gebhart/patrepeval huggingface dataset:
TEN AMINO ACIDS ESSENTIAL FOR PLASMA PROTEIN PRODUCTION EFFECTIVE ORALLY OR INTRAVENOUSLY (1943)

When blood plasma proteins are depleted by bleeding with return of the washed red cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet protein intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. When the protein intake of such dogs is completely replaced by the growth mixture (Rose) of crystalline amino acids, plasma protein production is excellent, weight and nitrogen balance are maintained. This growth mixture consists of ten amino acids, threonine, valine, leucine, isoleucine, tryptophane, lysine, phenylalanine, methionine, histidine, arginine, and is as effective as most diet proteins in plasma protein production. The above amino acid mixture in aqueous solution may be given by vein with equally good plasma protein production and no apparent clinical disturbance even when given rapidly. Cystine may replace methionine in the above mixture with equally good plasma protein production for 7 to 10 days but at the expense of the body tissues, that is, with weight loss and a negative nitrogen balance. The addition of cystine to the protein-free, otherwise adequate diet may result in the production of considerable new plasma protein during a period as long as 1 week (cystine effect). This reaction may depend upon the amino acid constitution of the preceding diet protein in that it occurred following a liver feeding but did not occur after pancreas feeding. Arginine is required in the diet of the protein depleted dog for fabrication of plasma protein. It is apparently not needed for nitrogen balance for as long as 1 or 2 weeks. The omission of either threonine or valine from the growth mixture is quickly followed by a sharp decline in plasma protein formation and by a negative nitrogen balance. When histidine, arginine, and most of the lysine are omitted from the growth mixture, nitrogen balance and weight may be maintained for as long as 1 week but plasma protein production falls off markedly. The findings indicate that the growth mixture of amino acids should be a valuable addition to transfusion and infusion therapy in disease states associated with deficient nitrogen intake or tissue injury and accelerated nitrogen loss, including shock, burns, and major operative procedures.
Laser-induced photo-polymerisation for creation of paper-based fluidic devices (2014)

Paper-based microfluidics is a rapidly progressing inter-disciplinary technology driven by the need for low-cost alternatives to conventional point-of-care diagnostic tools. For transport of reagents/analytes, such devices often consist of interconnected hydrophilic fluid-flow channels that are demarcated by hydrophobic barrier walls that extend through the thickness of the paper. Here, we present a laser-based fabrication procedure that uses polymerisation of a photopolymer to produce the required fluidic channels in paper. Experimental results showed that the structures successfully guide the flow of fluids and allow containment of fluids in wells, and hence the technique is suitable for fabrication of paper-based microfluidic devices. The minimum width for the hydrophobic barriers that successfully prevented fluid leakage was ~120 μm and the minimum width for the fluidic channels that can be formed was ~80 μm, the smallest reported so far for paper-based fluidic patterns.
Assembly and function of the T cell antigen receptor. Requirement of either the lysine or arginine residues in the transmembrane region of the alpha chain. (1990)

