gebhart/patrepeval huggingface dataset:
RORγt Recruits Steroid Receptor Coactivators to Ensure Thymocyte Survival (2005)

Thymocytes undergo apoptosis unless a functional TCR is assembled. Steroid receptor coactivators (SRCs) regulate nuclear receptor-mediated transcription by associated histone acetyltransferase activity. However, it has been a challenge to demonstrate the in vivo function of SRCs due to the overlapping functions among different members of SRCs. In this study, we show that recruitment of SRCs is required for thymic-specific retinoic acid-related orphan receptor gamma (RORgamma)t-regulated thymocyte survival in vivo. An activation function 2 domain, identified at the carboxyl terminus of RORgammat, is responsible for recruiting SRCs. A mutation in the activation function domain (Y479F) of RORgammat disrupted the interaction with SRCs and abolished RORgammat-mediated trans-activation but not its ability to inhibit transcription. Transgenes encoding the wild-type RORgammat, but not the mutant, restored thymocyte survival in RORgamma null mice. Our results thus clearly demonstrate that RORgammat recruits SRCs to impose a gene expression pattern required to expand the life span of thymocytes in vivo, which increases the opportunities for assembling a functional TCR.
Effect of medium osmolarity on hybridoma growth, metabolism, and antibody production (1991)

No Abstract.
Two Patterns of White Matter Abnormalities in Medication-Naive Patients With First-Episode Schizophrenia Revealed by Diffusion Tensor Imaging and Cluster Analysis (2015)

Two distinct patterns of white matter abnormalities exist at the early phase of schizophrenia, with those having global abnormalities experiencing more severe negative symptoms. The finding that distinct subgroups of patients with schizophrenia have different forms of white matter pathology may reflect qualitatively distinct genetic influences or neurodevelopmental alterations and thus represents a promising strategy for resolving neurobiological heterogeneity in the schizophrenia syndrome.
Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics (2010)

Acute graft-versus-host disease (aGVHD) is associated with high risk of morbidity and mortality and is a common complication after double umbilical cord blood (UCB) transplantation. To reduce these risks, we established a method of CD4(+)CD25(+)FoxP3(+) T regulatory cell (Treg) enrichment from cryopreserved UCB followed by a 18 (+) 1-day expansion culture including anti-CD3/anti-CD28 antibody-coated beads and recombinant human interleukin-2. In a "first-in-human" clinical trial, we evaluated the safety profile of UCB Treg in 23 patients. Patients received a dose of 0.1-30 × 10(5)UCB Treg/kg after double UCB transplantation. The targeted Treg dose was achieved in 74% of cultures, with all products being suppressive in vitro (median 86% suppression at a 1:4 ratio). No infusional toxicities were observed. After infusion, UCB Treg could be detected for 14 days, with the greatest proportion of circulating CD4(+)CD127(-)FoxP3(+) cells observed on day (+)2. Compared with identically treated 108 historical controls without Treg, there was a reduced incidence of grade II-IV aGVHD (43% vs 61%, P = .05) with no deleterious effect on risks of infection, relapse, or early mortality. These results set the stage for a definitive study of UCB Treg to determine its potency in preventing allogeneic aGVHD. This study is registered at http://www.clinicaltrials.gov as NCT00602693.
Improving Oral Drug Transport via Prodrugs (1999)

I. PRODRUG APPROACH A. Introduction A prodrug is a chemical derivative of a parent drug molecule that undergoes transformation within the body to release an active moiety. The activation or conversion to the parent drug should be in a controlled, quantitative fashion, producing by-products that are pharmacologically inert and with no intrinsic toxicity. The chemical derivative that satisfies the prodrug requirements, once released, must be an endogenous substance in its own right and rapidly eliminated from the body [1]. The conversion of prodrug to its active moiety usually takes place during or after absorption or at the specific site of the action in the body, although conversion prior to this may also occur. This transformation of prodrug to the original moiety in the body can be accomplished by different reactions. Most oral prodrugs require an enzymatic catalysis in order to release the parent drug molecule [2]. Active drug species containing hydroxyl, carboxyl, and amine groups have been derivatized to produce prodrugs and optimize delivery. These prodrugs are converted back to the original parent drug by the action of enzymes (e.g., esterase) within the body.
Passively transferred anti-MUC1 antibodies cause neither autoimmune disorders nor immunity against transplanted tumors in MUC1 transgenic mice (1999)

