gebhart/patrepeval huggingface dataset:
Blockade of Programmed Death-1 Engagement Accelerates Graft-Versus-Host Disease Lethality by an IFN-γ-Dependent Mechanism (2003)

Acute graft-vs-host disease (GVHD) is influenced by pathways that can enhance or reduce lethality by providing positive or negative signals to donor T cells. To date, the only reported pathway to inhibit GVHD is the CTLA-4:B7 pathway. Because absence of the programmed death-1 (PD-1) pathway has been implicated in a predisposition to autoimmunity and hence a lack of negative signals, the effect of PD-1 pathway blockade on GVHD was explored using several distinct approaches. In each, GVHD lethality was markedly accelerated. Coblockade of CTLA-4 and PD-1 was additive in augmenting GVHD, indicating that these pathways are not fully redundant. Although neither perforin nor Fas ligand expression was required for GVHD enhancement, donor IFN-gamma production was required for optimal GVHD acceleration in the absence of PD-1 ligation. These data indicate that PD-1 ligation down-regulates GVHD through modulation of IFN-gamma production and suggest a novel therapeutic target for inhibiting GVHD lethality.
The Alternative Sigma Factor, ς E , Is Critically Important for the Virulence of Salmonella typhimurium (1999)

In Escherichia coli, extracytoplasmic stress is partially controlled by the alternative sigma factor, RpoE (sigmaE). In response to environmental stress or alteration in the protein content of the cell envelope, sigmaE upregulates the expression of a number of genes, including htrA. It has been shown that htrA is required for intramacrophage survival and virulence in Salmonella typhimurium. To investigate whether sigmaE-regulated genes other than htrA are involved in salmonella virulence, we inactivated the rpoE gene of S. typhimurium SL1344 by allelic exchange and compared the phenotype of the mutant (GVB311) in vitro and in vivo with its parent and an isogenic htrA mutant (BRD915). Unlike E. coli, sigmaE is not required for the growth and survival of S. typhimurium at high temperatures. However, GVB311 did display a defect in its ability to utilize carbon sources other than glucose. GVB311 was more sensitive to hydrogen peroxide, superoxide, and antimicrobial peptides than SL1344 and BRD915. Although able to invade both macrophage and epithelial cell lines normally, the rpoE mutant was defective in its ability to survive and proliferate in both cell lines. The effect of the rpoE mutation on the intracellular behavior of S. typhimurium was greater than that of the htrA mutation. Both GVB311 and BRD915 were highly attenuated in mice. Neither strain was able to kill mice via the oral route, and the 50% lethal dose (LD50) for both strains via the intravenous (i.v.) route was very high. The i.v. LD50s for SL1344, BRD915, and GVB311 were <10, 5.5 x 10(5), and 1.24 x 10(7) CFU, respectively. Growth in murine tissues after oral and i.v. inoculation was impaired for both the htrA and rpoE mutant, with the latter mutant being more severely affected. Neither mutant was able to translocate successfully from the Peyer's patches to other organs after oral infection or to proliferate in the liver and spleen after i.v. inoculation. However, the htrA mutant efficiently colonized the livers and spleens of mice infected i.v., but the rpoE mutant did not. Previous studies have shown that salmonella htrA mutants are excellent live vaccines. In contrast, oral immunization of mice with GVB311 was unable to protect any of the mice from oral challenge with SL1344. Furthermore, i.v. immunization with a large dose ( approximately 10(6) CFU) of GVB311 protected less than half of the orally challenged mice. Thus, our results indicate that genes in the sigmaE regulon other than htrA play a critical role in the virulence and immunogenicity of S. typhimurium.
Ion kinetic-energy distributions and Balmer-alpha (Hα) excitation in Ar-H2 radio-frequency discharges (1995)

