gebhart/patrepeval huggingface dataset:
PARK7 and Nucleoside Diphosphate Kinase A as Plasma Markers for the Early Diagnosis of Stroke (2005)

PARK7 and NDKA may be useful plasma biomarkers for the early diagnosis of stroke. In addition, this study demonstrated the utility of analysis of postmortem CSF proteins as a first step in the discovery of plasma markers of ischemic brain injury.
The isolation and sequencing of human gastric inhibitory peptide (GIP) (1984)

Human GIP 1-42 and fragments of human GIP corresponding to GIP 10-42, GIP 11-42, and GIP 17-42 were isolated from acid-ethanol extracts of human small intestines with the aid of an anti-GIP serum specific for the extreme C-terminal portion of the GIP molecule. The full sequence of human GIP has been established by Edman degradation of these peptides and fragments thereof by automatic gas-phase sequencing. Human GIP differs from porcine GIP at residues 18 and 34. The sequence of human GIP is thus: (Formula: see text) Amino acid residues 18 and 34 are Arg and Ser, respectively, in porcine GIP.
The cytochrome oxidases ofBacillus subtilis: mapping of a gene affecting cytochromeaa3and its replacement by cytochromeoin a mutant strain (1989)

A mutant of Bacillus subtilis has been isolated that fails to grow on succinate as the source of carbon, yet grows on glucose. Intact cells of the mutant and cytoplasmic membranes derived therefrom lack cytochromes a and a3 but contain a cytochrome o-like pigment, which forms a photodissociable compound with CO and is reactive with oxygen. The mutation in the genome has been located and lies at about 130 degrees on the chromosomal map between the metC and pyrD loci. The designation cox is suggested for this gene.
Treatment of antibiotic-associated colitis with vancomycin (1984)

Sixty-five patients were treated with oral vancomycin for Clostridium difficile colitis associated with treatment of infection by antibiotics. Colitis was confirmed by endoscopy in patients with diarrhoea and positive tests on diarrhoeal stools for Cl. difficile and/or its cytotoxin or, if endoscopy could not be performed, by the presence of fever and peripheral or faecal leucocytosis. Vancomycin dosage ranged from 125 to 500 mg four times daily for an average of about ten days. The mean duration of diarrhoea after starting therapy was four days; abdominal pain and fever usually resolved in two or three days. Post-treatment carriage of Cl. difficile was common. Eighteen per cent of patients developed a recurrence of colitis after treatment was discontinued, but responded to treatment with oral vancomycin, metronidazole, or bacitracin. After comparison of our results with those reported by others we concluded that vancomycin remains the treatment of choice for patients who are acutely and severely ill with Cl. difficile.
High-Affinity Interactions between Peptides and Heat Shock Protein 70 Augment CD8+ T Lymphocyte Immune Responses (2006)

Exogenously delivered antigenic peptides complexed to heat shock proteins (HSPs) are able to enter the endogenous Ag-processing pathway and prime CD8+ CTL. It was determined previously that a hybrid peptide containing a MHC class I-binding epitope and HSP70-binding sequence Javelin (J0) in complex with HSP70 could induce cytotoxic T cell responses in vivo that were more robust than those induced by the minimal epitope complexed with HSP70. The present study introduces a novel, higher-affinity HSP70-binding sequence (J1) that significantly enhances binding of various antigenic peptides to HSP70. A competition binding assay revealed a dissociation constant that was 15-fold lower for the H2-K(b) OVA epitope SIINFEKL-J1 compared with SIINFEKL-J0, indicating a substantially higher affinity for HSP70. Further, modifying the orientation of the hybrid epitope and introducing a cleavable linker sequence between the Javelin and the epitope results in even greater immunogenicity, presumably by greater efficiency of epitope processing. The enhanced immunogenicity associated with Javelin J1 and the cleavable linker is consistently observed with multiple mouse and human epitopes. Thus, by creating a series of epitopes with uniform, high-affinity binding to HSP70, successful multiple epitope immunizations are possible, with equal delivery of each antigenic epitope to the immune system via HSP70. These modified epitopes have the potential for creating successful multivalent vaccines for immunotherapy of both infectious disease and cancer.
Life (2008)

