gebhart/patrepeval huggingface dataset:
Construction and Screening of an Antigen-Derived Peptide Library Displayed on Yeast Cell Surface for CD4+ T Cell Epitope Identification (2013)

Antigenic peptides (termed T cell epitopes) are assembled with major histocompatibility complex (MHC) molecules and presented on the surface of antigen-presenting cells (APCs) for T cell recognition. T cells engage these peptide-MHCs using T cell receptors (TCRs). Because T cell epitopes determine the specificity of a T cell immune response, their prediction and identification are important steps in developing peptide-based vaccines and immunotherapies. In recent years, a number of computational methods have been developed to predict T cell epitopes by evaluating peptide-MHC binding; however, the success of these methods has been limited for MHC class II (MHCII) due to the structural complexity of MHCII antigen presentation. Moreover, while peptide-MHC binding is a prerequisite for a T cell epitope, it alone is not sufficient. Therefore, T cell epitope identification requires further functional verification of the MHC-binding peptide using professional APCs, which are difficult to isolate, expand, and maintain. To address these issues, we have developed a facile, accurate, and high-throughput method for T cell epitope mapping by screening antigen-derived peptide libraries in complex with MHC protein displayed on yeast cell surface. Here, we use hemagglutinin and influenza A virus X31/A/Aichi/68 as examples to describe the key steps in identification of CD4+ T cell epitopes from a single antigenic protein and the entire genome of a pathogen, respectively. Methods for single-chain peptide MHC vector design, yeast surface display, peptide library generation in Escherichia coli, and functional screening in Saccharomyces cerevisiae are discussed.
Microbial‐based motor fuels: science and technology (2008)

The production of biofuels via microbial biotechnology is a very active field of research. A range of fuel molecule types are currently under consideration: alcohols, ethers, esters, isoprenes, alkenes and alkanes. At the present, the major alcohol biofuel is ethanol. The ethanol fermentation is an old technology. Ongoing efforts aim to increase yield and energy efficiency of ethanol production from biomass. n-Butanol, another microbial fermentation product, is potentially superior to ethanol as a fuel but suffers from low yield and unwanted side-products currently. In general, biodiesel fuels consist of fatty acid methyl esters in which the carbon derives from plants, not microbes. A new biodiesel product, called microdiesel, can be generated in engineered bacterial cells that condense ethanol with fatty acids. Perhaps the best fuel type to generate from biomass would be biohydrocarbons. Microbes are known to produce hydrocarbons such as isoprenes, long-chain alkenes and alkanes. The biochemical mechanisms of microbial hydrocarbon biosynthesis are currently under study. Hydrocarbons and minimally oxygenated molecules may also be produced by hybrid chemical and biological processes. A broad interest in novel fuel molecules is also driving the development of new bioinformatics tools to facilitate biofuels research.
La gestión de marketing del producto financiero socialmente responsable en la prestación comercial de las sociedades cooperativas de crédito y cajas de ahorro (2007)

En mercados maduros y altamente competitivos las entidades financieras buscan estrategias de diferenciacion. Una de estas consiste en la promocion de productos de inversion socialmente responsables (ISR). Dichos productos financieros se encuentran en una fase reciente de desarrollo en Espana, aunque no asi en paises de nuestro entorno. Lo que sigue presenta los datos mas significativos de un estudio sobre las entidades financieras de la economia social (cajas de ahorros y cooperativas de credito) y sus estrategias de marketing en relacion a la inversion considerada socialmente responsable. Los resultados permiten concluir que el mercado ISR en Espana, segun el tipo de entidad, esta en una etapa de introduccion y/o crecimiento. Al mismo tiempo, el esfuerzo y la estrategia de marketing lleva a plantear, en contra de lo que podria parecer, que las entidades de economia social, en general, no estan potenciando estos productos en su cartera debido en gran parte a que la demanda es todavia incipiente.
Microwave aquametry : electromagnetic wave interaction with water-containing materials (1996)