Excited neutrals and fast ions produced in a 13.56 MHz radio-frequency discharge in a 90% argon −10% hydrogen gas mixture were investigated, respectively, by spatially and temporally resolved optical emission spectroscopy, and by mass-resolved measurements of ion kinetic energy distributions at the grounded electrode. The electrical characteristics of the discharge were also measured and comparisons are made with results obtained for discharges in pure H2 under comparable conditions. Measurements of Balmer-alpha (Hα) emission show Doppler-broadened emission that is due to the excitation of fast atomic hydrogen neutrals formed from ion neutralization processes in the discharge. Temporally and spatially resolved emission profiles of the Hα radiation from the Ar-H2 mixture are presented for the ‘‘slow’’ component produced predominately by electron-impact dissociative excitation of H2, and for the ‘‘fast’’ component corresponding to energies much greater than can be derived from dissociative excitation. For the Ar-H2 mixture, the fast component is significantly enhanced relative to the slow component. The measured kinetic-energy distributions and fluxes of predominant ions in the Ar-H2 mixture, such as H3+, H2+, H+, and ArH+, suggest mechanisms for the formation of fast hydrogen atoms. The interpretation of results indicate that H+ and/or H3+, neutralized and backscattered by collision with the powered electrode, are the likely sources of fast hydrogen atoms that produce Doppler-shifted Hα emission in the discharge. There is also evidence at the highest pressures and voltages of ‘‘runaway’’ H+ ions formed near the powered electrode, and detected with kinetics energies exceeding 100 eV at the grounded electrode.
Eribulin in Cancer Treatment (2015)

Halichondrin B is a complex, natural, polyether macrolide derived from marine sponges. Eribulin is a structurally-simplified, synthetic, macrocyclic ketone analogue of Halichondrin B. Eribulin was approved by United States Food and Drug Administration in 2010 as a third-line therapy for metastatic breast cancer patients who have previously been treated with an anthracycline and a taxane. It has a unique microtubule dynamics inhibitory action. Phase III studies have either been completed or are currently ongoing in breast cancer, soft tissue sarcoma, and non-small cell lung cancer. Phase I and II studies in multiple cancers and various combinations are currently ongoing. This article reviews the available information on eribulin with respect to its clinical pharmacology, pharmacokinetics, pharmacodynamics, mechanism of action, metabolism, preclinical studies, and with special focus on clinical trials.
Text input methods for eye trackers using off-screen targets (2000)

Text input with eye trackers can be implemented in many ways such as on-screen keyboards or context sensitive menu-selection techniques. We propose the use of off-screen targets and various schemes for decoding target hit sequences into text. Off-screen targets help to avoid the Midas' touch problem and conserve display area. However, the number and location of the off-screen targets is a major usability issue. We discuss the use of Morse code, our Minimal Device Independent Text Input Method (MDITIM), QuikWriting, and Cirrin-like target arrangements. Furthermore, we describe our experience with an experimental system that implements eye tracker controlled MDITIM for the Windows environment.
Congestive Heart Failure (1992)

This is the 17th in a series of interactive patient management programs that analyze problems common in the primary care setting. The programs have been published by Cardinal Health Systems Inc since 1982 and include such topics as type II diabetes, coronary artery disease, acute respiratory failure, and hypertension. "the essentials in 612 kilobytes and 67 pages" The program<i>Congestive Heart Failure</i>is for teaching medical students and residents and provides practicing physicians with an opportunity to review their skills. It consists of three modules of tutorials, tools, and five case studies. The printed text presents information on the approach to evaluation and treatment. We all remember the complicated schemes with which our teachers tried to make us understand the intricacies of the pathophysiology of congestive heart failure (CHF), a condition that appears to affect all organ systems at some time in its natural history. It has been difficult to
Systemic Immunotherapy for Urothelial Cancer: Current Trends and Future Directions (2017)

Urothelial cancer of the bladder, renal pelvis, ureter, and other urinary organs is the fifth most common cancer in the United States, and systemic platinum-based chemotherapy remains the standard of care for first-line treatment of advanced/metastatic urothelial carcinoma (UC). Until recently, there were very limited options for patients who are refractory to chemotherapy, or do not tolerate chemotherapy due to toxicities and overall outcomes have remained very poor. While the role of immunotherapy was first established in non-muscle invasive bladder cancer in the 1970s, no systemic immunotherapy was approved for advanced disease until the recent approval of a programmed death ligand-1 (PD-L1) inhibitor, atezolizumab, in patients with advanced/metastatic UC who have progressed on platinum-containing regimens. This represents a significant milestone in this disease after a void of over 30 years. In addition to atezolizumab, a variety of checkpoint inhibitors have shown a significant activity in advanced/metastatic urothelial carcinoma and are expected to gain Food and Drug Administration (FDA) approval in the near future. The introduction of novel immunotherapy agents has led to rapid changes in the field of urothelial carcinoma. Numerous checkpoint inhibitors are being tested alone or in combination in the first and subsequent-line therapies of metastatic disease, as well as neoadjuvant and adjuvant settings. They are also being studied in combination with radiation therapy and for non-muscle invasive bladder cancer refractory to BCG. Furthermore, immunotherapy is being utilized for those ineligible for firstline platinum-based chemotherapy. This review outlines the novel immunotherapy agents which have either been approved, or are currently being investigated in clinical trials in UC.
Interleukin-2 Receptor γ Chain: a Functional Component of the Interleukin-4 Receptor (1993)

