gebhart/patrepeval huggingface dataset:
Selective Peptide Antagonist of the Class E Calcium Channel from the Venom of the TarantulaHysterocrates gigas (1998)

We describe the first potent and selective blocker of the class E Ca2+channel. SNX-482, a novel 41 amino acid peptide present in the venom of the African tarantula, Hysterocrates gigas, was identified through its ability to inhibit human class E Ca2+ channels stably expressed in a mammalian cell line. An IC50 of 15-30 nM was obtained for block of the class E Ca2+ channel, using either patch clamp electrophysiology or K+-evoked Ca2+ flux. At low nanomolar concentrations, SNX-482 also blocked a native resistant or R-type Ca2+ current in rat neurohypophyseal nerve terminals, but concentrations of 200-500 nM had no effect on R-type Ca2+ currents in several types of rat central neurons. The peptide has the sequence GVDKAGCRYMFGGCSVNDDCCPRLGCHSLFSYCAWDLTFSD-OH and is homologous to the spider peptides grammatoxin S1A and hanatoxin, both peptides with very different ion channel blocking selectivities. No effect of SNX-482 was observed on the following ion channel activities: Na+ or K+ currents in several cultured cell types (up to 500 nM); K+ current through cloned potassium channels Kv1.1 and Kv1. 4 expressed in Xenopus oocytes (up to 140 nM); Ca2+ flux through L- and T-type Ca2+ channels in an anterior pituitary cell line (GH3, up to 500 nM); and Ba2+ current through class A Ca2+ channels expressed in Xenopus oocytes (up to 280 nM). A weak effect was noted on Ca2+ current through cloned and stably expressed class B Ca2+ channels (IC50 > 500 nM). The unique selectivity of SNX-482 suggests its usefulness in studying the diversity, function, and pharmacology of class E and/or R-type Ca2+ channels.
Modeling of failure probability and statistical design of SRAM array for yield enhancement in nanoscaled CMOS (2005)

In this paper, we have analyzed and modeled failure probabilities (access-time failure, read/write failure, and hold failure) of synchronous random-access memory (SRAM) cells due to process-parameter variations. A method to predict the yield of a memory chip based on the cell-failure probability is proposed. A methodology to statistically design the SRAM cell and the memory organization is proposed using the failure-probability and the yield-prediction models. The developed design strategy statistically sizes different transistors of the SRAM cell and optimizes the number of redundant columns to be used in the SRAM array, to minimize the failure probability of a memory chip under area and leakage constraints. The developed method can be used in an early stage of a design cycle to enhance memory yield in nanometer regime.
Electrochemical velocimetry on centrifugal microfluidic platforms (2013)

Expanding upon recent applications of interfacing electricity with centrifugal microfluidic platforms, we introduce electrochemical velocimetry to monitor flow in real-time on rotating fluidic devices. Monitoring flow by electrochemical techniques requires a simple, compact setup of miniaturized electrodes that are embedded within a microfluidic channel and are connected to a peripherally-located potentiostat. On-disc flow rates, determined by electrochemical velocimetry, agreed well with theoretically expected values and with optical measurements. As an application of the presented techniques, the dynamic process of droplet formation and release was recorded, yielding critical information about droplet frequency and volume. Overall, the techniques presented in this work advance the field of centrifugal microfluidics by offering a powerful tool, previously unavailable, to monitor flow in real-time on rotating microfluidic systems.
High-Density Lipoprotein Function, Dysfunction, and Reverse Cholesterol Transport (2012)

Although high high-density lipoprotein (HDL)-cholesterol levels are associated with decreased cardiovascular risk in epidemiological studies, recent genetic and pharmacological findings have raised doubts about the beneficial effects of HDL. Raising HDL levels in animal models by infusion or overexpression of apolipoprotein A-I has shown clear vascular improvements, such as delayed atherosclerotic lesion progression and accelerated lesion regression, along with increased reverse cholesterol transport. Inflammation and other factors, such as myeloperoxidase-mediated oxidation, can impair HDL production and HDL function, with regard to its reverse cholesterol transport, antioxidant, and anti-inflammatory activities. Thus, tests of HDL function, which have not yet been developed as routine diagnostic assays, may prove useful and be a better predictor of cardiovascular risk than HDL-cholesterol levels.
Optoelectronic Control of the Phase and Frequency of Semiconductor Lasers (2011)

