gebhart/patrepeval huggingface dataset:
E-cadherin regulates the function of the EphA2 receptor tyrosine kinase. (1999)

EphA2 is a member of the Eph family of receptor tyrosine kinases, which are increasingly understood to play critical roles in disease and development. We report here the regulation of EphA2 by E-cadherin. In nonneoplastic epithelia, EphA2 was tyrosine-phosphorylated and localized to sites of cell-cell contact. These properties required the proper expression and functioning of E-cadherin. In breast cancer cells that lack E-cadherin, the phosphotyrosine content of EphA2 was decreased, and EphA2 was redistributed into membrane ruffles. Expression of E-cadherin in metastatic cells restored a more normal pattern of EphA2 phosphorylation and localization. Activation of EphA2, either by E-cadherin expression or antibody-mediated aggregation, decreased cell-extracellular matrix adhesion and cell growth. Altogether, this demonstrates that EphA2 function is dependent on E-cadherin and suggests that loss of E-cadherin function may alter neoplastic cell growth and adhesion via effects on EphA2.
Pharmacokinetics of dolutegravir in HIV-seronegative subjects with severe renal impairment (2013)

The modest reductions in mean PK exposures for DTG and increases for DTG-Gluc in the severe renal impairment group are not considered clinically significant. DTG does not require dose adjustment in patients with renal impairment.
Prediction of Polymer Properties (2002)

Highlighting a broad range multiscale modeling and methods for anticipating the morphologies and the properties of interfaces and multiphase materials, this reference covers the methodology of predicting polymer properties and its potential application to a wider variety of polymer types than previously thought possible. A comprehensive source, the
Tear Flow Analysis Through the Upper and Lower Systems (1990)

Using quantitative lacrimal scintillography, tear flow in the normal state was analyzed in 11 asymptomatic volunteers. The results were compared to states with the superior punctum occluded, and to those with the inferior punctum occluded. No significant difference in tear flow between the superior and inferior canaliculi was appreciated (P less than 0.05). Furthermore, no significant difference was noted in overall basal tear flow when one canaliculus was blocked compared to the patent system (P less than 0.05). This implies increased tear flow through the patent canaliculus when the opposite one is blocked. The clinical implications of these results are important in canaliculus repair after injury.
Dronedarone: An Emerging Agent with Rhythm‐ and Rate‐Controlling Effects (2006)

Of current antiarrhythmic agents, amiodarone is among the most effective with the additional advantage of having little proarrhythmic potential. However, it can cause potentially serious extracardiac side effects, stimulating the search for safer derivatives. Dronedarone, a new antiarrhythmic drug that is structurally related to amiodarone, lacks an iodine moiety and, thus, amiodarone's iodine-related organ toxicity, while its methane sulfonyl group decreases lipophilicity so shortening half-life and decreasing tissue accumulation. Electrophysiological studies show that dronedarone shares amiodarone's multichannel blocking effects, inhibiting transmembrane Na(+), K(+), Ca(2+), and slow L-type calcium channels, as well as its antiadrenergic effects. Unlike amiodarone, it has little effect at thyroid receptors. Possessing both rate- and rhythm-control properties, dronedarone has proved safe and effective in preventing recurrence of atrial fibrillation (AF) in patients with persistent AF in the Dronedarone Atrial Fibrillation Study After Electrical Cardioversion (DAFNE) trial, the first prospective randomized trial to evaluate its efficacy and safety. Dronedarone has since undergone further extensive evaluation in three pivotal phase III trials. In two sister studies, the European Trial in Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm (EURIDIS) and American-Australian-African Trial with Dronedarone in Atrial Fibrillation/Flutter Patients for the Maintenance of Sinus Rhythm (ADONIS), dronedarone 400 mg b.i.d. showed significant efficacy against placebo in prevention of AF recurrence. Additionally, in patients with permanent AF, dronedarone was highly effective at controlling ventricular rate on top of standard rate-controlling therapies in the Efficacy and Safety of Dronedarone for the Control of Ventricular Rate during Atrial Fibrillation (ERATO) study.
Extracellular matrix degrading metalloproteinases in the pathogenesis of arteriosclerosis (1994)