The interleukin-2 (IL-2) receptor γ chain (IL-2Rγ) is an essential component of high- and intermediate-affinity IL-2 receptors. IL-2Rγ was demonstrated to be a component of the IL-4 receptor on the basis of chemical cross-linking data, the ability of IL-2Rγ to augment IL-4 binding affinity, and the requirement for IL-2Rγ in IL-4-mediated phosphorylation of insulin receptor substrate-1. The observation that IL-2Rγ is a functional component of the IL-4 receptor, together with the finding that IL-2Rγ associates with the IL-7 receptor, begins to elucidate why deficiency of this common γ chain (gamma; c ) has a profound effect on lymphoid function and development, as seen in X-linked severe combined immunodeficiency.
Qualitative review of SNRIs in anxiety. (2004)

Anxiety disorders pose a problem for a significant number of individuals, with a 1-year prevalence rate estimated at 13.1% to 17.1%. Many pharmacologic agents have been used to treat anxiety disorders, and among those in current use are newer benzodiazepines (alprazolam), azapirones (buspirone), selective serotonin reuptake inhibitors (paroxetine and sertraline), and venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI). The likely role of abnormal serotonergic neurotransmission in anxiety is widely supported, while the role of norepinephrine is less clear. Still, many lines of evidence support the hypothesis that a perturbation in norepinephrine neurotransmission contributes to the symptoms of anxiety. Therefore, it is conceivable that modulation of both serotonin and norepinephrine systems by dual-reuptake inhibitors may be an advantage in the treatment of anxiety disorders. Given this, the current review examines evidence on the possible role of venlafaxine in the treatment of anxiety disorders. From this review it is clear that venlafaxine is as efficacious as selective serotonin reuptake inhibitors in treating anxiety, with comparable tolerability. Future research will be valuable in determining if antidepressants that combine pharmacologic actions on serotonergic and noradrenergic systems have advantages over more selective agents in treating anxiety disorders.
50-kD integrin-associated protein does not detectably influence several functions of glycoprotein IIb-IIIa complex in human platelets (1995)

A 50-kD integrin-associated protein (IAP) has been reported to be associated with beta 3 integrins and to modulate their function, especially vitronectin receptor in human erythroleukemia (HEL) cells and leukocyte response integrin in neutrophils. We studied the involvement of IAP in the function of platelet beta 3 integrin, glycoprotein (GP) IIb-IIIa complex. IAP was a widely distributed protein and was also expressed in the cells that do not have beta 3 integrin. Platelets from a patient with thrombasthenia, which lack GPIIb and IIIa, expressed IAP as well as normal platelets. Neither platelet aggregation nor intracellular Ca2+ elevation after stimulation was influenced by the anti-IAP antibody, B6H12, which was reported to be inhibitory for other beta 3 integrins. The expression level of GPIIb-IIIa complex was not influenced by coexpression of human IAP in the transfected Chinese hamster ovary (CHO) cells. IAP did not facilitate the binding of soluble fibrinogen to the CHO cells expressing GPIIb-IIIa complex. Furthermore, cell adhesion onto the immobilized fibrinogen via GPIIb-IIIa complex was not inhibited by B6H12 in HEL cells and was not altered by coexpression of human IAP in CHO cells. We concluded that expression of IAP is regulated independently with that of GPIIb-IIIa complex and that IAP does not influence the function of GPIIb-IIIa complex.
Coordination of Levels of Elongation Factors Tu, Ts, and G, and Ribosomal Protein S1 in Escherichia coli (1978)

