gebhart/patrepeval huggingface dataset:
Nucleoside Analog Inhibitors of Hepatitis C Virus Replication (2006)

Of the 30 compounds currently marketed in the United States for treatment of viral infections, 15 are nucleoside analogs, demonstrating the utility of this class of compound as a source of antiviral drugs. The success of nucleoside analogs in treating other viral infections provides a compelling rationale for the significant effort that is currently being devoted to the discovery and development of nucleoside analogs to treat infection by hepatitis C virus (HCV) that may lead to improvements in response rates compared to currently available therapies. Several different approaches have been adopted to identify promising analogs, including the use of surrogate viruses in cell culture assays, screening in the cell-based bicistronic HCV replicon assay, and screening nucleoside triphosphates for the ability to inhibit the activity of the HCV RNA-dependent RNA polymerase in vitro. Several classes of ribonucleoside analogs with modifications of the ribose inhibit HCV replication. Nucleoside analogs incorporating a 2'-C-methyl modification are potent inhibitors in the replicon assay in the absence of cytotoxicity, and appear to exert their inhibition by acting as functional chain terminators of RNA synthesis. NM283, a prodrug of 2'-C-methylcytidine, has entered clinical trials and demonstrated viral load reductions in subjects infected with genotype 1 HCV, a genotype known to be difficult to treat effectively with currently approved therapies. Overall, results to date offer encouragement that improved therapies to treat HCV infection including newly developed nucleoside analogs may become available within the next few years.
Semiempirical profile simulation of aluminum etching in a Cl2/BCl3 plasma (2002)

A semiempirical profile simulator to predict topographic evolution during Cl2/BCl3 plasma etching of photoresist patterned Al lines has been developed. Given incident flux distributions, the profile simulator uses a combination of a particle based Monte Carlo algorithm and analytic ray-tracing algorithm for solving feature-scale ion and neutral flux transport, respectively. We use angular and energy distributions for reflected ions that are consistent with experimental observation and molecular dynamic simulations. Etch yields with energy and angular dependence are experimentally determined for physical sputtering and ion-enhanced etching. The spontaneous etch rate of A1 by chlorine and the spontaneous desorption rate of Cl from photoresist are estimated from experimental results. Sticking coefficients for etchant, chlorine, and depositor, CClx, and depositing flux are determined by fitting simulated profiles to experimental data. A semiempirical site-balance model is developed to compute the surface coverage of etchant. The reaction probability of neutrals at surfaces is self-consistently determined from the surface coverage at incident location. Competition between etching and deposition on feature sidewalls is modeled. A shock-tracking method is used to advance the profile using computed etch/deposition rates. Simulation results are presented which demonstrate that facet formation, aspect ratio dependent etching, and critical dimension gain, are captured accurately by the calibrated profile simulator. In addition, the calibrated profile simulator along with results of a 23 design of experiments in which photoresist and Al etch rates were measured on open frame wafers have been used to create a plasma reactor model. The reactor model relates the operational parameters including inductively coupled power, rf bias and gas flow ratio to the flux variables, i.e., Cl flux, ion flux, ion energy, and depositor flux, that are used as inputs to the profile simulator. In this manner, calibration of the profile simulator requires a minimum of high resolution, expensive, patterned wafers. The reactor model so created is shown to be in quantitative agreement with results from the hybrid plasma equipment model (Ref. 1).
Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay (1993)

A reverse-hybridization assay, the line probe assay (LiPA), based on variations found in the 5' untranslated regions of the different hepatitis C virus (HCV) genotypes was developed, permitting simple and fast determination of four HCV genotypes and their subtypes. Using this assay, 61 PCR-positive Brazilian HCV sera were typed. Of the sera, 33% had a type 1 HCV infection, 38% had type 1b (related to HCV-J), 1.5% had type 2a (related to HC-J6), 24.5% had type 3 (related to E-b1 and HCV-T), and 3% of the sera were co-infected. This assay format was further evaluated using 13 sera from Belgium and the Netherlands, and all of these could be classified. Two pools of Japanese sera were classified as either type 2a or were co-infected with types 1b and 2a, but no type 2b sequences were detected. Another eight PCR-positive sera were obtained from Burundi and Gabon. The sequence of the 5' untranslated region of these African viruses was strongly divergent from the three previously described types. Therefore, these isolates were tentatively classified as type 4. These and some of the other non-type 1 sera often demonstrated weaker reactivities than type 1 isolates in currently used second generation antibody confirmation assays.
Chemokine signalling: pivoting around multiple phosphoinositide 3‐kinases (2002)