C57BL/6 mice transgenic for human MUC1 (MUC1.Tg) have been developed to investigate the autoimmune consequences of producing MUC1 tumor immunity in an animal that expresses MUC1 as a self-protein on normal ductal epithelia. Previous work showed that MUC1.Tg mice challenged with MUC1-bearing syngeneic tumors (B16.MUC1) developed progressively growing MUC1-expressing tumors and no detectable MUC1-specific antibody (Ab) response. In contrast, wild-type C57BL/6 (wt) mice developed MUC1-negative tumors at a significantly slower rate and produced approximately 50 μg IgG1 Ab reactive with the MUC1 tandem repeat (TR)/ml of sera. One milliliter of these sera was administered passively to MUC1.Tg or wt mice and the concentration of the MUC1 TR-reactive IgG1 Abs was monitored over time. The results indicate that circulating MUC1-reactive Abs were detectable in MUC1.Tg mice and that significant amounts of these Abs were not absorbed by organs that endogenously express MUC1. No evidence of autoimmune disease, either gross or histological, was observed in the MUC1.Tg recipients of sera suggesting that MUC1, an organ-specific protein expressed primarily by secretory epithelia, is inaccessible to circulating MUC1-reactive Abs. Additional studies showed that polyclonal sera containing IgG1 Abs reactive with MUC1 TR were unable to provide protection against the growth of syngeneic tumors expressing MUC1 in the MUC1.Tg animal model. Int. J. Cancer 80:595–599, 1999. © 1999 Wiley-Liss, Inc.
Vnodes: An Architecture for Multiple File System Types in Sun UNIX. (1986)

Fertility after myomectomy and GTN generally has an excellent prognosis.
Opponent Modeling in Real-Time Strategy Games. (2007)

Real-time strategy games present an environment in which game AI is expected to behave realistically. One feature of realistic behaviour in game AI is the ability to recognise the strategy of the opponent player. This is known as opponent modeling. In this paper, we propose an approach of opponent modeling based on hierarchi-cally structured models. The top-level of the hierarchy can classify the general play style of the opponent. The bottom-level of the hierarchy can classify specific strate-gies that further define the opponent’s behaviour. Ex-periments that test the approach are performed in the RTS game Spring. From our results we may conclude that the approach can be successfully used to classify the strategy of an opponent in the Spring game.
Future development of InGaP/(In)GaAs based multijunction solar cells (2005)

Although technologies for the InGaP/InGaAs/Ge cell have been matured, there is still room for improvement of the InGaP/(In)GaAs/Ge cell in practical level. Band gap of the top cell should be increased a little to get higher V/sub OC/. Thinning the Ge substrate is thought to be effective to increase a power per weight even for rigid panel. For concentrator application, grid pitch, cell size and current matching design should be optimized with taking account of the spectrum of concentrated light. The InGaP/(In)GaAs based solar cells shall be cornerstone in high efficiency multijunction solar cells in future. High efficiency cell consisted of 1 eV lattice-match material such as InGaAsN is strongly desired for high efficiency 4-junction or 6-junction cell. Wafer bonding and layer transfer techniques might be sophisticated to make solar cells. Paper-like InGaP/GaAs solar cells with efficiency of 29.4% on flexible metal film developed by SHARP Corp. are newly reported. Material cost of the cell is basically very low, because it has only very thin layers of III-V compounds and cheap metal film. Thin film technology shall be a hint for future cells.
Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome (2003)

Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Hyperinsulinemia and insulin action were initially proposed as the common preceding factors of hypertension, low high-density lipoprotein cholesterol, hypertriglyceridemia, abdominal obesity, and altered glucose tolerance, linking all these abnormalities to the development of coronary heart disease. The similarities of insulin resistance with another inflammatory state, atherosclerosis, have been described only in the last few decades. Atherosclerosis and insulin resistance share similar pathophysiological mechanisms, mainly due to the actions of the two major proinflammatory cytokines, TNF-alpha and IL-6. Genetic predisposition to increased transcription rates of these cytokines is associated with metabolic derangement and simultaneously with coronary heart disease. Dysregulation of the inflammatory axis predicts the development of insulin resistance and type 2 diabetes mellitus. The knowledge of how interactions between metabolic and inflammatory pathways occur will be useful in future therapeutic strategies. The effective administration of antiinflammatory agents in the treatment of insulin resistance and atherosclerosis is only the beginning of a promising approach in the management of these syndromes.
Solid‐Phase Synthesis and Combinatorial Technologies (2000)

