gebhart/patrepeval huggingface dataset:
Effect of epitope flanking residues on the presentation of N-terminal cytotoxic T lymphocyte epitopes (1999)

We here demonstrate that placing two distinct influenza virus nucleoprotein epitopes at the N terminus of a cytosolic protein selectively blocks their presentation to specific cytotoxic T lymphocytes. The block is a cytosolic phenomenon, which can be overcome by distancing the epitope from the protein N terminus by two or more amino acids. Shortening the protein's C terminus fails to relieve the antigen presentation block. These results demonstrate that events at the N terminus of the target protein, rather than at its C terminus, are responsible for the lack of presentation of N-terminal epitopes. We also show that lack of presentation of N terminal epitopes is associated with a modification of the target protein which affects its electrophoretic mobility and isoelectric focusing point. This modification can be prevented by mutating the epitope's N-terminal flanking sequence, which results in an efficient presentation of the N-terminal epitope. Lack of presentation of the N-terminal epitopes results in a reduced ability of influenza-primed mice to clear acute infection with vaccinia virus encoding an N-terminal nucleoprotein epitope. Our results demonstrate that presentation of epitopes localized at the N terminus of cytosolic proteins can be modulated by events occurring at early stages of antigen processing.
On market dynamics of electric vehicle diffusion (2014)

A sequential game model is proposed to analyze a two-sided market and indirect network effects involving electrical vehicles (EV) and electric vehicle charging stations (EVCS). The investor maximizes his profit by choosing a set of locations to build charging stations or deferring his investment and earning interest at a fixed rate. The investor also decides the optimal pricing of charging. The consumer, on the other hand, decides whether to purchase an EV or a gasoline vehicle (GV) based on the price of EV, the cost of charging, and the availability of charging stations. The solution of the game provides a closed-form expression of the EV market share as a function of EV price, the price of charging, and the density of charging stations. An asymptotically optimal algorithm is proposed for solving the optimization of the investor's decision.
Extract of Reishi Polysaccharides Induces Cytokine Expression via TLR4-Modulated Protein Kinase Signaling Pathways (2004)

We have demonstrated that an extract of Ganoderma lucidum (Reishi or Ling-Zhi) polysaccharides (EORP) exerts immunomodulating activities by stimulating the expression of inflammatory cytokines from mouse spleen cells. Interestingly, via responding to LPS in genetic variation of murine macrophage HeNC2 and GG2EE cell lines, and using TLR4 Ab blockage in human blood-derived monocytic macrophages, we have found that the TLR4, but not complement receptor type 3, is a putative receptor of EORP, mediating the consequent immunomodulating events associated with IL-1 gene expression. Based on our studies of reactive oxygen species production, polymyxin B inhibition, and protein tyrosine kinase (PTK) activity, we ruled out the possibility of LPS contamination in EORP. We have found that EORP differentially modulates the protein kinase (PK)-mediated signal transduction pathways associated with inflammatory cytokine IL-1. In human macrophages and murine macrophage J774A.1 cells, EORP was found to up-regulate IL-1 secretion and pro-IL-1 (precursor of IL-1) as well as IL-1-converting enzyme expression. Specifically, EORP rapidly stimulates PTK-mediated phosphorylation, followed by induction of PKs and activation of MAPKs: ERK, JNK, and p38. Using PK inhibitors in the kinase activity assays, Western blot analyses and IL-1 ELISA, we have extensively examined and dissected the role of individual PK in the regulation of pro-IL-1/IL-1. Our findings establish that EORP-mediated signaling pathways are involved in the pro-IL-1/IL-1 regulation: PTK/protein kinase C/MEK1/ERK and PTK/Rac1/p21-activated kinase/p38.
Genetic control of fatty acid biosynthesis in rapeseed (Brassica napus L.) (1964)

