gebhart/patrepeval huggingface dataset:
Bone marrow-derived dendritic cells from experimental allergic encephalomyelitis induce immune tolerance to EAE in Lewis rats (2001)

We have previously shown that dendritic cells (DC), upon being pulsed in vitro with encephalitogenic myelin basic protein peptide 68-86 (MBP 68-86) and injected subcutaneously (s.c.) back to healthy Lewis rats, transfer immune tolerance to experimental allergic encephalomyelitis (EAE) induced by immunization with MBP 68-86 and Freund's complete adjuvant (FCA). We here assumed that DC become pulsed in EAE rats, and that expansion in vitro of such 'in vivo pulsed EAE-DC' might also have the capacity to induce immune tolerance to EAE, thereby eliminating the need for in vitro pulsing of DC with autoantigens which are still unknown in many autoimmune diseases in the human. In the present study, EAE-DC were generated from bone marrow of Lewis rats, with EAE induced with MBP 68-86 + FCA, and expanded in vitro by culture with GM-CSF and IL-4. In comparison with DC from normal rats, EAE-DC exhibited higher viability in the absence of growth factors, and presented specific antigen to naïve T cells in vitro. The DC derived from both EAE and healthy rats stimulated strong proliferation in an antigen-independent manner, lasting for 4 weeks after DC were s.c. injected into healthy rats. During this time, injection of EAE-DC did not induce clinical EAE. However, when these rats were immunized with MBP 68-86 + FCA, subsequent EAE was dramatically suppressed, and was associated with increased IFN-gamma expression, nitric oxide production, gradually reduced proliferation and cell apoptosis, compared with PBS-injected control EAE rats. LPS-treated DC did not induce tolerance, suggesting that the tolerance is mediated by an immature stage of DC. These observations support the hypothesis that EAE-DC can transfer immune tolerance to EAE, thereby omitting the step of characterizing specific autoantigen. Omitting the step of loading DC with antigen not only eliminates the extremely complex procedure of defining pathogenically-relevant autoantigens, but also avoids the risk of inducing immunogenicity of DC in the treatment of autoimmune diseases.
Spatial management of data (1980)

Spatial data management is a technique for organizing and retrieving information by positioning it in a graphical data space (GDS). This graphical data space is viewed through a color raster-scan display which enables users to traverse the GDS surface or zoom into the image to obtain greater detail. In contrast to conventional database management systems, in which users access data by asking questions in a formal query language, a spatial data management system (SDMS) presents the information graphically in a form that seems to encourage browsing and to require less prior knowledge of the contents and organization of the database. This paper presents an overview of the SDMS concept and describes its implementation in a prototype system for retrieving information from both a symbolic database management system and an optical videodisk.
Expression of interleukin‐21 receptor, but not interleukin‐21, in synovial fibroblasts and synovial macrophages of patients with rheumatoid arthritis (2004)

Our data demonstrate that IL-21R is expressed in RA synovium by RASFs and synovial macrophages. IL-21R is associated with the activated phenotype of RASFs independently of the major proinflammatory cytokines IL-1beta and TNFalpha, but correlates negatively with the destruction of articular cartilage and bone.
A Degradable Polyethylenimine Derivative with Low Toxicity for Highly Efficient Gene Delivery (2003)

Routine clinical implementation of human gene therapy awaits safe and efficient gene delivery methods. Polymeric vectors hold promise due to the availability of diverse chemistries, potentially providing targeting, low immunogenicity, nontoxicity, and robustness, but lack sufficient gene delivery efficiency. We have synthesized a versatile group of degradable polycations, through addition of 800-Da polyethylenimine (PEI) to small diacrylate cross-linkers. The degradable polymers reported here are similar in structure, size (14-30 kDa), and DNA-binding properties to commercially available 25-kDa PEI, but mediate gene expression two- to 16-fold more efficiently and are essentially nontoxic. These easily synthesized polymers are some of the most efficient polymeric vectors reported to date and provide a versatile platform for investigation of the effects of polymer structure and degradation rate on gene delivery efficiency.
Reduced activity of 11β-hydroxysteroid dehydrogenase in patients with cholestasis (2001)