The T cell receptor (TCR) for antigen consists, on the majority of peripheral lymphocytes, of an immunoglobulin-like, disulfide-linked heterodimeric glycoprotein: the alpha and beta chain. These proteins are noncovalently linked to at least four nonvariant proteins which comprise the CD3 complex: CD3 gamma, delta, epsilon, and zeta. Whereas the TCR alpha and beta proteins have positively charged residues in the transmembrane region, all the CD3 proteins have similarly placed negatively charged amino acid residues. It has been suggested that these basic and acidic amino acid residues may play an important role in TCR.CD3 complex assembly and/or function. In this paper, the structural and functional role of the lysine and arginine residues of the TCR alpha chain was addressed using oligonucleotide mediated site directed mutagenesis. The Arg256 and Lys261 residues of the TCR alpha cDNA of the HPB-ALL cell line were mutated to either Gly256 and/or Ile261. The altered cDNAs were transfected into a TCR alpha negative recipient mutant cell line of REX, clone 20A. Metabolic labeling of the T cell transfectants showed that mutation of either the Arg256 or Lys261 amino acid residues had no effect on the ability of the TCR alpha chain to form either a heterodimer with the TCR beta chain or a complex with the CD3 gamma, delta, and epsilon proteins. Consequently, the Arg256 to Gly256 and Lys261 to Ile261 mutations did not prevent the formation of a mature, functional TCR.CD3 complex on the cell surface as determined by immunofluorescence, cell surface radioiodination, and the ability of the transfectants to mobilize intracellular calcium after stimulation with a mitogenic anti-CD3 epsilon monoclonal antibody. In contrast, a mutant cDNA in which both the Arg256 and Lys261 residues were mutated to Gly256 and Ile261, respectively, failed to reconstitute the cell surface expression of the TCR.CD3 complex and, consequently, the ability to respond to mitogenic stimuli. In the absence of both the Arg256 and Lys261 residues, TCR alpha beta heterodimer formation was not observed. Cotransfection studies in COS cells showed that the failure of assembly of a heterodimer was likely due to an inability of the mutated TCR alpha chain to form a subcomplex with either the CD3 gamma, delta, epsilon, or zeta proteins.(ABSTRACT TRUNCATED AT 400 WORDS)
Modification of the melting properties of duplex DNA by attachment of a GC-rich DNA sequence as determined by denaturing gradient gel electrophoresis (1985)

The melting behavior of a DNA fragment carrying the mouse beta maj-globin promoter was investigated as a means of establishing procedures for separating DNA fragments differing by any single base substitution using the denaturing gradient gel electrophoresis procedure of Fischer and Lerman (1,2). We find that attachment of a 300 base pair GC-rich DNA sequence, termed a GC-clamp, to a 135 bp DNA fragment carrying the mouse beta-globin promoter significantly alters the pattern of DNA melting within the promoter. When the promoter is attached to the clamp, the promoter sequences melt without undergoing strand dissociation. The calculated distribution of melting domains within the promoter differs markedly according to the relative orientation of the clamp and promoter sequences. We find that the behavior of DNA fragments containing the promoter and clamp sequences on denaturing gradient polyacrylamide gels is in close agreement with the theoretical melting calculations. These studies provide the basis for critical evaluation of the parameters for DNA melting calculations, and they establish conditions for determining whether all single base substitutions within the promoter can be separated on denaturing gradient gels.
Effect of cultivation conditions on spore production from Bacillus amyloliquefaciens B128 and its antagonism to Botrytis elliptica (2008)

The spore yields obtained using bioreactors were much higher than those previously reported. The freshly produced spore preparations from the B128 strain significantly antagonized the grey mould pathogen B. elliptica.
Abdominal aortic aneurysms: preliminary technical and clinical results with transfemoral placement of endovascular self-expanding stent-grafts. (1996)

Exclusion of AAA from circulation was feasible, safe, and clinically effective with the new stent-graft.
Scientific Opinion on nitrofurans and their metabolites in food (2015)

