gebhart/patrepeval huggingface dataset:
A Protective Role for Dengue Virus-Specific CD8+ T Cells (2009)

Infection with one of the four serotypes of dengue virus (DENV1-4) can result in a range of clinical manifestations in humans, from dengue fever to the more serious dengue hemorrhagic fever/dengue shock syndrome. Although T cells have been implicated in the immunopathogenesis of secondary infections with heterologous DENV serotypes, the role of T cells in protection against DENV is unknown. In this study, we used a mouse-passaged DENV2 strain, S221, to investigate the role of CD8(+) T cells in the immune response to primary DENV infection. S221 did not replicate well in wild-type mice, but did induce a CD8(+) T cell response, whereas viral replication and a robust CD8(+) T cell response were observed after infection of IFN-alpha/betaR(-/-) mice. Depletion of CD8(+) T cells from IFN-alpha/betaR(-/-) mice before infection resulted in significantly higher viral loads compared with undepleted mice. Mapping the specificity of the CD8(+) T cell response led to the identification of 12 epitopes derived from 6 of the 10 DENV proteins, with a similar immunodominance hierarchy observed in wild-type and IFN-alpha/betaR(-/-) mice. DENV-specific CD8(+) T cells produced IFN-gamma, TNF-alpha, expressed cell surface CD107a, and exhibited cytotoxic activity in vivo. Finally, immunization with four of the immunodominant CD8(+) T cell epitopes enhanced viral clearance. Collectively, our results reveal an important role for CD8(+) T cells in the host defense against DENV and demonstrate that the anti-DENV CD8(+) T cell response can be enhanced by immunization, providing rationale for designing DENV-specific vaccines that induce cell-mediated immunity.
VLSI Implementation of a fast rank order filtering algorithm (2005)

A useful class of digital filters is the rank order filter, of which the median filter is the most popular. This paper details the NMOS IC design of a 6-bit rank order filter based upon the approach of Fitch, Coyle, and Gallagher. The chip provides for programmable window lengths of 3, 5, 7, and 9; the selection of any element in the rank order; operation in the nonrecursive or recursive modes; and the ability to function in a "ganged" mode so that two or more identical chips can accommodate samples of length seven or eight bits.
Function of the Human Insulin Promoter in Primary Cultured Islet Cells (1996)

Pancreatic islet beta cells regulate the rate of insulin gene transcription in response to a number of nutrients, the most potent of which is glucose. To test for its regulation by glucose, the promoter sequence was isolated from the human insulin gene. When linked to chloramphenicol acetyltransferase and transfected into primary islet cultures, the human insulin promoter is activated by glucose. In parallel islet transfections, glucose also activates the L-pyruvate kinase and islet amyloid chain ketoacid dehydrogenase E1a promoter, but it does not affect the beta cell glucose kinase promoter. Using deletion and substitution mutations of the proximal human insulin promoter, we mapped a metabolic response element to the E box, E1, at -100 base pairs relative to the transcription start site. Although the isolated E1 element responds to glucose, inclusion of either of two AT-rich sequences, A1 or A2/C1 on either side of E1, results in dramatic synergistic activation. Inclusion of A2/C1 also increases the response to glucose. The A2-E1-A1 region alone, however, does not explain all of the activity of the human insulin promoter in cultured islets, and other transcriptionally important elements likely to contribute to the glucose response as well.
So Long, and Thanks for All the Fish* (2009)

Roy Want presents his final introduction as Editor-in-chief, and announces Nigel Davies of Lancaster University, UK as the new EIC starting in 2010, along with a summary of his research and professional career. A synopsis of the magazines evolution in the last four years is also presented. To conclude, he describes the importance of "Virtual Machines (VM)" in pervasive computing, and for pervasive "Content Sharing", the two featured topics of this special issue.
Biochemistry and occurrence of O-demethylation in plant metabolism (2010)