Solid-Phase Synthesis: Basic Principles Solid-Phase Synthesis: Oligomeric Molecules Solid-Phase Synthesis: Small Organic Molecules Combinatorial Technologies: Basic Principles Synthetic Organic Libraries: Library Design and Properties Synthetic Organic Libraries: Solid-Phase Discrete Libraries Synthetic Organic Libraries: Solid-Phase Pool Libraries Synthetic Organic Libraries: Solution-Phase Libraries Applications of Synthetic Libraries Biosynthetic Combinatorial Libraries Materials and Polymeric Combinatorial Libraries Index.
Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. (1984)

Human T-cell clones and anti-T-cell-receptor antibodies (clonotypic) directed at surface receptors for antigen (T3-Ti molecular complex) as well as anti-interleukin 2 (IL-2) and anti-IL-2-receptor antibodies were utilized to investigate the mechanism by which alloantigens or antigen plus self-major histocompatibility complex (MHC) (i.e., physiologic ligand) trigger specific clonal proliferation. Soluble or Sepharose-bound anti-Ti monoclonal antibodies, like physiologic ligand, enhanced proliferative responses to purified IL-2 by inducing a 6-fold increase in surface IL-2 receptor expression. In contrast, only Sepharose-bound anti-Ti or physiologic ligand triggered endogenous clonal IL-2 production and resulted in subsequent proliferation. The latter was blocked by antibodies directed at either the IL-2 receptor or IL-2 itself. These results suggest that induction of IL-2 receptor expression but not IL-2 release occurs in the absence of T3-Ti receptor cross-linking. Perhaps more importantly, the findings demonstrate that antigen-induced proliferation is mediated through an autocrine pathway involving endogenous IL-2 production, release, and subsequent binding to IL-2 receptors.
Comparative Genomics of Listeria Species (2001)

Listeria monocytogenes is a food-borne pathogen with a high mortality rate that has also emerged as a paradigm for intracellular parasitism. We present and compare the genome sequences of L. monocytogenes (2,944,528 base pairs) and a nonpathogenic species, L. innocua (3,011,209 base pairs). We found a large number of predicted genes encoding surface and secreted proteins, transporters, and transcriptional regulators, consistent with the ability of both species to adapt to diverse environments. The presence of 270 L. monocytogenes and 149 L. innocua strain-specific genes (clustered in 100 and 63 islets, respectively) suggests that virulence in Listeria results from multiple gene acquisition and deletion events.
ANTIBIOTICS THAT INHIBIT FUNGAL CELL WALL DEVELOPMENT (1994)

The discovery of antifungal agents that possess selective toxicity against the eukaryotic fungal cell remains an important scientific challenge. The growing medical need for safe and effective antifungal agents stems from the rapidly increasing population of immunocompromised patients. Although the treatment of fungal infections is progressing steadily, currently available agents act on targets that are also found in mammalian cells. Ideally, a selectively toxic antifungal agent should be developed that interacts with a fungal target not found in other eukaryotic cells. This strategy involves selective inhibition of the biosynthesis of important structural elements in the fungal cell. The fungal cell wall is such a therapeutic target. In addition, antibiotics have been discovered that inhibit the development of the fungal cell. The major targets are glucan synthesis, inhibited by the echinocandin lipopeptides and the papulacandins; chitin synthesis, inhibited by the polyoxins and nikkomycins; and mannan, to which the pradimicins selectively bind. The extensively studied echinocandin lipopeptides are fungicidal agents with low toxicity, and one member, cilofungin--a semisynthetic analogue of echinocandin B--has been tested in the clinic. Newer echinocandins, such as LY303366 and the pneumocandins, have excellent activity against yeasts and Pneumocystis carinii infections in animals and show promise as potential clinical antifungal candidates. Chitin synthase inhibitors have been studied through chemical modification of the polyoxins and nikkomycins but are limited because of unfavorable pharmacokinetics. The pradimicins show the ability to bind mannan and thus exert an antifungal effect. The mode of action of this class of inhibitors is not fully understood, but their unique action may provide a better understanding of mannan as a target.
Thermal and electrical properties of Si/Si/sub 0.8/Ge/sub 0.2/ and B/sub 4/C/B/sub 9/C films (2002)

