gebhart/patrepeval huggingface dataset:
Regulation of Insulin Gene Transcription by the Immediate-Early Growth Response Gene Egr-1 (2006)

Changes in extracellular glucose levels regulate the expression of the immediate-early response gene and zinc finger transcription factor early growth response-1 (Egr-1) in insulin-producing pancreatic beta-cells, but key target genes of Egr-1 in the endocrine pancreas have not been identified. We found that overexpression of Egr-1 in clonal (INS-1) beta-cells increased transcriptional activation of the rat insulin I promoter. In contrast, reductions in Egr-1 expression levels or function with the introduction of either small interfering RNA targeted to Egr-1 (siEgr-1) or a dominant-negative form of Egr-1 decreased insulin promoter activation, and siEgr-1 suppressed insulin gene expression. Egr-1 did not directly interact with insulin promoter sequences, and mutagenesis of a potential G box recognition sequence for Egr-1 did not impair the Egr-1 responsiveness of the insulin promoter, suggesting that regulation of insulin gene expression by Egr-1 is probably mediated through additional transcription factors. Overexpression of Egr-1 increased, and reduction of Egr-1 expression decreased, transcriptional activation of the glucose-responsive FarFlat minienhancer within the rat insulin I promoter despite the absence of demonstrable Egr-1-binding activity to FarFlat sequences. Notably, augmenting Egr-1 expression levels in insulin-producing cells increased the mRNA and protein expression levels of pancreas duodenum homeobox-1 (PDX-1), a major transcriptional regulator of glucose-responsive activation of the insulin gene. Increasing Egr-1 expression levels enhanced PDX-1 binding to insulin promoter sequences, whereas mutagenesis of PDX-1-binding sites reduced the capacity of Egr-1 to activate the insulin promoter. We propose that changes in Egr-1 expression levels in response to extracellular signals, including glucose, can regulate PDX-1 expression and insulin production in pancreatic beta-cells.
Regulation of murine macrophage IL-12 production. Activation of macrophages in vivo, restimulation in vitro, and modulation by other cytokines (1996)

IL-12 is important in the host response to a variety of pathogens. It plays an adjuvant-like role in an initial immune response as well as a therapeutic role in established infections. Despite its well documented importance, comparatively little is known about the regulation of IL-12 production. In this study, we examined IL-12 production by cultured murine peritoneal macrophages from two perspectives: 1) macrophage activation in vivo, and 2) stimulation of IL-12 secretion in vitro. Macrophages were maximally activated within 48 h in vivo during infection with Listeria. Interestingly, although avirulent or heat-killed Listeria induced only minimal production of IL-12 by macrophages, the immunogenic combination of heat-killed bacteria and rIL-12 was highly stimulatory for IL-12 production. LPS and peritoneal inflammatory agents were also stimulatory, but latex beads were ineffective, indicating that microbial components were essential and phagocytosis alone was insufficient. Restimulation in vitro revealed similar patterns, in that infection and LPS were stimulatory but latex beads were not. A systematic survey of potential stimulatory agents showed that microbial heat shock proteins, crude bacterial extracts, bacterial superantigens, a yeast extract, and dsRNA induced IL-12 in vitro. Other cytokines also influenced IL-12 induction. IFN-gamma, which is up-regulated during infection, acted in synergy with other stimuli, suggesting an amplification loop for IL-12 production, whereas IL-4, IL-10, IL-13, and TGF-beta were inhibitory. The existence of a broad range of stimuli from a wide variety of pathogenic organisms underscores the fundamental importance of IL-12 in host defense.
Use of hepadnavirus core proteins as vaccine platforms (2009)

The first virus-like particle to be tested for use as a vaccine carrier was based on the hepatitis B virus nucleocapsid protein. This viral subunit, while not infectious on its own, is a 36-nm particle that is highly immunogenic during a natural infection. The self-assembly and high degree of immunogenicity is maintained when expressed as a recombinant protein and, moreover, can confer a high degree of immunogenicity on foreign antigens linked to the particle, either chemically or genetically. This review describes the current state of the hepadnaviral core protein as a vaccine carrier.
Comparison of Mesomorphic Behaviour and Electro-Optic Properties of Ferroelectric Mesogens With and Without Disiloxane End-Groups (1995)

