gebhart/patrepeval huggingface dataset:
Prevention of platelet alloimmunization. (1986)

Based on transfusion studies in patients and animal model systems, there are currently only two established methods of at least delaying platelet alloimmunization. These involve the administration of leukocyte-poor platelets and red cells or reducing a recipient's exposure to incompatible donor antigens by using single-donor pheresis products. The application of these approaches is limited by practical considerations of achieving sufficiently leukocyte-poor blood products to produce the desired effect, and by the availability and costs of pheresis products compared to pooled random donor platelet concentrates. Furthermore, in chronically transfused aplastic patients who are not receiving concurrent immunosuppressive chemotherapy, there is reason to believe that these transfusion programs may be less effective then in leukemic patients. Fortunately, newer insights into the pathways of antigen recognition have suggested other possible ways to prevent recipient recognition of transfused or transplanted donor tissues. Cyclosporin A specifically inhibits T cells that are central to immune recognition of foreign antigens, and thereby is a very effective immunosuppressive agent. Furthermore, a major pathway of immune recognition may involve direct stimulation of the recipient's T cells by APC in donor tissue; methods to eliminate these cells by physical removal, treatment with anti-Ia antisera, or inactivation with U-V light may represent major advances in preventing alloimmunization. In addition, there is evidence that HLA and B antigens may not be intrinsic to the platelet membrane, suggesting it may be possible to remove them before transfusion, thereby eliminating a major source of incompatability. Finally, as platelets do not express Class II MHC antigens on their surface, "pure" platelet transfusions may be not only non-immunogenic, but may actually induce tolerance to subsequent transfusions or transplants.
Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV (1991)

The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated a cDNA clone (MHVR1) encoding the MHV receptor. The sequence of this clone predicts a 424-amino-acid glycoprotein with four immunoglobulinlike domains, a transmembrane domain, and a short intracytoplasmic tail, MHVR1 is closely related to the murine CEA-related clone mmCGM1 (Mus musculus carcinoembryonic antigen gene family member). Western blot (immunoblot) analysis performed with antireceptor antibodies detected a glycoprotein of 120 kDa in BHK cells stably transfected with MHVR1. This corresponds to the size of the MHV receptor expressed in mouse intestine and liver. Human and hamster fibroblasts transfected with MHVR1 became susceptible to infection with MHV-A59. Like MHV-susceptible mouse fibroblasts, the MHVR1-transfected human and hamster cells were protected from MHV infection by pretreatment with monoclonal antireceptor antibody CC1. Thus, the 110- to 120-kDa CEA-related glycoprotein encoded by MHVR1 is a functional receptor for murine coronavirus MHV-A59.
The guanylyl cyclase receptor family. (1990)

Cyclic GMP (cGMP) signals through protein kinases, ion channels, and possibly other effector systems as a second messenger. Its synthesis is regulated by guanylyl cyclase, whose activity is found in various cellular compartments including the plasma membrane and cytosol. A soluble form of guanylyl cyclase, which occurs as a heterodimer, appears to serve as a receptor for nitric oxide or nitrosothiols, or both. Recent research suggests the presence of multiple subtypes of the soluble form of guanylyl cyclase and tissue-specific expression of the different forms. At least two different forms of the plasma membrane guanylyl cyclase are known to occur in various mammalian tissues. One form, GC-A, is a receptor for atrial natriuretic peptide, and the binding of ligand causes marked increases in cGMP production. The other form, GC-B, is stimulated more effectively by a brain natriuretic peptide than by atrial natriuretic peptide, but its natural ligand remains in question. Both plasma membrane forms of the enzyme contain a single, putative transmembrane domain. The intracellular region of both forms contains a protein kinase-like domain just within the transmembrane domain. The protein kinase-like domain is followed by a cyclase catalytic region near the carboxyl terminus that is homologous to two internally homologous domains found in a bovine brain adenylyl cyclase. The possibility that other guanylyl cyclase receptor subtypes exist is now being explored. If they do, we may subsequently find that a diversity of specific ligands signals through cGMP.
Structure-Based Identification of a Major Neutralizing Site in an Adenovirus Hexon (2006)