We review the importance of extracellular matrix remodelling to the processes of vascular smooth muscle cell migration and proliferation that contribute to morphogenesis of the atherosclerotic plaque. In particular, the role of the matrix degrading metalloproteinase (MMP) family is discussed. This family of neutral, ZN(2+)-requiring enzymes are capable, in principle, of degrading all matrix proteins. Their activity is tightly controlled, however, at the level of synthesis of the inactive zymogens, activation by limited proteolysis and binding to endogenous inhibitor proteins (TIMPs). Direct evidence is presented for the involvement of MMPs in proliferation and outgrowth of vascular smooth muscle cells from explants of rabbit aorta in vitro. This was obtained using two structurally-unrelated inhibitors of MMPs, Ro 31-4724 and Ro 31-7467, both of which inhibited proliferation of cells in a concentration-dependent manner, Ro 31-4724 also inhibited outgrowth. Rabbit aortic smooth muscle cells were further shown to release MMPs, namely a 95 and a 72 kDa gelatinases that were inhibited by Ro 31-4724 and Ro 31-7467. The evidence suggests that degradation of basement membrane by gelatinase is required for proliferation and outgrowth of these cells. The implications of these findings for the pathogenesis and treatment of atherosclerosis are also discussed.
Long-term molecular remissions in patients with indolent lymphoma treated with rituximab as a single agent or in combination with interferon alpha-2a: A randomized phase II study from the Nordic Lymphoma Group (2008)

The purpose of this phase II randomized trial was to evaluate the effect and safety of interferon-alpha2a (IFN) in combination with extended dosing rituximab in patients with symptomatic, advanced indolent lymphoma responding to a standard single course of rituximab. Totally 123 patients were treated with rituximab 375 mg/m2 once weekly for 4 weeks leading to 14 complete response (CR; 11%), 56 partial response (PR; 46%), and 13 minor responses (MR; 11%). Patients achieving either PR or MR were randomized to four more infusions of rituximab alone (n = 36) or in combination with five weeks of IFN (n = 33), with an overall response rate (CR + PR) of 78% and 94%, respectively. Significantly more patients in the combination arm improved their response from PR/MR to CR (P < 0.05) and more maintained their responses for > or = 24 months (72% versus 50%), respectively. Overall, 26 out of the 52 patients who achieved CR underwent minimal residual disease (MRD) evaluation. Totally 17 of these (65%) achieved MRD negativity, 14 of whom remain in CR after 4.8 years' follow-up. The addition of IFN to rituximab was generally safe, but reversible thrombocytopenia and neutropenia were noted in one and six patients, respectively, requiring a reduction in the IFN dose. Extended rituximab is effective and well tolerated and combination with IFN seems to improve both the quality and duration of the responses, providing the opportunity to achieve long-term molecular CRs and prolonged failure-free survival without chemotherapy.
361. The acid-catalysed polymerisation of cyclosiloxanes. Part I. The kinetics of the polymerisation of octamethylcyclotetrasiloxane catalysed by anhydrous ferric chloride–hydrogen chloride (1965)

T. C. Kendrick, J. Chem. Soc., 1965, 2027 DOI: 10.1039/JR9650002027
Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design:In VitroandIn VivoEvaluation (2014)

The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs) by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape with z-average 167-318 d·nm, PDI below 0.441, and -18.4 mV zeta potential with maximum % drug entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas model and showed initial burst release of 21.7 ± 1.3% with prolonged drug release of 69.5 ± 0.8% from optimized NPs up to 24 h. In vitro drug release data was found in agreement with ex vivo permeation data through sheep nasal mucosa. In vitro cell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway.
Therapeutic Uses of Botulinum Toxin (1991)

BOTULISM had been recognized by the 18th century, but the observation that a toxin produced by an anaerobic organism might be responsible for food poisoning was not made until 1897.1 Although seven immunologically distinct toxins have since been identified, only types A, B, and E have been linked to cases of botulism in humans.2 , 3 Botulinum toxin type A (hereafter referred to as botulinum toxin), one of the most lethal biologic toxins, has been found to be of therapeutic value in the treatment of a variety of neurologic and ophthalmologic disorders.4 The Food and Drug Administration recently approved botulinum toxin (Oculinum) . . .
An empirically derived framework for classifying parallel program performance tuning problems (1998)