The first book to address all theoretical and practical aspects of electromagnetic wave interaction with water and moist materials, this unique book features 29 full-length, peer-reviewed papers prepared by 69 of the world's experts in aquametry for a key Workshop held in conjunction with the IEEE MTT-S International Microwave Symposium in Atlanta, Georgia, 1993. Collectively, the papers illustrate the physical background of microwave techniques used for moisture content determination, present stimulating examples of applications of microwaves for nondestructive and accurate measurements, and demonstrate successful implementation of techniques in a variety of industries.
Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer’s Disease: Tangle Formation, Amyloid-β, and Microglia in Alzheimer’s Disease (2012)

Pathological hallmarks of Alzheimer's disease (AD) include senile plaques, neurofibrillary tangles (NFTs), synaptic loss, and neurodegeneration. Senile plaques are composed of amyloid-β (Aβ) and are surrounded by microglia, a primary immune effector cell in the central nervous system. NFTs are formed by the intraneuronal accumulation of hyperphosphorylated tau, and progressive synaptic and neuronal losses closely correlate with cognitive deficits in AD. Studies on responsible genes of familial AD and temporal patterns of pathological changes in brains of patients with Down's syndrome (Trisomy 21), who invariably develop neuropathology of AD, have suggested that Aβ accumulation is a primary event that influences other AD pathologies. Although details of the interaction between AD pathologies remain unclear, experimental evidences to discuss this issue have been accumulated. In this paper, we review and discuss recent findings that link the AD pathologies to each other. Further studies on the interaction between pathologies induced in AD brain may contribute to provide deep insight into the pathogenesis of AD and to develop novel therapeutic, prophylactic, and early diagnostic strategies for AD.
Interactions of plasma retinol-binding protein with its receptor. Specific binding of bovine and human retinol-binding protein to pigment epithelium cells from bovine eyes. (1975)

Bovine and human retinol-retinol-binding protein (RBP) were iodinated to high specific activity. At least 34% of the iodinated material was native and retained its retinol chromophore as judged by its characteristic ability to bind to plasma prealbumin. Bovine and human retinol-125I-RBP were found to bind specifically to intact isolated pigment epithelium cells from bovine eyes. The specific binding was complete in about 1 min with an estimated second order rate constant of about 10-8 M-minus 1 S-minus 1 (at 22 degrees). The specific binding was temperature dependent with the binding at 0 degrees being some 7-fold slower than at 22 degrees. The specific binding of both human and bovine retinol-125I-RBP was a linear function of the number of binding sites (number of cells) and was saturable with respect to retinol-125I-RBP. Bound iodinated retinol-RBP was rapidly displaced by the addition of unlabeled retinol-RBP, indicating that the specific binding process was a surface phenomenon and was not due to endocytosis. At saturation about 3.7 to 5.2 times 10-4 molecules of either bovine or human retinol-125I-RBP bound to one bovine pigment epithelium cell. The dissociation constant for the binding between retinol-125I-RBP and pigment epithelium receptor was estimated to be about 5 times 10-minus 12 M. Addition of human prealbumin (thyroxine-binding prealbumin) did not affect the binding of either human or bovine retinol-125I-RBP to pigment epithelium cells. Retinol-125I-RBP did not bind specifically to isolated bovine rod photoreceptor outer segments. Human apo-RBP was less effective in displacing bound retinol-125I-RBP than either native or reconstituted human retinol-RBP. These results suggest a mechanism whereby, after delivering its retinol to the cell, apo-RBP is displaced from the specific receptor on pigment epithelium cell by another retinol-RBP molecule. This postulated mechanism makes it possible to control the delivery of retinol to the target cell by the relative plasma concentrations of apo- and retinol-RBP and their relative affinities for the specific receptor binding site.
Natural Antibodies Directed Against Murine Lymphosarcoma Cells 2 (1975)

Natural antibodies reacting in a test of complement-dependent cytotoxicity with untreated murine lymphosarcoma cells of thymic origin were found in murine sera. Normal thymus cells were unaffected and unable to absorb the serum activity. The natural antibodies were IgM-like and stable at 56 degrees C. They were not uniformly distributed in the studied strains, and high (C3H/He and C3Hf), intermediate (AKR and CBA/J), and low level strains (BALB/c, DBA/2, C57BL, and C57BL/6J) were found. Hybrids between a high (C3Hf) and a low level strain (C57BL) had the same response as the parental C3Hf mice. An inverse relationship was demonstrated between cytotoxicity of, and susceptibility to, serum of lymphoma cells in a given strain, which suggested that an immunologic modulation was at work. Embryonic cells absorbed the cytotoxic activity of the normal serum.
Immediate recovery from spinal cord injury through molecular repair of nerve membranes with polyethylene glycol (2000)

