gebhart/patrepeval huggingface dataset:
Analysis of GPIIb/IIIa receptor number by quantification of 7E3 binding to human platelets (1996)

A large number of glycoprotein (GP) IIb/IIIa receptors are present on the surface of platelets. Studies to define precisely the number of GPIIb/IIIa receptors using specific monoclonal antibodies (MoAbs) or fibrinogen binding have, however, yielded varying estimates of receptor number. To refine the quantitative estimation of GPIIb/IIIa receptors on resting platelets, we have used the MoAb 7E3, which has high affinity for GPIIb/IIIa. Quantitative binding studies were performed using radiolabeled conjugates of 7E3 IgG, as well as fragments and derivatives of 7E3. For platelets obtained from any single individual, the numbers of 7E3 F(ab')2 and IgG molecules bound per platelet were equivalent (approximately 40,000), whereas the number of Fab molecules bound per platelet was consistently approximately twofold higher (approximately 80,000). To investigate the basis of the quantitative disparity in binding of intact 7E3 and 7E3 F(ab')2 versus 7E3 Fab, we studied the binding of a newly constructed, bispecific (Fab')2 molecule containing only a single 7E3 combining site. Because this construct bound to the same extent as the Fab species, the larger size of the intact 7E3 and 7E3 F(ab')2 molecules could not explain the reduced number of molecules that bound per platelet compared to the Fab fragment. Rather, it appears that the valency of the antibody is the critical factor determining the number of antibody molecules bound per platelet. Thus, we conclude that the binding of 7E3 Fab corresponds most closely with surface GPIIb/IIIa number and that the number of GPIIb/IIIa receptors is approximately 80,000 per platelet.
Detecting Aortic Valve Opening and Closing from Distal Body Vibrations (2016)

Objective: Proximal and whole-body vibrations are well studied in seismocardiography and ballistocardiography, yet distal vibrations are still poorly understood. In this paper we develop two methods to measure aortic valve opening (AVO) and closing (AVC) from distal vibrations. Methods: AVO and AVC were detected for each heartbeat with accelerometers on the upper arm (A), wrist (W), and knee (K) of 22 consenting adults following isometric exercise. Exercise-induced changes were recorded with impedance cardiography, and nine-beat ensemble averaging was applied. Our first method, FilterBCG, detects peaks in distal vibrations after filtering with individually-tuned bandpass filters while RidgeBCG uses ridge regression to estimate AVO and AVC without peaks. Pseudocode is provided. Results: In agreement with recent studies, we did not find peaks at AVO and AVC in distal vibrations, and the conventional R-J interval method from the literature also correlated poorly with AVO (r2 = 0.22 A, 0.14 W, 0.12 K). Interestingly, distal vibrations filtered with FilterBCG resembled seismocardiogram signals and yielded reliable peaks at AVO (r2 = 0.95 A, 0.94 W, 0.77 K) and AVC (r2 = 0.92 A, 0.89 W, 0.68 K). Conclusion: FilterBCG measures AVO and AVC accurately from arm, wrist, and knee vibrations, and it outperforms R-J intervals and RidgeBCG. Significance: To our knowledge, this study is the first to measure AVC accurately from distal vibrations. Finally, AVO timing is needed to assess cardiovascular disease risk with pulse wave velocity (PWV) and for cuff-less diastolic blood pressure measurement via aortic pulse-transit time (PTT).
Aperture fed rectangular and triangular dielectric resonators for use as magnetic dipole antennas (1993)

The Letter reports the results of investigations on aperture-fed rectangular and triangular shaped dielectric resonators for use as magnetic-dipole antenna elements. Measured results show that both antennas have a large bandwidth (&gt;10%) and their far field patterns are similar to that of a magnetic dipole.
Biochemical Nature and Cellular Distribution of the Paired Immunoglobulin-like Receptors, PIR-A and PIR-B (1999)