Demethylases play a pivitol role in numerous biological processes from covalent histone modification and DNA repair to specialized metabolism in plants and microorganisms. Enzymes that catalyze O- and N-demethylation include 2-oxoglutarate (2OG)/Fe(II)-dependent dioxygenases, cytochromes P450, Rieske-domain proteins and flavin adenine dinucleotide (FAD)-dependent oxidases. Proposed mechanisms for demethylation by 2OG/Fe(II)-dependent enzymes involve hydroxylation at the O- or N-linked methyl group followed by formaldehyde elimination. Members of this enzyme family catalyze a wide variety of reactions in diverse plant metabolic pathways. Recently, we showed that 2OG/Fe(II)-dependent dioxygenases catalyze the unique O-demethylation steps of morphine biosynthesis in opium poppy, which provides a rational basis for the widespread occurrence of demethylases in benzylisoquinoline alkaloid metabolism.
Mitochondrial Respiratory-Chain Diseases (2003)

The mitochondrial respiratory chain has the crucial function of supplying the cell with energy in the form of ATP. Mutations affecting this chain can arise in mitochondrial or nuclear DNA and cause diseases known as mitochondrial encephalomyopathies. Because the rules of inheritance of mitochondrial and nuclear DNA differ considerably, these brain–muscle syndromes often have unpredictable clinical and genetic features.
The elevated natural killer sensitivity of targets carrying surface-attached C3 fragments require the availability of the iC3b receptor (CR3) on the effectors. (1988)

Human serum-treated Raji and Daudi cells were shown to bind C3 fragments on their surface as a consequence of their capacity to activate C via the alternative pathway. C3 molecules were detectable on the cell surfaces up to 24 h after serum exposure. The C3 fragment-coated cells showed increased sensitivity to spontaneous lymphocyte-mediated cytotoxicity. The effector lymphocytes involved in the enhanced cytotoxicity were NK cells with low buoyant density, carrying both CR3 and FcR. Blocking of the FcR and CR3 with F(ab)2 fragments from Leu-11c or Leu-15 mAb, respectively, did not influence the lysis of targets that did not carry C3 fragments. In contrast, the accessibility of CR3 on the effector lymphocytes was essential for the C3 fragment-mediated enhancement of cytotoxicity. In addition to the Leu-15 antibody, N-acetyl-D-Glucosamine, a compound known to block iC3b binding to CR3, also abrogated the C3 fragment-imposed effect. Our previous experiments showed that the C3 fragments bind to acceptor sites on target cells. The present experiments show that the C3 fragments fixed onto the target bind to CR3 on effector cells. These data substantiate the hypothesis that the bivalent C3 fragments, which are fixed on the targets, promote their interaction with lytic lymphocytes by bridging the two cells.
General principles of stress and well-being. (2014)

Although many of the examples in this chapter have come from research conducted with the chicken, the authors' experimental animal, the implications are relevant to all forms of livestock and poultry that are husbanded in flocks and herds. In our opinion, the most important factor affecting the well-being of livestock and poultry is their relationship with their human associates. Kind care (socialization) has many well-being and production benefits. Socialized animals are easier to work with, have enhanced productivity, are more adaptable to adverse environments, are more resistant to diseases and develop better immunity. These factors make genetic selection easier. The responses of individuals within groups are also more uniform, thus reducing the number of animals needed for research. Further, socialization can be applied to large and small groups of animals as well as intensive and extensive production systems.
Quantitative Proteomic Analysis of Oligodendrogliomas With and Without 1p/19q Deletion (2010)

