gebhart/patrepeval huggingface dataset:
Heterodimerization-independent Functions of Cell Death Regulatory Proteins Bax and Bcl-2 in Yeast and Mammalian Cells (1997)

The pro-apoptotic protein Bax can homodimerize with itself and heterodimerize with the anti-apoptotic protein Bcl-2, but the significance of these protein-protein interactions remains unclear. Alanine substitution mutations were created in a well conserved IGDE motif found within the BH3 domain of Bax (residues 66-69) and the resulting mutant Bax proteins were tested for ability to homodimerize with themselves and to heterodimerize with Bcl-2. Correlations were made with cell death induction by these mutants of Bax both in mammalian cells where Bax may function through several mechanisms, and in yeast where Bax may exert its lethal actions through a more limited repertoire of mechanisms perhaps related to its ability to form ion channels in intracellular membranes. Two of the mutants, Bax(D68A) and Bax(E69A), retained the ability to homodimerize but failed to interact with Bcl-2 as determined by yeast two-hybrid assays and co-immunoprecipitation analysis using transfected mammalian cells. The Bax(E69A) protein exhibited a lethal phenotype in yeast, which could be specifically suppressed by co-expression of Bcl-2, despite its failure to dimerize with Bcl-2. Both the Bax(D68A) and Bax(E69A) proteins induced apoptosis when overexpressed in human 293 cells, despite an inability to bind to Bcl-2. Moreover, co-expression of Bcl-2 with Bax(D68A) and Bax(E69A) rescued mammalian cells from apoptosis. In contrast, a mutant of Bax lacking the IGDE motif, Bax(DeltaIGDE), was incapable of either homodimerizing with itself or heterodimerizing with Bcl-2 and was inactive at promoting cell death in either yeast or mammalian cells. Although failing to interact with Bcl-2, the Bax(D68A) and Bax(E69A) mutants retained the ability to bind to Bid, a putative Bax-activating member of the Bcl-2 family, and collaborated with Bid in inducing apoptosis. When taken together with previous observations, these findings indicate that (i) Bax can induce apoptosis in mammalian cells irrespective of heterodimerization with Bcl-2 and (ii) Bcl-2 can rescue both mammalian cells and yeast from the lethal effects of Bax without heterodimerizing with it. However, these results do not exclude the possibility that BH3-dependent homodimerization of Bax or interactions with Bax activators such as Bid may either assist or be required for the cell death-inducing mechanism of this protein.
Site-Specific Regulation of P2X7 Receptor Function in Microglia Gates Morphine Analgesic Tolerance (2017)

Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated in opioid tolerance, but the core mechanisms regulating their response to opioids remain obscure. By selectively ablating microglia in the spinal cord using a saporin-conjugated antibody to Mac1, we demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats. Increased P2X7 receptor (P2X7R) activity is a cardinal feature of microglial activation, and in this study we found that morphine potentiates P2X7R-mediated Ca<sup>2+</sup> responses in resident spinal microglia acutely isolated from morphine tolerant rats. The increased P2X7R function was blocked in cultured microglia by PP2, a Src family protein tyrosine kinase inhibitor. We identified Src family kinase activation mediated by μ-receptors as a key mechanistic step required for morphine potentiation of P2X7R function. Furthermore, we show by site-directed mutagenesis that tyrosine (Y<sub>382-384</sub>) within the P2X7R C-terminus is differentially modulated by repeated morphine treatment and has no bearing on normal P2X7R function. Intrathecal administration of a palmitoylated peptide corresponding to the Y<sub>382-384</sub> site suppressed morphine-induced microglial reactivity and preserved the antinociceptive effects of morphine in male rats. Thus, site-specific regulation of P2X7R function mediated by Y<sub>382-384</sub> is a novel cellular determinant of the microglial response to morphine that critically underlies the development of morphine analgesic tolerance.<b>SIGNIFICANCE STATEMENT</b> Controlling pain is one of the most difficult challenges in medicine and its management is a requirement of a large diversity of illnesses. Although morphine and other opioids offer dramatic and impressive relief of pain, their impact is truncated by loss of efficacy (analgesic tolerance). Understanding why this occurs and how to prevent it are of critical importance in improving pain therapies. We uncovered a novel site (Y<sub>382-384</sub>) within the P2X7 receptor that can be targeted to blunt the development of morphine analgesic tolerance, without affecting normal P2X7 receptor function. Our findings provide a critical missing mechanistic piece, site-specific modulation by Y<sub>382-384</sub>, that unifies P2X7R function to the activation of spinal microglia and the development of morphine tolerance.
Enhanced T cell responses against hepatitis C virus by ex vivo targeting of adenoviral particles to dendritic cells (2011)