Virus-specific neutralizing antibodies present an obstacle to the effective use of adenovirus vectors for gene therapy and vaccination. The specific sites recognized by neutralizing antibodies have not been identified for any adenovirus, but they have been proposed to reside within the hexon, in small regions of the molecule that are exposed on the capsid surface and possess sequences that vary among serotypes. We have mapped the epitopes recognized by a panel of seven hexon-specific monoclonal antibodies that neutralize the chimpanzee adenovirus 68 (AdC68). Surface plasmon resonance experiments revealed that the antibodies compete for a single hexon binding site, and experiments with synthetic peptides indicated that this site resides within just one small surface loop. Mutations within this loop (but not in other surface loops) permitted virus to escape neutralization by all seven monoclonal antibodies and to resist neutralization by polyclonal antisera obtained from animals immunized against AdC68. These results indicate that a single small surface loop defines a major neutralization site for AdC68 hexon.
Rosetta in CASP4: Progress in ab initio protein structure prediction (2001)

Rosetta ab initio protein structure predictions in CASP4 were considerably more consistent and more accurate than previous ab initio structure predictions. Large segments were correctly predicted (>50 residues superimposed within an RMSD of 6.5 A) for 16 of the 21 domains under 300 residues for which models were submitted. Models with the global fold largely correct were produced for several targets with new folds, and for several difficult fold recognition targets, the Rosetta models were more accurate than those produced with traditional fold recognition models. These promising results suggest that Rosetta may soon be able to contribute to the interpretation of genome sequence information.
Rational design of low-molecular weight heparins with improved in vivo activity (2003)

Heparin and low-molecular weight heparins (LMWHs), complex, sulfated polysaccharides isolated from endogenous sources, are potent modulators of hemostasis. Heparin and LMWHs interact with multiple components of the coagulation cascade to inhibit the clotting process. Pharmaceutical preparations of these complex polysaccharides, typically isolated from porcine intestinal mucosa, are heterogeneous in length and composition and, hence, highly polydisperse. Because of the structural heterogeneity of heparin and LMWHs, correlating their activity with a particular structure or structural motif has been a challenging task. Herein, we demonstrate a practical analytical method that enables the measurement of a structural correlate to in vivo anticoagulant function. With this understanding we have developed LMWHs with increased anticoagulant activity and decreased polydispersity. In addition to the pronounced anti-Xa and anti-IIa activity of these LMWHs, we also demonstrate that they possess desirable in vivo pharmacokinetic properties, the ability to cause the release of tissue factor pathway inhibitor (TFPI) from the endothelium, complete bioavailability through s.c. delivery, and the ability to inhibit both venous and arterial thromboses. Importantly, from a clinical safety point of view, unlike LMWHs presently used in the clinic, we show that these LMWHs are rapidly and completely neutralized by protamine. Together, the findings presented herein demonstrate a facile approach for the creation of designer LMWHs with optimal activity profiles.
Blockade of Lymphocyte Chemotaxis in Visceral Graft-versus-Host Disease (2012)

In this study, inhibition of lymphocyte trafficking was a specific and potentially effective new strategy to prevent visceral acute GVHD. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00948753.).
RF Technologies for Low Power Wireless Communications (2001)

A survey of microwave technology tailored for professionals in wireless communications RF Technologies for Low Power Wireless Communications updates recent developments in wireless communications from a hardware design standpoint and offers specialized coverage of microwave technology with a focus on the low power wireless units required in modern wireless systems. It explores results of recent research that focused on a holistic, integrated approach to the topics of materials, devices, circuits, modulation, and architectures rather than the more traditional approach of research into isolated topical areas. Twelve chapters deal with various fundamental research aspects of low power wireless electronics written by world-class experts in each field. The first chapter offers an overview of wireless architecture and performance, followed by detailed coverage of: Advanced GaAs-based HBT designs InP-based devices and circuits Si/SiGe HBT technology Noise in GaN devices Power amplifier architectures and nonlinearities Planar-oriented components MEMS and micromachined components Resonators, filters, and low-noise oscillators Antennas Transceiver front-end architectures With a clear focus and expert contributors, RF Technologies for Low Power Wireless Communications will be of interest to a wide range of electrical engineering disciplines working in wireless technologies.
A Survey of Distributed Data Stream Processing Frameworks (2019)