This thesis explores the precise control of the phase and frequency of the output of semiconductor lasers (SCLs), which are the basic building blocks of most modern optical communication networks. Phase and frequency control is achieved by purely electronic means, using SCLs in optoelectronic feedback systems, such as optical phase-locked loops (OPLLs) and optoelectronic swept-frequency laser (SFL) sources. Architectures and applications of these systems are studied. OPLLs with single-section SCLs have limited bandwidths due to the nonuniform SCL frequency modulation (FM) response. To overcome this limitation, two novel OPLL architectures are designed and demonstrated, viz. (i) the sideband-locked OPLL, where the feedback into the SCL is shifted to a frequency range where the FM response is uniform, and (ii) composite OPLL systems, where an external optical phase modulator corrects excess phase noise. It is shown, theoretically and experimentally, and in the time and frequency domains, that the coherence of the master laser is “cloned” onto the slave SCL in an OPLL. An array of SCLs, phase-locked to a common master, therefore forms a coherent aperture, where the phase of each emitter is electronically controlled by the OPLL. Applications of phase-controlled apertures in coherent power-combining and all-electronic beam-steering are demonstrated. An optoelectronic SFL source that generates precisely linear, broadband, and rapid frequency chirps (several 100 GHz in 0.1 ms) is developed and demonstrated using a novel OPLL-like feedback system, where the frequency chirp characteristics are determined solely by a reference electronic oscillator. Results from high-sensitivity biomolecular sensing experiments utilizing the precise frequency control are reported. Techniques are developed to increase the tuning range of SFLs, which is the primary requirement in high-resolution three-dimensional imaging applications. These include (i) the synthesis of a larger effective bandwidth for imaging by stitching measurements taken using SFLs chirping over different regions of the optical spectrum; and (ii) the generation of a chirped wave with twice the chirp bandwidth and the same chirp characteristics by nonlinear four-wave mixing of the SFL output and a reference monochromatic wave. A quasi-phase-matching scheme to overcome dispersion in the nonlinear medium is described and implemented.
Crystal Structure of the Potassium Channel KirBac1.1 in the Closed State (2003)

The KirBac1.1 channel belongs to the inward-rectifier family of potassium channels. Here we report the structure of the entire prokaryotic Kir channel assembly, in the closed state, refined to a resolution of 3.65 angstroms. We identify the main activation gate and structural elements involved in gating. On the basis of structural evidence presented here, we suggest that gating involves coupling between the intracellular and membrane domains. This further suggests that initiation of gating by membrane or intracellular signals represents different entry points to a common mechanistic pathway.
Logical Forms in the core language engine (1989)

This paper describes a 'Logical Form' target language for representing the literal meaning of English sentences, and an intermediate level of representation ('Quasi Logical Form') which engenders a natural separation between the compositional semantics and the processes of scoping and reference resolution. The approach has been implemented in the SRI Core Language Engine which handles the English constructions discussed in the paper.
Structural and Functional Study of the Apelin-13 Peptide, an Endogenous Ligand of the HIV-1 Coreceptor, APJ (2003)

The APJ receptor is widely expressed in the human central nervous system (CNS). Apelin was recently identified as the endogenous peptidic ligand for human APJ. Studies with animal models suggested that APJ and apelin play an important role in the hypothalamic regulation of water intake and the endocrine axis, in the regulation of blood pressure, and in cardiac contractility. Apelin has been found to block the activity of APJ as a human immunodeficiency virus type I (HIV-1) coreceptor. In this study, we combined chemical synthetic approaches with alanine substitution to evaluate the structural requirements for interactions with the APJ receptor. We demonstrated that apelin peptides in aqueous solution adopt a random conformation, and the positive charge and hydrophobic residues of apelin-13 play important roles in interactions with the APJ receptor. We have observed an important correlation between receptor binding affinity and cell-cell fusion inhibitory activity. The elucidation of structural requirements of apelin-13 in its interaction with the APJ receptor is critical for further investigation of apelin-APJ functions in vivo and in the design of small molecular inhibitors for potential treatment of HIV-1 infection in the CNS.
Denervation supersensitivity in skeletal muscle: analysis with a cloned cDNA probe. (1984)