DCs transduced with AdNS3 and the adapter molecule CFm/h40L exhibit enhanced immunostimulatory functions, induce robust anti-HCV NS3 immunity in animals, and can induce antiviral immune responses in subjects with chronic HCV infection. This strategy may serve as therapeutic vaccination for patients with chronic hepatitis C.
Elaidate, an 18‐Carbon trans‐Monoenoic Fatty Acid, Inhibits β‐Oxidation in Human Peripheral Blood Macrophages (2013)

Consumption of trans-unsaturated fatty acids promotes atherosclerosis, but whether degradation of fats in macrophages is altered by trans-unsaturated fatty acids is unknown. We compared the metabolism of oleate (C18:1Δ9-10 cis; (Z)-octadec-9-enoate), elaidate (C18:Δ9-10 trans; (E)-octadec-9-enoate), and stearate (C18:0, octadecanoate) in adherent peripheral human macrophages. Metabolism was followed by measurement of acylcarnitines in cell supernatants by MS/MS, determination of cellular fatty acid content by GC/MS, and assessment of β-oxidation rates using radiolabeled fatty acids. Cells incubated for 44 h in 100 µM elaidate accumulated more unsaturated fatty acids, including both longer- and shorter-chain, and had reduced C18:0 relative to those incubated with oleate or stearate. Both C12:1 and C18:1 acylcarnitines accumulated in supernatants of macrophages exposed to trans fats. These results suggested β-oxidation inhibition one reaction proximal to the trans bond. Comparison of [1-(14)C]oleate to [1-(14)C]elaidate catabolism showed that elaidate completed the first round of fatty acid β-oxidation at rates comparable to oleate. Yet, in competitive β-oxidation assays with [9,10-(3)H]oleate, tritium release rate decreased when unlabeled oleate was replaced by the same quantity of elaidate. These data show specific inhibition of monoenoic fat catabolism by elaidate that is not shared by other atherogenic fats.
A point process model of respiratory dynamics in early physiological development (2011)

Interbreath interval (IBI), the time interval between breaths, and its variations in time around the mean, the IBI variability, are important measures associated with irregularity of breathing. The IBI histogram generally follows a power law distribution with its characterizing parameters changing with maturation. To assess the dynamics of breathing we propose a point process model of IBI with a lognormal parametric structure to appropriately represent the stochastic nature of the IBI distribution. We estimate the time varying evolution of the characterizing parameters to represent the dynamic nature of breathing, and thereby provide a time-varying measure of irregularity in breathing. The reliability of the model to capture the data is assessed using Kolmogorov-Smirnov (KS) and independence tests. Our results validate the novel approach in the assessment of the irregularity of breathing by analyzing respiratory recordings from newborn rats and preterm infants.
SIMULADOR DE CÓDIGO ABERTO PARA A PLATAFORMA POLOLU 3PI (2019)

Robos seguidores de linha tem a capacidade de detectar e seguir uma linha desenhada em uma superficie. Possuem em seu principio de funcionamento elementos que servem como referencia para o desenvolvimento de varias outras tecnologias autonomas, com aplicacoes em educacao e na industria. O simulador desenvolvido visa facilitar uma das problematicas que envolvem este tipo de ferramenta: a necessidade de realizar diversos testes para validar um projeto. Usando como modelo fisico o Pololu 3pi Robot, o software simula seu funcionamento, age de acordo com a estrutura do robo real e e capaz de realizar leituras da superficie, permitindo observar o desempenho do robo ao seguir a linha operando com determinado codigo. O simulador desenvolvido foi validado a partir de experimentos que envolveram analise de movimentos e medicoes de tempo de execucao de tarefas previamente estabelecidas, para que sua resposta fosse analoga ao que acontece na realidade.
Human thymic epithelial cells produce interleukin 1. (1987)