Big data processing systems are evolving to be more stream oriented where each data record is processed as it arrives by distributed and low-latency computational frameworks on a continuous basis. As the stream processing technology matures and more organizations invest in digital transformations, new applications of stream analytics will be identified and implemented across a wide spectrum of industries. One of the challenges in developing a streaming analytics infrastructure is the difficulty in selecting the right stream processing framework for the different use cases. With a view to addressing this issue, in this paper we present a taxonomy, a comparative study of distributed data stream processing and analytics frameworks, and a critical review of representative open source (Storm, Spark Streaming, Flink, Kafka Streams) and commercial (IBM Streams) distributed data stream processing frameworks. The study also reports our ongoing study on a multilevel streaming analytics architecture that can serve as a guide for organizations and individuals planning to implement a real-time data stream processing and analytics framework.
P55, an immunogenic but nonprotective 55-kilodalton Borrelia burgdorferi protein in murine Lyme disease (1996)

Immunization of C3H mice with P55 (previously called S1), a 55-kDa Borrelia burgdorferi antigen that is immunogenic after infection, elicited a strong antibody response but did not protect mice against B. burgdorferi challenge. Mice immunized with a P55 fusion protein in complete Freund's adjuvant developed anti-P55 antibodies, detectable at a titer of 1:10,000 by immunoblotting. To determine, if a protective response had been elicited, P55-vaccinated mice were fed upon by ticks infected with B. burgdorferi. The frequency of B. burgdorferi infection was similar in P55-immunized and control mice, and spirochetes were not destroyed within ticks that fed on P55-vaccinated mice. P55 is an immunogenic antigen that does not induce a protective response in the vertebrate or invertebrate host.
The effects of copper deficiency on human lymphoid and myeloid cells: anin vitromodel (1996)

Cu has long been known to influence immune responses. An in vitro model system was established in which human myeloid (HL-60), B-lymphoid (Raji) and T-lymphoid (Molt-3) cell lines could be grown in culture media of varying Cu levels. Initially Cu was removed from the medium by dialysis of fetal calf serum against a metal-ion chelator, minor depletion of other trace metals being obviated by repletion with appropriate metal salts. The growth rate of HL-60 was significantly (P < 0.05) inhibited by 72 h Cu depletion. Molt-3 cells required a longer period, up to 144 h, in Cu-depleted medium before growth was impaired. Raji-cell growth was not affected. These results confirmed clinical observations that T-cell functions were more sensitive to Cu deprivation than B cells. Analysis of intracellular metal levels in Molt-3 cells showed that Cu levels had been significantly lowered (P < 0.05) although Ca2+ levels were raised. Intracellular activity of the antioxidant enzyme superoxide dismutase (EC 1.15.1.1) was significantly impaired (P < 0.05) in Molt-3 cells grown in Cu-depleted medium. Activity of the mitochondrial enzyme cytochrome c oxidase (EC 1.9.3.1) was also significantly impaired (P < 0.05) by Cu depletion. Each of these findings indicates an increase in the potential for cellular damage by reduced antioxidant activity, impairment of normal mitochondrial activity and excessive Ca2+ influx. A major consequence of the type of damage occurring under these circumstances is membrane disruption. This was confirmed by scanning electron microscopy of Molt-3 cells grown under varying Cu levels.
Ectopic expression of the TERE1 (UBIAD1) protein inhibits growth of renal clear cell carcinoma cells: Altered metabolic phenotype associated with reactive oxygen species, nitric oxide and SXR target genes involved in cholesterol and lipid metabolism (2013)