What has been termed the “enigma” of Edgar Allan Poe remains very much with us, even though he died in 1849. Some aspects of this enigma, which amount to slanting the truth, or to outright lies, originated with Poe himself. Others were supplied by persons who knew him, by others who supposed that they knew about his personal circumstances and career, or by still others who falsified the record because they took suspect “facts” at face value. Consequently, a “Poe legend” emerged, which retains widespread currency today. One may not exaggerate in remarking that a biography, brief or lengthy, of Poe is published nearly every year, although exceedingly few facts about his life and career have been discovered since the late 1930s/early 1940s, and much must remain speculative about that life. The most reliable biography continues to be Arthur H. Quinn's Edgar Allan Poe: A Critical Biography, which dates from 1941, but which as a factual narrative account of Poe's life maintains its value.
Vigorous but Short-Term Gamma Interferon T-Cell Responses against a Dominant HLA-A*02-Restricted Measles Virus Epitope in Patients with Measles (2003)

The absolute and relative abundance of major histocompatibility complex class I-presented viral epitopes is important in the induction and maintenance of antiviral cytotoxic-T-lymphocyte (CTL) responses. We demonstrate that the supra-abundant HLA-A*0201-restricted peptide KLWESPQEI of the measles virus nonstructural C protein induces strong gamma interferon CD8(+)-T-cell responses in children with acute measles. However, longitudinal analysis indicates that these responses are only short-lived. Thus, some viral epitopes that can be immunodominant during primary infection may fail to establish memory CTL responses.
Dimethylated lysine 9 of histone 3 is elevated in schizophrenia and exhibits a divergent response to histone deacetylase inhibitors in lymphocyte cultures (2009)

Our results provide further evidence that schizophrenia is associated with a restrictive chromatin state that is also less modifiable using HDAC inhibitors.
Viral Vectors for Gene Therapy: Translational and Clinical Outlook (2015)

In a range of human trials, viral vectors have emerged as safe and effective delivery vehicles for clinical gene therapy, particularly for monogenic recessive disorders, but there has also been early work on some idiopathic diseases. These successes have been enabled by research and development efforts focusing on vectors that combine low genotoxicity and immunogenicity with highly efficient delivery, including vehicles based on adeno-associated virus and lentivirus, which are increasingly enabling clinical success. However, numerous delivery challenges must be overcome to extend this success to many diseases; these challenges include developing techniques to evade preexisting immunity, to ensure more efficient transduction of therapeutically relevant cell types, to target delivery, and to ensure genomic maintenance. Fortunately, vector-engineering efforts are demonstrating promise in the development of next-generation gene therapy vectors that can overcome these barriers. This review highlights key historical trends in clinical gene therapy, the recent clinical successes of viral-based gene therapy, and current research that may enable future clinical application.
Wax Ester Synthesis under Aerobic and Anaerobic Conditions in Euglena gracilis (1985)

In Euglena gracilis distribution of radioactivity from labeled acetate into cellular components was quite different under aerobic and anaerobic conditions, and a large part of it was found in wax esters in anoxia. Wax ester synthesis from acetate was immediately stimulated about 30 times by transfer of the cells into anaerobiosis, and reversed result was shown by back to aerobiosis. Similar observations were made with labeled myristic acid, but radioactivity of labeled myristyl alcohol was incorporated solely into wax esters both in aerobiosis and anaerobiosis. The activity of reduction from fatty acids to alcohols in cell-free extract was hardly changed when the cells were transferred into anaerobiosis.
Cyclophilin-dependent stimulation of transcription by cyclosporin A. (1993)

Exposure to cyclosporin A (CspA) increased laccase (lac-1) transcript accumulation in the chestnut blight fungus Cryphonectria parasitica. This response was suppressed by compounds that interfere with calcium-dependent signal transduction and by the presence of a virulence-attenuating mycovirus. CspA stimulated the accumulation of mRNA from a nonhomologous reporter fused to the lac-1 promoter, indicating that the increased transcript levels resulted from an increase in promoter activity. Based on the current model for the regulation of lac-1 transcription, these results suggest that CspA interferes with a negative regulatory pathway that normally constrains lac-1 promoter activity. Significantly, CspA did not stimulate lac-1 transcription in mutant strains deficient in CspA binding activity, directly demonstrating a requirement for the interaction of CspA and cyclophilin in the modulation of lac-1 transcription. Our results establish that CspA treatment can stimulate gene transcription and that cyclophilin is the cellular receptor that mediates this activity.
Insulin and Glucagon Degradation by the Same Enzyme (1974)

