gebhart/patrepeval huggingface dataset:
Data from Modulation of Endoplasmic Reticulum Stress Controls CD4<sup>+</sup> T-cell Activation and Antitumor Function (2023)

&lt;div&gt;Abstract&lt;p&gt;The endoplasmic reticulum (ER) is an energy-sensing organelle with intimate ties to programming cell activation and metabolic fate. T-cell receptor (TCR) activation represents a form of acute cell stress and induces mobilization of ER Ca&lt;sup&gt;2+&lt;/sup&gt; stores. The role of the ER in programming T-cell activation and metabolic fate remains largely undefined. Gp96 is an ER protein with functions as a molecular chaperone and Ca&lt;sup&gt;2+&lt;/sup&gt; buffering protein. We hypothesized that the ER stress response may be important for CD4&lt;sup&gt;+&lt;/sup&gt; T-cell activation and that gp96 may be integral to this process. To test our hypothesis, we utilized genetic deletion of the gp96 gene &lt;i&gt;Hsp90b1&lt;/i&gt; in a CD4&lt;sup&gt;+&lt;/sup&gt; T cell–specific manner. We show that gp96-deficient CD4&lt;sup&gt;+&lt;/sup&gt; T cells cannot undergo activation-induced glycolysis due to defective Ca&lt;sup&gt;2+&lt;/sup&gt; mobilization upon TCR engagement. We found that activating naïve CD4&lt;sup&gt;+&lt;/sup&gt; T cells while inhibiting ER Ca&lt;sup&gt;2+&lt;/sup&gt; exchange, through pharmacological blockade of the ER Ca&lt;sup&gt;2+&lt;/sup&gt; channel inositol trisphosphate receptor (IP&lt;sub&gt;3&lt;/sub&gt;R), led to a reduction in cytosolic Ca&lt;sup&gt;2+&lt;/sup&gt; content and generated a pool of CD62L&lt;sup&gt;high&lt;/sup&gt;/CD44&lt;sup&gt;low&lt;/sup&gt; CD4&lt;sup&gt;+&lt;/sup&gt; T cells compared with wild-type (WT) matched controls. &lt;i&gt;In vivo&lt;/i&gt; IP&lt;sub&gt;3&lt;/sub&gt;R-inhibited CD4&lt;sup&gt;+&lt;/sup&gt; T cells exhibited elevated tumor control above WT T cells. Together, these data show that ER-modulated cytosolic Ca&lt;sup&gt;2+&lt;/sup&gt; plays a role in defining CD4&lt;sup&gt;+&lt;/sup&gt; T-cell phenotype and function. Factors associated with the ER stress response are suitable targets for T cell–based immunotherapies. &lt;i&gt;Cancer Immunol Res; 5(8); 666–75. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
The Surgical Bed After BCNU Polymer Wafer Placement for Recurrent Glioma: Serial Assessment on CT and MR Imaging (2003)

BCNU polymer wafers have a specific appearance on CT and MR imaging with which radiologists should be familiar: gas in the surgical bed is an expected transient finding, and tumor regrowth in patients receiving BCNU polymer wafers appeared to occur at a slower rate than in those receiving the placebo.
Oxidation and Reduction (2007)

This chapter contains sections titled: Oxidation by Metal Ions and Related Species Oxidation by Compounds of Non-metallic Elements Miscellaneous Oxidations Ozonolysis and Ozonation Peracids and Peroxides Photo-oxygenation, Singlet Oxygen, and Superoxide Atomic Oxygen, Autoxidation, and Other Reactions of Oxygen Reduction by Complex Metal Hydrides Reductions by Metals, Metal Ions, and Metal Complexes Miscellaneous Reductions Hydrogenation Reductions and Oxidations of Biological Interest
DNA hypomethylation silences anti-tumor immune genes in early prostate cancer and CTCs (2023)