Abstract Isolation of rapeseed plants containing no erucic acid in their seed oil gave simultaneous selection for low eicosenoic acid. Genetic analy‐sis of populations segregating for erucic acid content indicated that the synthesis of these fatty acids was controlled, in the developing embryo, by two genes which displayed no domi‐nance and acted in an additive manner. As the genetic capacity for erucic acid synthesis de‐creased, there was an increase in percentage of oleic acid with no corresponding decrease in total oil content. The percentage of eicosenoic acid re‐mained relatively constant with decreasing erucic acid except in the zero erucic acid genotype where only 1% eicosenoic was detected instead of approx 12%. These observations were in‐terpreted to mean that eicosenoic and erucic acids were formed by a genetically controlled carbon chain lengthening system operating by the addi‐tion of acetate molecules to the carboxyl end of oleic acid. This hypothesis was supported by data obtained from the injection of radioactive sodium acetate into immature rapeseed pods. In the monoene fraction of the oil, eicosenoate had three times the specific activity of oleate and erucate had twice the activity of eicosenoate. On oxidation, the monocarboxylic fragments of these three acids had low and similar specific activities while in the dicarboxylic acids, where chain elongation has presumably taken place, activity increased in the ratio of 1:5:19.
In Vivo Intradiscal Pressure Measurement in Healthy Individuals and in Patients With Ongoing Back Problems (1999)

The spinal load was highly dependent on the angle of the motion segment in normal discs in vivo. The intradiscal pressure in degenerated discs was significantly reduced compared with that of normal discs. However, further studies on the effect of respiratory movement on intradiscal pressure, the difference between vertical and the horizontal pressures, and the difference in the spinal load between standing and the sitting body positions are necessary. The data obtained from the current study are fundamental to understanding the pathomechanisms and biomechanical problems of disc disease.
High-dose cytosine arabinoside therapy for refractory leukemia (1983)

Fifty-seven patients with refractory acute leukemia were treated with high-dose cytosine arabinoside to establish the maximum tolerated dose and duration and to determine the antileukemic activity. The maximum tolerated regimen was found to be 3 g/sq m every 12 hr for 6 days. At this dose, nonhematologic toxicity was limited to conjunctivitis in approximately half of the patients, and liver toxicity (transient elevations in transaminase, alkaline phosphatase, or bilirubin) was frequently observed, but neither was dose-limiting. Extending the duration of treatment to 8 days resulted in excessive diarrhea and skin toxicity (painful erythema with bullae), while increasing the dose to 4.5 g/sq m q. 12 hr for 6 days resulted in severe cerebellar toxicity. Myelosuppression was severe, but was not related to the intensity of treatment; granulocyte recovery occurred a median of 28 days (range 22-40 days) after initiating therapy, and platelet recovery occurred after a median of 25 days (range 16-41 days). Antileukemic activity was evaluable in the 46 patients who survived at least 3 wk. Complete remissions were obtained in 1 of 6 patients with chronic myelogenous leukemia (CML) in accelerated phase and 1 of 3 acute lymphoblastic leukemia (ALL) patients. A more detailed analysis of response was possible for the 37 evaluable patients with acute nonlymphoblastic leukemia: 70% of these patients responded, with 51% complete remissions. The median unmaintained response was 4 mo (range 2-26+ mo). The complete response rate was higher in patients who received at least 12 doses of high-dose cytosine arabinoside compared to shorter regimens [17/28 (61%) versus 2/9 (22%), p less than 0.05]. Resistance to cytosine arabinoside in conventional doses was documented in 11 patients, 5 of whom responded (2 complete remissions) to high-dose regimens. We conclude that high-dose cytosine arabinoside in the maximally tolerated regimen of 3 g/sq m every 12 hr for 6 days has substantial antileukemic activity in patients refractory to standard therapy. Durable unmaintained remissions can be achieved, even in patients who fail to respond to cytosine arabinoside in conventional doses.
Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men. (1991)