Current studies of the TERE1 (UBIAD1) protein emphasize its multifactorial influence on the cell, in part due to its broad sub-cellular distribution to mitochondria, endoplasmic reticulum and golgi. However, the profound effects of TERE1 relate to its prenyltransferase activity for synthesis of the bioactive quinones menaquinone and COQ10. Menaquinone (aka, vitamin K-2) serves multiple roles: as a carrier in mitochondrial electron transport, as a ligand for SXR nuclear hormone receptor activation, as a redox modulator, and as an alkylator of cellular targets. We initially described the TERE1 (UBIAD1) protein as a tumor suppressor based upon reduced expression in urological cancer specimens and the inhibition of growth of tumor cell lines/xenografts upon ectopic expression. To extend this potential tumor suppressor role for the TERE1 protein to renal cell carcinoma (RCC), we applied TERE1 immunohistochemistry to a TMA panel of 28 RCC lesions and determined that in 57% of RCC lesions, TERE1 expression was reduced (36%) or absent (21%). Ectopic TERE1 expression caused an 80% decrease in growth of Caki-1 and Caki-2 cell lines, a significantly decreased colony formation, and increased caspase 3/7 activity in a panel of RCC cell lines. Furthermore, TERE1 expression increased mitochondrial oxygen consumption and hydrogen production, oxidative stress and NO production. Based on the elevated cholesterol and altered metabolic phenotype of RCC, we also examined the effects of TERE1 and the interacting protein TBL2 on cellular cholesterol. Ectopic TERE1 or TBL2 expression in Caki-1, Caki-2 and HEK 293 cells reduced cholesterol by up to 40%. RT-PCR analysis determined that TERE1 activated several SXR targets known to regulate lipid metabolism, consistent with predictions based on its role in menaquinone synthesis. Loss of TERE1 may contribute to the altered lipid metabolic phenotype associated with progression in RCC via an uncoupling of ROS/RNS and SXR signaling from apoptosis by elevation of cholesterol.
Performance Characterization of a 10-Gigabit Ethernet TOE (2006)

Though traditional Ethernet based network architectures such as Gigabit Ethernet have suffered from a huge performance difference as compared to other high performance networks (e.g, InfiniBand, Quadrics, Myrinet), Ethernet has continued to be the most widely used network architecture today. This trend is mainly attributed to the low cost of the network components and their backward compatibility with the existing Ethernet infrastructure. With the advent of 10-Gigabit Ethernet and TCP offload engines (TOEs), whether this performance gap be bridged is an open question. In this paper, we present a detailed performance evaluation of the Chelsio T110 10-Gigabit Ethernet adapter with TOE. We have done performance evaluations in three broad categories: (i) detailed micro-benchmark performance evaluation at the sockets layer, (ii) performance evaluation of the message passing interface (MPI) stack atop the sockets interface, and (iii) application-level evaluations using the Apache Web server. Our experimental results demonstrate latency as low as 8.9 /spl mu/s and throughput of nearly 7.6 Gbps for these adapters. Further, we see an order-of-magnitude improvement in the performance of the Apache Web server while utilizing the TOE as compared to the basic 10-Gigabit Ethernet adapter without TOE.
Cloning of cDNA sequences of human adenosine deaminase. (1983)

Cloned cDNA sequences of human adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4) have been isolated from a cDNA library constructed in bacteriophage lambda gt10. The cDNA for the library was prepared from poly(A)+ RNA isolated from a human T-lymphoblast cell line, CCRF-CEM. The library was initially screened by differential plaque hybridization to labeled cDNA prepared from human T- and B-lymphoblast cell lines with a 21-fold difference in levels of translatable ADA mRNA. Two recombinants containing cloned cDNA sequences for ADA were identified by hybridization-selected translation. Both recombinants contained approximately 1,600 base pairs of inserted human DNA. Restriction maps of the two inserts were not identical. One contained approximately 40 base pairs of additional DNA toward the center of the cDNA. The cloned cDNA specifically hybridized to five fragments generated by HindIII digestion of human genomic DNA. It also hybridized to human lymphoblast RNA species 1.6 and 5.8 kilobases in length. The cDNA was used as a probe to estimate ADA mRNA levels in human lymphoblast cell lines. ADA mRNA levels correlate closely with levels of ADA catalytic activity and ADA protein in cell lines containing structurally normal ADA. A leukemic T-lymphoblast line produced 6 to 9 times as much ADA protein and ADA mRNA as transformed B-lymphoblast lines. Two mutant B-lymphoblast lines from patients with hereditary ADA deficiency contained unstable ADA protein but had 3 to 4 times the normal level of ADA mRNA.
Liposome‐bound APO2L/TRAIL is an effective treatment in a rabbit model of rheumatoid arthritis (2010)

