gebhart/patrepeval huggingface dataset:
An Alternative Mechanism of Bicarbonate-mediated Peroxidation by Copper-Zinc Superoxide Dismutase (2003)

Hydrogen peroxide can interact with the active site of copper-zinc superoxide dismutase (SOD1) to generate a powerful oxidant. This oxidant can either damage amino acid residues at the active site, inactivating the enzyme (the self-oxidative pathway), or oxidize substrates exogenous to the active site, preventing inactivation (the external oxidative pathway). It is well established that the presence of bicarbonate anion dramatically enhances the rate of oxidation of exogenous substrates. Here, we show that bicarbonate also substantially enhances the rate of self-inactivation of human wild type SOD1. Together, these observations suggest that the strong oxidant formed by hydrogen peroxide and SOD1 in the presence of bicarbonate arises from a pathway mechanistically distinct from that producing the oxidant in its absence. Self-inactivation rates are further enhanced in a mutant SOD1 protein (L38V) linked to the fatal neurodegenerative disorder, familial amyotrophic lateral sclerosis. The 1.4 A resolution crystal structure of pathogenic SOD1 mutant D125H reveals the mode of oxyanion binding in the active site channel and implies that phosphate anion attenuates the bicarbonate effect by competing for binding to this site. The orientation of the enzyme-associated oxyanion suggests that both the self-oxidative and external oxidative pathways can proceed through an enzyme-associated peroxycarbonate intermediate.
Single‐donor spray‐dried plasma (2018)

ODP demonstrates coagulation function comparable to that of FFP. The spray drying system can be implemented in blood centers and is capable of producing units of ODP.
Protein kinase C in heart failure: a therapeutic target? (2008)

Heart failure (HF) afflicts about 5 million people and causes 300,000 deaths a year in the United States alone. An integral part of the pathogenesis of HF is cardiac remodelling, and the signalling events that regulate it are a subject of intense research. Cardiac remodelling is the sum of responses of the heart to causes of HF, such as ischaemia, myocardial infarction, volume and pressure overload, infection, inflammation, and mechanical injury. These responses, including cardiomyocyte hypertrophy, myocardial fibrosis, and inflammation, involve numerous cellular and structural changes and ultimately result in a progressive decline in cardiac performance. Pharmacological and genetic manipulation of cultured heart cells and animal models of HF and the analysis of cardiac samples from patients with HF are all used to identify the molecular and cellular mechanisms leading to the disease. Protein kinase C (PKC) isozymes, a family of serine-threonine protein kinase enzymes, were found to regulate a number of cardiac responses, including those associated with HF. In this review, we describe the PKC isozymes that play critical roles in specific aspects of cardiac remodelling and dysfunction in HF.
Design considerations of form birefringent microstructures (1995)

Diffraction characteristics of high-spatial-frequency (HSF) gratings are evaluated for application to polarization-selective computer-generated holograms by the use of two different approaches: second-order effective-medium theory (EMT) and rigorous coupled-wave analysis (RCWA). The reflectivities and the phase differences for TE- and TM-polarized waves are investigated in terms of various input parameters, and results obtained with second-order EMT and RCWA are compared. It is shown that although the reflection characteristics can be accurately modeled with the second-order EMT, the phase difference created by form birefringence for TE- and TM-polarized waves requires the use of a more rigorous, RCWA approach. The design of HSF gratings in terms of their form birefringence and reflectivity properties is discussed in conjunction with polarization-selective computer-generated holograms. A specific design optimization example furnishes a grating profile that provides a trade-off between the largest form birefrin gence and the lowest reflectivities.
TRIFLIC ACID CATALYZED DOUBLE-CYCLIZATION OF N,N-DIBENZYL-2-PROPYNYLAMINE AND REIATED COMPOUNDS (1978)

Abstract Triflic acid catalyzed double-cyclization reactions of N,N-dibenzyl-2-propynylamine, N-benzyl-N-phenethyl-2-propynylamine, and N-(α-benzylphenethyl)-2-propynylamine afforded 1-aza-5-methyldibenzo [c,f]bicyclo [3.3.1] nona-3,6-diene,1-aza-6-irethyldibenzo[d,q]bicyclo[4.3.1]deca-4,7-diene and 6-aza-1-methyldibenzo[b,i]bicyclo[3.3.2]nona-2,8-diene in high isolated yields, respectively.
Immunolocalization of heparan sulfate proteoglycans to the prion protein amyloid plaques of Gerstmann-Straussler syndrome, Creutzfeldt-Jakob disease and scrapie. (1990)