The liver enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are responsible for the oxidative metabolism of ethanol, are polymorphic in humans. An allele encoding an inactive form of the mitochondrial ALDH2 is known to reduce the likelihood of alcoholism in Japanese. We hypothesized that the polymorphisms of both ALDH and ADH modify the predisposition to development of alcoholism. Therefore, we determined the genotypes of the ADH2, ADH3, and ALDH2 loci of alcoholic and nonalcoholic Chinese men living in Taiwan, using leukocyte DNA amplified by the PCR and allele-specific oligonucleotides. The alcoholics had significantly lower frequencies of the ADH2*2, ADH3*1, and ALDH2*2 alleles than did the nonalcoholics, suggesting that genetic variation in both ADH and ALDH, by modulating the rate of metabolism of ethanol and acetaldehyde, influences drinking behavior and the risk of developing alcoholism.
High prevalence of NSAID enteropathy as shown by a simple faecal test (1999)

Assay of faecal calprotectin provides a simple practical method for diagnosing NSAID enteropathy in man. Forty four per cent of patients receiving these drugs had NSAID induced enteropathy when assessed by this technique; 20% of these had comparable levels of inflammation to that previously reported in patients with inflammatory bowel disease.
Model updating by adding known masses (2001)

Abstract New approaches are developed that use measured data to adjust the analytical mass and stiffness matrices of a system so that the agreement between the analytical modes of vibration and the modal survey is improved. By adding known masses to the structure of interest, measuring the modes of vibration of this mass‐modified system, and finally using this set of new data in conjunction with the initial modal survey, the analytical mass matrix of the structure can be corrected, after which the analytical stiffness matrix can be readily updated. By manipulating the correction matrices into vector forms, the connectivity information can be enforced, thereby preserving the physical configuration of the system and reducing the sizes of the least‐squares problems that need to be solved. Solution techniques for updating the system matrices are introduced, and the numerical issues associated with solving overdetermined and underdetermined least squares problems are investigated. The effects of round‐off errors are also studied, and heuristic criteria are given for determining the minimum number of modes that need to be measured in order to ensure sufficiently accurate updated mass and stiffness matrices. Numerical experiments are presented to validate the proposed model‐updating techniques, to illustrate the effects of the number of measured modes on the quality of the updated model, to show how the magnitudes and locations of the added masses influence the updated matrices, and to highlight the numerical issues discussed in this paper. Copyright © 2001 John Wiley &amp; Sons, Ltd.
Lead Exposure Promotes Translocation of Protein Kinase C Activities in Rat Choroid Plexusin Vitro,but Notin Vivo (1998)

Lead (Pb) exposure reportedly modulates PKC activity in brain endothelial preparations, which may underlie Pb-induced damage at the blood-brain barrier. Our previous work indicates that Pb accumulates in the choroid plexus and causes dysfunction of this blood-cerebrospinal fluid (CSF) barrier. The present studies were undertaken to test the hypothesis that Pb in the choroid plexus may alter PKC activity and thus affect the functions of the blood-CSF barrier. When choroidal epithelial cells in a primary culture were exposed to Pb (10 microM in culture medium), the membrane-bound PKC activity increased by 5.2-fold, while the cytosolic PKC activities decreased, an indication of the induction of PKC translocation by Pb. The effect of Pb on cellular PKC was concentration dependent in the range of 0.1-10 microM. We further evaluated PKC activity of the choroid plexus in rats chronically exposed to Pb in the drinking water (control, 50 or 250 micrograms Pb/ml) for 30, 60, or 90 days. Two-way analysis of variance revealed a significant age-related decline of PKC activities in both cytosol and membrane of the choroid plexus. However, Pb treatment did not alter plexus PKC activities. In addition, we found that short-term, acute Pb exposure in rats did not significantly change PKC activities nor did it affect the expression of PKC isoenzymes in the choroid plexus. Our results suggest that Pb exposure may promote the translocation of PKC from cytosol to membrane in rat blood-CSF barrier in vitro, but not in vivo.
Networks of DNA and RecA protein are intermediates in homologous pairing (1985)