Abstract Low molar mass liquid crystals with phase properties similar to polymers may be obtained by the addition of a disiloxane tail to an organic mesogen. We present a comparison of the properties of two chiral mesogens (based on the 4-((S)-(+) 2-Methylbutanoyloxy)phenyl 4-(9-decenyloxy)benzoate and 4-((2S)-2-Chloro-3- methylbutanoyl)phenyl 4′-(9-decenyloxy)benzoate moieties) with and without a pentamethyl disiloxane tail and with their vinyl-terminated analogues. We show a general decrease in transition temperatures, and a widening of the mesophase range in the disiloxane-substituted materials due to a suppression of the crystallisation temperature. The phases exhibited are modified, with a tilted smectic-C phase favoured on substitution of the disiloxane tail, eliminating the smectic-A phase found in the unsubstituted mesogen; this gives high tilt angle (28–36°) single mesophase materials. We summarise the electro-optic properties of a series of the disiloxane-substituted materials, which show low viscosity (∼500mPas) and moderate spontaneous polarisation (20–150nCcm−2) across the range of materials, and show their variation with temperature. We demonstrate the variations of these properties with varying alkyl spacer length, alkyl tail length and changing chiral end-group.
Design Considerations for a Transmission and Distribution System for SMPTE Time-Code Signals (1977)

To be able to assign videotape machines to editing systems as they have been to studios and master control areas requires that time-code signals be routed along with the audio and video signals. If the SMPTE time code employs 1200-Hz/2400-Hz frequency-shift keying and search speeds from 1/10 to 100 times normal are needed, the bandwidth required will extend from 120 Hz to 240 kHz or more. In the system described, the transmitted signal comes from an interfacing device in the VTR which provides serial time code as a quasi-balanced complementary signal at transistor-transistor-logic level. Problems of ground-loop hum, crosstalk with adjacent audio circuits, and reduced maximum transmission speed when using a shielded twisted pair were overcome by using a send-processor passive network for the output signal and a time-code reconstitutor for the received signal. Additional possible applications of the system include dubbing the time code along with the audio and video signals when making multiple copies of programs and driving time-code readers that are far from the associated VTR.
Evaluation of purified UspA from Moraxella catarrhalis as a vaccine in a murine model after active immunization (1996)

Moraxella catarrhalis causes otitis media, laryngitis, and respiratory infections in humans. A high-molecular-weight outer membrane protein from this bacterium named ubiquitous surface protein A (UspA) is present on all isolates. A monoclonal antibody (MAb) to UspA that recognizes a conserved epitope of this protein has been shown to promote pulmonary clearance of bacteria in passively immunized mice. In the present study, M. catarrhalis heterologous isolates were screened by dot blot with a panel of four additional MAbs specific for surface-exposed epitopes of UspA from M. catarrhalis isolate 035E. Three of the MAbs were specific for 035E, and the fourth reacted with 17 (74%) of the 23 isolates tested. Thus, UspA contains highly conserved, semiconserved, and variable surface-exposed epitopes. The UspA was purified from the 035E isolate by ion-exchange and size-exclusion chromatography, formulated with the adjuvant QS-21, and used to immunize BALB/c mice. Upon pulmonary challenge with either 035E or the heterologous isolate TTA24, significantly fewer bacteria were recovered from the lungs of immunized mice 6 h postchallenge than from control mice. The immune sera from mice or guinea pigs contained high titers of antibodies to the homologous isolate and heterologous isolates in a whole-bacterial-cell enzyme-linked immunosorbent assay. Sera against UspA, whether prepared in mice or guinea pigs, had complement-dependent bactericidal activity toward homologous and 11 heterologous M. catarrhalis isolates. These results indicate that the conserved epitopes of the UspA are highly immunogenic and elicit broadly reactive and biologically functional antibodies. UspA may offer protection against M. catarrhalis infections and is being further evaluated as a vaccine candidate.
Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model (2008)