The results of research into the use of parallel program performance tuning tools demonstrate that, despite the large number of tools described in the literature, very few of them are actually used on any scale within the parallel programming community.
Cellular immune response of ducks to duck hepatitis B virus infection (1999)

Duck hepatitis B virus (DHBV) has been a useful model for hepadnavirus infection. There have been few studies on immunity to DHBV and none describing the cell-mediated immune response by acute and chronically infected ducks. A duck hepatitis B antigen-specific blastogenesis assay was used to measure DHBV antigen-specific responses of duck peripheral blood (PBMC) and splenic mononuclear cells (SMCs) from uninfected control ducks, ducks acutely or chronically infected with DHBV, and ducks immune to DHBV. A comparison of the group mean responses by PBMC to DHBV surface antigen (DHBsAg) found that the immune group was significantly different to the other three groups (controls or unexposed, P < 0.0001; acutely infected, P < 0.01; chronically infected, P < 0.01). The responses to DHBsAg by PBMC of the acute group (P < 0.01) were significantly different also to that of the unexposed group. For DHBV core antigen (DHBcAg), significant differences in the responses were found between immune ducks and unexposed (P < 0.0005) and acutely infected (P < 0.05) groups. The SMC showed a significant difference between unexposed ducks and immune ducks (P < 0.05) in the group mean responses to DHBsAg. The responses to DHBcAg were significantly different between the immune group and the acute (P < 0.01) and unexposed (P < 0.01) groups. The group mean of unexposed ducks was also significantly different to that of acutely infected ducks (P < 0.01). This study indicates that the cellular immune response in immune animals differs from acutely and chronically infected ducks. Further studies of these differences may provide some explanations for the differing outcomes of DHBV infection. J. Med. Virol. 58:19–25, 1999. © 1999 Wiley-Liss, Inc.
The architecture of massively parallel processor CP-PACS (2002)

CP-PACS (Computational Physics by Parallel Array Computer System) is a massively parallel processor with 2048 processing units, built at the Center for Computational Physics, University of Tsukuba, Japan. The node processor of CP-PACS is a RISC microprocessor enhanced by pseudo vector processing, which can realize high performance vector processing. The interconnection network is the 3 dimensional Hyper-Crossbar Network, which has high flexibility and embeddability for various network topologies and communication patterns. The theoretical peak performance of the whole system is 614.4 GFLOPS. We present an overview of the CP-PACS architecture and several special architectural characteristics of it. A performance evaluation on the parallel LINPACK benchmark is also shown.
Clinical outcome of de novo acute myeloid leukaemia patients with normal cytogenetics is affected by molecular genetic alterations: a concise review (2007)

Normal cytogenetics are detected pretreatment in approximately 45% of patients with de novo acute myeloid leukaemia (AML); thus this constitutes the single largest cytogenetic group of AML. Recently, molecular genetic alterations with prognostic significance have been reported in these patients. They include internal tandem duplication of the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA and NPM1 genes and aberrant expression of the BAALC, ERG and MN1 genes. Additionally, gene-expression profiling has been applied to identify prognostically relevant subgroups. Substantial progress has been made in the understanding of molecular pathways deregulated in leukaemogenesis and how these defects can be targeted by novel therapeutic compounds. Here we critically review the molecular heterogeneity among AML patients with normal cytogenetics and discuss how these data may translate into a prognostic, molecular-based treatment stratification that may improve the currently unsatisfactory outcome of these patients.
Inhibition of Human Immunodeficiency Virus Envelope Glycoprotein- Mediated Single Cell Lysis by Low-Molecular-Weight Antagonists of Viral Entry (2006)