Partial coating of single-stranded DNA by recA protein causes its aggregation, but conditions that promote complete coating inhibit independent aggregation of single strands and, instead, cause the mutually dependent conjunction of single- and double-stranded DNA in complexes that sediment at more than 10 000 S. This coaggregation is independent of homology but otherwise shares key properties of homologous pairing of single strands with duplex DNA: both processes require ATP, MgCl2, and stoichiometric amounts of recA protein; both are very sensitive to inhibition by salt and ADP. Coaggregates are closed domains that are intermediates in homologous pairing: they form faster than joint molecules, they include virtually all of the DNA in the reaction mixture, and they yield joint molecules nearly an order of magnitude faster than they exchange DNA molecules with the surrounding solution. The independent aggregation of single-stranded DNA differs in all respects except the requirement for Mg2+, and its properties correlate instead with those associated with the renaturation of complementary single strands by recA protein.
Fibrinolysis at the Interface of Thrombosis and Inflammation — The Role of Neutrophil Extracellular Traps (2014)

Fibrinolysis at the Interface of Thrombosis and Inflammation — The Role of Neutrophil Extracellular Traps
Relationship between peripheral and coronary function using laser Doppler imaging and transthoracic echocardiography (2008)

Vascular dysfunction in the coronary and peripheral circulations is an early prognostic marker of future cardiovascular events. Measurements of coronary and peripheral vascular function in resistance vessels can be made, but rely on invasive procedures, which make them unsuitable for routine application. An assessment of the direct correlation between vascular responses in skin and coronary vessels has not been made previously. In 27 normal healthy subjects (18-55 years of age), we examined the relationship between peripheral and coronary vascular function. Cutaneous perfusion was measured using the non-invasive technique of laser Doppler imaging during iontophoresis of acetylcholine and sodium nitroprusside, and cutaneous vascular conductance was calculated (laser Doppler perfusion/mean arterial pressure). Coronary flow reserve was measured using transthoracic echocardiography during intravenous adenosine infusion. Mean diastolic velocities were measured at baseline and peak hyperaemic conditions from the Doppler signal recordings. CVR (coronary velocity reserve) was defined as the ratio of hyperaemic to basal mean diastolic velocities. There were significant positive correlations between CVR and cutaneous vascular conductance for acetylcholine (r=0.399, P=0.039) and sodium nitroprusside (r=0.446, P=0.020). These results support the idea that peripheral measurements of skin blood flow are representative of generalized microvascular function including that of the coronary circulation in normal healthy subjects.
A simple genotyping method to detect small CRISPR-Cas9 induced indels by agarose gel electrophoresis (2019)

CRISPR gene editing creates indels in targeted genes that are detected by genotyping. Separating PCR products generated from wild-type versus mutant alleles with small indels based on size is beyond the resolution capacity of regular agarose gel electrophoresis. To overcome this limitation, we developed a simple genotyping method that exploits the differential electrophoretic mobility of homoduplex versus heteroduplex DNA hybrids in high concentration agarose gels. First, the CRISPR target region is PCR amplified and homo- and hetero-duplexed amplicons formed during the last annealing cycle are separated by 4-6% agarose gel electrophoresis. WT/mutant heteroduplexes migrate more slowly and are distinguished from WT or mutant homoduplexes. Heterozygous alleles are immediately identified as they produce two distinct bands, while homozygous wild-type or mutant alleles yield a single band. To discriminate the latter, equal amounts of PCR products of homozygous samples are mixed with wild-type control samples, subjected to one denaturation/renaturation cycle and products are electrophoresed again. Samples from homozygous mutant alleles now produce two bands, while those from wild-type alleles yield single bands. This method is simple, fast and inexpensive and can identify indels >2 bp. in size in founder pups and genotype offspring in established transgenic mice colonies.
Two-Domain MHC Class II Molecules Form Stable Complexes with Myelin Basic Protein 69–89 Peptide That Detect and Inhibit Rat Encephalitogenic T Cells and Treat Experimental Autoimmune Encephalomyelitis (1998)