Two-dimensional quantum wells have been synthesized by alternating layers of B/sub 4/C and B/sub 9/C in one system and alternating layers of Si and Si/sub 0.8/Ge/sub 0.2/ in another system. Such nanostructures are being investigated as candidate thermoelectric materials for high figures of merit (Z). The predicted enhancement is attributed to the confined motion of charge carriers and phonons in the two dimensions and separating them from the ion scattering centers. MBE and sputtering techniques have been used to prepare these multilayer films. Films have been deposited on single-crystal silicon substrates. The /spl alpha/ and /spl rho/ properties of these films have been determined over a broad range of temperatures from 4.2 K to 1200 K and were previously reported. The /spl alpha//sup 2///spl rho/ values for these P type B-C and N type SiGe films were more than a factor of 10 to 30 times higher than bulk P type B-C and N type SiGe. Recently, thermal conductivities have also been measured with a modified 3-/spl omega/ method. The room temperature thermal conductivity of Si and Si/sub 0.8/Ge/sub 0.2/ were also encouraging smaller, and about one third (1/3) of the bulk values and in line with theoretical predictions. The performance of the MBE films have been systematically compared with bulk materials. Preliminary thermoelectric measurements of the multilayer structures, lead us to believe that significant gains in the thermoelectric figure of merit (Z) may be possible with this approach. The first quantum well thermoelectric couple with N-type Si/Si/sub 0.8/Ge/sub 0.2/ and P-type B/sub 4/C/B/sub 9/C was fabricated from these films. The test results generated continue to indicate that much higher thermoelectric efficiencies can be achieved in the quantum wells compared to the bulk materials. Also, the potential cost of fabricating quantum well modules will be discussed and are expected to be much lower than present bulk thermoelectric module on a cost/watt basis.
SCAMP5, NBEA and AMISYN: three candidate genes for autism involved in secretion of large dense-core vesicles (2010)

Autism is a neurodevelopmental disorder characterized by impaired social reciprocity, impaired communication and stereotypical behaviors. Despite strong evidence for a genetic basis, few susceptibility genes have been identified. Here, we describe the positional cloning of SCAMP5, CLIC4 and PPCDC as candidate genes for autism, starting from a person with idiopathic, sporadic autism carrying a de novo chromosomal translocation. One of these genes, SCAMP5 is silenced on the derivative chromosome, and encodes a brain-enriched protein involved in membrane trafficking, similar to the previously identified candidate genes NBEA and AMISYN. Gene silencing of Nbea, Amisyn and Scamp5 in mouse beta-TC3 cells resulted in a 2-fold increase in stimulated secretion of large dense-core vesicles (LDCVs), while overexpression suppressed secretion. Moreover, ultrastructural analysis of blood platelets from the patients with haploinsufficieny of one of the three candidate genes, showed morphological abnormalities of dense-core granules, which closely resemble LDCVs. Taken together, this study shows that in three independent patients with autism three different negative regulators of LDCV secretion are affected, respectively, suggesting that in at least a subgroup of patients the regulation of neuronal vesicle trafficking may be involved in the pathogenesis of autism.
[The study on the effects of the oil from Hippophae rhamnoides in hematopoiesis]. (2003)

OHR can improve the hematopoiesis of erythroid linage. Like G-CSF, OHR can stimulate the recovery of hematopoiesis after chemotherapy.
Linear vs. function-based dose algorithm designs (2011)