Visceral leishmaniasis (VL) is a fatal disease for humans, and no vaccine is currently available. Sand fly salivary proteins have been associated with protection against cutaneous leishmaniasis. To test whether vector salivary proteins can protect against VL, a hamster model was developed involving intradermal inoculation in the ears of 100,000 Leishmania infantum chagasi parasites together with Lutzomyia longipalpis saliva to mimic natural transmission by sand flies. Hamsters developed classical signs of VL rapidly, culminating in a fatal outcome 5-6 months postinfection. Saliva had no effect on the course of infection in this model. Immunization with 16 DNA plasmids coding for salivary proteins of Lu. longipalpis resulted in the identification of LJM19, a novel 11-kDa protein, that protected hamsters against the fatal outcome of VL. LJM19-immunized hamsters maintained a low parasite load that correlated with an overall high IFN-gamma/TGF-beta ratio and inducible NOS expression in the spleen and liver up to 5 months postinfection. Importantly, a delayed-type hypersensitivity response with high expression of IFN-gamma was also noted in the skin of LJM19-immunized hamsters 48 h after exposure to uninfected sand fly bites. Induction of IFN-gamma at the site of bite could partly explain the protection observed in the viscera of LJM19-immunized hamsters through direct parasite killing and/or priming of anti-Leishmania immunity. We have shown that immunity to a defined salivary protein (LJM19) confers powerful protection against the fatal outcome of a parasitic disease, which reinforces the concept of using components of arthropod saliva in vaccine strategies against vector-borne diseases.
Polychromatic (eight‐color) slide‐based cytometry for the phenotyping of leukocyte, NK, and NKT subsets (2005)

With our adaptations it is possible to discriminate tandem conjugates of Cy5, Cy5.5, and Cy7 for eight-color immunophenotyping. Using this method, novel rare subsets of NK and NKT cells that are CD4/CD8 double positive are reported for the first time.
Prediction of the Secondary Structure of Proteins from their Amino Acid Sequence (1979)

This chapter contains sections titled: Historical Introduction The Chou and Fasman Predictive Method Definition of Conformational Regions Refinement of Conformational Parameters Application of Chou-Fasman Method Comparison of Predictive Methods Computerized Chou-Fasman Method Future Directions
Mn 3 Ga , a compensated ferrimagnet with high Curie temperature and low magnetic moment for spin torque transfer applications (2007)

This work reports about the electronic, magnetic, and structural properties of the binary compound Mn3Ga. The tetragonal DO22 phase of Mn3Ga was successfully synthesized and investigated. It has been found that the material is hard magnetic with an energy product of Hc×Br=52.5kJm−3 and an average saturation magnetization of about 0.25μB∕at. at 5K. The saturation magnetization indicates a ferrimagnetic order with partially compensating moments at the Mn atoms on crystallographically different sites. The Curie temperature is above 730K where the onset of decomposition is observed. The electronic structure calculations indicate a nearly half-metallic ferrimagnetic order with 88% spin polarization at the Fermi energy.
Wild-Type Huntingtin Protects from Apoptosis Upstream of Caspase-3 (2000)

Expansion of a polyglutamine sequence in the N terminus of huntingtin is the gain-of-function event that causes Huntington's disease. This mutation affects primarily the medium-size spiny neurons of the striatum. Huntingtin is expressed in many neuronal and non-neuronal cell types, implying a more general function for the wild-type protein. Here we report that wild-type huntingtin acts by protecting CNS cells from a variety of apoptotic stimuli, including serum withdrawal, death receptors, and pro-apoptotic Bcl-2 homologs. This protection may take place at the level of caspase-9 activation. The full-length protein also modulates the toxicity of the poly-Q expansion. Cells expressing full-length mutant protein are susceptible to fewer death stimuli than cells expressing truncated mutant huntingtin.
Relative Reactivity of C4 Olefins toward the Polyisobutylene Cation (2006)