Our findings indicate that binding APO2L/TRAIL to the liposome membrane increases its bioactivity and results in effective treatment of AIA.
Preservation of urinary continence and potency after cystoprostatectomy. (1992)

Between 1980-1989 a total of 349 patients underwent one-stage radical cystoprostatectomy and an orthotopic bladder substitution. 278 patients underwent the Camey I bladder replacement and in 71 patients a detubularized ileal loop was utilized (Camey II). 75 patients underwent a potency-sparing cystectomy (32 patients of the Camey I and 43 patients of the Camey II groups). All patients were followed at least one year and had continence and potency assessment. Among the patients who underwent the Camey I procedure, 66% achieved daytime continence and 21% night-time continence 6 months after surgery. One year after surgery 86% of patients had normal continence during the day and 47% was continent during the night. 14% of patients had episodes of day-time incontinence one year after surgery. Among the patients who underwent the Camey II bladder replacement 86% achieved day-time continence and 59% night-time continence 6 months after surgery. At one year after surgery 91% was continent during the day, 72% was dry during the night and only 9% had episodes of diurnal incontinence. Potency was achieved in 24 of 32 patients (75%) with the Camey I bladder substitution, and in 34 of the 43 patients (79%) with the Camey II bladder substitution. Our data demonstrate that excellent rates of continence and potency are achievable in the post-cystectomy population. Patients with the Camey II bladder replacement achieve continence earlier than patients with the Camey I bladder substitution. Diurnal continence is slightly better after the Camey II procedure, one year after surgery, but the difference is not statistically significant. Nocturnal continence is significantly better with the Camey II bladder substitution.
Plasmapheresis and guillain‐barré syndrome: Analysis of prognostic factors and the effect of plasmapheresis (1988)

Abstract The time course of recovery in the Guillain‐Barré syndrome is known to vary widely, but factors associated with differences have not been previously defined. In this study we used multivariate analysis to identify such factors and to determine whether the presence or absence of specific factors would influence treatment decisions, particularly the use of plasmapheresis. Data from 245 patients randomized into conventional and plasmapheresis arms were used to assess the time to walk independently (Grade 2), the time to improve one grade, and the percentage improved at 4 weeks. Individually, many factors were associated with outcome. In the multivariate analysis, four factors correlate with poorer outcomes: mean amplitude of compound muscle action potential on stimulating distally of 20% of normal or less, older age, time from onset of disease of 7 days or less, and need for ventilatory support. The most powerful predictor of outcome was the abnormal mean amplitude of compound muscle action potential on stimulating distally. Plasmapheresis, the only variable the physician can influence, has a beneficial effect over and above any or all of these factors. The plasmapheresis patients on continuous flow machines had better outcomes than those on intermittent flow machines. From these data, tables of expected outcome probabilities have been developed.
Inhibition of Mitochondrial Respiration (2003)

Cancer cells are under intrinsic increased oxidative stress and vulnerable to free radical-induced apoptosis. Here, we report a strategy to hinder mitochondrial electron transport and increase superoxide O2. radical generation in human leukemia cells as a novel mechanism to enhance apoptosis induced by anticancer agents. This strategy was first tested in a proof-of-principle study using rotenone, a specific inhibitor of mitochondrial electron transport complex I. Partial inhibition of mitochondrial respiration enhances electron leakage from the transport chain, leading to an increase in O2. generation and sensitization of the leukemia cells to anticancer agents whose action involve free radical generation. Using leukemia cells with genetic alterations in mitochondrial DNA and biochemical approaches, we further demonstrated that As2O3, a clinically active anti-leukemia agent, inhibits mitochondrial respiratory function, increases free radical generation, and enhances the activity of another O2.-generating agent against cultured leukemia cells and primary leukemia cells isolated from patients. Our study shows that interfering mitochondrial respiration is a novel mechanism by which As2O3 increases generation of free radicals. This novel mechanism of action provides a biochemical basis for developing new drug combination strategies using As2O3 to enhance the activity of anticancer agents by promoting generation of free radicals.