Previous histochemical studies have demonstrated highly sulfated glycosaminoglycans (GAGs) localized to the amyloid plaques in the brains of humans and animals with prion diseases (Snow et al., Acta Neuropathol 77:337, 1989). However, the identity of the specific class of proteoglycan/GAG present was not known. The current investigation used immunocytochemical techniques to identify and localize heparan sulfate proteoglycans (HSPGs) in human cases of Gerstmann-Straussler syndrome and Creutzfeldt-Jakob disease, as well as in experimental scrapie of hamsters. Polyclonal and monoclonal antibodies to either the protein core or GAG moiety of the basement membrane-derived HSPG were utilized. The results demonstrate that both the protein core and the GAG chains of HSPGs are immunolocalized to the prion protein amyloid plaques in each of these diseases. HSPG immunostaining was also evident in these tissues in blood vessels, choroid plexus, myelinated axons, and in the cytoplasm of certain neuronal and astrocytic populations, particularly those in close proximity to the amyloid plaques. Additionally, in Creutzfeldt-Jakob disease and Gerstmann-Straussler syndrome cerebellum, positive immunostaining for heparan sulfate GAGs was observed within the cell bodies of Purkinje cells. The specific accumulation of HSPGs in the amyloid deposits of both the prion diseases and Alzheimer's disease (Snow et al., Am J Pathol 133:456, 1988), suggests that a common mechanism involving HSPGs may occur in the pathogenesis of amyloidosis in each of these diseases.
Spontaneously occurring neutralizing antibodies against granulocyte–macrophage colony‐stimulating factor in patients with autoimmune disease (1999)

There is increasing evidence that spontaneous anticytokine autoantibodies are associated with chronic infections and autoimmune diseases. We report the sporadic occurrence in autoimmune diseases of such autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine involved in inflammation and the regulation of proliferation, differentiation and function of granulocytic and monocytic cell lineages. In 41 of 425 patients tested, we found low to moderate levels of autoantibodies binding to GM-CSF in serum or plasma. These were most prevalent in patients with myasthenia gravis (MG). However, neutralizing autoantibodies against GM-CSF were very rare, being found in only three patients. Two had autoimmune MG, one with thymoma (Patient A) and the other (Patient B) with 'seronegative' MG, i.e. without the antiacetylcholine receptor autoantibodies characteristic of most MG patients, and a third (Patient D) had multiple sclerosis. Only very limited amounts of Patient A and Patient D serum/plasma were available for analysis and therefore further studies were carried out on the more plentiful samples from Patient B. The anti-GM-CSF autoantibodies of Patient B were predominantly polyclonal immunoglobulin G and strongly neutralized recombinant human (rh) GM-CSF derived from different expression systems. They had similar immunological and immunochemical characteristics to anti-GM-CSF antibodies that developed in immunocompetent colorectal carcinoma patients following (rh)GM-CSF therapy. In serial samples from Patient B, the anti-GM-CSF autoantibodies were undetectable from diagnosis at age 8 years until at least age 13, but then developed spontaneously during (temporary) withdrawal of immunosuppressive treatment. Their neutralizing activity has persisted since their first detection at age 15 years 1 month, and was at its highest level recently at age 17 years 7 months. There was no obvious association with other autoimmune phenomena, nor were any haematological deficiencies overtly manifested, suggesting that any loss of GM-CSF function may have been compensated for by other cytokines.
Hexavalent bispecific antibodies represent a new class of anticancer therapeutics: 1. Properties of anti-CD20/CD22 antibodies in lymphoma (2009)

The dock and lock (DNL) method is a new technology for generating multivalent antibodies. Here, we report in vitro and in vivo characterizations of 20-22 and 22-20, a pair of humanized hexavalent anti-CD20/22 bispecific antibodies (bsAbs) derived from veltuzumab (v-mab) and epratuzumab (e-mab). The 22-20 was made by site-specific conjugation of e-mab to 4 Fabs of v-mab; 20-22 is of the opposite configuration, composing v-mab and 4 Fabs of e-mab. Each bsAb translocates both CD22 and CD20 into lipid rafts, induces apoptosis and growth inhibition without second-antibody crosslinking, and is significantly more potent in killing lymphoma cells in vitro than their parental antibodies. Although both bsAbs triggered antibody-dependent cellular toxicity, neither displayed complement-dependent cytotoxicity. Intriguingly, 22-20 and 20-22 killed human lymphoma cells in preference to normal B cells ex vivo, whereas the parental v-mab depleted malignant and normal B cells equally. In vivo studies in Daudi tumors revealed 20-22, despite having a shorter serum half-life, had antitumor efficacy comparable with equimolar v-mab; 22-20 was less potent than 20-22 but more effective than e-mab and control bsAbs. These results indicate multiple advantages of hexavalent anti-CD20/22 bsAbs over the individual parental antibodies and suggest that these may represent a new class of cancer therapeutics.
Exploiting instruction level parallelism in the presence of conditional branches (1997)