Although the thymus plays a critical role in generation of immunocompetent T lymphocytes, the precise role of the epithelial component of the thymus in the induction of T cell proliferation and maturation remains unknown. Since interleukin 1 (IL 1) is required for mature T cell activation, we have determined whether human thymic epithelial (TE) cells produce IL 1. By using a system for longterm culture of human TE cells, we found that human TE cells produced an IL 1-like factor (TE-IL 1) that augmented the proliferation of C3H/HeJ mouse thymocytes to phytohemagglutinin. IL 1 activity (20 to 200 U/ml) was detected in supernatants of TE cultures from all individuals (2 to 13 yr old) tested. IL 1 activity was also detected in supernatants of TE cultures from a 17-wk fetus but not from a 10-wk fetus. Production of TE-IL 1 was dependent on TE cell density and time in culture with optimal TE-IL 1 activity observed at 10(6) TE cells/ml after 48 to 72 hr of culture. With the use of high performance liquid chromatography, TE-IL 1 chromatographed as a molecule of 18,000 to 20,000 relative molecular mass, and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, TE-IL 1 migrated at 15,000 to 17,000 Mr. With the use of isoelectrofocusing gels, charge heterogeneity of TE-IL 1 was demonstrated with two major isoelectric points of 5.7 to 5.8 and 6.9 to 7.0. Polyclonal antibody to human monocyte IL 1 markedly inhibited the TE-IL 1 activity. In indirect immunofluorescence assay of frozen human thymic sections, rabbit anti-IL 1 antibody reacted with epithelial cells in human thymic cortex and medulla. Furthermore, high performance liquid chromatography-purified TE-IL 1 augmented human thymocyte proliferation to suboptimal concentrations of phytohemagglutinin. Thus, thymic epithelial cells are capable of providing an intrathymic source of IL 1-like cytokine (TE-IL 1), which affects thymocyte proliferation. We propose that TE-IL 1 may play an important role in intrathymic proliferation and differentiation of human thymocytes.
Design and synthesis of a new ferroelectric liquid crystal family. Liquid crystals containing a nonracemic 2-alkoxy-1-propoxy unit (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign and synthesis of a new ferroelectric liquid crystal family. Liquid crystals containing a nonracemic 2-alkoxy-1-propoxy unitDavid M. Walba, Stacey C. Slater, William N. Thurmes, Noel A. Clark, Mark A. Handschy, and Frank. SuponCite this: J. Am. Chem. Soc. 1986, 108, 17, 5210–5221Publication Date (Print):August 1, 1986Publication History Published online1 May 2002Published inissue 1 August 1986https://pubs.acs.org/doi/10.1021/ja00277a027https://doi.org/10.1021/ja00277a027research-articleACS PublicationsRequest reuse permissionsArticle Views306Altmetric-Citations118LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Cellular and molecular bases of B-cell clonal expansions. (1996)

The concept that lymphomagenesis is a multistep process is now widely accepted. Various factors are involved in the development and malignant progression of B-cell lymphoproliferative disorders. The most frequently recognized alterations in these disorders are chromosomal translocations which lead to the activation of proto-oncogenes (c-myc) or genes encoding for proteins involved in the control of the cell cycle (cyclin D1), differentiation (bcl-6) and apoptosis (bcl-2). In addition, genetic changes that inactivate tumor suppressor genes (p53, Rb, p16) have recently been identified. Infectious agents may also play a role in lymphomagenesis either by directly driving B-cell proliferation (EBV) or by inducing a chronic antigenic stimulation (EBV, HCV, HBV, helicobacter pylori). Finally, several data indicate that local cytokine networks and, in particular, autocrine (IL-6, IL-10) and/or paracrine (IL-2, IL-4, IL-6) loops probably play a contributory role in the development and evolution of B-cell lymphoproliferation. In the last few years, the advent of molecular biology techniques has allowed important advances in the definition of the events involved i the earlier phases of lymphoma development. This has been made possible, in particular, by the study of a series of oligoclonal or monoclonal lymphoproliferative disorders characterized by an indolent or "smoldering" clinical course, such as follicular lymphoma and the lymphoproliferation associated with autoimmune diseases, which are at high risk of evolution to a highly malignant lymphoma. In nearly all of these conditions, the clonal B-cells responsible for the early stages of the disease are probably not fully transformed and retain various degrees of responsiveness to a wide variety of microenvironmental stimuli (antigen or autoantigen stimulation, interactions with "reactive" T lymphocytes, local cytokine networks). These latter in turn may induce the regression of pathological lesions, maintain the disease in an active state or contribute to the evolution towards an overtly malignant lymphoma. These findings open new avenues for the design of unconventional strategies of intervention aimed at preventing the malignant evolution of pre-lymphomatous lesions and controlling the clinical course of certain low-grade B-cell lymphomas.
Development of a Tunable UV Laser System Synchronizing Precisely with Synchrotron Radiation Pulses from UVSOR (1997)