Cancer is characterized by hypomethylation-associated silencing of large chromatin domains, whose contribution to tumorigenesis is uncertain. Through high-resolution genome-wide single-cell DNA methylation sequencing, we identify 40 core domains that are uniformly hypomethylated from the earliest detectable stages of prostate malignancy through metastatic circulating tumor cells (CTCs). Nested among these repressive domains are smaller loci with preserved methylation that escape silencing and are enriched for cell proliferation genes. Transcriptionally silenced genes within the core hypomethylated domains are enriched for immune-related genes; prominent among these is a single gene cluster harboring all five CD1 genes that present lipid antigens to NKT cells and four IFI16-related interferon-inducible genes implicated in innate immunity. The re-expression of CD1 or IFI16 murine orthologs in immuno-competent mice abrogates tumorigenesis, accompanied by the activation of anti-tumor immunity. Thus, early epigenetic changes may shape tumorigenesis, targeting co-located genes within defined chromosomal loci. Hypomethylation domains are detectable in blood specimens enriched for CTCs.
Continuous Enantioselective Hydrogenation with a Molecular Catalyst in Supported Ionic Liquid Phase under Supercritical CO2 Flow (2010)

Highly efficient continuous-flow asymmetric catalysis was achieved by combination of supported ionic liquid phase (SILP) catalysts with supercritical CO2 (scCO2) as the mobile phase, as demonstrated for enantioselective hydrogenation in the presence of a molecular rhodium–QUINAPHOS complex. The integrated reaction and separation process yielded chemically and enantiomerically pure products without the need for organic solvents. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Correction: Secondary ligand-induced orthogonal self-assembly of silver nanoclusters into superstructures with enhanced NIR emission (2023)

Correction for 'Secondary ligand-induced orthogonal self-assembly of silver nanoclusters into superstructures with enhanced NIR emission' by Korath Shivan Sugi, <i>et al.</i>, <i>Nanoscale</i>, 2023, https://doi.org/10.1039/d3nr02561f.
Temporal Imaging System with Simple External Clock Synchronization (2009)

We demonstrate a temporal imaging system that allows simple synchronization to an external clock by using a spectrally broadened time-lens-based pump laser. We integrate this pump laser into an ultrafast oscilloscope scheme and demonstrate 2 ps resolution with 130 ps record length.
DIFFERENTIAL EXPRESSION OF T-CELL GROWTH FACTORS IN REJECTING MURINE ISLET AND HUMAN RENAL ALLOGRAFTS (1998)

IL-9 is conspicuously absent despite vigorous expression of IL-2, IL-4, IL-7, and IL-15 genes during acute allograft rejection.
Lead Optimization to Advance Protease-Activated Receptor-1 Antagonists in Early Discovery (2022)

Vorapaxar is an approved drug for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Subsequent to the discovery of Vorapaxar, medicinal chemistry efforts were continued to identify structurally differentiated leads. Toward this goal, extensive structure-activity relationship studies using a C-ring-truncated version of Vorapaxar culminated in the discovery of three leads, represented as <b>13</b>, <b>14</b>, and <b>23</b>. Among these leads, compound <b>14</b> possessed favorable pharmacokinetic properties and an off-target profile, which supported additional profiling in an exploratory rat toxicology study.
Trispecific CD19-CD20-CD22–targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models (2021)

A substantial number of patients with leukemia and lymphoma treated with anti-CD19 or anti-CD22 monoCAR-T cell therapy relapse because of antigen loss or down-regulation. We hypothesized that B cell tumor antigen escape may be overcome by a chimeric antigen receptor (CAR) design that simultaneously targets three B cell leukemia antigens. We engineered trispecific duoCAR-T cells with lentiviral vectors encoding two CAR open reading frames that target CD19, CD20, and CD22. The duoCARs were composed of a CAR with a tandem CD19- and CD20-targeting binder, linked by the P2A self-cleaving peptide to a second CAR targeting CD22. Multiple combinations of intracellular T cell signaling motifs were evaluated. The most potent duoCAR architectures included those with ICOS, OX40, or CD27 signaling domains rather than those from CD28 or 4-1BB. We identified four optimal binder and signaling combinations that potently rejected xenografted leukemia and lymphoma tumors in vivo. Moreover, in mice bearing a mixture of B cell lymphoma lines composed of parental triple-positive cells, CD19-negative, CD20-negative, and CD22-negative variants, only the trispecific duoCAR-T cells rapidly and efficiently rejected the tumors. Each of the monoCAR-T cells failed to prevent tumor progression. Analysis of intracellular signaling profiles demonstrates that the distinct signaling of the intracellular domains used may contribute to these differential effects. Multispecific duoCAR-T cells are a promising strategy to prevent antigen loss-mediated relapse or the down-regulation of target antigen in patients with B cell malignancies.
Enhancing rural connectivity with software defined networks (2013)

