gebhart/patrepeval huggingface dataset:
Helicobacter pylori Vacuolating Cytotoxin Inhibits T Lymphocyte Activation (2003)

Helicobacter pylori (Hp) vacuolating cytotoxin VacA induces cellular vacuolation in epithelial cells. We found that VacA could efficiently block proliferation of T cells by inducing a G1/S cell cycle arrest. It interfered with the T cell receptor/interleukin-2 (IL-2) signaling pathway at the level of the Ca2+-calmodulin-dependent phosphatase calcineurin. Nuclear translocation of nuclear factor of activated T cells (NFAT), a transcription factor acting as a global regulator of immune response genes, was abrogated, resulting in down-regulation of IL-2 transcription. VacA partially mimicked the activity of the immunosuppressive drug FK506 by possibly inducing a local immune suppression, explaining the extraordinary chronicity of Hp infections.
Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction (1996)

Thrombopoietin (TPO), the ligand for c-mpl, stimulates proliferation of committed megakaryocytic progenitors and induces maturation of megakaryocytes. To better understand factors regulating TPO levels, we measured blood levels of TPO in patients with impaired platelet production due to aplastic anemia (AA) and with platelet destructive disorders, including idiopathic thrombocytopenic purpura (ITP), posttransfusion purpura (PTP), drug purpura (DP), and X-linked thrombocytopenia (XLTP). The TPO receptor capture enzyme immunoassay (EIA) used had a detection limit of integral of approximately-150 to 200 pg/mL. TPO was undetectable in 88 of 89 normal individuals. Eighteen of 19 patients with AA and a mean platelet count (MPC) of 18,000/microliters (2,000 to 61,000/microliters) had markedly elevated TPO levels (mean, 1,467 pg/mL; range, 597 to 3,834 pg/mL). Eight AA patients who responded to immunosuppressive therapy with their MPC increasing to 140,000/microliters (92,000 to 175,000/microliters) had substantial decreases in TPO (mean, 440 pg/mL; range, 193 to 771 pg/mL). Initial TPO levels did not differ significantly between responders and nonresponders. In contrast, all 21 patients with ITP and an MPC of 16,000/microliters (1,000 to 51,000 /microliters) had undetectable TPO levels, as did 6 patients with acute PTP or DP and 2 patients with XLTP. Megakaryocyte mass, reflected in the rate of platelet production, appears to be the major determinant of TPO levels in thrombocytopenic patients rather than circulating platelet levels per se. Measurement of serum TPO may be useful in differentiating thrombocytopenias due to peripheral destruction from those due to thrombopoietic failure.
Glutamic acid decarboxylase 67-reactive T cells: a marker of insulin-dependent diabetes. (1993)

Glutamic acid decarboxylase (GAD) has been shown to be a target of autoantibodies in insulin-dependent diabetes (IDD). Two forms of GAD, with molecular weights of 67,000 and 65,000, have been cloned from separate genes. As pancreatic islet beta cell destruction DD is an autoimmune process mediated by T cells, we sought to determine if recombinant GAD67 was recognized by T cells in IDD subjects and particularly their first-degree relatives with islet cell antibodies known to be at risk for IDD. The central regions of human islet and brain GAD67 (amino acids 208-404) were cloned as fusion proteins with glutathione-S-transferase (GST). Proliferation of peripheral blood T cells in the presence of recombinant GAD67 was significantly higher in both at-risk relatives and recent-onset IDD subjects than in other autoimmune disease subjects and human histocompatibility leukocyte antigen (HLA)-matched healthy controls. Thus, 12 of 29 (41%) at-risk relatives and 11 of 29 (38%) recent-onset IDD subjects responded to GAD67, compared with 1 of 7 (14%) other autoimmune disease subjects and 1 of 23 (4%) HLA-matched controls. T cell responses to GST alone or to tetanus toxoid were not different between the groups. These findings demonstrate that GAD67 is a target autoantigen of T cells in IDD and suggest the possibility that GAD-reactive T cells may delineate asymptomatic subjects at increased risk for IDD.
Fully isolated lateral bipolar—MOS transistors fabricated in zone-melting-recrystallized Si films on SiO2 (1983)