Abstract Nitrofurans are antimicrobial agents not authorised for use in food‐producing animals in the European Union. Nitrofurans are rapidly metabolised, occurring in animal tissues as protein‐bound metabolites. The European Commission requested EFSA to provide a scientific opinion on the risks to human health related to the presence of nitrofurans in food and whether a reference point for action (RPA) of 1.0 µg/kg for the marker metabolites is adequate to protect public health. Data on occurrence of nitrofuran marker metabolites in food were extracted from the national residue monitoring plan results and from the Rapid Alert System for Food and Feed (RASFF). The CONTAM Panel concluded that these data were too limited to carry out a reliable human dietary exposure assessment. Instead, human dietary exposure was calculated for a scenario in which a single nitrofuran marker metabolite is present at 1.0 µg/kg in foods of animal origin, excluding milk and dairy products. The mean chronic dietary exposure for this worst‐case scenario would range from 3.3 to 8.0 and 1.9 to 4.3 ng/kg b.w. per day for toddlers and adults, respectively. Nitrofurans and their marker metabolites, generally, are genotoxic and carcinogenic and, also, have non‐neoplastic effects in animals. Margins of exposure (MOEs) were calculated at 2.0 × 105 or greater for carcinogenicity and at 2.5 × 103 or greater for non‐neoplastic effects. The CONTAM Panel concluded that it is unlikely that exposure to food contaminated with nitrofuran marker metabolites at or below 1.0 µg/kg is a health concern. A scenario in which foods are considered to be contaminated with semicarbazide, from use of carrageenan as a food additive, at 1 µg/kg was used to assess whether it is appropriate to apply the RPA to foods of non‐animal origin; MOEs of greater than 104 calculated for non‐neoplastic effects do not indicate a health concern.
Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to response to treatment. (1998)

Alteration of the p53 gene is the most frequent genetic alteration in human cancer, and it leads to the accumulation of mutant p53 in the nucleus of tumor cells. In addition, it has been shown that patients with various types of neoplasias have p53 antibodies in their sera. ELISA was used to detect anti-p53 antibodies in their sera of 167 patients with lung cancer. Among these, 32 individuals (16 positive for p53 antibodies and 16 negative) were monitored over a period of 30 months for p53 antibodies. Twelve of 16 antibody positive patients had reduced titers during chemotherapy that led to partial or complete remissions of disease. The specificity of these antibodies was confirmed by two different ELISA procedures and by immunoprecipitation. The very rapid, specific decrease in these antibodies during therapy suggests that a constant level of tumoral cells with nuclear accumulating p53 protein is necessary for a detectable humoral anti-p53 response. The good correlation found between the specific evolution of the p53 antibody titer and the response to therapy suggests that p53 antibodies could represent a useful tool for checking the response to therapy and for monitoring some relapses before they are clinically detectable.
A Nanoporous Silicon Membrane Electrode Assembly for On-Chip Micro Fuel Cell Applications (2006)

Silicon-based fuel cells are under active development for chip-scale electrical power supply. One of the greatest challenges in micro-fuel-cell research is the development of a suitable proton conducting membrane material that is compatible with standard silicon microfabrication technology. In this paper, the use of nanoporous silicon as a novel proton conducting membrane material in a microscale fuel cell membrane electrode assembly (MEA) is demonstrated. The devices were fabricated by first creating 100-/spl mu/m-thick silicon windows in a standard silicon wafer, anodizing to create pores in the windows, and then painting catalyst layers and insulators onto the porous structures. Using 5 M formic acid and 0.5 M sulfuric acid as the fuel, the fuel cell peak power density reached about 30 mW/cm/sup 2/ at current density level of about 120 mA/cm/sup 2/. These results represent the successful integration of a new class of protonic conductor into a microfabricated silicon fuel cell.
The pharmacology of intravenous and oral etoposide (1991)