The role of chemokines in mediating directional cell migration is well established, but more recently it has become evident that chemokines are able to couple to distinct signalling pathways that are involved in not only chemotaxis, but also cell growth and transcriptional activation. The signalling pathway controlled by the phosphoinositide 3-kinase (PI3K) family of lipid kinases has been the focus of much attention with respect to their role in chemokine-mediated functional responses. Indeed, there now exists convincing biochemical, pharmacological and genetic evidence that both CC and CXC chemokines stimulate PI3K-dependent chemotaxis of inflammatory cells such as eosinophils, macrophages, neutrophils and T lymphocytes. This review considers the role of individual PI3Ks (e.g. the p85/p110 heterodimer, PI3Kgamma and PI3KC2alpha) as well their downstream effector targets in mediating chemokine-stimulated cell migration.
Graphical Analysis of Reversible Radioligand Binding from Time—Activity Measurements Applied to [N-11C-Methyl]-(−)-Cocaine PET Studies in Human Subjects (1990)

A graphical method of analysis applicable to ligands that bind reversibly to receptors or enzymes requiring the simultaneous measurement of plasma and tissue radioactivities for multiple times after the injection of a radiolabeled tracer is presented. It is shown that there is a time t after which a plot of integral of t0ROI(t')dt'/ROI(t) versus integral of t0Cp(t')dt'/ROI(t) (where ROI and Cp are functions of time describing the variation of tissue radioactivity and plasma radioactivity, respectively) is linear with a slope that corresponds to the steady-state space of the ligand plus the plasma volume,.Vp. For a two-compartment model, the slope is given by lambda + Vp, where lambda is the partition coefficient and the intercept is -1/[kappa 2(1 + Vp/lambda)]. For a three-compartment model, the slope is lambda(1 + Bmax/Kd) + Vp and the intercept is -[1 + Bmax/Kd)/k2 + [koff(1 + Kd/Bmax)]-1) [1 + Vp/lambda(1 + Bmax/Kd)]-1 (where Bmax represents the concentration of ligand binding sites and Kd the equilibrium dissociation constant of the ligand-binding site complex, koff (k4) the ligand-binding site dissociation constant, and k2 is the transfer constant from tissue to plasma). This graphical method provides the ratio Bmax/Kd from the slope for comparison with in vitro measures of the same parameter. It also provides an easy, rapid method for comparison of the reproducibility of repeated measures in a single subject, for longitudinal or drug intervention protocols, or for comparing experimental results between subjects. Although the linearity of this plot holds when ROI/Cp is constant, it can be shown that, for many systems, linearity is effectively reached some time before this. This analysis has been applied to data from [N-methyl-11C]-(-)-cocaine ([11C]cocaine) studies in normal human volunteers and the results are compared to the standard nonlinear least-squares analysis. The calculated value of Bmax/Kd for the high-affinity binding site for cocaine is 0.62 +/- 0.20, in agreement with literature values.
AWNT4Mutation Associated with Müllerian-Duct Regression and Virilization in a 46,XX Woman (2004)

WNT4, a secreted protein that suppresses male sexual differentiation, is thought to repress the biosynthesis of gonadal androgen in female mammals. An 18-year-old woman presented with primary amenorrhea and an absence of müllerian-derived structures, unilateral renal agenesis, and clinical signs of androgen excess--a phenotype resembling the Mayer-Rokitansky-Küster-Hauser syndrome and remarkably similar to that of female Wnt4-knockout mice. A genetic evaluation revealed a loss-of-function mutation in the WNT4 gene. WNT4 appears to be important in the development and maintenance of the female phenotype in women, by means of the regulation of müllerian-duct formation and control of ovarian steroidogenesis.
Small molecules that dramatically alter multidrug resistance phenotype by modulating the substrate specificity of P -glycoprotein (2001)