PIR-A and PIR-B, paired immunoglobulin-like receptors encoded, respectively, by multiple Pira genes and a single Pirb gene in mice, are relatives of the human natural killer (NK) and Fc receptors. Monoclonal and polyclonal antibodies produced against a recombinant PIR protein identified cell surface glycoproteins of approximately 85 and approximately 120 kD on B cells, granulocytes, and macrophages. A disulfide-linked homodimer associated with the cell surface PIR molecules was identified as the Fc receptor common gamma (FcRgammac) chain. Whereas PIR-B fibroblast transfectants expressed cell surface molecules of approximately 120 kD, PIR-A transfectants expressed the approximately 85-kD molecules exclusively intracellularly; PIR-A and FcRgammac cotransfectants expressed the PIR-A/ FcRgammac complex on their cell surface. Correspondingly, PIR-B was normally expressed on the cell surface of splenocytes from FcRgammac-/- mice whereas PIR-A was not. Cell surface levels of PIR molecules on myeloid and B lineage cells increased with cellular differentiation and activation. Dendritic cells, monocytes/macrophages, and mast cells expressed the PIR molecules in varying levels, but T cells and NK cells did not. These experiments define the coordinate cellular expression of PIR-B, an inhibitory receptor, and PIR-A, an activating receptor; demonstrate the requirement of FcRgammac chain association for cell surface PIR-A expression; and suggest that the level of FcRgammac chain expression could differentially affect the PIR-A/PIR-B equilibrium in different cell lineages.
Preclinical Evaluation of Chimeric Antigen Receptors Targeting CD70-Expressing Cancers (2016)

<b>Purpose:</b> CD70 expression in normal tissues is restricted to activated lymphoid tissues. Targeting CD70 on CD70-expressing tumors could mediate "on-target, off-tumor" toxicity. This study was to evaluate the feasibility and safety of using anti-human CD70 CARs to treat cancer patients whose tumors express CD70.<b>Experimental Design:</b> Seven anti-human CD70 CARs with binding moieties from human CD27 combined with CD3-zeta and different costimulatory domains from CD28 and/or 41BB were constructed. <i>In vitro</i> functionality of these receptors was compared and <i>in vivo</i> treatment efficacy was evaluated in a xenograft mouse model. A homologous, all murine anti-CD70 CAR model was also used to assess treatment-related toxicities.<b>Results:</b> The CAR consisting of the extracellular binding portion of CD27 fused with 41BB and CD3-zeta (trCD27-41BB-zeta) conferred the highest IFNγ production against CD70-expressing tumors <i>in vitro</i>, and NSG mice bearing established CD70-expressing human tumors could be cured by human lymphocytes transduced with this CAR. In the murine CD27-CD3-zeta CAR model, significant reduction of established tumors and prolonged survival were achieved using CAR-transduced splenocytes in a dose-dependent manner. Host preirradiation enhanced treatment efficacy but increased treatment-related toxicities such as transient weight loss and hematopoetic suppression. The treatment did not appear to block adaptive host immune responses.<b>Conclusions:</b> Preclinical testing supports the safety and efficacy of a CD27-containing CAR targeting CD70-expressing tumors. <i>Clin Cancer Res; 23(9); 2267-76. ©2016 AACR</i>.
Lower body negative pressure as a model to study progression to acute hemorrhagic shock in humans (2004)

Hemorrhage is a leading cause of death in both civilian and battlefield trauma. Survival rates increase when victims requiring immediate intervention are correctly identified in a mass-casualty situation, but methods of prioritizing casualties based on current triage algorithms are severely limited. Development of effective procedures to predict the magnitude of hemorrhage and the likelihood for progression to hemorrhagic shock must necessarily be based on carefully controlled human experimentation, but controlled study of severe hemorrhage in humans is not possible. It may be possible to simulate hemorrhage, as many of the physiological compensations to acute hemorrhage can be mimicked in the laboratory by applying negative pressure to the lower extremities. Lower body negative pressure (LBNP) sequesters blood from the thorax into dependent regions of the pelvis and legs, effectively decreasing central blood volume in a similar fashion as acute hemorrhage. In this review, we compare physiological responses to hemorrhage and LBNP with particular emphasis on cardiovascular compensations that both share in common. Through evaluation of animal and human data, we present evidence that supports the hypothesis that LBNP, and resulting volume sequestration, is an effective technique to study physiological responses and mechanisms associated with acute hemorrhage in humans. Such experiments could lead to clinical algorithms that identify bleeding victims who will likely progress to hemorrhagic shock and require lifesaving intervention(s).
Quantitation, selection, and functional characterization of Epstein-Barr virus–specific and alloreactive T cells detected by intracellular interferon-γ production and growth of cytotoxic precursors (2002)