Enhanced renal sodium retention and potassium loss in patients with cirrhosis is due to activation of mineralocorticoid receptors (MRs). Increased aldosterone concentrations, however, do not entirely explain the activation of MR in cirrhosis. Here, we hypothesize that cortisol activates MRs in patients with cholestasis. We present evidence that access of cortisol to MRs is a result of bile acid−mediated inhibition of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), an MR-protecting enzyme that converts cortisol to cortisone. Twelve patients with biliary obstruction and high plasma bile acid levels were studied before and after removal of the obstruction. The urinary ratio of (tetrahydrocortisol + 5α-tetrahydrocortisol)/tetrahydrocortisone, a measure of 11β-HSD2 activity, decreased from a median of 1.91 during biliary obstruction to 0.78 at 4 and 8 weeks after removal of the obstruction and normalization of plasma bile acid concentrations. In order to demonstrate that bile acids facilitate access of cortisol to the MR by inhibiting 11β-HSD2, an MR translocation assay was performed in HEK-293 cells transfected with human 11β-HSD2 and tagged MR. Increasing concentrations of chenodeoxycholic acid led to cortisol-induced nuclear translocation of MR. In conclusion, 11β-HSD2 activity is reduced in cholestasis, which results in MR activation by cortisol.
Intracellular immunization of human T cells with a hairpin ribozyme against human immunodeficiency virus type 1. (1994)

T-cell lines (Jurkat and Molt-4) were transduced with retroviral vectors containing a hairpin ribozyme that targets a conserved sequence in the 5' transcribed leader sequence of human immunodeficiency virus (HIV) type 1. Stable cell lines were generated which constitutively and persistently expressed the ribozyme gene driven by either the Moloney retroviral long terminal repeat (LTR) or an internal human tRNA(val) promoter. There was no apparent deleterious effect of long-term ribozyme expression on cell proliferation or viability. Cells expressing ribozyme were resistant to challenge from diverse strains of HIV, including an uncloned clinical isolate. No reverse transcriptase activity or virus infectivity was detectable in the culture supernatants of Jurkat cells expressing the ribozyme driven by the tRNA(val) promoter up to 35 days after challenge with HIV-1/HXB2. Expression of the ribozyme also significantly decreased (by approximately 50- to 100-fold) the efficiency of incoming virus to synthesize viral DNA. These and previously reported results indicate that transfer and expression of the ribozyme gene interfere with both early and late events in the HIV replication cycle and confer long-term resistance to HIV-1 infection.
High-level design verification of microprocessors via error modeling (1998)

A design verification methodology for microprocessor hardware based on modeling design errors and generating simulation vectors for the modeled errors via physical fault testing techniques is presented. We have systematically collected design error data from a number of microprocessor design projects. The error data is used to derive error models suitable for design verification testing. A class of basic error models is identified and shown to yield tests that provide good coverage of common error types. To improve coverage for more complex errors, a new class of conditional error models is introduced. An experiment to evaluate the effectiveness of our methodology is presented. Single actual design errors are injected into a correct design, and it is determined if the methodology will generate a test that detects the actual errors. The experiment has been conducted for two microprocessor designs and the results indicate that very high coverage of actual design errors can be obtained with test sets that are complete for a small number of synthetic error models.
Middlebox communication architecture and framework (2002)

A principal objective of this document is to describe the underlying framework of middlebox communications (MIDCOM) to enable complex applications through the middleboxes, seamlessly using a trusted third party.This document and a companion document on MIDCOM requirements ([REQMTS]) have been created as a precursor to rechartering the MIDCOM working group.There are a variety of intermediate devices in the Internet today that require application intelligence for their operation.Datagrams pertaining to real-time streaming applications, such as SIP and H.323, and peer-to-peer applications, such as Napster and NetMeeting, cannot be identified by merely examining packet headers.Middleboxes implementing Firewall and Network Address Translator services typically embed application intelligence within the device for their operation.The document specifies an architecture and framework in which trusted third parties can be delegated to assist the middleboxes to perform their operation, without resorting to embedding application intelligence.Doing this will allow a middlebox to continue to provide the services, while keeping the middlebox application agnostic.
Fundamental Limits on the Mobility of Nanotube‐Based Semiconducting Inks (2010)