The coexpression of human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins and receptors leads to the lysis of single cells by a process that is dependent upon membrane fusion. This cell lysis was inhibited by low-molecular-weight compounds that interfere with receptor binding or with receptor-induced conformational transitions in the envelope glycoproteins. A peptide, T20, potently inhibited cell-cell fusion but had no effect on single cell lysis mediated by the HIV-1 envelope glycoproteins. Thus, critical events in the lysis of single cells by the HIV-1 envelope glycoproteins occur in intracellular compartments accessible only to small inhibitory compounds.
NONLINEAR DEPTH SCALING FOR IMMERSIVE VIDEO APPLICATIONS (2003)

In this paper we discuss the minimum required accuracy of depth or disparity information for a typical immersive video application. Our approach benefits from the fact that in many cases the navigation range of the virtual camera is limited. We develop a simple geometric problem formulation and compare it with the more general plenoptic sampling approach. In this way we bridge the gap between classical 3D warp applications and the more general plenoptic sampling theorem. From this we derive general rules for the design of a typical immersive video application scenario. We provide a solution for the scalability of depth or disparity map designs in dependency of application scenarios.
Photogeneration of acid: VI: a review of basic principles for resist imaging applications (1985)

Les sels d'aryldiazonium, de diaryliododium et de triarylsulfonium avec des anions non nucleophiles tels que des halogenures metalliques complexes, produisent de l'acide par photolyse qui peut etre un photoinitiateur de photopolymerisation
Infusion of clinical‐grade enriched regulatory T cells delays experimental xenogeneic graft‐versus‐host disease (2013)

Infusion of clinical-grade enriched Treg delayed the occurrence of xenogeneic GVHD without inducing toxicity in this murine model.
Development of a sensitive chemiluminometric assay for the detection of beta-galactosidase in permeabilized coliform bacteria and comparison with fluorometry and colorimetry (1995)

We developed a chemiluminometric assay of beta-galactosidase in coliform bacteria, using a phenylgalactose-substituted 1,2-dioxetane derivative as a substrate. Permeabilization of cells is required to ensure the efficient cellular uptake of this compound. By this method, one coliform seeded in 100 ml of sterile water can be detected after a 6- to 9-h propagation phase followed by a 45-min enzyme assay in the presence of polymyxin B. Compared with fluorometry and colorimetry, chemiluminometry afforded 4- and 1,000-fold increases in sensitivity and 1- and 6-h increases in the speed of detection, respectively.
Mycobacterium canettii, the Smooth Variant of M. tuberculosis, Isolated from a Swiss Patient Exposed in Africa (1998)

An exceptionally smooth and glossy morphotype of Mycobacterium tuberculosis complex was isolated from a 56-year-old Swiss patient with mesenteric tuberculosis. Direct 16S rRNA sequence analysis of the hypervariable signature gene regions revealed a 100% homology to the specific M. tuberculosis complex sequence. Spoligotyping and restriction fragment length polymorphism analyses using the insertion sequences IS6110 and IS1081 and the polymorphic GC-rich sequence as additional genetic markers identified the isolate as the novel taxon M. canettii. Like a Somali child with a similar case, this patient probably contracted the infection in Africa, which raises questions about the geographic distribution of M. canettii.
Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop (2012)

Human immunodeficiency virus-1 (HIV-1) replication and gene expression entails specific interaction of the viral protein Tat with its transactivation responsive element (TAR), to form a highly stable stem-bulge-loop structure. Previously, we described triphenylphosphonium (TPP) cation-based vectors that efficiently deliver nucleotide analogs (PNAs) into the cytoplasm of cells. In particular, we showed that the TPP conjugate of a linear 16-mer PNA targeting the apical stem-loop region of TAR impedes Tat-mediated transactivation of the HIV-1 LTR in vitro and also in cell culture systems. In this communication, we conjugated TPP to cyclic and hairpin PNAs targeting the loop region of HIV-1 TAR and evaluated their antiviral efficacy in a cell culture system. We found that TPP-cyclic PNAs containing only 8 residues, showed higher antiviral potency compared to hairpin PNAs of 12 or 16 residues. We further noted that the TPP-conjugates of the 8-mer cyclic PNA as well as the 16-mer linear PNA displayed similar antiviral efficacy. However, cyclic PNAs were shown to be highly specific to their target sequences. This communication emphasizes on the importance of small constrained cyclic PNAs over both linear and hairpin structures for targeting biologically relevant RNA hairpins.
Approaches to the Asymmetric Synthesis of Unusual Amino Acids (2003)