The epipodophyllotoxin derivative etoposide (VP-16) has been in widespread use both alone and in combination chemotherapy for the past decade. It has phase-specific cytotoxicity that acts in the last S and G2 phases of the cell cycle. Although its mode of action is not certain, it appears to act by causing breaks in DNA by interaction with DNA-topoisomerase II or by the formation of free radicals. Most studies show biexponential decay after the intravenous (IV) administration of etoposide. Approximately 30% to 70% of administered etoposide is excreted, with approximately 45% present in the urine. Etoposide is available in oral and IV preparations. It is highly schedule-dependent, with once-daily doses (e.g., for 5 to 8 days every 21 days) giving results superior to intermittent administration. The bioavailability of oral etoposide is approximately 50%, but its absorption is not linear with increasing dose (e.g., greater than 200 mg/d, bioavailability decreases). Factors influencing the bioavailability of oral etoposide include patient status, concurrent medications, hepatic and renal function, and nausea and vomiting. In numerous clinical trials, etoposide has demonstrated excellent activity against a range of tumors, including small cell lung cancer (SCLC), malignant lymphomas, gestational trophoblastic tumors, Ewing's and soft tissue sarcomas, and germ cell tumors, with more modest activity in other tumors (e.g., non-SCLC). Although few comparative studies have been carried out, available data suggest that oral etoposide administered daily during 5 to 8 days is similar to the IV preparation in range of activity. In a study of 53 elderly patients with SCLC treated with etoposide (200 mg/d for five times), there was a response rate of 79% and a median survival of 9.5 months. These results were similar to those achieved with more intensive IV regimens. Several studies of chronic oral etoposide (50 mg/m2/d for 21 times) have been reported recently. Responses were observed in SCLC and germ cell tumors among patients who had relapsed after standard etoposide-containing regimens. These data suggest that etoposide may be a "new" drug when given in this schedule. The high response rates with oral etoposide suggest that oral administration may be substituted for IV administration. This substitution may allow for greater flexibility in chemotherapeutic administration, less hospitalization, and more acceptable toxicity.
Optimized rule induction (1993)

Swap-1, a state-of-the-art system for learning decision rules from data, is presented. The method embodied in Swap-1 generates reduced-complexity solutions by inducing compact solutions in larger dimensions where many rules might be needed to make accurate predictions. For many applications, such systems can automatically construct relatively compact rule sets with highly predictive performance.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The immunopeptidomic landscape of clear cell renal cell carcinoma: identification and characterization of T-cell epitopes for immunotherapeutic approaches (2018)

Current therapy of ccRCC is commonly constrained by low response rates and frequent resistance against administered drugs. In recent years, drug discovery is focusing on the positive modulation of the immune system. The lately approved checkpoint ab nivolumab for treatment of ccRCC is the first drug in the upcoming era of immunotherapy. Being an immunogenic tumor entity, specific immunotherapies have the potential to increase the anti-cancer response with lower side effects. To identify suitable targets for a specific immunotherapy a comprehensive analysis on the HLA ligandome of 58 ccRCC samples and corresponding adjacent benign tissues was conducted by LC-MS/MS and compared to an additional in-house database of benign immunopeptidomes. TUMAPs were selected according to several evaluations focusing on tumor exclusivity, quantitative expression and HLA restriction as well as the biological role of the source antigens. Overall, 26 peptides from six HLA alleles were selected and screened for their immunogenicity in CD8+ T cell priming experiments, with 19 peptides exhibiting immune recognition. This set of peptides can be considered for future specific immunotherapeutic approaches. HLA-C as well as HLA-E and HLA-G molecules possess important roles in both the innate and adaptive immunity with different immunomodulatory functions. However, the uncovering of the peptide motifs received insufficient attention until recent data from in vitro binding experiments for HLA-C allotypes. For this purpose, the characterization of the binding specificities of the most frequent HLA-C allotypes as well as HLA-E and HLA-G were accomplished by LC-MS/MS-based identification of naturally processed and presented HLA ligands from monoallelic C1R transfectants. HLA-C allotypes display anchors in the B or C pocket (position 2 or 3 within the peptide) and a less variable anchor in pocket F (C-terminal position within the peptide). Overall, 20,156 HLA-C ligands were identified. For HLA-E the previously reported small ligand repertoire could be confirmed with five identified ligands, whereas a large ligand repertoire for HLA-G (2258 ligands) could be unveiled with anchor positions 3 and 9 and an auxiliary anchor at position 1. The data was utilized to establish SYFPEITHI matrices for epitope prediction and for peptide assignment to the correct HLA. Especially for HLA-G the number of HLA ligands could be tremendously increased from three prior known HLA ligands within the IEDB database to more than 2000 HLA ligands.
Enhanced Mechanical Properties of Nanocomposites at Low Graphene Content (2009)