The performance requirements prescribed in IEC 62387-1, 2007 recommend linear, additive algorithms for external dosimetry [IEC. Radiation protection instrumentation--passive integrating dosimetry systems for environmental and personal monitoring--Part 1: General characteristics and performance requirements. IEC 62387-1 (2007)]. Neither of the two current standards for performance of external dosimetry in the USA address the additivity of dose results [American National Standards Institute, Inc. American National Standard for dosimetry personnel dosimetry performance criteria for testing. ANSI/HPS N13.11 (2009); Department of Energy. Department of Energy Standard for the performance testing of personnel dosimetry systems. DOE/EH-0027 (1986)]. While there are significant merits to adopting a purely linear solution to estimating doses from multi-element external dosemeters, differences in the standards result in technical as well as perception challenges in designing a single algorithm approach that will satisfy both IEC and USA external dosimetry performance requirements. The dosimetry performance testing standards in the USA do not incorporate type testing, but rely on biennial performance tests to demonstrate proficiency in a wide range of pure and mixed fields. The test results are used exclusively to judge the system proficiency, with no specific requirements on the algorithm design. Technical challenges include mixed beta/photon fields with a beta dose as low as 0.30 mSv mixed with 0.05 mSv of low-energy photons. Perception-based challenges, resulting from over 20 y of experience with this type of performance testing in the USA, include the common belief that the overall quality of the dosemeter performance can be judged from performance to pure fields. This paper presents synthetic testing results from currently accredited function-based algorithms and new developed purely linear algorithms. A comparison of the performance data highlights the benefits of each approach and demonstrates that, at least for some dosemeter designs, it is possible for a single purely linear algorithm to satisfy both US and IEC performance requirements.
"Wired" Enzyme Electrodes for Amperometric Determination of Glucose or Lactate in the Presence of Interfering Substances (1994)

Glucose oxidase (GOX) or lactate oxidase (LOX) were immobilized in an osmium-based three-dimensional redox hydrogel that electrically connected the enzyme's redox centers to electrodes. The enzyme "wiring" hydrogel was formed by cross-linking poly(1-vinylimidazole) (PVI) complexed with Os-(4,4'-dimethylbpy)2Cl (termed PVI15-dmeOs) with poly(ethylene glycol) diglycidyl ether (peg). Glucose and lactate sensors exhibited typical limiting current densities of 250 and 500 microA/cm2, respectively. When the electrodes were poised at 200 mV (SCE), the currents resulting from electrooxidation of ascorbate, urate, acetaminophen, and L-cysteine were negligible. When a Nafion film was employed, the linear range was extended from 6 to 30 mM glucose and from 4 to 7 mM lactate. The redox potential of the gel-forming polymer was 95 mV (SCE). Glucose and lactate measurements performed in bovine calf serum correlated well with a substrate calibration in phosphate buffer.
Antigen-Specific Regulatory T Cells and Low Dose of IL-2 in Treatment of Type 1 Diabetes (2016)

Regulatory T cells (Tregs) play an important role in preventing effector T-cell (Teff) targeting of self-antigens that can lead to tissue destruction in autoimmune settings, including type 1 diabetes (T1D). Autoimmunity is caused in part by an imbalance between Teff and Tregs. Early attempts to treat with immunosuppressive agents have led to serious side effects, thus requiring a more targeted approach. Low-dose IL-2 (LD IL-2) can provide immunoregulation with few side effects by preferentially acting on Tregs to drive tolerance. The concept of LD IL-2 as a therapeutic approach is supported by data in mouse models where autoimmunity is cured and further strengthened by success in human clinical studies in hepatitis C virus-induced vasculitis, chronic graft-versus-host disease, and Alopecia areata. Treatment will require identification of a safe therapeutic window, which is a difficult task given that patients are reported to have deficient or defective IL-2 production or signaling and have experienced mild activation of NK cells and eosinophils with LD IL-2 therapy. In T1D, an LD IL-2 clinical trial concluded that Tregs can be safely expanded in humans; however, the study was not designed to address efficacy. Antigen-specific therapies have also aimed at regulation of the autoimmune response but have been filled with disappointment despite an extensive list of diverse islet antigens tested in humans. This approach could be enhanced through the addition of LD IL-2 to the antigenic treatment regimen to improve the frequency and function of antigen-specific Tregs, without global immunosuppression. Here, we will discuss the use of LD IL-2 and islet antigen to enhance antigen-specific Tregs in T1D and focus on what is known about their immunological impact, their safety, and potential efficacy, and need for better methods to identify therapeutic effectiveness.