Approximately 50-80% of oligodendrogliomas demonstrate a combined loss of chromosome 1p and 19q. Chromosome 1p/19q deletion, appearing early in tumorigenesis, is associated with improved clinical outcomes, including response to chemotherapy and radiation. Although many hypotheses have been proposed, the molecular mechanisms underlying improved clinical outcomes with 1p/19q deletion in oligodendrogliomas have not been characterized fully. To investigate the molecular differences between oligodendrogliomas, we employed an unbiased proteomic approach using microcapillary liquid chromatography mass spectrometry, along with a quantitative technique called isotope-coded affinity tags, on patient samples of grade II oligodendrogliomas. Following conventional biochemical separation of pooled tumor tissue from five samples of undeleted and 1p/19q deleted grade II oligodendrogliomas into nuclei-, mitochondria-, and cytosol-enriched fractions, relative changes in protein abundance were quantified. Among the 442 total proteins identified, 163 nonredundant proteins displayed significant changes in relative abundance in at least one of the three fractions between oligodendroglioma with and without 1p/19q deletion. Bioinformatic analyses of differentially regulated proteins supported the potential importance of metabolism and invasion/migration to the codeleted phenotype. A subset of altered proteins, including the pro-invasive extracellular matrix protein BCAN, was further validated by Western blotting as candidate markers for the more aggressive undeleted phenotype. These studies demonstrate the utility of proteomic analysis to identify candidate biological motifs and molecular mechanisms that drive differential malignancy related to 1p19q phenotypes. Future analysis of larger patient samples are warranted to further refine biomarker panels to predict biological behavior and assist in the identification of deleted gene products that define the 1p/19q phenotype.
Photonic bands of metallic systems. II. Features of surface plasmon polaritons (2001)

The photonic band structure of a two-dimensional square lattice composed of metallic cylinders was calculated for the H polarization by means of the numerical simulation of dipole radiation based on the finite-difference time-domain method. The presence of radiational eigenmodes that originate from surface plasmon polaritons was clearly shown by the symmetry and the localized nature of the field distribution.
THE STRUCTURE OF MELITTIN. I. STRUCTURE DETERMINATION AND PARTIAL REFINEMENT. (1981)

Melittin is the principal protein component of bee venom and is thought to function as a lytic agent. Despite its predominantly hydrophobic character, melittin is soluble as a tetramer in aqueous salt solutions. We report here on the determination of the crystal structure of tetrameric melittin at 2.8-A resolution by the method of multiple isomorphous replacement, followed by partial atomic refinement at 2.0-A resolution. The melittin tetramer contains a noncrystallographic 2-fold axis of symmetry in addition to a crystallographic 2-fold axis, so that the four polypeptide chains have nearly identical structures. The noncrystallographic 2-fold axis was utilized twice during the determination of the structure. The multiple isomorphous replacement electron density map was averaged over this 2-fold axis before model building and strict noncrystallographic symmetry was assumed during the initial stages of atomic refinement. The 2.8-A resolution electron density map suggests that the melittin monomer contains two alpha-helical regions separated by a non-alpha-helical segment at residues 11 and 12. Difference maps at 2.0-A resolution tend to confirm this structure and reveal that at least six solvent molecules are bound to the melittin tetramer in the crystal. The relatively high occupancies of four of these suggest that they are ions of crystallization rather than water molecules.
Association Between Baseline LDL-C Level and Total and Cardiovascular Mortality After LDL-C Lowering (2018)

In these meta-analyses and meta-regressions, more intensive compared with less intensive LDL-C lowering was associated with a greater reduction in risk of total and cardiovascular mortality in trials of patients with higher baseline LDL-C levels. This association was not present when baseline LDL-C level was less than 100 mg/dL, suggesting that the greatest benefit from LDL-C-lowering therapy may occur for patients with higher baseline LDL-C levels.
Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis (2009)