By screening a chemical library for the compounds protecting cells from adriamycin (Adr), a series of small molecules was isolated that interfered with the accumulation of Adr in mouse fibroblasts by enhancing efflux of the drug. Isolated compounds also stimulated efflux of Rhodamine 123 (Rho-123), another substrate of multidrug transporters. Stimulation of drug efflux was detectable in the cells expressing P-glycoprotein (P-gp), but not in their P-gp-negative variants, and was completely reversible by the P-gp inhibitors. A dramatic stimulation of P-gp activity against Adr and Rho-123 by the identified compounds was accompanied by suppression of P-gp-mediated efflux of other substrates, such as Taxol (paclitaxel) or Hoechst 33342, indicating that they act as modulators of substrate specificity of P-gp. Consistently, P-gp modulators dramatically altered the pattern of cross-resistance of P-gp-expressing cells to different P-gp substrates: an increase in resistance to Adr, daunorubicin, and etoposide was accompanied by cell sensitization to Vinca alkaloids, gramicidin D, and Taxol with no effect on cell sensitivity to colchicine, actinomycin D, puromycin, and colcemid, as well as to several non-P-gp substrates. The relative effect of P-gp modulators against different substrates varied among the isolated compounds that can be used as fine tools for analyzing mechanisms of drug selectivity of P-gp. These results raise the possibility of a rational control over cell sensitivity to drugs and toxins through modulation of P-gp activity by small molecules.
In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography (2008)

Optical micro-angiography (OMAG), based on Fourier domain optical coherence tomography (OCT), is a recently developed imaging modality that provides dynamic blood flow imaging within microcirculation tissue beds in vivo. This paper presents its first application in imaging the blood circulations in posterior chamber of human eye. To eliminate/minimize the motion artifacts in OMAG flow image caused by the inevitable subject movement, we describe a method to compensate the bulk tissue motion by use of phase changes in sequential OCT A scan signals. By use of a fast OMAG/OCT imaging system at ~840nm wavelength band, we show that OMAG is capable of providing volumetric vasculatural images in retina and choroids, down to capillary level imaging resolution, within approximately 10 s. The depth-resolved volumetric views of the separate retina and choroid vasculatures are also presented. In the end of this paper, we provide a comparison of the OMAG results with those from Doppler OCT and optical coherence angiography.
Serial OX40 Engagement on CD4+ T Cells and Natural Killer T Cells Causes Allergic Airway Inflammation (2009)

OX40 on not only CD4(+) T cells but also NKT cells is involved in allergic airway inflammation. Notably, pulmonary blockade of OX40 ligation on NKT cells has therapeutic implications.
Mimicking the Lotus Effect:  Influence of Double Roughness Structures and Slender Pillars (2004)

Surface roughness is known to amplify hydrophobicity. The apparent contact angle of a drop on a rough surface is often modeled using either Wenzel's or Cassie's formulas. These formulas, along with an appropriate energy analysis, are critical in designing superhydrophobic substrates for applications in microscale devices. In this paper we propose that double (or multiple) roughness structures or slender pillars are appropriate surface geometries to develop "self-cleaning" surfaces. The key motivation behind the double structured roughness is to mimic the microstructure of superhydrophobic leaves (such as lotus). Theoretical analysis similar to that presented in the paper can be used to obtain optimal geometric parameters for the rough surface. The calculation procedure should result in surface geometries with excellent water repellent properties.
A novel approach for coding color quantized images (1993)

An approach to the lossy compression of color images with limited palette that does not require color quantization of the decoded image is presented. The algorithm is particularly suited for coding images using an image-dependent palette. The technique restricts the pixels of the decoded image to take values only in the original palette. Thus, the decoded image can be readily displayed without having to be quantized. For comparable quality and bit rates, the technique significantly reduces the decoder computational complexity.
Feasibility of transcranial, localized drug-delivery in the brain of Alzheimer's-model mice using focused ultrasound (2006)

