues and an arginine that are important for catalysis. Similar residues are essential for di-metal-mediated catalysis in mammalian adenylyl cyclases and a family of DNA polymerases and nucleotidyltransferases. This suggests that edema factor may utilize a similar catalytic mechanism.
Rapid screening for resistance to ganciclovir and foscarnet of primary isolates of human cytomegalovirus from culture-positive blood samples (1995)

A rapid screening assay for the detection of resistance to ganciclovir and foscarnet of primary isolates of human cytomegalovirus from culture-positive blood samples was developed by using single doses of both drugs and an immediate-early antigen plaque reduction assay. Results of the rapid assay with peripheral blood leukocytes as the viral inoculum were compared with those of a conventional assay with cell-free virus from the relevant viral isolates. Both assays gave overlapping results. The rapid assay offers the following major advantages: (i) it provides results within 4 to 6 days, (ii) it can be performed with peripheral blood leukocytes, and (iii) it reliably detects drug-resistant human cytomegalovirus strains.
RSFQ microprocessor: new design approaches (1997)

We present a revised version of our previous RSFQ (Rapid Single Flux Quantum) microprocessor architecture and discuss approaches that we are using in the design of its functional units. In particular, the data processing pipeline built of D/sup 2/ cells, a 16-bit pipelined register block and an all-RSFQ self-reset decoder suitable for pipelined implementation are described in detail. Methods of VHDL description and verification of RSFQ circuitry are also discussed.
Recent advances in pulmonary drug delivery using large, porous inhaled particles (1998)

The ability to deliver proteins and peptides to the systemic circulation by inhalation has contributed to a rise in the number of inhalation therapies under investigation. For most of these therapies, aerosols are designed to comprise small spherical droplets or particles of mass density near 1 g/cm3 and mean geometric diameter between approximately 1 and 3 micron, suitable for particle penetration into the airways or lung periphery. Studies performed primarily with liquid aerosols have shown that these characteristics of inhaled aerosols lead to optimal therapeutic effect, both for local and systemic therapeutic delivery. Inefficient drug delivery can still arise, owing to excessive particle aggregation in an inhaler, deposition in the mouth and throat, and overly rapid particle removal from the lungs by mucocilliary or phagocytic clearance mechanisms. To address these problems, particle surface chemistry and surface roughness are traditionally manipulated. Recent data indicate that major improvements in aerosol particle performance may also be achieved by lowering particle mass density and increasing particle size, since large, porous particles display less tendency to agglomerate than (conventional) small and nonporous particles. Also, large, porous particles inhaled into the lungs can potentially release therapeutic substances for long periods of time by escaping phagocytic clearance from the lung periphery, thus enabling therapeutic action for periods ranging from hours to many days.
Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists (2013)

By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relationships (SARs) of target compounds were concluded in this study, and five compounds were found to exhibited medium to potent CCR5 fusion activities with IC(50) values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC(50) value of 6.29 µM and an anti-HIV-1 inhibitor with an IC(50) value of 0.44 µM.
Femmes, citoyenneté et politique dans les années 1920 et 1930 au Québec (1994)

Women, citizenship and policies in Québec in the 1920's and 1930's. This text presents a historical overview of the rich life of feminine associative network in order to explain the context in which Canadian women obtained the right to vote in the 1920's. The author argues that in this feminine movement is practised the enlargement of social action, mainly in Québec, where women were still excluded from the right to vote until 1940. They were therefore developing alternative modes of intervention, which analysts did not readily defined as political but social, but which eventually evolved into social policies adopted by the Welfare State. Through the presentation of the Québec case, the author underlines the close relationships that existed between those women associations in articulating a strategy, often ambivalent, to enlarge women pratice of citizenship.
Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages (1995)

Studies over the past 20 years have established that the development of new capillaries from an existing vascular network (a process called angiogenesis) is an essential component of tumor growth. Malignant tumors do not grow beyond 2-3 mm3 in size unless they stimulate the formation of new blood vessels and thus provide a route for the increased inflow of nutrients and oxygen and outflow of waste products. Tumor angiogenesis also provides an essential exit route for metastasizing tumor cells from the tumor to the bloodstream. Indeed, extensive neovascularization is a poor prognostic factor in several forms of human cancer. Angiogenesis is a complex, multistep process driven by many local signals within the tumor. This involves the degradation of the extracellular matrix around a local venule after the release of collagenases and proteases, the proliferation and migration of capillary endothelial cells, and their differentiation into functioning capillaries. Cytokines produced by various cell types present within the microenvironment of solid tumors form a complex, dynamic network in which they have multiple effects on tumor progression. Herein we review our work on the presence, and possible regulatory influence on tumor angiogenesis, of a number of these cytokines within invasive breast carcinomas. We have combined immunocytochemistry with a single cell cytokine release assay called the reverse hemolytic plaque assay to investigate the cellular sources of the key angiogenic cytokines, vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor-alpha. Tumor-associated macrophages in the stromal compartment of these tumors and/or malignant epithelial cells were seen to be a major producer cell for these cytokines, whereas tumor necrosis factor-alpha receptors were expressed by leukocytes, malignant cells, and endothelial cells in tumor blood vessels.
Autoinducer 3 and Epinephrine Signaling in the Kinetics of Locus of Enterocyte Effacement Gene Expression in Enterohemorrhagic Escherichia coli (2006)