Multiple sclerosis is a T cell-mediated demyelinating disease of the central nervous system. Interleukin-17-producing T helper cells, named Th17 cells, represent a novel CD4+ T cell effector subset involved in the response against extracellular pathogens. In addition, Th17 cells are pathogenic in several animal models of autoimmune disease, including the animal model for multiple sclerosis, but their function in multiple sclerosis remains to be elucidated. In this study, we analysed the frequency and the phenotype of Th17 cells in the cerebrospinal fluid and peripheral blood of multiple sclerosis patients. We show that the frequency of Th17 cells is significantly higher in the cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis during relapse, in comparison to relapsing-remitting patients in remission or to patients with other non-inflammatory neurological diseases. Similarly, in patients with clinically isolated syndrome during their first neurological episode, Th17 cells are more abundant than in clinically isolated syndrome patients with no acute symptoms. Patients with inflammatory neurological diseases other than multiple sclerosis also showed increased frequency of Th17 cells compared to patients with no inflammatory diseases. To assess a potential pathological impact of Th17 cells in disease, we generated T cell clones from the cerebrospinal fluid and peripheral blood of patients with multiple sclerosis. We found that Th17 clones expressed higher basal levels of the activation markers CD5, CD69, CD2 and human leukocyte antigen-DR as well as of the CD28-related family of co-stimulatory molecules, when compared to Th1 clones, and confirmed these findings with ex vivo human T cells. Molecules involved in T cell adhesion to endothelium, such as CD49d, CD6 and the melanoma cell adhesion molecule, were also more abundant on the Th17 than on the Th1 cells. Furthermore, functional assays showed that Th17 clones were more prone than Th1 clones to melanoma cell adhesion molecule-mediated adhesion to endothelial cells, and that Th17 cells had a higher proliferative capacity and were less susceptible to suppression than Th1 cells. Altogether our data suggest that Th17 cells display a high pathogenic potential and may constitute a relevant pathogenic subset in multiple sclerosis.
Solvatochromic Reagents for Multicomponent Reactions and their Utility in the Development of Cell‐Permeable Macrocyclic Peptide Vectors (2011)

Sensitive scaffolds: An isocyanide equipped with an environment-sensitive fluorophore was used to synthesize peptide macrocycles. The photophysical properties of the product macrocycles are sensitive to both peptide sequence and configuration. A mitochondria-penetrating peptide was constrained within a cyclic peptide framework and showed increased uptake and localization relative to a linear control (see scheme). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Beneficial effects of a long-term oral l-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients (2006)

Because chronic L-arginine supplementation improves insulin sensitivity and endothelial function in nonobese type 2 diabetic patients, the aim of this study was to evaluate the effects of a long-term oral L-arginine therapy on adipose fat mass (FM) and muscle free-fat mass (FFM) distribution, daily glucose levels, insulin sensitivity, endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance who were treated with a combined period of hypocaloric diet and exercise training. Thirty-three type 2 diabetic patients participated in a hypocaloric diet plus an exercise training program for 21 days. Furthermore, they were divided into two groups in randomized order: the first group was also treated with L-arginine (8.3 g/day), and the second group was treated with placebo. Although in the placebo group body weight, waist circumference, daily glucose profiles, fructosamine, insulin, and homeostasis model assessment index significantly decreased, L-arginine supplementation further decreased FM (P < 0.05) and waist circumference (P < 0.0001), preserving FFM (P < 0.03), and improved mean daily glucose profiles (P < 0.0001) and fructosamine (P < 0.03). Moreover, change in area under the curve of cGMP (second messenger of nitric oxide; P < 0.001), superoxide dismutase (index of antioxidant capacity; P < 0.01), and adiponectin levels (P < 0.02) increased, whereas basal endothelin-1 levels (P < 0.01) and leptin-to-adiponectin ratio (P < 0.05) decreased in the L-arginine group. Long-term oral L-arginine treatment resulted in an additive effect compared with a diet and exercise training program alone on glucose metabolism and insulin sensitivity. Furthermore, it improved endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance.
Expression of Escherichia coli Glycogen Synthase in the Tubers of Transgenic Potatoes (Solanum tuberosum) Results in a Highly Branched Starch (1994)