A four-terminal device that can be operated either as a lateral n-p-n bipolar transistor or as a conventional n-channel MOSFET has been fabricated in silicon-on-insulator films prepared by graphite-strip-heater zone-melting recrystallization. Common-emitter current gain close to 20 and emitter-base breakdown voltage in excess of 10 V have been obtained for bipolar operation. As a MOSFET, the device exhibits well-behaved enhancement-mode characteristics with a field-effect mobility of ∼ 600 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> /V.s and drain breakdown voltage exceeding 15 V.
A bacterial‐biofilm‐induced oral osteolytic infection can be successfully treated by immuno‐targeting an extracellular nucleoid‐associated protein (2016)

Periodontal disease exemplifies a chronic and recurrent infection with a necessary biofilm component. Mucosal inflammation is a hallmark response of the host seen in chronic diseases, such as colitis, gingivitis, and periodontitis (and the related disorder peri-implantitis). We have taken advantage of our recently developed rat model of human peri-implantitis that recapitulates osteolysis, the requirement of biofilm formation, and the perpetuation of the bona fide disease state, to test a new therapeutic modality with two novel components. First we used hyperimmune antiserum directed against the DNABII family of proteins, now known to be a critical component of the extracellular matrix of bacterial biofilms. Second we delivered the antiserum as cargo in biodegradable microspheres to the site of the biofilm infection. We demonstrated that delivery of a single dose of anti-DNABII in poly(lactic-co-glycolic acid) (PLGA) microspheres induced significant resolution of experimental peri-implantitis, including marked reduction of inflammation. These data support the continued development of a DNABII protein-targeted therapeutic for peri-implantitis and other chronic inflammatory pathologies of the oral cavity in animals and humans.
The zinc finger protein GLI transforms primary cells in cooperation with adenovirus E1A. (1991)

The GLI gene was previously isolated by virtue of its amplification in human glioblastomas. We have now found that GLI expression can result in the in vitro transformation of both primary and secondary rodent cells. When coexpressed with adenovirus E1A, the GLI protein functions analogously to RAS, resulting in the formation of dense foci of cells which are tumorigenic in nude mice.
Laser Beam Shaping (2000)

Preface Editor Contributors Introduction Todd E. Lizotte and Fred M. Dickey Hitachi Via Mechanics (USA), Inc., Londonderry, New Hampshire and FMD Consulting, LLC, Springfield, Missouri, USA The Mathematical and Physical Theory of Lossless Beam Shaping Louis A. Romero and Fred M. Dickey Department of Computational and Applied Mathematics, Sandia National Laboratories, Albuquerque, New Mexico, USA and FMD Consulting, LLC, Springfield, Missouri, USA Laser-Beam-Splitting Gratings Louis A. Romero and Fred M. Dickey Department of Computational and Applied Mathematics, Sandia National Laboratories, Albuquerque, New Mexico, USA and FMD Consulting, LLC, Springfield, Missouri, USA Vortex Beam Shaping Carlos Lopez-Mariscal and Julio C. Gutierrez-Vega US Naval Research Laboratory, Washington, District of Columbia, USA and Photonics and Mathematical Optics Group, Tecnologico de Monterrey, Mexico Gaussian Beam Shaping: Diffraction Theory and Design Fred M. Dickey and Scott C. Holswade FMD Consulting, LLC, Springfield, Missouri, USA and Sandia National Laboratories, Albuquerque, New Mexico, USA Geometrical Methods David L. Shealy and John A. Hoffnagle Department of Physics, University of Alabama at Birmingham, USA and Picarro, Inc., Santa Clara, California, USA Optimization-Based Designs Alexander Laskin, David L. Shealy, and Neal C. Evans AdlOptica GmbH, Berlin, Germany, Department of Physics, University of Alabama at Birmingham, USA, and PointClear Solutions, Inc., Innovation Depot, Birmingham, Alabama, USA Beam Shaping with Diffractive Diffusers Jeremiah D. Brown and David R. Brown JENOPTIK Optical Systems, Inc., Huntsville, Alabama, USA and MEMS Optical, LLC, Huntsville, Alabama, USA Engineered Microlens Diffusers Tasso R. M. Sales RPC Photonics Inc., Rochester, New York, USA Multi-Aperture Beam Integration Systems Daniel M. Brown, Fred M. Dickey, and Louis S. Weichman Optosensors Technology, Inc., Gurley, Alabama, USA, FMD Consulting, LLC, Springfield, Missouri, USA, and Sandia National Laboratories, Albuquerque, New Mexico, USA Axicon Ring Generation Systems Fred M. Dickey, Carlos Lopez-Mariscal, and Daniel M. Brown FMD Consulting, LLC, Springfield, Missouri, USA, US Naval Research Laboratory, Washington, District of Columbia, USA, and Optosensors Technology, Inc., Gurley, Alabama, USA Current Technology of Beam Profile Measurement Kevin D. Kirkham and Carlos B. Roundy Ophir-Spiricon, LLC, North Logan, Utah, USA Classical (Nonlaser) Methods David L. Shealy Department of Physics, University of Alabama at Birmingham, USA Index
Optimizing resource allocation for approximate real-time query processing (2013)