High mobility and high on/off ratio thin-film transistors are fabricated using solution-based deposition of purified semiconducting carbon nanotubes. A comprehensive spectrum of the density starting from less than 10 tubes μm−2 to the high end of around 100 tubes μm−2 is investigated. This study provides the first important roadmap for the tradeoffs between mobility and on/off ratio in nanotube-based semiconducting inks. 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.
Fiber Optic Development For Use On The Fiber Optic Helmet Mounted Display (1989)

The Fiber Optic Helmet Mounted Display (FOHMD) developed by CAE for the US Air Force Human Resources Laboratory (AFHRL), requires very large format, coherant fiber optic cables. These cables must support the FOHMD&apos;s demanding modulation transfer function (MTF) requirements in full color and be flexible, durable, lightweight, and up to six feet long. These requirements have so constrained glass technology that conventional approaches are not capable of delivering the requisite performance. The cables currently used on FOHMD systems have alternating layers of inactive material to buffer linear arrays of multifibers so that a lighter weight 25 by 19 mm end size is achieved with 5 micron core size individual fibers. This skip-layer, multifiber approach delivers reasonable performance when using spectral multiplexing across the inactive layers. However, residual fixed pattern noise, broken multifibers, and inadequate resolution have reduced system performance. Because of the critical influence of the fiber optic cables on overall system performance, an alternative, but riskier process, is being explored. Several smaller experimental cables have been assembled using leachable, fused, multifibers arrayed in a hexagonal pattern. The inconspicuous mating of hexagonal elements should be possible now because of an order of magnitude improvement in cable drawing technology. Fused/leached fiber optic cables have the potential to provide image transmission capability equal to ten channels of the best available computer image generators. When coupled with chromatic enhancement to mask fixed pattern and broken fiber noise, the resulting MTF of the FOHMD optics would deliver a resolution equal to 1.5 arc minutes per pixel.
Plasma levels of platelet-derived growth factor BB and transforming growth factor in patients with failed hip prostheses (2005)

Background The role of growth factors in prosthesis loosening is unclear. We evaluated the levels of plate-let-derived growth factor BB (PDGF-BB), transforming growth factors β1 (TGF-β1) and β2 (TGF-β2), both before and after activation, in patients with aseptic loosening of their hip prosthesis.Patients and methods 26 patients with loosened hip implants were compared with 21 patients who had stable hip prostheses, and 28 patients undergoing primary hip replacement. The plasma levels of the growth factors were analyzed by enzyme immunoassay. TGF-β1 and TGF-β2 were determined both before and after activation.Results Patients with aseptic loosening had significantly lower PDGF-BB levels than patients undergoing primary hip replacement, and significantly lower TGF-β2 levels than patients with a stable implant. Patients with stable prostheses had significantly higher TGF-β1 and TGF-β2 levels than patients undergoing primary hip replacement.Interpretation It is possible that the prosthetic implant itself causes a local increase in PDGF-BB, TGF-β1 and TGF-β2, released by osteoblasts and other cells in the microenvironment. The plasma PDGF-BB measured does not correspond to local release, which is probably due to local consumption or degradation. The consumption of PDGF-BB is low in stable implants, and TGF-β1 and TGF-β2 levels increase during bone formation. In loosening, PDGF-BB consumption is higher and causes a significant reduction in plasma levels as compared to presurgery. The formation of poor-quality bone may be related to the scarce increase in TGF-β1 and TGF-β2. In conclusion, compared with patients with a stable implant, a reduction in bone-forming growth factors appears to occur in individuals with aseptic loosening.
Evolution of Function of a Fused Metazoan tRNA Synthetase (2010)