In this study, the mechanical properties of epoxy nanocomposites with graphene platelets, single-walled carbon nanotubes, and multi-walled carbon nanotube additives were compared at a nanofiller weight fraction of 0.1 +/- 0.002%. The mechanical properties measured were the Young's modulus, ultimate tensile strength, fracture toughness, fracture energy, and the material's resistance to fatigue crack propagation. The results indicate that graphene platelets significantly out-perform carbon nanotube additives. The Young's modulus of the graphene nanocomposite was approximately 31% greater than the pristine epoxy as compared to approximately 3% increase for single-walled carbon nanotubes. The tensile strength of the baseline epoxy was enhanced by approximately 40% with graphene platelets compared to approximately 14% improvement for multi-walled carbon nanotubes. The mode I fracture toughness of the nanocomposite with graphene platelets showed approximately 53% increase over the epoxy compared to approximately 20% improvement for multi-walled carbon nanotubes. The fatigue resistance results also showed significantly different trends. While the fatigue suppression response of nanotube/epoxy composites degrades dramatically as the stress intensity factor amplitude is increased, the reverse effect is seen for graphene-based nanocomposites. The superiority of graphene platelets over carbon nanotubes in terms of mechanical properties enhancement may be related to their high specific surface area, enhanced nanofiller-matrix adhesion/interlocking arising from their wrinkled (rough) surface, as well as the two-dimensional (planar) geometry of graphene platelets.
Maturation and Endosomal Targeting of β-Site Amyloid Precursor Protein-cleaving Enzyme (2000)

The amyloidogenic Abeta peptide is liberated from the amyloid precursor protein (APP) by two proteolytic activities, beta-secretase and gamma-secretase. Recently, a type I membrane protein termed BACE (beta-site APP cleaving enzyme) with characteristics of an aspartyl protease has been identified as the beta-secretase. We undertook a series of biochemical and morphological investigations designed to characterize the basic properties of this protein. Initial studies indicated that BACE undergoes N-linked glycosylation at three of four potential sites. Metabolic pulse-chase experiments revealed that after core glycosylation, BACE is rapidly and efficiently transported to the Golgi apparatus and distal secretory pathway. BACE was also found to be quite stable, being turned over with a t(12) of approximately 16 h. Retention of BACE in the endoplasmic reticulum by introduction of a C-terminal dilysine motif prevented complex carbohydrate processing and demonstrated that propeptide cleavage occurs after exit from this organelle. BACE exhibited intramolecular disulfide bonding but did not form oligomeric structures by standard SDS-polyacrylamide gel electrophoresis analysis and sedimented as a monomer in sucrose velocity gradients. Immunofluorescence studies showed a largely vesicular staining pattern for BACE that colocalized well with endosomal, but not lysosomal, markers. Measurable levels of BACE were also detected on the plasma membrane by both immunostaining and cell surface biotinylation, and cycling of the protein between the cell membrane and the endosomes was documented. A cytoplasmic dileucine motif was found to be necessary for normal targeting of BACE to the endosomal system and accumulation of the protein in this intracellular site.
Computation of characteristic modes for conducting bodies (1971)

A procedure for computing the characteristic modes for conducting bodies of arbitrary shape is developed. The method is applied to conducting bodies of revolution and to wire objects, and general computer programs are discussed. Illustrative examples of the computation of characteristic currents and characteristic fields are given for a cone-sphere, a disk, and a wire arrow. Modal solutions using these modes are computed for representative antenna and scattering problems to illustrate convergence of the solution as the number of modes is increased.
The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Update 2012 on the long-term treatment of bipolar disorder (2013)

Although major advances have been made since the first edition of this guideline in 2004, there are still areas of uncertainty, especially the prevention of depressive episodes and optimal long-term treatment of Bipolar II patients.