We designed and expressed in bacteria a single-chain two-domain MHC class II molecule capable of binding and forming stable complexes with antigenic peptide. The prototype "beta1alpha1" molecule included the beta1 domain of the rat RT1.B class II molecule covalently linked to the amino terminus of the alpha1 domain. In association with the encephalitogenic myelin basic protein (MBP) 69-89 peptide recognized by Lewis rat T cells, the beta1alpha1/MBP-69-89 complex specifically labeled and inhibited activation of MBP-69-89 reactive T cells in an IL-2-reversible manner. Moreover, this complex both suppressed and treated clinical signs of experimental autoimmune encephalomyelitis and inhibited delayed-type hypersensitivity reactions and lymphocyte proliferation in an Ag-specific manner. These data indicate that the beta1alpha1/MBP-69-89 complex functions as a simplified natural TCR ligand with potent inhibitory activity that does not require additional signaling from the beta2 and alpha2 domains. This new class of small soluble polypeptide may provide a template for designing human homologues useful in detecting and regulating potentially autopathogenic T cells.
Current opinions in headache pathogenesis: introduction and synthesis (1998)

Henry Ford Hospital and Health Sciences Center, Department of Neurology, Detroit, Michigan, USA Correspondence to K.M.A. Welch, MD, Headache and NMR Research Centers, Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI, USA Tel: +1 313 876 3396; fax: +1 313 876 1324 Abbreviations; CADASIL: cerebral autosomal dominant arteriopathy with subcortical leukoencephalopathy and stroke; CBF: cerebral blood flow; FHM: familial hemiplegic migraine
Human nucleotide excision nuclease removes thymine dimers from DNA by incising the 22nd phosphodiester bond 5' and the 6th phosphodiester bond 3' to the photodimer. (1992)

By using a human cell-free system capable of nucleotide excision repair, a synthetic substrate consisting of a plasmid containing four thymidine dimers at unique locations, and deoxyribonucleoside 5'-[alpha-thio]triphosphates for repair synthesis, we obtained DNA fragments containing repair patches with phosphorothioate linkages. Based on the resistance of these linkages to digestion by exonuclease III and their sensitivity to cleavage by I2, we were able to delineate the borders of the repair patch to single-nucleotide resolution and found an asymmetric patch with sharp boundaries. That the repair patch was produced by filling in a gap generated by an excision nuclease and not by nick-translation was confirmed by the finding that the thymidine dimer was released in a 27- to 29-nucleotide oligomer.
Acute Coagulopathy of Trauma: Hypoperfusion Induces Systemic Anticoagulation and Hyperfibrinolysis (2008)

Acute coagulopathy of trauma is associated with systemic hypoperfusion and is characterized by anticoagulation and hyperfibrinolysis. There was no evidence of coagulation factor loss or dysfunction at this time point. Soluble thrombomodulin levels correlate with thrombomodulin activity. Thrombin binding to thrombomodulin contributes to hyperfibrinolysis via activated protein C consumption of PAI-1.
Long-Term Follow-Up of Donor Chimerism and Tolerance After Human Liver Transplantation (2009)

We aimed to quantify peripheral donor chimerism (DC) and to analyze its association with graft and recipient outcome. Forty-two liver transplant recipients and their respective donors were studied, providing a total of 148 posttransplantation serum samples. DC was assessed with real-time quantitative polymerase chain reaction (qPCR) to detect polymorphic markers. DC did not decrease with time post-transplantation and was higher in child recipients versus adults and in recipients of deceased donor liver transplants versus recipients of live donor liver transplants. Higher levels of DC were detected in Rh-positive blood group donors, in O blood group recipients versus A blood group recipients, and in recipients with hepatitis C virus versus recipients with alcoholic cirrhosis. High DC was associated with patients with organ damage due to recurrent disease and rejection. Stable, high levels of DC, in the absence of other major clinical events, may thus be a marker of transplantation tolerance, and this knowledge may help to tailor immunosuppressive treatment. In conclusion, qPCR is a useful technique for DC follow-up in liver transplantation, although the evolution of DC levels should be analyzed in accordance with the clinical outcome of the patient.