This chapter will focus on critically evaluating some selected new methods to achieve the asymmetric synthesis of a-amino acids. It is not meant to be comprehensive, but rather to reflect some of the possibilities opening up in this area. The study of a-amino acids is one of fundamental importance to many areas of chemistry and its relation to molecular biology. Nature only utilizes 20 amino acids in the production of polypeptides on genes, yet the combinations of these amino acids have provided a wonderful diversity of chemical structures and functions, The number of naturally occurring or synthetically derived nonproteogenic a-amino acids is rapidly increasing and, depending on definitions, might already have exceeded 1000. In addition, because of the significant advances in the technology of synthesizing polypeptides (e.g., the solid-phase Merrifield method), the possibilities in the design and synthesis of new enzymes, hormones, synthetic immunostimulants, drugs, and countless other important biopolymers have been dramatically increased. Certain nonproteogenic amino acids have already proven of considerable experimental value in probing amino acid chemistry and function, as a tool for enhanced understanding of the roles and functions of proteins, in understanding the chemistry and biochemistry of interactions in living systems, and as analogs of naturally occurring hormones, neurotransmitters, growth factors, enzyme inhibitors, neuromodulation, immunomodulators, and many other biologically significant compounds.
Rituximab and CHOP Induction Therapy for Newly Diagnosed Mantle-Cell Lymphoma: Molecular Complete Responses Are Not Predictive of Progression-Free Survival (2002)

Favorable clinical and molecular response rates associated with rituximab and CHOP chemotherapy do not translate into prolonged PFS in MCL. Nevertheless, rituximab and combination chemotherapy may transiently clear PB or BM of detectable tumor cells, prompting additional consideration of antibody-based in vivo purging in subsequent clinical trials.
Dominant negative effect of a germ-line mutant p53: a step fostering tumorigenesis. (1993)

Lysates derived from the fibroblasts of individuals who are homozygous for normal p53 or heterozygous for the germ-line p53 mutation characteristic of certain Li-Fraumeni cancer-prone families were assessed for p53 function utilizing the binding of p53 protein to a p53-specific consensus oligonucleotide sequence. As expected, control nuclear lysates containing only mutant p53 or no p53 displayed little or no such binding. However, the nuclear lysates from heterozygous fibroblasts containing similar amounts of normal p53 and 245D mutant p53 displayed binding that was significantly below 50% of that seen with homozygous wild-type p53 in normal cell lysates. The nuclear lysates of these heterozygous or homozygous fibroblasts exhibited similar levels of DNA binding to a consensus oligonucleotide specific for the transcription factor, AP-1. These results indicate that mutant p53 has a transdominant effect on the binding of DNA by normal p53. These findings also suggest that p53 complexes formed in vivo that contain mutant p53 are functionally impaired even if normal p53 is also present in the complex. The implications of a trans-dominant effect of mutant p53 on the cancer-prone phenotype of individuals heterozygous for mutated p53 in Li-Fraumeni families is discussed.
In vitro and in vivo effects of glucocorticoids on gene transfer to skeletalmuscle (1999)

As a pharmacological approach to potentially improve gene transfer efficiency into skeletal muscle cells, glucocorticoids were shown here to allow efficient transfection of cultured and mouse human myoblasts, human pulmonary A549 cells, but not dog myoblasts, independently of the transfection protocol, the reporter gene and the transcription promoter employed. Transduction with adenovirus was also increased by dexamethasone. Pretreatment of cells 48 h prior to transfection was most effective and was shown to be concentration-dependent. This effect is mediated by binding to the glucocorticoid receptor, but not by glucocorticoid responsive elements present in the vectors. The acute dexamethasone effect could be due to increased plasmid entry into the cells as suggested by Southern blot, whereas the sustained increase of luciferase activity in dexamethasone-treated cultures may be related to intracellular mechanisms following cell entry. In mice in vivo, a similar increase of luciferase activity upon glucocorticoid treatment was found.