The origin and evolution of multidomain proteins are driven by diverse processes including fusion/fission, domain shuffling, and alternative splicing. The 20 aminoacyl-tRNA synthetases (AARS) constitute an ancient conserved family of multidomain proteins. The glutamyl-prolyl tRNA synthetase (EPRS) of bilaterian animals is unique among AARSs, containing two functional enzymes catalyzing ligation of glutamate and proline to their cognate transfer RNAs (tRNAs). The ERS and PRS catalytic domains in multiple bilaterian taxa are linked by variable number of helix-turn-helix domains referred to as WHEP-TRS domains. In addition to its canonical aminoacylation activities, human EPRS exhibits a noncanonical function as an inflammation-responsive regulator of translation. Recently, we have shown that the WHEP domains direct this auxiliary function of human EPRS by interacting with an mRNA stem-loop element (interferon-gamma-activated inhibitor of translation [GAIT] element). Here, we show that EPRS is present in the cnidarian Nematostella vectensis, which pushes the origin of the fused protein back to the cnidarian-bilaterian ancestor, 50-75 My before the origin of the Bilateria. Remarkably, the Nematostella EPRS mRNA is alternatively spliced to yield three isoforms with variable number and sequence of WHEP domains and with distinct RNA-binding activities. Whereas one isoform containing a single WHEP domain binds tRNA, a second binds both tRNA and GAIT element RNA. However, the third isoform contains two WHEP domains and like the human ortholog binds specifically to GAIT element RNA. These results suggest that alternative splicing of WHEP domains in the EPRS gene of the cnidarian-bilaterian ancestor gave rise to a novel molecular function of EPRS conserved during metazoan evolution.
Antithrombin Pittsburgh: an alpha1-antitrypsin variant causing hemorrhagic disease (1978)

A 10-year-old boy had a severe lifelong hemorrhagic disorder that had necessitated more than 50 hospitalizations. Laboratory examination showed prolonged bleeding, clotting, partial thromboplastin, prothrombin, and thrombin times. These findings were due to a potent inhibitor of the thrombin-fibrinogen reaction. This inhibitor was similar to heparin in that it acted immediately and did not interfere with the coagulant activities of certain venoms. It differed from heparin in not being adsorbed to barium citrate or neutralized by protamine sulfate. The inhibitory effect was found in the alpha1-globulin fraction. It was identified immunologically and functionally as a double-banded alpha1-antitrypsin of a previously unreported phenotype. The inhibitory effects were depressed by trypsin and heterologous anti-alpha1-antitrypsin.
Identifying and manipulating structural determinates linking catalytic specificities in terpene synthases (2006)

Terpene synthases are a mechanistically intriguing family of enzymes that catalyze complex, multistep reactions that are capable of generating hundreds of structurally diverse hydrocarbon and oxygenated scaffolds of biological and commercial importance. Interestingly, distantly related terpene synthases from fungi to plants all contain an invariant three-dimensional fold, and molecular comparisons of their active sites indicate that they are enriched with relatively inert amino acid residues that do not react directly with the reaction intermediates. Therefore, catalytic specificity appears to rely on the contour and dynamics of the active site created by the positioning of amino acid backbones and side chains on this catalytic surface and by supporting layers of residues surrounding the synthase active site cavity. Despite the high degree of structural relatedness among terpene synthases, previous studies suggest that no clear relationship between phylogenic organization and catalytic specificities is easily deciphered. We now report on the reciprocal interconversion of catalytic specificities between two distinct yet evolutionarily related terpene synthases based on the systematic identification and mutational replacement of variable residues within and surrounding the active site. Furthermore, we uncover previously undocumented biosynthetic activity during the interconversion, activity that could have been present in a common ancestor of these two highly related synthases. These results provide a simplified means for mapping structural features that are responsible for functional attributes and a strategy for identifying residues that differentiate divergent biosynthetic properties in phylogenetically related terpene synthases.
In vivo local determination of tissue optical properties: applications to human brain (1999)