Software-defined networks (SDNs) have simplified management of complex data center and enterprise networks. We argue that SDNs can play a similar role in rural wireless networks, especially those in developing regions. Operating a rural network in the developing world means coping with unpredictability, low profit margins, and resource constraints; the increased flexibility and simplified management that software-defined networks provide are a major benefit in this context. Network virtualization, also enabled by SDN, could allow rural networks to operate as infrastructure providers to existing ISPs, thus enabling cooperation rather than competition with powerful incumbent providers.
Migration towards optical transparency in Metro- and Backbone Transport Networks (2006)

In this paper the potential benefits and challenges for the introduction of optically transparent network elements in metro and backbone networks are discussed. The migration from current to next technology generation transport equipment is assessed.
Verifiable Manufacturing Using Blockchain (2023)

We propose a blockchain-based solution for enabling verifiability of manufacturing processes. We base our solution on the methodology of verifiable computing which, originally developed for cloud computing, enables clients to outsource computations to more powerful servers without the need to trust that the server correctly performed desired computation. Verifiable computing accomplishes this by enabling the client to generate cryptographic objects that the server must use to produce a cryptographic proof that verifies the correctness of results. The black box nature of servers in cloud computing is analogous to that of the manufacturing processes of an upstream manufacturer. In this work, we develop a one-to-one correspondence between physical processes and their digital representations as state sequences which is needed for the implementation of verifiable computing. Because direct application of verifiable computing in this case would be computationally prohibitive, we introduce a blockchain to provide a computationally feasible methodology for verifiable computing applied to physical processes. We implement and show the results of our implementation on a proof of concept, developed on Hyperledger Fabric.
Intradermal-delivered DNA vaccine induces durable immunity mediating a reduction in viral load in a rhesus macaque SARS-CoV-2 challenge model (2021)

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health and social and economic infrastructures. Here, we assess the immunogenicity and anamnestic protective efficacy in rhesus macaques of an intradermal (i.d.)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800, currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and induced spike antigen and RBD binding antibodies with ADCP and ADCD activity. Sera from the animals neutralized both the D614 and G614 SARS-CoV-2 pseudotype viruses. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T cell and neutralizing antibody responses. These responses were associated with lower viral loads in the lung. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system, which are likely important for providing durable protection against COVID-19 disease.
Manipulating Optical Properties of ZnO/Ga:ZnO Core–Shell Nanorods Via Spatially Tailoring Electronic Bandgap (2015)

Enhancing optical and electrical properties of ZnO nanostructures via surface doping is demonstrated by Ga:ZnO–ZnO core–shell nanorods, which are grown by a genetic two-step method. Low-temperature photoluminescence and X-ray photoelectron spectroscopy prove the n + shell significantly suppresses the surface-related recombination by spatially modulating the electronic band structure. The study provides a significant physical insight in designing optoelectronic devices.
Immunotoxin Complementation of HAART to Deplete Persisting HIV-Infected Cell Reservoirs (2010)

E.A.B. and I.P. are co-inventors on NIH-owned issued patents and patent applications for CD4-PE and 3B3-PE.



This work was supported in part by the Intramural Program of the NIH (National Institute of Allergy and Infectious Diseases; National Cancer Institute), including the NIH Intramural AIDS Targeted Antiviral Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Cation Diffusion Facilitator family: Structure and function (2015)

The Cation Diffusion Facilitators (CDFs) form a family of membrane-bound proteins capable of transporting zinc and other heavy metal ions. Involved in metal tolerance/resistance by efflux of ions, CDF proteins share a two-modular architecture consisting of a transmembrane domain (TMD) and C-terminal domain (CTD) that protrudes into the cytoplasm. Discovery of a Zn²⁺ and Cd²⁺ CDF transporter from a marine bacterium Maricaulis maris that does not possess the CTD questions current perceptions regarding this family of proteins. This article describes a new, CTD-lacking subfamily of CDFs and our current knowledge about this family of proteins in the view of these findings.
Experimental Human Infection with Haemophilus ducreyi (1994)