Techniques for the quantitation of virus-specific and alloantigen-reactive T cells vary in their measurement of clinically relevant T-cell effector populations, their sensitivity and quantitative accuracy, and the time required to obtain measurable results. We compared frequencies of Epstein-Barr virus (EBV)-specific and major alloantigen-reactive T cells as measured by flow cytometric analysis of responding T cells producing intracellular interferon-gamma (IFN-gamma) and by limiting-dilution analysis (LDA) of cytotoxic T-cell precursors (CTLp) at sequential time points during the generation of EBV-specific T-cell lines. The expansion of EBV-specific T lymphocytes and the depletion of alloreactive T cells in cultures of T cells sensitized with autologous EBV-transformed targets followed similar kinetics when measured by either method. Frequencies of EBV- specific T cells generating intracellular IFN-gamma exceeded by 25- to 90-fold the frequencies of responding CTLp at each stage of expansion, whereas the frequencies of alloreactive T cells generating intracellular IFN-gamma exceeded by 30- to 220-fold those detected by LDA. The assay that quantitated T cells producing IFN-gamma yielded more reproducible and precise results than LDA. Furthermore, frequencies detected by the enumeration of T cells responding to immunodominant EBNA 3a and EBNA 3c peptides by IFN-gamma production or their capacity to bind peptide-HLA tetramers were strikingly similar and represented significant fractions of T cells generating IFN-gamma in response to autologous EBV B lymphoblastoid cell line. Functional analysis of responding viable T cells, fractionated on the basis of their secretion of IFN-gamma, demonstrated that EBV-specific and alloantigen cytotoxic T cells were predominantly or exclusively detected in the CD8(+)IFN-gamma(+) fraction of T cells. Strikingly, the CD4(+)IFN-gamma(+) cell fractions were not cytotoxic against EBV-transformed or allogeneic targets.
Groups, algebras, and the non-linearity of geophysical inverse problems (1997)

Mathematical methods from the theory of continuous groups are used to determine whether a non-linear inverse problem, in the form of a functional, can be transformed into a linear inverse problem.If such transformations exist they can be constructed from the soiutions of a linear system of differential equations.A n illustration of the methodology is given by the linearization of the functional relating basement topography to observed surface gravity.The linearized inversion of gravity data for basement topography is applied to observations from Yucca Mountain, Nevada.A 2.0 k m step in the basement to the west of Yucca Mountain, corresponding to the Bare Mountain fault, matches the Bouguer gravity anomaly.The resolution and uncertainty associated with the estimates of basement topography indicate that the structure directly beneath the gravity line is well constrained.
Effect of nanofluid on the heat transport capability in an oscillating heat pipe (2006)

By combining nanofluids with thermally excited oscillating motion in an oscillating heat pipe (OHP), we developed an ultrahigh-performance cooling device, called the nanofluid oscillating heat pipe. Experimental results show that when the OHP is charged with nanofluid, heat transport capability significantly increases. For example, at the input power of 80.0W, diamond nanofluid can reduce the temperature difference between the evaporator and the condenser from 40.9to24.3°C. This study will accelerate the development of a highly efficient cooling device for ultrahigh-heat-flux electronic systems.
Dynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure (2007)