Therapeutic agents are difficult to deliver to the brain because of brains natural defense: the Blood-Brain Barrier (BBB). It has been shown that Focused Ultrasound can produce reversible and localized BBB opening in the brain when applied in the presence of ultrasound contrast agents (1). However, a major limitation of ultrasound in the brain is the strong phase aberration and attenuation of the skull bone. Thus, despite the high potential of non-invasive adaptive focusing techniques, no study of trans-cranial ultrasound-targeted drug treatment in the brain has been reported as of yet. In this study, the feasibility of BBB opening in the hippocampus of Alzheimers-model mice using focused ultrasound through the intact skull and skin was investigated. A high power focused transducer (1.5 MHz central frequency) was mounted on a 3D positioning system and a 7.5 MHz single element diagnostic transducer was placed through the center of the focused transducer and aligned with the high power beam in order to achieve high precision targeting. In order to investigate the effect of the skull, simulations of ultrasound wave propagation through the skull using µCT data, and needle hydrophone measurements through an ex-vivo skull were made. The pressure field showed minimal attenuation (18% of the pressure amplitude was attenuated) and a well-focused pattern through the left and right halves of the parietal bone. In in-vivo experiments, the brains of four mice were sonicated through intact skull and skin. Ultrasound sonications were set to a burst length of 20 ms at a 20% duty cycle and was applied 5 times for 30 s per shot with a 30 s delay between shots. The acoustic pressure ranged from 2.0 to 2.7 MPa. Prior to sonication, ultrasonographic contrast agents (Optison; 0.05 mL) were injected in the mice intravenously. Contrast-enhanced high resolution T1 and T2-weighted MR Imaging (9.4 Tesla) with an in-plane resolution of 75 µm was able to distinguish opening of large vessels in the region of the hippocampus. These results demonstrate the feasibility of potentially, locally opening the BBB in the mouse hippocampus using focused ultrasound through the intact skull and skin. Future investigations will deal with optimization and repeatability of the technique as well as feasibility on Alzheimer's-affected mice.
Effects of GR 68755 on d-amphetamine-induced changes in mood, cognitive performance, appetite, food preference, and caloric and macronutrient intake in humans (1996)

Pre-clinical studies have suggested that 5-HT(3) antagonists such as GR 68755 oppose mesocorticolimbic dopamine release, which may mediate the important effects of d-amphetamine on positive subjective mood, anorexia, and performance. Twenty-six healthy male volunteers received each of the following treatments in a double-blind, randomized, cross-over design separated by a period of four to seven days: (a) d-amphetamine (20mg orally); (b) placebo; (c) GR 68755 (2mg orally); and (d) GR 68755 plus d-amphetamine. Subjects completed subjective measures of mood, hunger, and satiety. Caloric and macronutrient intake were measured using a test meal. Performance and attention were assessed using standardized computerized tasks. GR 68755 enhanced accuracy on the computerized attention task but failed to reverse significantly any of the effects of d-amphetamine. These results suggest that at these doses GR 68755 pre-treatment does not significantly reduce the effects of d-amphetamine.
Dimebon (Latrepirdine) Enhances Mitochondrial Function and Protects Neuronal Cells from Death (2010)

Dimebon, a drug currently being evaluated in multiple Phase III Alzheimer's disease trials, has previously been shown to have effects on isolated mitochondria at muM concentrations. Here the effects of nM concentrations of Dimebon on mitochondrial function were investigated both in primary mouse cortical neurons and human neuroblastoma cells (SH-SY5Y). Under non-stress conditions nM concentrations of Dimebon increased succinate dehydrogenase activity (MTT-assay), mitochondrial membrane potential (DeltaPsim), and cellular ATP levels. Dimebon treatment had no effect on mitochondria DNA content, implying that mitochondrial biogenesis was not induced. Under stress conditions, mitochondria in Dimebon-treated neurons showed increased resistance to elevated intracellular calcium concentrations, thus, maintaining their DeltaPsim throughout the experiment, in contrast to control neurons, which rapidly lost their DeltaPsim. Moreover, we show that serum-starved differentiated SH-SY5Y cells treated with Dimebon had an increased survival rate as compared to untreated cells. In conclusion, these data demonstrate that Dimebon enhances mitochondrial function both in the absence and presence of stress and Dimebon-treated cells are partially protected to maintain cell viability.
Large-population passages of vesicular stomatitis virus in interferon-treated cells select variants of only limited resistance (1996)