A brief application of the hydrophilic polymer polyethylene glycol (PEG) swiftly repairs nerve membrane damage associated with severe spinal cord injury in adult guinea pigs. A 2 min application of PEG to a standardized compression injury to the cord immediately reversed the loss of nerve impulse conduction through the injury in all treated animals while nerve impulse conduction remained absent in all sham-treated guinea pigs. Physiological recovery was associated with a significant recovery of a quantifiable spinal cord dependent behavior in only PEG-treated animals. The application of PEG could be delayed for approximately 8 h without adversely affecting physiological and behavioral recovery which continued to improve for up to 1 month after PEG treatment.
Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH): revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma (2009)

To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related) than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level.
HIV-1 replication is controlled at the level of T cell activation and proviral integration. (1990)

During progression of the Acquired Immune Deficiency Syndrome (AIDS), the human immunodeficiency virus type 1 (HIV-1) is harbored in CD4+ T cells, which act as the primary reservoir for the virus. In vitro, HIV-1 requires activated T cells for a productive infection; however, in vivo, the number of circulating T cells in the activated state that are potential targets for HIV-1 infection is low. We have investigated the ability of HIV-1 to infect resting T cells, and the consequences of such an infection. T cell activation was not required for HIV-1 infection; however, viral DNA was unable to integrate in resting T cells and was maintained extrachromosomally. Subsequent T cell activation allowed integration of extrachromosomal forms and led to a productive viral life cycle. Extrachromosomal forms of viral DNA were found to persist for several weeks after infection of resting T cells and, following T cell activation, these forms maintained their ability to integrate and act as a template for infectious virus. Several lines of evidence, including temporal analysis of HIV-1 replication and analysis of an HIV-1 integrase deletion mutant, indicated that extra-chromosomal HIV-1 DNA genomes were transcriptionally active. These results are compatible with a model whereby HIV-1 can persist in a non-productive extra-chromosomal state in resting T cells until subsequent antigen-induced or mitogen-induced T cell activation, virus integration and release. Thus agents that induce T cell activation may control the rate of HIV-1 replication and spread during AIDS progression.
Phosphodiesterase‐linked inhibition of nonmicturition activity in the isolated bladder (2004)

The mechanisms influencing the frequency of agonist-induced phasic activity in the isolated bladder are slowed by cAMP. Degradation of intracellular cAMP in the cells responsible for phasic activity appears to involve primarily PDE-4. The importance of these observations in relation to the overall physiological regulation of the bladder are discussed, and the possible importance of these findings in the development of pharmacological strategies to modulated bladder activity reviewed.
Emerging therapeutic agents for transmissible spongiform encephalopathies: a review (2003)

Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative disorders associated with misfolding of prion protein, from PrPC to PrPSc. Different types of experimental studies have resulted in a better understanding of the pathogenesis of the prion diseases. Genetic and molecular properties of PrP isoforms have been explained but the conformational conversion of the PrPC isoform to the PrPSc isoform has not yet been entirely elucidated. However, a number of possible therapeutic agents have been tried and some have proven to be effective against TSEs but most have limitations in terms of toxicity and pharmacokinetics. Congo red (CR), anthracyclines, and polyanionic dextran sulfate have limited ability to cross the blood-brain barrier and may be toxic. The efficacy of polyene antibiotics seems to be restricted to certain scrapie strains. Tetrapyrroles and tetracyclines with low toxicities and favorable pharmacokinetics could be useful in preventing PrPSc accumulation. Compounds like branched polyamines, Cp-60, analogs of CR, quinacrine and chlorpromazine, beta-sheet breaker peptides and inhibitory peptides, active immunization using recombinant PrP and passive immunization with anti-PrP antibodies, have potential use as therapeutic agents but would need further research and clinical trials.
Evaluation of a Pharmacy Checklist During Blood and Marrow Transplant Admission (2011)