Motor neurons regulate the acetylcholine sensitivity of the muscles they innervate: denervated muscle fiber become "supersensitive" to acetylcholine, due to insertion of newly synthesized acetylcholine receptors (AChRs) in the plasma membrane. We used hybridization analysis with a cloned cDNA specific for AChR alpha-subunit to compare the abundance of AChR mRNA in innervated and denervated adult mouse muscles. Within 3 d of denervation, levels of AChR mRNA increased 100-fold; levels of actin mRNA changed little. The increase in AChR mRNA level was sufficiently large and rapid to account for denervation supersensitivity.
Identification and mapping of an immunogenic region of Mycoplasma hyopneumoniae p65 surface lipoprotein expressed in Escherichia coli from a cloned genomic fragment (1990)

A previously characterized lipid-modified amphiphilic surface protein of Mycoplasma hyopneumoniae, p65, has been defined by its reaction with a surface-binding monoclonal antibody (MAb) and by its exclusive partitioning into the detergent phase during Triton X-114 phase fractionation (K. S. Wise and M. F. Kim, J. Bacteriol. 169:5546-5555, 1987). In the current study, polyclonal mouse antibody (PAb) to gel-purified p65 was used to identify recombinant phage plaques expressing p65-related epitopes. Several characteristic partial tryptic fragments of p65 were recognized by both PAb and p65 and MAb to p65, but the PAb population specifically eluted from recombinant phage plaques bound only epitopes restricted to the largest of these fragments. Graded carboxypeptidase-Y digestion of intact M. hyopneumoniae generated C terminally truncated peptides that were recognized by PAb to p65 and MAb to p65, indicating that the C terminus and much of the adjoining region of p65 were present and accessible on the external face of the membrane. However, antibody eluted from recombinant phage plaques bound only to the largest truncated polypeptide, suggesting that a recombinant product corresponding to the C-terminal region of p65 was expressed in Escherichia coli. A 19-kilodalton recombinant protein (p19), which was recognized by PAb to p65 but not by MAb to p65, was detected in recombinant phage lysates. Serum antibodies from swine taken after, but not before, experimentally induced M. hyopneumoniae pneumonia preferentially recognized the native, amphiphilic p65 lipoprotein and also bound specifically to the p19 recombinant product. This confirmed that the p65 lipoprotein is a major immunogen of M. hyopneumoniae recognized during disease and identified its C-terminal region as an immunogenic domain.
[Research progress of bonding strength between porcelain veneer and enamel]. (2014)

Porcelain veneer had gained more and more attention in dental clinical applications due to its advantages such as good esthetic effects and minor invasiveness. The reliable and consistent adhesive bonding were the key to success. The enamel which featured high mineralization and low moisture would be the ideal bonding part for porcelain veneer. This article was aimed to summarize the research progress regarding to those factors that might had effect on the bonding strength between the porcelain veneer and the enamel including the restoration types of resin adhesives and bonding surface preparations.
Binding of colchicine to purified microtubule protein. (1975)

The binding of colchicine to tubulin, purified by two cycles of assembly-disassembly, has been studied. Equilibrium studies indicated a dissociation constant which declined during incubation approaching a minimum value of approximately 0.30 times 10- minus 6 M after 13 hours of incubation. Because tubulin is unstable during prolonged incubation (t1/2 of 5.2 hours for free tubulin, t1/2 of 12.5 hours for tubulin bound to colchicine), the equilibrium Kd was felt to be an overestimation of the true Kd. The rate constant of dissociation (k-1 equal to 0.009 hour- minus 1 hour- minus 1) and the rate constant of association (k1 equal to 0.37 times 10-6 M-minus 1) were measured under conditions designed to circumvent or correct for tubulin instability. The dissociation constant determined by the ratio k-1/k1 was 0.024 times -minus 6 M. To determine whether the discrepancy between the "equilibrium" and "kinetic" determined dissociation constants could be accounted for on the basis of tubulin instability, the binding reaction was computer-simulated using the measured association and dissociation rate constants and the rate constants for decay of bound and free tubulin. Computer simulation was in close agreement with the experimentally determined behavior of the reaction during a 13-hour incubation. It is concluded that the Kd determined by equilibrium methodology results in a considerable overestimation due to the instability of tubulin, and that the best estimate for the Kd of the colchicine-tubulin equilibrium is the value determined by the ratio of the rate constants.
Cellulase-free xylanases fromBacillusand other microorganisms (2000)