End-stage heart failure (HF) is characterized by changes in conduction velocity (CV) that predispose to arrhythmias. Here, we investigate the time course of conduction changes with respect to alterations in connexin 43 (Cx43) properties and mechanical function during the development of HF. We perform high-resolution optical mapping in arterially perfused myocardial preparations from dogs subjected to 0, 3, 7, 14, and 21 days of rapid pacing to produce variable degrees of remodeling. CV is compared with an index of mechanical function [left ventricular end-diastolic pressure (LVEDP)] and with dynamic changes in the expression, distribution, and phosphorylation of Cx43. In contrast to repolarization, CV was preserved during early stages of remodeling (3 and 7 days) and significantly reduced at later stages, which were associated with marked increases in LVEDP. Measurements of differentially phosphorylated Cx43 isoforms revealed early, sustained downregulation of pan-Cx43 that preceded changes in CV and LVEDP, a gradual rise in a dephosphorylated Cx43 isoform to over twofold baseline levels in end-stage HF, and a late abrupt increase in pan-Cx43, but not dephosphorylated Cx43, lateralization. These data demonstrate that 1) CV slowing occurs only at advanced stages of remodeling, 2) total reduction of pan-Cx43 is an early event that precedes mechanical dysfunction and CV slowing, 3) changes in Cx43 phosphorylation are more closely associated with the onset of HF, and 4) Cx43 lateralization is a late event that coincides with marked CV reduction. These data reveal a novel paradigm of remodeling based on the timing of conduction abnormalities relative to changes in Cx43 isoforms and mechanical dysfunction.
The production of recombinant proteins in transgenic barley grains (2000)

The grain of the self-pollinating diploid barley species offers two modes of producing recombinant enzymes or other proteins. One uses the promoters of genes with aleurone-specific expression during germination and the signal peptide code for export of the protein into the endosperm. The other uses promoters of the structural genes for storage proteins deposited in the developing endosperm. Production of a protein-engineered thermotolerant (1, 3-1, 4)-beta-glucanase with the D hordein gene (Hor3-1) promoter during endosperm development was analyzed in transgenic plants with four different constructs. High expression of the enzyme and its activity in the endosperm of the mature grain required codon optimization to a C+G content of 63% and synthesis as a precursor with a signal peptide for transport through the endoplasmic reticulum and targeting into the storage vacuoles. Synthesis of the recombinant enzyme in the aleurone of germinating transgenic grain with an alpha-amylase promoter and the code for the export signal peptide yielded approximately 1 microgram small middle dotmg(-1) soluble protein, whereas 54 microgram small middle dotmg(-1) soluble protein was produced on average in the maturing grain of 10 transgenic lines with the vector containing the gene for the (1, 3-1, 4)-beta-glucanase under the control of the Hor3-1 promoter.
Detection of nitro-polynuclear aromatic compounds by surface-enhanced Raman spectrometry (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetection of nitro-polynuclear aromatic compounds by surface-enhanced Raman spectrometryPaul D. Enlow and Tuan. Vo-DinhCite this: Anal. Chem. 1986, 58, 6, 1119–1123Publication Date (Print):May 1, 1986Publication History Published online1 May 2002Published inissue 1 May 1986https://pubs.acs.org/doi/10.1021/ac00297a031https://doi.org/10.1021/ac00297a031research-articleACS PublicationsRequest reuse permissionsArticle Views224Altmetric-Citations85LEARN 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
A novel method to generate T-cell receptor–deficient chimeric antigen receptor T cells (2018)

Practical methods are needed to increase the applicability and efficacy of chimeric antigen receptor (CAR) T-cell therapies. Using donor-derived CAR-T cells is attractive, but expression of endogenous T-cell receptors (TCRs) carries the risk for graft-versus-host-disease (GVHD). To remove surface TCRαβ, we combined an antibody-derived single-chain variable fragment specific for CD3ε with 21 different amino acid sequences predicted to retain it intracellularly. After transduction in T cells, several of these protein expression blockers (PEBLs) colocalized intracellularly with CD3ε, blocking surface CD3 and TCRαβ expression. In 25 experiments, median TCRαβ expression in T lymphocytes was reduced from 95.7% to 25.0%; CD3/TCRαβ cell depletion yielded virtually pure TCRαβ-negative T cells. Anti-CD3ε PEBLs abrogated TCRαβ-mediated signaling, without affecting immunophenotype or proliferation. In anti-CD3ε PEBL-T cells, expression of an anti-CD19-41BB-CD3ζ CAR induced cytokine secretion, long-term proliferation, and CD19<sup>+</sup> leukemia cell killing, at rates meeting or exceeding those of CAR-T cells with normal CD3/TCRαβ expression. In immunodeficient mice, anti-CD3ε PEBL-T cells had markedly reduced GVHD potential; when transduced with anti-CD19 CAR, these T cells killed engrafted leukemic cells. PEBL blockade of surface CD3/TCRαβ expression is an effective tool to prepare allogeneic CAR-T cells. Combined PEBL and CAR expression can be achieved in a single-step procedure, is easily adaptable to current cell manufacturing protocols, and can be used to target other T-cell molecules to further enhance CAR-T-cell therapies.
Efficient color histogram indexing (2002)