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is responsible for causing outbreaks of bloody diarrhea and hemolytic-uremic syndrome throughout the world. The locus of enterocyte effacement (LEE) consists of five major operons and is required for the formation of attaching and effacing lesions that disrupt intestinal epithelial microvilli. We have previously reported that expression of EHEC LEE genes is regulated by the luxS quorum-sensing system. The luxS gene in EHEC affects the production of autoinducer 3 (AI-3), which activates the LEE. Epinephrine and norepinephrine also activate the LEE in a manner similar to that of AI-3. Previous studies of quorum-sensing regulation of LEE transcription have thus far been restricted to using reporter systems in an E. coli K-12 background. Here, we examined the kinetics of LEE gene transcription, protein expression, and function of the LEE type III secretion apparatus in wild-type (WT) EHEC and an isogenic luxS mutant. The results revealed that the luxS mutant had diminished transcription from the LEE promoters during the mid-exponential growth phase; decreased protein levels of EscJ, Tir, and EspA; and reduced secretion of EspA and EspB. The luxS mutation also caused a delay in the formation of attaching and effacing lesions on cultured epithelial cells compared to the wild type. Epinephrine enhanced LEE expression in both the WT and the luxS mutant, but the WT still exhibited greater LEE activation. The results suggest a possible synergistic relationship between AI-3 and epinephrine. The combined effects of these two signaling molecules may lead to greater LEE expression and a more efficient infection.
A multiple dose study of prasugrel (CS‐747), a novel thienopyridine P2Y12 inhibitor, compared with clopidogrel in healthy humans (2006)

Compared with clopidogrel 75 mg, prasugrel 10 mg and 20 mg daily for 10 days resulted in more rapid, more consistent, and higher levels of platelet inhibition.
Antiproliferative and antimetastatic effects of gossypol on Dunning prostate cell-bearing Copenhagen rats. (1993)

Gossypol, a polyphenolic aldehyde naturally present in cottonseed, has long been recognized as a male contraceptive and recently as a potential anticancer agent. Our study used a rodent model to evaluate gossypol's potential for the treatment of human prostatic carcinoma. Two-month-old Copenhagen male rats received subcutaneous implants of a subpassage of MAT-LyLu prostatic cancer line, a highly metastatic, androgen-independent Dunning prostate tumor subline that specifically metastasizes to lymph nodes and lungs of recipients. After 2 weeks of gossypol treatment (0 or 12.5 mg/kg B.W./day S.C.) initiated immediately after transplantation, the rats were sacrificed and evaluated for prostate tumor growth and metastasis. Testosterone and gossypol levels in tumor tissue and various reproductive organs and serum potassium level were measured by radioimmunoassay (RIA), high pressure liquid chromatography (HPLC) and atomic emission spectroscopy (AES), respectively. Gossypol-treated rats exhibited weight reductions in developed MAT-LyLu prostate tumor mass and prostate of 24% (p < 0.05) and 31% (p < 0.05), respectively; whereas testicular and epididymal weights were not significantly affected. Few metastases (20%) were observed in either lymph nodes or lungs of gossypol-treated recipients. The control rats, however, had a much higher rate of lung (60%) and lymph node metastasis (40%). Testicular testosterone levels, as measured by RIA, were significantly lower in gossypol-treated rats than in controls (p < 0.05), but serum testosterone levels were not different. Extractable gossypol content in the prostate tumor, as measured by HPLC, reached 19.67 ng/gm and was 1.28 times higher than in liver, 1.98 times higher than in testes, but was 3.3% of that in prostate. Moreover, serum had the highest gossypol content (10.7 micrograms/ml). Serum potassium levels, as measured by AES, were significantly higher in gossypol-treated individuals than controls (p < 0.05). Our results indicate for the first time that gossypol has antiproliferative and antimetastatic effects on MAT-LyLu prostate cancer cells and can be explored as a potential therapeutic agent for androgen-independent human prostatic carcinoma.