Xylanases are used mainly in the pulp and paper industries for the pretreatment of Kraft pulp prior to bleaching to minimize use of chlorine, the conventional bleaching agent. This application has great potential as an environmentally safe method. Hydrolysis by xylanases of relocated and reprecipitated xylan on the surface of cellulose fibres formed during Kraft cooking facilitates the removal of lignin by increasing permeability to oxidising agents. Most of the xylanases reported in the literature contained significant cellulolytic activity, which make them less suitable for pulp and paper industries. The need for large quantities of xylanases which would be stable at higher temperatures and pH values and free of cellulase activity has necessitated a search for novel enzymes. We have isolated and characterised several xylanase-producing cultures, one of which (an alkalophilic Bacillus SSP-34) produced more than 100 IU ml(-1) of xylanase activity. The SSP-34 xylanases have optimum activity at 50 degrees C in a pH range 6-8, with only small amounts of cellulolytic activity (CMCase (0.4 IU ml(-1), pH 7), FPase (0.2 IU ml(-1), pH 7) and no activity at pH 9).
Major Radiation Exposure — What to Expect and How to Respond (2002)

This article reviews possible sources of major exposure to radiation, summarizes the physical and biologic principles of radiation exposure, and describes the main syndromes. The authors explain the medical management of radiation exposure, as well as the components of preparation for crisis management.
Genetic Diversity in Yeast Assessed With Whole-Genome Oligonucleotide Arrays (2003)

The availability of a complete genome sequence allows the detailed study of intraspecies variability. Here we use high-density oligonucleotide arrays to discover 11,115 single-feature polymorphisms (SFPs) existing in one or more of 14 different yeast strains. We use these SFPs to define regions of genetic identity between common laboratory strains of yeast. We assess the genome-wide distribution of genetic variation on the basis of this yeast population. We find that genome variability is biased toward the ends of chromosomes and is more likely to be found in genes with roles in fermentation or in transport. This subtelomeric bias may arise through recombination between nonhomologous sequences because full-gene deletions are more common in these regions than in more central regions of the chromosome.
Clonal populations of CD4+ and CD8+ T cells in patients with multiple myeloma and paraproteinemia (1996)

Patients with paraproteinemia have abnormalities in their T-cell subsets including inversion of the CD4:CD8 ratio and increased expression of activation markers. Recently, distortions in T-cell receptor (TCR) TCRAV and TCRBV gene segment expression have been reported, although the significance of these observations is unclear given the finding of clonal populations of CD8+ T cells in healthy elderly individuals. We have used an extensive range of TCR V-region-specific monoclonal antibodies to assess TCRAV and TCRBV expression in patients with myeloma and paraproteinemia. TCR sequence analysis was used to assess the clonality of expansions and 3-color fluorescence-activated cell sorting analysis determined the phenotype of the expanded populations. The patients show novel oligoclonal expansions within the CD4+ subset and show an increased frequency of CD8+ expansions. Oligoclonal CD4+ T cells belong to the rare CD4+CD28- T-cell subset, a phenotype associated with granular morphology. CD45RA and CD11b are expressed on many of the CD8 T-cell expansions. Comparison of T-cell receptor sequences from two T-cell clones in one patient suggests a possible role for a common peptide antigen in the generation of the expansions. Further work is needed to identify the relevance of such T cells to the B-cell proliferation.
Abstract 4131: Overcoming aryl hydrocarbon receptor mediated tumor immunosuppression (2019)