Clinical pharmacist review is an important opportunity for quality control in the blood and marrow transplant (BMT) process. The Manitoba BMT program developed a formalized process for this review in the form of an admission checklist that is completed by a BMT pharmacist. The checklist documents pharmacist review of all relevant components of the transplant regimen. Included is verification of chemotherapy regimen, prophylaxis for graft versus host disease, infectious diseases, and tumor lysis. Other verifications include antiemetic regimen, growth factors, intrathecal therapy, cell infusion orders, and medication reconciliation. The need for dose adjustments based on organ function is also included. The checklists of 32 consecutive adult patients admitted to the transplant ward were audited. The purpose of the audit was to assess checklist completion by a BMT pharmacist. All patients (100%) had a checklist attached to their pharmacy profile. In 15% (n = 5) of patients, there was no verification that the transplant regimen was the same as the planned regimen written in the primary transplant physician comprehensive transplant workup package. Verification of MUGA results in 28% (n = 9) of patients and an intrathecal therapy plan in 15% (n = 5) was not documented. Confirmation of medication reconciliation was present in 72% (n = 23) of admissions. The presence of a patient summary by an outpatient pharmacist prior to admission was documented in only 72% (n = 23) of admissions. There were no reported "near misses" or critical events related to the admission orders. 82% of pharmacy checklist sheets had at least one explanatory note written on the checklist. The use of a checklist at time of BMT admission has helped develop a consistent and thorough review, thus preventing medication errors and omissions. The checklist is a useful tool for training new staff and education purposes. It is being explored as a communication tool between inpatient and outpatient pharmacists. It has evolved to include patient specific explanatory comments, thus adopting a communication role in addition to being a process documentation tool. This also prevents repeat questions posed to prescribers. This process has identified quality improvement opportunities in the areas of handover from outpatient to inpatient pharmacy and in the standardized order sets and admission paperwork.
A fully human chimeric immune receptor for retargeting T-cells to CEA-expressing tumor cells. (2007)

This L45scFv-CIR gene, consisting of four human genes, may be a useful tool for eradication of CEA-expressing but HLA-downregulated tumor cells.
Cross-Reactivity of Various Tetrahydrocannabinol Metabolites with a Monoclonal Antibody against Tetrahydrocannabinolic Acid. (2000)

A monoclonal antibody (MAb-4A4) against Δ9-tetrahydrocannabinolic acid (THCA) was prepared and its cross-reactivity analyzed with various cannabinoids including tetrahydrocannabinol metabolites by competitive enzyme-linked immunoassay (ELISA). Δ9-THC (1-100μg/ml) could be determined by the ELISA. Many metabolites of Δ8-THC and Δ9-THC reacted with the antibody, and their cross-reactivities were 44-157% of Δ8-THC. However, the antibody did not recognize the lipophilic compounds cholesterol, testosterone, β-carotene, androstene-3, 17-dione or an endogenous cannabinoid, anandamide.
Asymptomatic Brady arrhythmias as a Marker for Sleep Apnea: Appropriate Recognition and Treatment May Reduce the Need for Pacemaker Therapy (1996)