Query optimization techniques are proved to be essential for high performance of database management systems. In the context of new querying paradigms, such as similarity based search, exact query evaluation is neither computationally feasible nor meaningful, and approximate query evaluation is the only reasonable option. In this paper a problem of resource allocation for approximate evaluation of complex queries is considered. An approximate algorithm for a near-optimal resource allocation is presented, providing the best feasible quality of the output subject to a limited total cost of a query. The results of experiments have shown that the approximate resource allocation algorithm is accurate and efficient.
Musculosketal Symptoms and Non-REM Sleep Disturbance in Patients with “Fibrositis Syndrome” and Healthy Subjects (1975)

In sleep studies of (a) patients with the "fibrositis syndrome" and (b) healthy subjects undergoing stage 4 sleep deprivation, we observed in both groups the anomalous presence of alpha-rhythms in the non-rapid-eye-movement (NREM) sleep EEG. This phenomenon has been termed alpha-delta sleep. In the healthy subjects stage 4 deprivation was accompanied by the temporary appearance of muscoloskeletal and mood symptoms comparable to the symptoms seen chronically in the patients. It is suggested that the external arousing stimulus, which induced alpha-delta sleep in the subjects, is paralleled in the patients by an internal arousing mechanism. Such a mechanism, acting in competition with the NREM sleep system, would impair the presumed restorative function of NREM sleep and lead to the development of symptoms. It is proposed that the "fibrositis" symptom complex be considered a "non-restorative sleep syndrome". Evidence froms presented in support of the hypothesis that a disorder of serotonin metabolism serves as a basis for both the EEG sleep disturbance and the symptoms.
Visibility-driven Mesh Analysis and Visualization through Graph Cuts (2008)

In this paper we present an algorithm that operates on a triangular mesh and classifies each face of a triangle as either inside or outside. We present three example applications of this core algorithm: normal orientation, inside removal, and layer-based visualization. The distinguishing feature of our algorithm is its robustness even if a difficult input model that includes holes, coplanar triangles, intersecting triangles, and lost connectivity is given. Our algorithm works with the original triangles of the input model and uses sampling to construct a visibility graph that is then segmented using graph cut.
A comparison between the TORUS and AFIR axial-flux permanent-magnet machine using finite element analysis (2011)

This paper presents a comparison between TORUS and AFIR, the two topologies for double-sided axial-flux permanent-magnet machines. Their slotted and non-slotted topologies were investigated and compared in terms of power density and torque quality. The critical field analysis of the topologies was by finite element method. Results show TORUS topology's high power-density in high current-density and low electrical-loading. AFIR topology has high power in low current-density and high electrical-loading. Non-slotted TORUS and AFIR AFPM machines have negligible cogging torque and lower ripple torque than their slotted counterparts.
Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret (2010)

Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge.
HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma (2015)

HOXD10, a key regulator of cell-differentiated phenotype maintainence, has been demonstrated to be involved in the tumorigenesis of many human malignacies. However, the status of HOXD10 expression and its biological function in cholangiocellular carcinoma (CCC) remain to be clarified. In the present study, we investigated the clinical significance and biological functions of HOXD10 in CCC and found that the expression of HOXD10 and its downstream effector RHOC was significantly different in well-differentiated CCC tissues compared with poorly-differentiated lesions. We also observed a significant correlation between low HOXD10 and high RHOC expression levels and worse prognosis. The stable overexpression of HOXD10 by lentivirus vector significantly inhibited cell invasion partly by downregulating the expression of MMP2 and MMP9, and significantly increased early apoptosis in CCC cell lines and induced G1 phase cell cycle arrest, contributing to the inhibition of cell proliferation in vitro. Additionally, we demonstrated that the inactivation of the RHOC/AKT/MAPK pathway was involved in the tumor‑suppressive functions of HOXD10 in CCC. These results suggested that HOXD10 may be a putative suppressor gene and can act as a prognostic marker and potentially a novel therapeutic target for CCC.
Sequence specificity in recognition of the epidermal growth factor receptor by protein tyrosine phosphatase 1B. (1993)

Protein tyrosine phosphatases all contain a conserved cysteine that forms an intermediate thiophosphate ester bond during tyrosine phosphate hydrolysis. A bacterial glutathione S-transferase fusion protein containing rat brain phosphatase PTP1b was constructed in which this conserved cysteine was mutated to serine. The resulting catalytically inactive enzyme was labeled in vivo to high specific activity with 35S, and the binding of this labeled fusion protein to the immunoprecipitated epidermal growth factor (EGF) receptor was evaluated. The binding was ligand-dependent, and saturation analysis revealed a nonlinear Scatchard plot, with a Kd for high affinity binding of approximately 100 nM. A number of glutathione S-transferase fusion proteins containing src homology 2 (SH2) domains attenuated phosphatase binding in a concentration-dependent manner. Phospholipase C (PLC) gamma and the GTPase-activating protein of ras were the most potent inhibitors. Tyrosine-phosphorylated EGF receptor peptide fragments were evaluated for specific inhibition of PTP1b and PLC gamma SH2 binding to the activated receptor. One such peptide, modeled on EGF receptor tyrosine 992, blocked the binding of both fusion proteins. Another phosphopeptide, modeled on tyrosine 1148, inhibited the binding of PTP1b but not the PLC gamma fusion protein. This site specificity was confirmed by analysis of equilibrium binding of the fusion proteins to EGF receptors mutated in each of these phosphorylation sites. The results revealed clear sequence specificity in the binding of proteins involved in the regulation of intracellular signaling by receptor tyrosine kinases.
Insulin Glulisine Complementing Basal Insulins: A Review of Structure and Activity (2007)

The advancement in protein engineering offers targeted development of insulin analogs that display either faster absorption kinetics or longer time-action profiles compared with human insulin and, therefore, more closely mimic endogenous insulin secretion. Insulin glulisine (3(B)Lys29(B) Glu-human insulin) is a new fast-acting analog that provides absorption and onset of action more rapidly with a shorter duration of action compared with regular human insulin, and thus better resembles physiologic mealtime insulin requirements. Insulin glulisine has been designed to exhibit intrinsic stability while maintaining rapid deployment of insulin monomers. Pharmacokinetic and pharmacodynamic profiling of insulin glulisine in healthy subjects and patients with type 1 and type 2 diabetes not only confirms the rapid absorption and fast action of insulin glulisine compared with human insulin, but also provides evidence that the unique drug formulation may offer additional benefits. Insulin glulisine complements insulin glargine (21(A)-Gly30(Ba)-L-Arg-30(Bb)-L-Arg-human insulin), the first long-acting basal insulin analog that displays a smoothed time-action profile with a 24-h duration of action. Together these analogs offer patients a more physiologic approach to insulin replacement.
LMSD: LIPID MAPS structure database (2006)