Abstract Checkpoint inhibitors (CPIs) have become the cornerstone of immune-based oncology therapy; still many cancer patients do not benefit from these agents. Resistance to checkpoint inhibitors is due in part to the presence of immunosuppressive molecules which prevent immune activation despite T cell checkpoint inhibition. Aryl Hydrocarbon Receptor (AHR) is a transcription factor that mediates the immune response in multiple innate and adaptive immune cells subsequent to binding of a diverse set of endogenous and exogenous ligands. One such AHR agonist is kynurenine. Kynurenine, metabolized from tryptophan by indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2), binds to AHR and leads to a net immunosuppressive tumor microenvironment. Given that kynurenine can be synthesized by both IDO1 and TDO2 and that AHR is activated by endogenous ligands other than kynurenine, AHR inhibition provides a novel approach to reverse immunosuppression in a broad range of tumor types. We demonstrated that AHR antagonism affects multiple immune cell types and can lead to pro-inflammatory phenotypes in human T cells and myeloid cells in vitro and in murine tumor models. AHR antagonism inhibits growth in the B16-IDO, CT26 and MC38 models and reverses the immunosuppressive microenvironment as indicated by changes in T cell and myeloid cell populations. Immune signature changes characterized via Nanostring in multiple tumor models treated with AHR antagonists were also assessed. Oral dosing of AHR antagonists led to tumor growth inhibition as a single agent and increased anti-tumor activity when combined with checkpoint inhibitors. In addition, beneficial anti-tumor activity occurred with AHR antagonists combined with chemotherapy or with radiation therapy in syngeneic mouse tumor models. Our data indicate that reversing AHR-mediated immune suppression in the tumor microenvironment drives anti-tumor activity alone and in combination with other therapeutic modalities. Overall, our data demonstrates that AHR is an attractive target for reversing immune suppression in tumors. Therefore, we are developing AHR antagonists and translational insights to treat patients most likely to benefit from this approach. Citation Format: Jeremy Tchaicha, Silvia Coma, Meghan Walsh, Jill Cavanaugh, Marta Sanchez-Martin, X. Michelle Zhang, Alfredo Castro, Jeff Ecsedy, Mark Manfredi, Karen McGovern. Overcoming aryl hydrocarbon receptor mediated tumor immunosuppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4131.
Design and implementation of virtual environments training of the visually impaire (2002)

This paper presents the virtual reality applications developed for the feasibility study tests of the EU funded IST project ENORASI. ENORASI aims at developing a highly interactive and extensible haptic VR training system that allows visually impaired people, especially those blind from birth, to study and interact with various virtual objects. A number of custom applications have been developed based on the interface provided by the CyberGrasp haptic device. Eight test categories were identified and corresponding tests were developed for each category. Twenty-six blind persons conducted the tests and the evaluation results have shown the degree of acceptance of the technology and the feasibility of the proposed approach.
TRAF3 regulates the effector function of regulatory T cells and humoral immune responses (2013)

Regulatory T cells (Treg cells) control different aspects of immune responses, but how the effector functions of Treg cells are regulated is incompletely understood. Here we identified TNF receptor-associated factor 3 (TRAF3) as a regulator of Treg cell function. Treg cell-specific ablation of TRAF3 impaired CD4 T cell homeostasis, characterized by an increase in the Th1 type of effector/memory T cells. Moreover, the ablation of TRAF3 in Treg cells resulted in increased antigen-stimulated activation of follicular T helper cells (TFH cells), coupled with heightened formation of germinal centers and production of high-affinity IgG antibodies. Although the loss of TRAF3 did not reduce the overall frequency of Treg cells, it attenuated the antigen-stimulated production of follicular Treg cells (TFR cells). TRAF3 signaling in Treg cells was required to maintain high level expression of inducible co-stimulator (ICOS), which in turn was required for TFR cell generation and inhibition of antibody responses. These findings establish TRAF3 as a mediator of Treg cell function in the regulation of antibody responses and suggest a role for TRAF3 in mediating ICOS expression in Treg cells.