Local and superficial near-infrared (NIR) optical-property characterization of turbid biological tissues can be achieved by measurement of spatially resolved diffuse reflectance at small source-detector separations (<1.4 mm). However, in these conditions the inverse problem, i.e., calculation of localized absorption and the reduced scattering coefficients, is necessarily sensitive to the scattering phase function. This effect can be minimized if a new parameter of the phase function gamma, which depends on the first and the second moments of the phase function, is known. If gamma is unknown, an estimation of this parameter can be obtained by the measurement, but the uncertainty of the absorption coefficient is increased. A spatially resolved reflectance probe employing multiple detector fibers (0.3-1.4 mm from the source) is described. Monte Carlo simulations are used to determine gamma, the reduced scattering and absorption coefficients from reflectance data. Probe performance is assessed by measurements on phantoms, the optical properties of which were measured by other techniques [frequency domain photon migration (FDPM) and spatially resolved transmittance]. Our results show that changes in the absorption coefficient, the reduced scattering coefficient, and gamma can be measured to within +/-0.005 mm(-1), +/-0.05 mm(-1), and +/-0.2, respectively. In vivo measurements performed intraoperatively on a human skull and brain are reported for four NIR wavelengths (674, 811, 849, 956 nm) when the spatially resolved probe and FDPM are used. The spatially resolved probe shows optimum measurement sensitivity in the measurement volume immediately beneath the probe (typically 1 mm(3) in tissues), whereas FDPM typically samples larger regions of tissues. Optical-property values for human skull, white matter, scar tissue, optic nerve, and tumors are reported that show distinct absorption and scattering differences between structures and a dependence on the phase-function parameter gamma.
A new correlation-based measure of spike timing reliability (2020)

We introduce a new correlation-based measure of spike timing reliability. Unlike other measures, it does not require the definition of a posteriori “events”. It relies on only one parameter, which relates to the timescale of spike timing precision. We test the measure on surrogate data sets with varying amounts of spike time jitter, and missing or additional spikes, and compare it with a widely used histogram-based measure. The measure is efficient and faithful in characterizing spike timing reliability and produces smaller errors in the reliability estimate than the histogram-based measure based on the same number of trials.
Optical Learning In A Smart Spatial Light Modulator (2005)

A synaptic plane rendered by an array of smart pixels was described regarding its application as a complementary component for neural network implementation. The smart spatial light modulator featured auto-modification abilities. Thus, an optical system incorporating this device can show self-reliant optical learning. Furthermore, the optical system design, in the area of its optical interconnection scheme, is highly flexible since the independent weight-plane pixels eliminated the difficulty between weight update calculation and weight representation.
Presentation of an exogenous antigen by major histocompatibility complex class I molecules (1994)

Cytotoxic T lymphocytes (CTL) generally recognize peptides derived from endogenously expressed proteins in association with nascent major histocompatibility complex (MHC) class I molecules. In contrast, peptides derived from exogenous proteins associate with MHC class II following endocytosis to an endosomal compartment. However, we have recently demonstrated that exogenous fusion proteins consisting of the binding and translocating domains of Pseudomonas exotoxin (PE) fused with CTL epitopes derived from either influenza matrix protein (PEMa) or nucleoprotein are internalized, processed, targeted to and presented by MHC class I (Donnelly et al. 1993, Proc. Natl. Acad. Sci. USA 1993. 90: 3530). PE is known to be internalized, processed in endosomes, and translocated to the cytosol during intoxication of cells. However, our present studies demonstrate that, unlike PE, PEMa does not require translocation to the cytosol to exert its effect. First, two inhibitors of PE toxicity that exert their effects at steps subsequent to endosomal processing had no effect on the sensitization of target cells for CTL-mediated lysis by PEMa. NH4Cl, which inhibits PE by raising endosomal pH, and brefeldin A, which inhibits PE by disrupting the Golgi complex, did not inhibit sensitization of targets cells by PEMa. Second, PEMa was capable of sensitizing for lysis T2 mutant cells, which are defective in transport of peptides from the cytosol to the lumen of the endoplasmic reticulum for presentation by MHC class I. These results suggest that PEMa is proteolytically processed in endosomes, and association with MHC class I does not require nascent MHC molecules. Such a process may involve internalized MHC class I, and subsequent expression of the peptide-MHC complexes on the cell surface would then lead to recognition by CTL.