A mode-locked Ti:sapphire laser is made to oscillate at the frequency of the UVSOR storage ring, 90.115 MHz, in a multi-bunch operation mode. The third harmonic of the laser is available in the wavelength range 243-280 nm. Synchrotron radiation from an undulator is monochromated by a grazing-incidence monochromator and introduced coaxially with the laser. The temporal profile of the photon pulses is monitored in situ by a luminescing substance/photomultiplier combination. The delay timing between the laser and synchrotron radiation can be changed from 0 to 11 ns by adjusting an electronic module that provides phase-locked loop stabilization of the laser pulse. The reliability and feasibility of this laser-synchrotron radiation combination technique are demonstrated by applying pump-probe experiments to two physical systems. The first system is photodissociation of iodomethane (CHA) with a laser photon, followed by photoionization of I and CH3 fragments with synchrotron radiation. The second, two-photon ionization of He atoms, is studied as the prototype of a time-resolved experiment. The He+ signal counts as a function of the laser-synchrotron radiation delay are found to be enhanced in a narrow time window, which can be interpreted in terms of a short lifetime of the resonant state, He*(1s2p 1P), produced by primary synchrotron radiation excitation.
The influence of short-term fixture congestion on position specific match running performance and external loading patterns in English professional soccer (2018)

The aim of the current study was to investigate positional specific physical performance and external load responses to short term fixture congestion in English professional soccer. A total of 515 match observations were categorised as G1: the first game in a week with >4 days following a previous game, G2: the second game in a week played <4 days since G1, and G3: the third game in a week played with <4 days between each of the previous games. Global positioning system and accelerometer-based metrics were partitioned into fifteen-minute epochs. These data were then analysed using a linear mixed model to assess both the within and between game positional differences. Total, low-intensity (<4.0 m·s<sup>-1</sup>), medium-intensity (MID; 4.0-5.5 m·s<sup>-1</sup>), and sprint distance (>7.0 m·s<sup>-1</sup>) were significantly different across games. No between game positional differences were identified; however, within match position specific differences were observed for measures of MID and HID. No significant differences were evident for accelerometer derived metrics between games or across positions. The current data suggests that the use of fifteen minute within game epochs enables the detection of alterations in physical output during congested schedules. The observed within game positional differences has implications for player specific conditioning and squad rotation strategies.
Single Nanoparticle Detection for Multiplexed Protein Diagnostics with Attomolar Sensitivity in Serum and Unprocessed Whole Blood (2013)