The capping reaction of living polyisobutylene cation (PIB+) with 1-butene, cis-2-butene, trans-2-butene, or 1,3-butadiene in hexanes (Hex)/methyl chloride (MeCl) 60/40 (v/v) solvent mixtures at −80 °C was studied. The reaction products were characterized by elemental analysis, gel permeation chromatography, and NMR spectroscopy. Monoaddition (capping) was observed with 1-butene and cis-2-butene but not with trans-2-butene, which did not react with PIB+. Monoaddition of 1,3-butadiene followed by instantaneous halide transfer from the counteranion and selective formation of the 1,4-adduct were observed in Hex/MeCl 60/40 (v/v) solvent mixtures at −80 °C at [1,3-butadiene] ≤ 0.05 mol L-1. The polymerization of isobutylene (IB) was studied in the presence of 1-butene, cis-2-butene, trans-2-butene, or 1,3-butadiene as capping agent in Hex/MeCl 80/20 to 40/60 (v/v) in the temperature range of −40 to −80 °C. From the limiting conversion and limiting number-average degrees of polymerization the reactivity ratio, kp±/kc± (where kp± is the absolute rate constant of propagation for IB and kc± is the cross-propagation (capping) rate constant from PIB+ cation to the C4 olefins), was calculated. Since the propagation of IB (addition of IB to PIB+) does not have an enthalpic barrier, the activation energy for cross-propagation was calculated to be 5.1−6.0 kJ mol-1. By extrapolating the plot of kp±/kc± vs hexanes (vol %), the reactivity ratios were calculated for 100% hexanes at −80 °C. From the cross-propagation activation energy and the calculated reactivity ratios at −80 °C in 100% hexanes, the reactivity ratios for 0 °C have also been calculated. According to these values at 0 °C, isobutylene is ∼17 times more reactive than 1,3-butadiene, ∼543 times more reactive than 1-butene, and ∼294 times more reactive than cis-2-butene.
Global Analysis of Protein Damage by the Lipid Electrophile 4-Hydroxy-2-nonenal (2008)

Lipid peroxidation yields a variety of electrophiles, which are thought to contribute to the molecular pathogenesis of diseases involving oxidative stress, yet little is known of the scope of protein damage caused by lipid electrophiles. We identified protein targets of the prototypical lipid electrophile 4-hydroxy-2-nonenal (HNE) in RKO cells treated with 50 or 100 mum HNE. HNE Michael adducts were biotinylated by reaction with biotinamidohexanoic acid hydrazide, captured with streptavidin, and the captured proteins were resolved by one dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, digested with trypsin, and identified by liquid chromatography-tandem mass spectrometry. Of the 1500+ proteins identified, 417 displayed a statistically significant increase in adduction with increasing HNE exposure concentration. We further identified 18 biotin hydrazide-modified, HNE-adducted peptides by specific capture using anti-biotin antibody and analysis by high resolution liquid chromatography-tandem mass spectrometry. A subset of the identified HNE targets were validated with a streptavidin capture and immunoblotting approach, which enabled detection of adducts at HNE exposures as low as 1 mum. Protein interaction network analysis indicated several subsystems impacted by endogenous electrophiles in oxidative stress, including the 26 S proteasomal and chaperonin containing TCP-1 (CCT) systems involved in protein-folding and degradation, as well as the COP9 signalosome, translation initiation complex, and a large network of ribonucleoproteins. Global analyses of protein lipid electrophile adducts provide a systems-level perspective on the mechanisms of diseases involving oxidative stress.
Pharmacokinetic and Pharmacodynamic Analysis of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis From 2 Randomized, Controlled Trials: SUMMACTA and BREVACTA (2016)

Tocilizumab is a humanized anti-interleukin-6 receptor antibody for treating rheumatoid arthritis. Pharmacokinetic/pharmacodynamic analysis was performed on the 24-week double-blind parts of 2 randomized, controlled trials: SUMMACTA and BREVACTA. SUMMACTA compared subcutaneous tocilizumab 162 mg every week to intravenous tocilizumab 8 mg/kg every 4 weeks, whereas BREVACTA evaluated 162 mg subcutaneous tocilizumab every 2 weeks versus placebo. In addition to noncompartmental analysis, a 2-compartment population pharmacokinetic model, with first-order absorption (for subcutaneous) and linear and Michaelis-Menten elimination was used. Mean observed steady-state predose tocilizumab concentrations in week 24 were 40 and 7.4 μg/mL for subcutaneous every-week and every-2-week dosing, respectively, and 18 μg/mL for intravenous dosing. In the population PK model, body weight was an important covariate affecting clearance and volume of distribution. Mean ± SD population-predicted predose concentration for patients ≥100 kg was 23.0 ± 13.5 μg/mL for subcutaneous tocilizumab every week and 1.0 ± 1.6 μg/mL for every 2 weeks. Efficacy was lowest with subcutaneous every-2-week dosing in patients > 100 kg, reflecting lower exposure. The subcutaneous every-2-week regimen is not recommended for these patients. Pharmacodynamic responses were comparable for the every-week subcutaneous and every-4-week intravenous regimens and less pronounced with the every-2-week subcutaneous regimen. No trend was observed for increased adverse events with increasing tocilizumab exposure. The results of this analysis are consistent with the noninferiority of efficacy of the every-week subcutaneous regimen to the every-4-week intravenous regimen and the superiority of the every-2-week subcutaneous regimen to placebo. These results support the label recommendations for subcutaneous dosing of tocilizumab in rheumatoid arthritis patients.
Neutralization of HIV-1 by F105, a human monoclonal antibody to the CD4 binding site of gp120. (1993)