The LIPID MAPS Structure Database (LMSD) is a relational database encompassing structures and annotations of biologically relevant lipids. Structures of lipids in the database come from four sources: (i) LIPID MAPS Consortium's core laboratories and partners; (ii) lipids identified by LIPID MAPS experiments; (iii) computationally generated structures for appropriate lipid classes; (iv) biologically relevant lipids manually curated from LIPID BANK, LIPIDAT and other public sources. All the lipid structures in LMSD are drawn in a consistent fashion. In addition to a classification-based retrieval of lipids, users can search LMSD using either text-based or structure-based search options. The text-based search implementation supports data retrieval by any combination of these data fields: LIPID MAPS ID, systematic or common name, mass, formula, category, main class, and subclass data fields. The structure-based search, in conjunction with optional data fields, provides the capability to perform a substructure search or exact match for the structure drawn by the user. Search results, in addition to structure and annotations, also include relevant links to external databases. The LMSD is publicly available at www.lipidmaps.org/data/structure/.
The STEAP protein family: Versatile oxidoreductases and targets for cancer immunotherapy with overlapping and distinct cellular functions (2012)

The human six-transmembrane epithelial antigen of the prostate (STEAP) protein family contains at least five homologous members. The necessity of multiple homologous STEAP proteins is still unclear, but their peculiar and tissue-specific expression suggests that they are assigned to distinct functional tasks. This concept is supported by the fact that especially STEAP1, and to a lesser extent STEAP2 and -4, are highly over-expressed in many different cancer entities, while being only minimally expressed in a few normal tissues. Despite their very similar domain organisation, STEAP3 seems to act as a potent metalloreductase essential for physiological iron uptake and turnover, while in particular STEAP4 appears to be rather involved in responses to nutrients and inflammatory stress, fatty acid and glucose metabolism. Moreover, individual STEAP proteins possess overlapping functions important for growth and survival of cancer cells. Due to their membrane-bound localisation and their high expression in many different cancers such as prostate, breast and bladder carcinoma as well as Ewing's sarcoma, STEAP proteins have been recognised and utilised as promising targets for cell- and antibody-based immunotherapy. This review summarises our present knowledge of the individual members of the human STEAP family and highlights the functional differences between them.
Creating Animal Models of Genetic Disease (2003)

There are many methods for creating animal models of human genetic disease, and it is not possible for a short chapter to provide complete details of the methods used. There are four general approaches that will be discussed. One involves embryonic stem cells and another transgenic mice, each of which are the subject of major portions of other methods books (1,2). This chapter will provide only an overview of the general approaches and some specific details about several of them. Additionally, it provides references to primary papers or other review sources, in order to enable the investigator to find further details of the methods. Each of the methods has particular strengths and weaknesses, and a goal of this chapter is to help readers choose the approach that might be appropriate to their problem.
Two Distinct Phosphorylation Pathways Have Additive Effects on Abl Family Kinase Activation (2003)

The activities of the related Abl and Arg nonreceptor tyrosine kinases are kept under tight control in cells, but exposure to several different stimuli results in a two- to fivefold stimulation of kinase activity. Following the breakdown of inhibitory intramolecular interactions, Abl activation requires phosphorylation on several tyrosine residues, including a tyrosine in its activation loop. These activating phosphorylations have been proposed to occur either through autophosphorylation by Abl in trans or through phosphorylation of Abl by the Src nonreceptor tyrosine kinase. We show here that these two pathways mediate phosphorylation at distinct sites in Abl and Arg and have additive effects on Abl and Arg kinase activation. Abl and Arg autophosphorylate at several sites outside the activation loop, leading to 5.2- and 6.2-fold increases in kinase activity, respectively. We also find that the Src family kinase Hck phosphorylates the Abl and Arg activation loops, leading to an additional twofold stimulation of kinase activity. The autoactivation pathway may allow Abl family kinases to integrate or amplify cues relayed by Src family kinases from cell surface receptors.