An insulin-degrading enzyme has been previously isolated from rat skeletal muscle and highly purified by a series of procedures including affinity chromatography on insulin-agarose. Glucagon-degrading activity was also found in each of the purification steps including the final highly purified material. Insulin- and glucagon-degrading activities were associated with the same band on polyacrylamide gel and both activities were obtained from affinity chromatography on glucagon-agarose. Insulin- and glucagon-degrading activities could not be differentiated by the effect of sulfhydryl reagents, pH, or by heat inactiva-tion. Insulin served as a competitive inhibitor of glucagon degradation (Ki = 1.5 × 10−8M) and glucagon was a competitive inhibitor of insulin degradation (Ki = 5.3 × 10−6M). On the basis of these studies it appears that insulin and glucagon can be degraded by the same enzyme which is found in the soluble fraction of rat skeletal muscle homogenate.
KNEE JOINT CHANGES AFTER MENISCECTOMY (1948)

Changes in the knee joint after meniscectomy include ridge formation, narrowing of the joint space, and flattening of the femoral condyle. Investigations suggest that these changes are due to loss of the weight-bearing function of the meniscus. Meniscectomy is not wholly innocuous; it interferes, at least temporarily, with the mechanics of the joint. It seems likely that narrowing of the joint space will predispose to early degenerative changes, but a connection between these appearances and later osteoarthritis is not yet established and is too indefinite to justify clinical deductions.
Periostin Is Expressed in Pericryptal Fibroblasts and Cancer-associated Fibroblasts in the Colon (2008)

Periostin is a unique extracellular matrix protein, deposition of which is enhanced by mechanical stress and the tissue repair process. Its significance in normal and neoplastic colon has not been fully clarified yet. Using immunohistochemistry and immunoelectron microscopy with a highly specific monoclonal antibody, periostin deposition was observed in close proximity to pericryptal fibroblasts of colonic crypts. The pericryptal pattern of periostin deposition was decreased in adenoma and adenocarcinoma, preceding the decrease of the number of pericryptal fibroblasts. Periostin immunoreactivity appeared again at the invasive front of the carcinoma and increased along the appearance of cancer-associated fibroblasts. ISH showed periostin signals in cancer-associated fibroblasts but not in cancer cells. Ki-67-positive epithelial cells were significantly decreased in the colonic crypts of periostin-/- mice (approximately 0.6-fold) compared with periostin+/+ mice. In three-dimensional co-culture within type I collagen gel, both colony size and number of human colon cancer cell line HCT116 cells were significantly larger ( approximately 1.5-fold) when cultured with fibroblasts derived from periostin+/+ mice or periostin-transfected NIH3T3 cells than with those from periostin-/- mice or periostin-non-producing NIH3T3 cells, respectively. Periostin is secreted by pericryptal and cancer-associated fibroblasts in the colon, both of which support the growth of epithelial components.
Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface (1995)