A chimeric gene containing the patatin promoter and the transit-peptide region of the small-subunit carboxylase gene was utilized to direct expression of Escherichia coli glycogen synthase (glgA) to potato (Solanum tuberosum) tuber amyloplasts. Expression of the glgA gene product in tuber amyloplasts was between 0.007 and 0.028% of total protein in independent potato lines as determined by immunoblot analysis. Tubers from four transgenic potato lines were found to have a lowered specific gravity, a 30 to 50% reduction in the percentage of starch, and a decreased amylose/amylopectin ratio. Total soluble sugar content in these selected lines was increased by approximately 80%. Analysis of the starch from these potato lines also indicated a reduced phosphorous content. A very high degree of branching of the amylopectin fraction was detected by comparison of high and low molecular weight carbohydrate chains after debranching with isoamylase and corresponding high-performance liquid chromatography analysis of the products. Brabender viscoamylograph analysis and differential scanning calorimetry of the starches obtained from these transgenic potato lines also indicate a composition and structure much different from typical potato starch. Brabender analysis yielded very low stable paste viscosity values (about 30% of control values), whereas differential scanning calorimetry values indicated reduced enthalpy and gelatinization properties. The above parameters indicate a novel potato starch based on expression of the glgA E. coli gene product in transgenic potato.
Optical hyperparametric oscillations in a whispering-gallery-mode resonator: Threshold and phase diffusion (2005)

We present a theoretical analysis of optical parametric oscillations through four-wave mixing in a nonlinear high-$Q$ whispering-gallery-mode resonator. It is shown that even a small flux of pump photons is sufficient to reach the threshold of the oscillations. We demonstrate that due to narrow bandwidth of the resonator modes as well as the high efficiency of the resonant frequency conversion the oscillator produces a stable narrow-band beat note of the pump, signal, and idler waves making an all-optical secondary frequency reference feasible.
Electronic Energy Transfer in CdSe Quantum Dot Solids (1996)

We demonstrate electronic energy transfer between close packed quantum dots using cw and time resolved photoluminescence. Optically clear and thin, close packed quantum dot solids were prepared from mixtures of small and large CdSe quantum dots (38.5 and 62 \AA{}, $\ensuremath{\sigma}&lt;4.5%$). Quenching of the luminescence (lifetime) of the small dots accompanied by enhancement of the luminescence (lifetime) of the large dots is consistent with long-range resonance transfer of electronic excitations from the more electronically confined states of the small dots to the higher excited states of the large dots.
Tissue Inhibitor of Metalloproteinase-1 Protects Human Breast Epithelial Cells from Extrinsic Cell Death: A Potential Oncogenic Activity of Tissue Inhibitor of Metalloproteinase-1 (2005)

Tissue inhibitors of metalloproteinases (TIMPs) inhibit matrix metalloproteinases and some members of a disintegrin and metalloproteinase domain (ADAM) family. In addition, recent studies unveiled novel functions of TIMPs in the regulation of apoptosis. TIMP-1 inhibits intrinsic apoptosis by inducing TIMP-1 specific cell survival pathways involving focal adhesion kinase (FAK). TIMP-3, however, was shown to enhance extrinsic cell death by inhibiting the shedding of the cell surface death receptors mediated by tumor necrosis factor-alpha converting enzymes (TACE/ADAM-17). Here, we examined whether TIMP-1, an inhibitor of some of the ADAM family members, enhances the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced extrinsic apoptotic pathway. Surprisingly, we found that TIMP-1 effectively protects human breast epithelial cells from TRAIL-induced apoptosis, demonstrating opposite roles of TIMP-1 and TIMP-3 for the regulation of extrinsic apoptosis. TIMP-1 inhibition of TRAIL-induced apoptosis does not depend on its ability to inhibit matrix metalloproteinases or ADAM activities and is unrelated to its ability to stabilize active or decoy death receptors. Importantly, inhibition of PI 3-kinase signaling by wortmannin and down-regulation of FAK expression using siRNA significantly diminish TIMP-1 protection of human breast epithelial cells against TRAIL-induced extrinsic apoptosis. In addition, the in vitro three-dimensional culture studies showed that TIMP-1 inhibits lumen formation and apoptosis during morphogenesis of MCF10A acini. Taken together, these studies suggest that TIMP-1 may exert oncogenic activity in breast cancer through inhibition of both intrinsic and extrinsic apoptosis involving the FAK survival signal transduction pathway.