Vesicular stomatitis virus (VSV) populations were repeatedly passaged in L-929 cells treated with alpha interferon (IFN-alpha) at levels of 25 U/ml. This IFN-alpha concentration induced a 99.9% inhibition of viral yield in standard infections. Analysis of viral fitness (overall replicative ability measured in direct competition with a reference wild-type VSV) after 21 passages in IFN-treated cells showed only a limited increase or no increase in fitness, compared with the greater increase upon parallel passage in cells not treated with IFN-alpha. However, this limited increase in fitness was more pronounced when competition assays were carried out with IFN-alpha-treated cells, suggesting the selection of VSV populations with a low level of resistance to IFN-alpha. Thus, despite the extensively documented capacity of VSV to adapt to changing environments, the antiviral state induced by IFN-alpha imposes adaptive constraints on VSV which are not readily overcome.
Purification and Characterization of A61 (2001)

Plasmin, a broad spectrum proteinase, is inactivated by an autoproteolytic reaction that results in the destruction of the heavy and light chains of the protein. Recently we demonstrated that a 61-kDa plasmin fragment was one of the major products of this autoproteolytic reaction (Fitzpatrick, S. L., Kassam, G., Choi, K. S., Kang, H. M., Fogg, D. K., and Waisman, D. M. (2000)Biochemistry 39, 1021-1028). In the present communication we have identified the 61-kDa plasmin fragment as a novel four kringle-containing protein consisting of the amino acid sequence Lys(78)-Lys(468). To avoid confusion with the plasmin(ogen) fragment, angiostatin(R) (Lys(78)-Ala(440)), we have named this protein A(61). Unlike angiostatin, A(61) was produced in vitro from plasmin autodigestion in the absence of sulfhydryl donors. A(61) bound to lysine-Sepharose and also underwent a large increase in fluorescence yield upon binding of the lysine analogue, trans-4-aminomethylcyclohexanecarboxylic acid. Circular dichroism suggested that A(61) was composed of 21% beta-strand, 14% beta-turn, 18% 3(1)-helix and 8% 3(10)-helix. A(61) was an anti-angiogenic protein as indicated by the inhibition of bovine capillary endothelial cell proliferation. Plasminogen was converted to A(61) by HT1080 cells and bovine capillary endothelial cells. Furthermore, a plasminogen fragment similar to A(61) was present in the serum of humans as well as normal and tumor-bearing mice. These results establish that plasmin turnover can generate anti-angiogenic plasmin fragments in a nonpathological setting.
A Robust Ionic Liquid as Reaction Medium and Efficient Organocatalyst for Carbon Dioxide Fixation (2007)

A quick fix of CO2: Ionic liquid 1 functions both as efficient organocatalyst and reaction medium in the addition reaction of epoxides with carbon dioxide under mild conditions to give cyclic carbonates. The new ionic liquid is robust and can be recycled and reused continuously without showing any significant loss in catalytic activity. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2476/2008/z700097_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Measuring Closure Properties of Patent Sublanguages (2013)

Patent search is an important information retrieval problem in scientific and busi-ness research. Semantic search would be a large improvement to current technolo-gies, but requires some insight into the lan-guage of patents. In this article we test the fit of the language of patents to the sublan-guage model, focussing on closure prop-erties. The research presented here is rel-evant to the topic of sublanguage identi-fication for different domains, and to the study of the language of patents. We in-vestigate the hypothesis that fit to the sub-language model increases as one moves down the International Patent Classifica-tion hierarchy. The analysis employs a general English corpus and patent docu-ments from the MAREC corpus. It is shown that patents generally fit the sub-language model, with some variability be-tween categories in the extent of the fit. 1