Sleep apnea is associated with many adverse cardiovascular sequelae, including hypertension, nocturnal angina, decreased cardiac output, and bradyarrhythmias. The purpose of this study was to determine if patients referred for pacemaker therapy with asymptomatic bradyarrhythmias have underlying sleep apnea as the etiology of their bradyarrhythmias. This study included eight patients (7 males, 1 female) referred to a cardiac electrophysiology practice for pacemaker therapy. Patients included had asymptomatic bradyarrhythmias that consisted of severe sinus bradycardia, second-degree atrioventricular block, and complete heart block. In 7 of 8 patients, the bradyarrhythmias occurred at night or during the day while asleep. No patients were conditioned athletes. Symptoms often associated with bradyarrhythmias, such as lightheadedness and syncope, were not present. However, seven patients had at least one symptom suggestive of sleep apnea, such as excessive daytime fatigue, snoring, cessation of breathing during sleep (apnea), or frequent night-time awakenings. Overnight polysomnography studies were obtained on patients who had one or more symptoms suggestive of sleep apnea. In this study 7 of 8 patients (88%) referred for pacemaker therapy with asymptomatic bradyarrhythmias were documented by polysomnography to have sleep apnea. When treated with either sleep position modification, nasal continuous positive airway pressure (nasal CPAP), or tracheostomy, all seven patients had improvement in sleep apnea symptoms and remained asymptomatic from their bradyarrhythmias without pacemaker therapy over an average follow-up period of 22 months. One patient without symptoms suggestive of sleep apnea declined pacemaker therapy and remained asymptomatic. From these results, we concluded that asymptomatic transient bradyarrhythmias may suggest a diagnosis of sleep apnea. The evaluation of a patient referred for pacemaker therapy with asymptomatic bradyarrhythmias should include questions related to sleep apnea symptoms. Establishing the diagnosis of sleep apnea may reduce the need for pacemaker therapy and permit appropriate treatment of the underlying cause of these bradyarrhythmias.
Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease) (2005)

We have identified specific allele variants of CFH and CFHR5 associated with the MPGN II/DDD disease phenotype. While our data can be interpreted to further implicate complement in the pathogenesis of MPGN II/DDD, these associations could also be unrelated to disease pathophysiology. Functional studies are required to resolve this question.
Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma. (1996)

A Phase I/II dose escalation study of 90Y-murine anti-CD20 monoclonal antibody (mAb) in patients with recurrent B-cell lymphoma was performed. The primary objectives of the study were: (a) to determine the effect of the preinfusion of unlabeled anti-CD20 mAb on the biodistribution of 111In-anti-CD20 mAb; (b) to determine the maximal tolerated dose of 90Y-anti-CD20 mAb that does not require bone marrow transplantation; and (c) to evaluate the safety and antitumor effect of 90Y-anti-CD20 mAb in patients with recurrent B-cell lymphoma. Eighteen patients with relapsed low- or intermediate-grade non-Hodgkin's lymphoma were treated. Biodistribution studies with 111In-anti-CD20 mAb were performed prior to therapy. Groups of three or four patients were treated at dose levels of approximately 13.5, 20, 30, 40, and 50 mCi 90Y-anti-CD20 mAb. Three patients were retreated at the 40-mCi dose level. The use of unlabeled antibody affected the biodistribution favorably. Nonhematological toxicity was minimal. The only significant toxicity was myelosuppression. The overall response rate following a single dose of 90Y-anti-CD20 mAb therapy was 72%, with six complete responses and seven partial responses and freedom from progression of 3-29+ months following treatment. Radioimmunotherapy with </=50 mCi 90Y-anti-CD20 mAb resulted in minimal nonhematological toxicity and durable clinical responses in patients with recurrent B-cell lymphoma. Doses of </=40 mCi 90Y-anti-CD20 mAb were not myeloablative.
Nonviral Gene Therapy Approaches to Hemophilia (2004)

The goal of hemophilia gene therapy is to obtain long-term therapeutic levels of factor VIII (FVIII) or factor IX (FIX) without stimulating an immune response against the transgene product or the vector. The success of gene therapy is largely dependent on the development of appropriate gene delivery vectors. Both viral vectors and nonviral vectors have been considered for the development of hemophilia gene therapy. In general, viral vectors are far more efficient than nonviral gene delivery approaches and resulted in long-term therapeutic levels of FVIII or FIX in preclinical animal models. However, there are several reasons why a nonviral treatment would still be desirable, particularly because some viral vectors are associated with inflammatory reactions, that render transgene expression transient, or with an increased risk of insertional oncogenesis when random integrating vectors are used. Nonviral vectors may obviate some of these concerns. Since nonviral vectors are typically assembled in cell-free systems from well-defined components, they have significant manufacturing advantages over viral vectors. The continued development of improved nonviral gene delivery approaches offers new perspectives for gene therapy of chronic diseases including hemophilia.
The Mitochondrion — A Trojan Horse That Kicks Off Inflammation? (2010)

Sterile inflammation, which occurs in the post-traumatic systemic inflammatory response and other conditions such as myocardial infarction, may be spurred by mitochondria released from dying cells.