The amounts of the polypeptide chain elongation factors Tu, Ts, and G, and ribosomal protein SI were assessed under various growth conditions using three independent procedures: (a) Immunoprecipitation and gel electrophoresis, (b) radioimmune assay, and (c) activity measurements. It was demonstrated that, during balanced growth of E. coli, the intracellular levels of these proteins increased in proportion to the growth rate, and the ratio of EF-Tu:EF-Ts:EF-G:protein SI was 4-5:1:1:1, at all growth rates. The effects of isoleucine starvation on the rates of synthesis of these proteins were examined using a pair of isogenic stringent and relaxed strains. The syntheses of all these proteins were found to be under the influence of stringent control. These results indicate that in E. coli the syntheses of the above four proteins are regulated in a coordinated manner and are subject to stringent control.
Design of an internal antenna with wide and multiband characteristic for mobile handset (2006)

Abstract The development of a small electrical antenna plays an important role in the rapidly growing mobile communication market. This paper presents the design of a novel small and wideband planar inverted F‐antenna that simultaneously covers the GSM900/GPS/DCS1800/DCS1900/IMT2000/WLAN/DMB service bands. A very wide impedance‐bandwidth characteristic was achieved by optimizing both the distance between the feed line and short strip and the width of a short strip. The commercial electromagnetic software CST Microwave Studio is used to design the structure. The maximum gains at the frequencies of 915, 1850, 2025, and 2450 MHz were 1.79, 3.56, 3.65, and 1.67 dBi, respectively. The overall radiation pattern is suitable for mobile application. © 2006 Wiley Periodicals, Inc. Microwave Opt Technol Lett 48: 947–950, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.21528
Mixotrophic Production of Marine Microalga Phaeodactylum tricornutum on Various Carbon Sources (2006)

We investigated the potential use of various carbon sources (fructose, glucose, mannose, lactose, and glycerol) for culturing Phaeodactylum tricornutum UTEX-640 in mixotrophic and heterotrophic batch cultures. Concentrations of carbon substrates tested ranged from 0.005 M to 0.2 M. P. tricornutum did not grow heterotrophically on any of the C-sources used, but successive additions of organic carbon in mixotrophic growth mode substantially increased the biomass concentration and productivity relative to photoautotrophic controls. The maximum biomass productivities in mixotrophic cultures for glycerol, fructose, and glucose were 21.30 mg/l h, 15.80 mg/l h, and 10.20 mg/l h, respectively. These values were respectively 10-, 8-, and 5-fold higher than those obtained in the corresponding photoautotrophic control cultures. Mannose and lactose did not significantly affect microalgal growth. The biomass lipids, eicosapentaenoic acid (EPA) and pigments contents were considerably enhanced with glycerol and fructose in relation to photoautotrophic controls. The EPA content was barely affected by the sugars, but were more than 2-fold higher in glycerol-fed cultures than in photoautotrophic controls.
Direct in Vivo Screening of Intrabody Libraries Constructed on a Highly Stable Single-chain Framework (2002)

Single-chain Fv antibody fragments (scFv) represent a convenient antibody format for intracellular expression in eukaryotic or prokaryotic cells. These so-called intrabodies have great potential in functional genomics as a tool to study the function of newly identified proteins in vivo, for example by binding-induced modulation of their activity or by blocking interactions with other proteins. However, the intracellular expression and activity of many single-chain Fvs are limited by their instability and folding efficiency in the reducing intracellular environment, where the highly conserved intrachain disulfide bonds do not form. In the present work, we used an in vivo selection system to isolate novel antigen-binding intrabodies. We screened two intrabody libraries carrying a randomized third hypervariable loop onto the heavy chain of a stable framework, which had been further optimized by random mutagenesis for better behavior in the selection system, and we biophysically characterized the selected variants to interpret the outcome of the selection. Our results show that single-framework intrabody libraries can be directly screened in vivo to rapidly select antigen-specific intrabodies.
Purification of Fibronectin from Human Plasma (2003)

Fibronectin is an ubiquitous extracellular glycoprotein that exists in a soluble form in body fluids and in an insoluble form in the extracellular matrix. It plays a major role in many important physiological processes, such as embryogen-esis, wound healing, hemostasis, and thrombosis (1). Fibronectin is secreted as a dimer, with a monomer molecular weight of approx 220–250 kDa; the monomers are joined by two disulfide bonds near the carboxyl terminus of the protein (2). Like many proteins of the extracellular matrix, fibronectin is a mosaic protein composed of modular units (3). Fibronectin is composed almost entirely of three types of modules (types 1–3). The modules are organized into functional domains that are resistant to proteolysis and contain binding sites for extracellular matrix proteins such as collagen and thrombospondin, cell-surface receptors such as integrins, circulating blood proteins such as fibrin, and glycosaminoglycans such as heparin and chondroitin sulfate (4). In general, fibronectin is synthesized by and is present around fibroblasts, endothelial cells, chondrocytes, glial cells, and myocytes. Fibronectin is abundant in the connective tissue matrix and in basement membranes (5). The distribution is quite characteristic for each cell and tissue. Although blood cells, such as lymphocytes, myelocytes, and erythrocytes, lack fibronectin, this gly-coprotein is abundant in the plasma (about 30 mg/100 mL). Actually, this body fluid represents the main source for fibronectin purification.
Modern Room Temperature Ionic Liquids, a Simple Guide to Understanding Their Structure and How It May Relate to Dynamics (2015)