Four subjects were experimentally infected with Haemophilus ducreyi. Lesions developed only at sites where live bacteria were inoculated on abraded skin. No subject developed fever, lymphadenopathy, or disseminated infection during a 3-day observation period. Two subjects who were rechallenged 2 months after initial infection also developed lesions. The amount of H. ducreyi recovered from 10 of 12 biopsies that were semiquantitatively cultured varied widely. Similar histologic features were present in initial and second infections. The epidermis contained pustules; the dermis contained an infiltrate of T cells and macrophages and reactive endothelial cells. Keratinocytes and T cells expressed HLA-DR, consistent with a delayed-type hypersensitivity response. The subjects did not mount humoral responses to bacterial proteins and to lipooligosaccharides after primary and secondary challenges. Thus, human experimental infection with H. ducreyi is well tolerated and safe. Recruitment of T cells and macrophages into chancroid lesions may partially explain the association between chancroid and human immunodeficiency virus transmission.
Computer modeling of planar myocardial perfusion imaging: effect of heart rate and ejection fraction on wall thickness and chamber size. (1986)

Myocardial perfusion imaging is generally performed as a static acquisition without regard for dynamic changes in the cardiac cycle. The effect of heart rate and ejection fraction on the appearance of left ventricular chamber size and wall thickness as perceived in 201Tl scintigrams has not, to our knowledge, been previously studied. A dynamic computer model of the left ventricle was constructed, capable of varying the heart rate and ejection fraction. Parallel slices through the model were convolved with experimentally derived 201Tl point spread functions at corresponding depths to incorporate the effects of scatter and attenuation. Both gated and static left anterior oblique images were created at three clinically encountered heart rates and ejection fractions, with constant end-diastolic volume and left ventricular mass. Results of the study indicate that perceived and quantified wall thickness increases and chamber size decreases appreciably with increasing ejection fraction and (slightly) with increasing heart rate. Thus, evaluation of wall thickness and chamber size in planar images should take into account variations in heart rate and contractility. This is especially pertinent to estimates of left ventricular hypertrophy and chamber size, attempted from nongated myocardial perfusion images.
Effects of oligosaccharides in a soybean meal-based diet on fermentative and immune responses in broiler chicks challenged with Eimeria acervulina (2012)

Fermentable oligosaccharides, particularly those found in soybean meal (SBM), may modulate fermentation in the ceca, thus affecting intestinal immune responses to intestinal pathogens. We hypothesized that fermentable oligosaccharides found in SBM would positively affect cecal fermentation and intestinal immune status in chicks challenged with an acute coccidiosis (Eimeria acervulina) infection and fed either a SBM-based diet or a semi-purified soy protein isolate- (SPI) based diet. Using a completely randomized design, 1-d-old broiler chicks (n = 200; 5 replications/treatment; 5 chicks/replication) were assigned to 1 of 4 SBM- or SPI-based diets containing either dietary cellulose (4%) or a fermentable carbohydrate, galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex (4%). On d 9 posthatch, an equal number of chicks on each diet were inoculated with either distilled water (sham control) or E. acervulina (1 × 10(6) oocysts) and then euthanized on d 7 postinoculation. Overall, body weight gain and feed intake were greater (P < 0.01) for SBM-fed chicks, regardless of infection status. Gain:feed ratio was greater (P ≤ 0.05) for SPI-fed chicks except during d 3-7 postinoculation. Infection status, but not fiber source, affected propionate, isobutyrate, isovalerate, and total branched-chain fatty acid concentrations (P ≤ 0.02). Soybean meal-based diets resulted in greater (P ≤ 0.04) short-chain fatty acid and branched-chain fatty acid concentrations than SPI-based diets. Messenger RNA fold changes relative to uninfected SBM-cellulose-fed chicks of all duodenal cytokines were greater (P ≤ 0.01) for infected chicks, and SBM-fed chicks had greater (P < 0.01) interferon-γ and interleukin-12β expression compared with SPI-fed chicks. Cecal tonsil cytokine expression was also affected (P ≤ 0.02) by infection; however, protein source only affected (P < 0.01) interleukin-1β expression in this tissue. Overall, a SBM-based diet, compared with a semi-purified SPI-based diet with a different ingredient composition, resulted in greater weight gain, feed intake, and short-chain fatty acid production regardless of infection status, and also greater duodenal cytokine expression in E. acervulina- infected chicks, which is hypothesized to be related to the nutrients and oligosaccharides found in SBM.
M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment (2015)