The protein C anticoagulant system generates an "on demand" physiologic anticoagulant response. The pathway is initiated when thrombin binds to the endothelial cell thrombin binding protein, thrombomodulin. The complex exhibits dramatically altered macromolecular specificity. It rapidly cleaves the protein C zymogen to form the anticoagulant, activated protein C. Complex formation between thrombin and thrombomodulin also prevents thrombin, the enzyme responsible for clot formation and a potent platelet activator, from being able to clot fibrinogen or to activate platelets. Structural, kinetic, and competition studies suggest that thrombomodulin blocks these clotting reactions by masking the binding sites for fibrinogen and the platelet thrombin receptor. Stimulation of protein C activation appears to occur through conformational changes in the extended binding pocket of thrombin. This prevents repulsive interactions with protein C that exist when the free enzyme attempts to dock with this substrate. In addition to protein-protein interactions, thrombomodulin has a covalently associated chondroitin sulfate moiety. Chondroitin sulfate binds to a basic surface on thrombin that is also involved in heparin interaction. The chondroitin sulfate enhances the affinity of thrombin for thrombomodulin approximately 10- to 20-fold, making thrombomodulin a more potent inhibitor of coagulation, altering thrombin's conformation and specificity, and accelerating thrombin inhibition by the serpin, antithrombin. These properties make thrombomodulin a molecular switch ideally suited to trigger an anticoagulant response when too much thrombin is generated. The importance of the system is documented by the clinical observation that patients deficient in protein C often die of massive thrombotic complications that can be reversed or prevented by infusion of protein C.
Fas antigen expression on CD34+ human marrow cells is induced by interferon gamma and tumor necrosis factor alpha and potentiates cytokine-mediated hematopoietic suppression in vitro (1995)

Activation of Fas antigen, a cell surface receptor molecule, by its ligand results in transduction of a signal for cell death. The Fas system has been implicated in target cell recognition, clonal development of immune effector cells, and termination of the cellular immune response. Fas antigen expression on lymphocytes is regulated by interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha), cytokines that also have inhibitory effects on hematopoiesis. We investigated Fas antigen expression on human marrow cells and the effects of Fas activation on hematopoiesis in vitro. Freshly isolated immature hematopoietic cells, as defined by the CD34 marker, did not express Fas antigen at levels detectable by fluorescent staining. CD34+ cells, which include progenitors and stem cells, showed low levels of Fas expression in culture, even in the presence of growth factors. Stimulation by TNF alpha and IFN gamma markedly increased Fas antigen expression on CD34+ cells. Anti-Fas antibody, which mimics the action of the putative ligand, enhanced IFN gamma- and TNF alpha-mediated suppression of colony formation by bone marrow (BM) in a dose-dependent manner. This effect did not require the presence of accessory cells. Colony formation from mature (CD34+ CD38+) and immature (CD34+ CD38-) progenitor cells and long-term culture initiating cells were susceptible to the inhibitory action of anti-Fas antibody in the presence of IFN gamma and TNF alpha. Apoptosis assays performed on total BM cells and CD34+ cells showed that anti-Fas antibody induced programmed cell death of CD34+ BM cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Fcγ receptors directly mediate cartilage, but not bone, destruction in murine antigen‐induced arthritis: Uncoupling of cartilage damage from bone erosion and joint inflammation (2006)

Activating FcgammaR are crucial in mediating cartilage destruction independently of joint inflammation. In contrast, FcgammaR are not directly involved in bone erosion. Indirectly, FcgammaR drive bone destruction by regulating joint inflammation.
The mitochondrial permeability transition pore (1999)

This chapter reviews recent advances in the identification of the structural elements of the permeability transition pore. The discovery that cyclosporin A (CsA) inhibits the pore proved instrumental. Various approaches indicate that CsA blocks the pore by binding to cyclophilin (CyP)-D. In particular, covalent labelling of CyP-D in situ by a photoactive CsA derivative has shown that pore ligands have the same effects on the degree to which CsA both blocks the pore and binds to CyP-D. The recognition that CyP-D is a key component has enabled the other constituents to be resolved. Use of a CyP-D fusion protein as affinity matrix has revealed that CyP-D binds very strongly to 1:1 complexes of the voltage-dependent anion channel (from the outer membrane) and adenine nucleotide translocase (inner membrane). Our current model envisages that the pore arises as a complex between these three components at contact sites between the mitochondrial inner and outer membranes. This is in line with recent reconstitutions of pore activity from protein fractions containing these proteins. The strength of interaction between these proteins suggests that it may be a permanent feature rather than assembled only under pathological conditions. Calcium, the key activator of the pore, does not appear to affect pore assembly; rather, an allosteric action allowing pore flicker into an open state is indicated. CsA inhibits pore flicker and lowers the binding affinity for calcium. Whether adenine nucleotide translocase or the voltage-dependent anion channel (via inner membrane insertion) provides the inner membrane pore has not been settled, and data relevant to this issue are also documented.
The Genuair® inhaler: a novel, multidose dry powder inhaler (2012)