The functional ability of the human monoclonal antibody (HMab) F105 to neutralize commonly available laboratory strains and a selection of primary isolates of human immunodeficiency virus (HIV)-1 was studied. F105 is representative of a class of human antibodies that react with conformational epitopes within the discontinuous CD4 binding site on HIV-1 envelope glycoprotein gp120. F105 binds with relatively similar affinities to native antigen expressed on the surfaces of cells infected with each of five laboratory isolates tested (IIIB, SF2, MN, RF, and CC) and neutralizes SF2, IIIB, and MN with concentrations of antibody ranging from 140 ng to 10 micrograms/ml. Nonetheless, neutralization by F105 alone of RF and CC is poor at modest antibody concentrations despite high affinity binding to surface gp120 on infected cells. Neutralization of HIV-1 strains by F105 is unaffected by normal sera and cooperativity is observed with serum samples from HIV-1 infected patients. Of significance, neutralization of RF and MN by F105 is enhanced by some HIV-seropositive sera at low concentrations. F105 also neutralized 30% of HIV-1 primary isolates in lymphocyte cultures. Although it is unclear how relevant in vitro studies will be to in vivo events, these data allow comparison of F105 with other HMabs to the CD4 binding site and V3 loop and provide an in vitro reference for in vivo activity. These studies demonstrate that antibody interactions among different classes of antibodies may be important in in vivo neutralization of HIV-1.
Induction of protective cytotoxic T cells with viral proteins (1994)

Induction of CD8+, class I-restricted T cells by non-infectious, exogenous antigens has been documented for model protein antigens such as ovalbumin and for major histocompatibility complex restricted short peptides in viral and tumor systems. However, the protective capacity of cytotoxic T cells induced by conventional proteins has not been tested in vivo so far. We, therefore, evaluated the induction of protective cytotoxic T cells against three different full-length recombinant viral proteins derived from a baculovirus expression system, i.e. the glycoprotein and nucleoprotein of lymphocytic choriomeningitis virus (LCMV) and the nucleoprotein of vesicular stomatitis virus (VSV). These viral proteins induced cytotoxic T cells in a T helper cell-independent fashion which lysed infected target cells in vitro and protected mice from viral replication, immunopathological disease and growth of a tumor expressing the same antigen as a tumor antigen. These results are surprising, since it had been shown earlier for completely inactivated nonreplicating viral vaccines and again here for beta-propiolactone-inactivated VSV or UV-light inactivated LCMV that nonreplicating viral vaccines were incapable of inducing protective cytotoxic T cells. Our data show that immunization of mice with as little as 10 micrograms of non-infectious viral proteins triggered long-lasting CD8+ T cell-mediated antiviral immunity. It was found that the protein alone was only weakly able to induce cytotoxic T cells, and that association with cellular debris functioned as an adjuvant. These findings may be relevant for our understanding of the phenomenon of cross-priming and have obvious implications for vaccine strategies.
Read disturb degradation mechanism for source erase flash memories (2002)

The read disturb degradation caused by source erase is studied. The anomalous Vth shift of about 1.0 V due to electron trapping is observed during read disturb. Vth shift due to electron trapping is more serious for high speed erase device. However, this Vth shift can be suppressed by using lower source voltage for erase.