Tumors contain a heterogeneous myeloid fraction comprised of discrete MHC-II(hi) and MHC-II(lo) tumor-associated macrophage (TAM) subpopulations that originate from Ly6C(hi) monocytes. However, the mechanisms regulating the abundance and phenotype of distinct TAM subsets remain unknown. Here, we investigated the role of macrophage colony-stimulating factor (M-CSF) in TAM differentiation and polarization in different mouse tumor models. We demonstrate that treatment of tumor-bearing mice with a blocking anti-M-CSFR monoclonal antibody resulted in a reduction of mature TAMs due to impaired recruitment, extravasation, proliferation, and maturation of their Ly6C(hi) monocytic precursors. M-CSFR signaling blockade shifted the MHC-II(lo)/MHC-II(hi) TAM balance in favor of the latter as observed by the preferential differentiation of Ly6C(hi) monocytes into MHC-II(hi) TAMs. In addition, the genetic and functional signatures of MHC-II(lo) TAMs were downregulated upon M-CSFR blockade, indicating that M-CSFR signaling shapes the MHC-II(lo) TAM phenotype. Conversely, granulocyte macrophage (GM)-CSFR had no effect on the mononuclear tumor infiltrate or relative abundance of TAM subsets. However, GM-CSFR signaling played an important role in fine-tuning the MHC-II(hi) phenotype. Overall, our data uncover the multifaceted and opposing roles of M-CSFR and GM-CSFR signaling in governing the phenotype of macrophage subsets in tumors, and provide new insight into the mechanism of action underlying M-CSFR blockade.
Iroquois homeobox gene 3 establishes fast conduction in the cardiac His–Purkinje network (2011)

Rapid electrical conduction in the His-Purkinje system tightly controls spatiotemporal activation of the ventricles. Although recent work has shed much light on the regulation of early specification and morphogenesis of the His-Purkinje system, less is known about how transcriptional regulation establishes impulse conduction properties of the constituent cells. Here we show that Iroquois homeobox gene 3 (Irx3) is critical for efficient conduction in this specialized tissue by antithetically regulating two gap junction-forming connexins (Cxs). Loss of Irx3 resulted in disruption of the rapid coordinated spread of ventricular excitation, reduced levels of Cx40, and ectopic Cx43 expression in the proximal bundle branches. Irx3 directly represses Cx43 transcription and indirectly activates Cx40 transcription. Our results reveal a critical role for Irx3 in the precise regulation of intercellular gap junction coupling and impulse propagation in the heart.
Evaluation of Concentrated Bone Marrow-derived Mesenchymal Stem Cells Produced from Two Different Cellular Concentrating Systems (2019)

Background. Concentrated bone marrow-derived mesenchymal stem cells (concentrated bMSCs) are used to improve in-vivo healing, yet in-vivo studies do not describe the cellular components that constitute the concentrated bMSCs. If different concentrating systems create concentrated bMSCs with different cellular components this could affect in-vivo study results. This study sought to compare the cellular components of concentrated bMSCs from two different separating systems. Methods. Matched bone marrow (BM) and whole blood were commercially obtained. BM was divided, processed then the concentrated bMSCs were plated and analyzed for cellular concentrates, morphology, triplex, and proliferation assays. The two separation systems used were Angel (system 1) produced from Arthrex, Inc, Naples FL and Smart-Prep (system 2) produced from Harvest Technologies, Lakewood, CO. Time points used were 1, 4, 24, 48, 72 and 96 hours. Blinded observers were used to assess morphology of cells at the 24 hour time point. Results. System 1 had significantly more CFUs (p=.0035) and more nucleated cells (p=.0056). Proliferation was significantly increased for system 1 at time points 1, 24, 48, 72, and 96 hours (p<.001). Cellular viability was significantly increased for system 1 at time points 1, 24 and 48 hours (p<.05). Apoptosis was significantly increased for system 1 at time points 1, 4, 24, 48, 72, 96 hours (p<.05). Cytotoxicity was significantly increased for system 1 at time points 1, 4, 24, 48, 72, 96 hours (p<.001). Morphology of System 1's cells were more consistent of mesenchymal stem cells (MSCs) (Kappa=0.44). Conclusion. Systems that are used to create concentrated bMSCs create populations of concentrated bMSCs with different cellular properties. Future in-vivo studies involving this cell population should describe the cellular properties of the concentrated bMSCs.