This article reviews the Genuair(®) inhaler, a novel, multidose, breath-actuated dry powder inhaler. The inhaler design includes visual and acoustic feedback to reassure patients that they have taken their medication correctly, a dose indicator and a lock-out mechanism to prevent the use of an empty inhaler. The inhaler has medium airflow resistance and uses an optimised dispersion system to ensure effective deagglomeration of the inhalation powder. In vitro studies have demonstrated that the inhaler delivers a reproducible aerodynamic aerosol quality and is reliable under various thermal and mechanical stress conditions. Further studies in vitro have demonstrated that the total emitted dose and fine particle dose are both consistent over a range of inhalation flows from 45 to 95 l/min, as well as being independent of inhalation volume (2 l vs. 4 l) and storage conditions. In healthy subjects, delivery of aclidinium bromide 200 μg via the inhaler achieved high lung deposition (approximately 30% of the metered dose). A further study has shown that patients with moderate or severe chronic obstructive pulmonary disease can generate sufficient inspiratory airflow through the inhaler to reliably inhale the full dose and reset the inhaler. The inhaler has been used to deliver aclidinium in many clinical trials and the available data indicate that it has high acceptability amongst patients.
Multi-packet signature detection using prefix bloom filters (2005)

It is now a fact that manual defenses against worm epidemics are not practical. Recently, various automatic worm identification methods are proposed to be deployed at high-speed network nodes to respond in time to fast infection rates of worms. Unfortunately, these methods can easily be evaded by fragmentation of the worm packets. The straightforward defragmentation method is not applicable for these high-speed nodes, due to its high storage (memory) requirement. In this paper, this problem, namely the multi-packet signature detection problem is addressed using a defragmentation-free, space-efficient solution. A new data structure - prefix bloom filters - along with a new heuristic, called the chain heuristic is proposed to significantly reduce the storage requirement of the problem, so that multi-packet signature detection becomes feasible for high-speed network nodes.
Long-Term Potentiation of Thalamocortical Transmission in the Adult Visual CortexIn Vivo (2001)

It has been suggested that NMDA receptor-dependent synaptic strengthening, like that observed after long-term potentiation (LTP), is a mechanism by which experience modifies responses in the neocortex. We report here that patterned (theta burst) stimulation of the dorsal lateral geniculate nucleus reliably induces LTP of field potentials (FPs) evoked in primary visual cortex (Oc1) of adult rats in vivo. The response enhancement is saturable, long-lasting, and dependent on NMDA receptor activation. To determine the laminar locus of these changes, current source density (CSD) analysis was performed on FP profiles obtained before and after LTP induction. LTP was accompanied by an enhancement of synaptic current sinks located in thalamorecipient (layer IV and deep layer III) and supragranular (layers II/III) cell layers. We also examined immunocytochemical labeling for the immediate early gene zif-268 1 hr after induction of LTP. In concert with the laminar changes observed in CSD analyses, we observed a significant increase in the number of zif-268-immunopositive neurons in layers II-IV that occurred over a wide extent of Oc1. Last, we investigated the functional consequences of LTP induction by monitoring changes in visually evoked potentials. After LTP, we observed that the cortical response to a full-field flash was significantly enhanced and that responses to grating stimuli were increased across a range of spatial frequencies. These findings are consistent with growing evidence that primary sensory cortex remains plastic into adulthood, and they show that the mechanisms of LTP can contribute to this plasticity.
SWEB: towards a scalable World Wide Web server on multicomputers (2002)

We investigate the issues involved in developing a scalable World Wide Web (WWW) server on a cluster of workstations and parallel machines. The objective is to strengthen the processing capabilities of such a server by utilizing the power of multicomputers to match huge demands in simultaneous access requests from the Internet. We have implemented a system called SWEB on a distributed memory machine, the Meiko CS-2, and networked workstations. The scheduling component of the system actively monitors the usages of CPU, I/O channels and the interconnection network to effectively distribute HTTP requests across processing units to exploit task and I/O parallelism. We present the experimental results on the performance of this system.