Modern room temperature ionic liquids are structurally defined by symmetries on different length scales. Polar-apolar alternation defines their nanoscale structural heterogeneity, whereas positive-negative charge alternation defines short length scale order. Much progress has been made in the past few years as it pertains to the theoretical interpretation of X-ray scattering experiments for these liquids. Our group has contributed to the development of theoretical interpretation guidelines for the analysis of their structure function. Perhaps less well developed is our understanding of how transport and dynamics in general couple to the very unique structure of ionic liquids which are often dynamically and structurally heterogeneous. This article attempts to present our most current understanding of ionic liquid structure in general and its coupling to transport and dynamics in minimally technical terms for the benefit of the broadest audience.
Studies on reactions of nucleoside H-phosphonates with bifunctional reagents. Part 1. Reaction with amino alcohols (1993)

The reaction of nucleoside H-phosphonates with amino alcohols in the presence of condensing agents has been studied. Depending on the coupling procedure used and the length of the polymethylene bridge in the amino alcohols, different H-phosphonate diesters, cyclic phosphoramidite derivatives or phosphite triesters can be produced. Oxidation of these species with iodine under various experimental conditions has been studied and a general procedure for synthesis of nucleoside alkyl phosphodiesters has been developed.
Chikusetsusaponin IVa Butyl Ester (CS-IVa-Be), a Novel IL6R Antagonist, Inhibits IL6/STAT3 Signaling Pathway and Induces Cancer Cell Apoptosis (2016)

Abstract The activation of IL6/STAT3 signaling is associated with the pathogenesis of many cancers. Agents that suppress IL6/STAT3 signaling have cancer-therapeutic potential. In this study, we found that chikusetsusaponin IVa butyl ester (CS-IVa-Be), a triterpenoid saponin extracted from Acanthopanas gracilistylus W.W.Smith, induced cancer cell apoptosis. CS-IVa-Be inhibited constitutive and IL6-induced STAT3 activation, repressed STAT3 DNA-binding activity, STAT3 nuclear translocation, IL6-induced STAT3 luciferase reporter activity, IL6-induced STAT3-regulated antiapoptosis gene expression in MDA-MB-231 cells, and IL6-induced TF-1 cell proliferation. Surprisingly, CS-IVa-Be inhibited IL6 family cytokines rather than other cytokines induced STAT3 activation. Further studies indicated that CS-IVa-Be is an antagonist of IL6 receptor via directly binding to the IL6Rα with a Kd of 663 ± 74 nmol/L and the GP130 (IL6Rβ) with a Kd of 1,660 ± 243 nmol/L, interfering with the binding of IL6 to IL6R (IL6Rα and GP130) in vitro and in cancer cells. The inhibitory effect of CS-IVa-Be on the IL6–IL6Rα–GP130 interaction was relatively specific as CS-IVa-Be showed higher affinity to IL6Rα than to LIFR (Kd: 4,910 ± 1,240 nmol/L) and LeptinR (Kd: 4,990 ± 915 nmol/L). We next demonstrated that CS-IVa-Be not only directly induced cancer cell apoptosis but also sensitized MDA-MB-231 cells to TRAIL-induced apoptosis via upregulating DR5. Our findings suggest that CS-IVa-Be as a novel IL6R antagonist inhibits IL6/STAT3 signaling pathway and sensitizes the MDA-MB-231 cells to TRAIL-induced cell death. Mol Cancer Ther; 15(6); 1190–200. ©2016 AACR.
Engineering of ferrite-graphite composite media for microwave shields (2006)

An electromagnetic shielding of objects using ferrite-graphite composites is considered. The analytical model, using the Maxwell Garnett formulation for multiphase mixtures, results of computations based on this model and plane-wave formulation, and some experimental results are represented.