In image retrieval based on color, the weighted distance between color histograms of two images, represented as a quadratic form, may be defined as a match measure. However, this distance measure is computationally expensive (naively O(N/sup 2/) and at best O(N) in the number N of histogram bins) and it operates on high dimensional features (O(N)). We propose the use of low-dimensional, simple to compute distance measures between the color distributions, and show that these are lower bounds on the histogram distance measure. Results on color histogram matching in large image databases show that pre-filtering with the simpler distance measures leads to significantly less time complexity because the quadratic histogram distance is now computed on a smaller set of images. The low-dimensional distance measure can also be used for indexing into the database.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. (1988)

We developed a novel promoter system, designated SR alpha, which is composed of the simian virus 40 (SV40) early promoter and the R segment and part of the U5 sequence (R-U5') of the long terminal repeat of human T-cell leukemia virus type 1. The R-U5' sequence stimulated chloramphenicol acetyltransferase (CAT) gene expression only when placed immediately downstream of the SV40 early promoter in the sense orientation. The SR alpha expression system was 1 or 2 orders of magnitude more active than the SV40 early promoter in a wide variety of cell types, including fibroblasts and lymphoid cells, and was capable of promoting a high level of expression of various lymphokine cDNAs. These features of the SR alpha promoter were incorporated into the pcD-cDNA expression cloning vector originally developed by Okayama and Berg.
Interactions between excitatory amino acids and dopamine systems in the forebrain (1995)

The midbrain dopamine neurones innervate not only the dorsal and ventral sectors of the striatum but also limbic structures and fronto-temporal association cortex. The forebrain structures providing and receiving dopaminergic input are highly interconnected. The dopamine pathways are now seen to provide modulation of widespread limbo- and cortico-striatal circuits involved in motivated behaviour. The nucleus accumbens is a pivotal structure of this ventral striatal system, whereas the caudate putamen of the dorsal striatum integrates sensori-motor coordination. These striatal sectors have access to complex parallel output pathways of the pallidal and the thalamo-cortical motor systems. Excitatory amino acids are now known to play an important role as neurotransmitters in the dorsal and ventral forebrain circuits and in the output pathways associated with dopamine neurones. Current drug treatment of both schizophrenia and Parkinson's disease focus on drugs which modify dopamine activity in the brain. Glutamatergic mechanisms may provide interesting alternative pharmacological targets for the treatment of such disorders.
Bromodomain Protein BRD4 Is Required for Estrogen Receptor-Dependent Enhancer Activation and Gene Transcription (2014)

The estrogen receptor α (ERα) controls cell proliferation and tumorigenesis by recruiting various cofactors to estrogen response elements (EREs) to control gene transcription. A deeper understanding of these transcriptional mechanisms may uncover therapeutic targets for ERα-dependent cancers. We show that BRD4 regulates ERα-induced gene expression by affecting elongation-associated phosphorylation of RNA polymerase II (RNAPII) and histone H2B monoubiquitination. Consistently, BRD4 activity is required for proliferation of ER(+) breast and endometrial cancer cells and uterine growth in mice. Genome-wide studies revealed an enrichment of BRD4 on transcriptional start sites of active genes and a requirement of BRD4 for H2B monoubiquitination in the transcribed region of estrogen-responsive genes. Importantly, we demonstrate that BRD4 occupancy on distal EREs enriched for H3K27ac is required for recruitment and elongation of RNAPII on EREs and the production of ERα-dependent enhancer RNAs. These results uncover BRD4 as a central regulator of ERα function and potential therapeutic target.