Although biomarkers exist for a range of disease diagnostics, a single low-cost platform exhibiting the required sensitivity, a large dynamic-range and multiplexing capability, and zero sample preparation remains in high demand for a variety of clinical applications. The Interferometric Reflectance Imaging Sensor (IRIS) was utilized to digitally detect and size single gold nanoparticles to identify protein biomarkers in unprocessed serum and blood samples. IRIS is a simple, inexpensive, multiplexed, high-throughput, and label-free optical biosensor that was originally used to quantify biomass captured on a surface with moderate sensitivity. Here we demonstrate detection of β-lactoglobulin, a cow's milk whey protein spiked in serum (>10 orders of magnitude) and whole blood (>5 orders of magnitude), at attomolar sensitivity. The clinical utility of IRIS was demonstrated by detecting allergen-specific IgE from microliters of characterized human serum and unprocessed whole blood samples by using secondary antibodies against human IgE labeled with 40 nm gold nanoparticles. To the best of our knowledge, this level of sensitivity over a large dynamic range has not been previously demonstrated. IRIS offers four main advantages compared to existing technologies: it (i) detects proteins from attomolar to nanomolar concentrations in unprocessed biological samples, (ii) unambiguously discriminates nanoparticles tags on a robust and physically large sensor area, (iii) detects protein targets with conjugated very small nanoparticle tags (~40 nm diameter), which minimally affect assay kinetics compared to conventional microparticle tagging methods, and (iv) utilizes components that make the instrument inexpensive, robust, and portable. These features make IRIS an ideal candidate for clinical and diagnostic applications.
An Evaluation of Hardware-Efficient Quantum Neural Networks for Image Data Classification (2022)

Quantum computing is expected to fundamentally change computer systems in the future. Recently, a new research topic of quantum computing is the hybrid quantum–classical approach for machine learning, in which a parameterized quantum circuit, also called quantum neural network (QNN), is optimized by a classical computer. This hybrid approach can have the benefits of both quantum computing and classical machine learning methods. In this early stage, it is of crucial importance to understand the new characteristics of quantum neural networks for different machine learning tasks. In this paper, we will study quantum neural networks for the task of classifying images, which are high-dimensional spatial data. In contrast to previous evaluations of low-dimensional or scalar data, we will investigate the impacts of practical encoding types, circuit depth, bias term, and readout on classification performance on the popular MNIST image dataset. Various interesting findings on learning behaviors of different QNNs are obtained through experimental results. To the best of our knowledge, this is the first work that considers various QNN aspects for image data.
Construction of Comprehensive Dosage-Matching Core Histone Mutant Libraries for Saccharomyces cerevisiae (2017)

<i>Saccharomyces cerevisiae</i> contains two genes for each core histone, which are presented as pairs under the control of a divergent promoter, <i>i.e.</i>, <i>HHT1-HHF1</i>, <i>HHT2-HHF2</i>, <i>HTA1-HTB1</i> and <i>HTA2-HTB2</i><i>HHT1-HHF1</i>, and <i>HHT2-HHF2</i> encode histone H3 and H4 with identical amino acid sequences but under the control of differently regulated promoters. Previous mutagenesis studies were carried out by deleting one pair and mutating the other one. Here, we present the design and construction of three additional libraries covering <i>HTA1-HTB1</i>, <i>HTA2-HTB2</i>, and <i>HHT1-HHF1</i> respectively. Together with the previously described library of <i>HHT2-HHF2</i> mutants, a systematic and complete collection of mutants for each of the eight core <i>S. cerevisiae</i> histone genes becomes available. Each designed mutant was incorporated into the genome, generating three more corresponding libraries of yeast strains. We demonstrated that, although, under normal growth conditions, strains with single-copy integrated histone genes lacked phenotypes, in some growth conditions, growth deficiencies were observed. Specifically, we showed that addition of a second copy of the mutant histone gene could rescue the lethality in some previously known mutants that cannot survive with a single copy. This resource enables systematic studies of function of each nucleosome residue in plasmid, single-copy, and double-copy integrated formats.
Interferometric In-Phase and Quadrature Oscilloscope (2009)

A technique is presented for measuring the in-phase and quadrature components of a modulated optical signal, using standard electrical and optical components and a high-bandwidth equivalent-time sampling oscilloscope. The measurement setup consists of an interferometer, optical mixer, and sampling oscilloscope with two low-speed sampling modules (50 kHz) and two high-speed optical sampling modules (65 GHz). The simultaneous measurement of four de-skewed signals allows for the separate determination of the phase noise, amplitude modulation, and phase modulation. From these results, the complete trajectory in time of the complex signal is constructed.
Quantum interference of electromechanically stabilized emitters in nanophotonic devices (2019)

We present a nano-electromechanical platform for controlling optical transitions from spatially separated color centers in diamond waveguides. We use this technology to greatly suppress spectral diffusion and demonstrate strain induced quantum interference between separate emitters.