Wide issue superscalar and VLIW processors utilize instruction-level parallelism (ILP) to achieve high performance. However, if insufficient ILP is found, the performance potential of these processors suffers dramatically. Branch instructions, which are one of the major limitations to exploiting ILP, enforce strict ordering conditions in programs to ensure correct execution. Therefore, it is difficult to achieve the desired overlap of instruction execution with branches in the instruction stream. To effectively exploit ILP in the presence of branches requires efficient handling of branches and the dependences they impose. This dissertation investigates two techniques for exposing and enhancing ILP in the presence of branches, speculative execution and predicated execution. Speculative execution enables an ILP compiler to remove dependences between instructions and prior branches. In this manner, the execution of instructions and predicted future instructions may be overlapped. Compiler-controlled speculative execution is employed using an efficient structure called the superblock. The formation and optimization of superblocks increase ILP along important execution paths by systematically removing constraints due to unimportant paths. In conjunction with superblock optimizations, speculative execution is utilized to remove control dependences in the superblock
Canine and Human Visual Cortex Intact and Responsive Despite Early Retinal Blindness from RPE65 Mutation (2007)

Visual cortical responses dramatically improve after retinal gene therapy in the canine model of RPE65-LCA. Human RPE65-LCA patients have preserved visual pathway anatomy and detectable cortical activation despite limited visual experience. Taken together, the results support the potential for human visual benefit from retinal therapies currently being aimed at restoring vision to the congenitally blind with genetic retinal disease.
Generating and Browsing Multiple Taxonomies Over a Document Collection (2003)

Abstract We present a novel system and methodology for generating and then browsing multiple taxonomies over a document collection. Taxonomies are generated using a broad set of capabilities, including meta data, key word queries, and automated clustering techniques that serve as a seed taxonomy.The taxonomy editor, eClassifier, provides powerful tools to visualize and edit each taxonomy to make it reflective of the desired theme. Cluster validation tools allow the editor to verify that documents received in the future can be automatically classified into each taxonomy with sufficiently high accuracy. In general, those seeking knowledge from a document collection may have only a vague notion of exactly what they are attempting to understand, and would like to explore related topics and concepts rather than simply being given a set of documents. For this purpose, we have developed MindMap, an interface utilizing multiple taxonomies and the ability to interact with a document collection. Keywords: DATA MININGDOCUMENT CLASSIFICATIONDOCUMENT CLUSTERINGTECHNIQUESKNOWLEDGE MANAGEMENTNAVIGATIONTAXONOMYTEXT MININGVISUALIZATION
Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections (2006)

Colonisation of the gastrointestinal tract by anaerobic bacteria, protozoa, trematodes, cestodes and/or nematodes and other infectious pathogens, including viruses, represents a major cause of morbidity and mortality in Africa, South America and southeast Asia, as well as other parts of the world. Nitazoxanide is a member of the thiazolide class of drugs with a documented broad spectrum of activity against parasites and anaerobic bacteria. Moreover, the drug has recently been reported to have a profound activity against hepatitis C virus infection. In addition, nitazoxanide exhibits anti-inflammatory properties, which have prompted clinical investigations for its use in Crohn's disease. Studies with nitazoxanide derivatives have determined that there must be significantly different mechanisms of action acting on intracellular versus extracellular pathogens. An impressive number of clinical studies have shown that the drug has an excellent bioavailability in the gastrointestinal tract, is fast acting and highly effective against gastrointestinal bacteria, protozoa and helminthes. A recent Phase II study has demonstrated viral response (hepatitis C) to monotherapy, with a low toxicity and an excellent safety profile over 24 weeks of treatment. Pre-clinical studies have indicated that there is a potential for application of this drug against other diseases, not primarily affecting the liver or the gastrointestinal tract.
Autonomous Driving in the iCity—HD Maps as a Key Challenge of the Automotive Industry (2016)

This article provides in-depth insights into the necessary technologies for automated driving in future cities. State of science is reflected from different perspectives such as in-car computing and data management, road side infrastructure, and cloud solutions. Especially the challenges for the application of HD maps as core technology for automated driving are depicted in this article.
Lipopenia and Skin Barrier Abnormalities in DGAT2-deficient Mice (2004)

The synthesis of triglycerides is catalyzed by two known acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. Although they catalyze the same biochemical reaction, these enzymes share no sequence homology, and their relative functions are poorly understood. Gene knockout studies in mice have revealed that DGAT1 contributes to triglyceride synthesis in tissues and plays an important role in regulating energy metabolism but is not essential for life. Here we show that DGAT2 plays a fundamental role in mammalian triglyceride synthesis and is required for survival. DGAT2-deficient (Dgat2(-/-)) mice are lipopenic and die soon after birth, apparently from profound reductions in substrates for energy metabolism and from impaired permeability barrier function in the skin. DGAT1 was unable to compensate for the absence of DGAT2, supporting the hypothesis that the two enzymes play fundamentally different roles in mammalian triglyceride metabolism.
Vaccination against pox diseases under immunosuppressive conditions. (1978)

Pox diseases, caused either by smallpox virus or zoonotic pox viruses or animals, continue to be of potential danger to a non-vaccinated population. Mass vaccinations will become necessary and will then also be administered to persons with immunological aberrations. The vaccines which are presently used against smallpox cause severe complications in such hosts. In contrast, the attenuated vaccinia virus strain MVA is safe even under the conditions of immunosuppression and is recommended for the production of smallpox vaccines. Because of the special epizootic situations and the numerous immunosuppressive factors present in developing countries, the use of such a safe pox vaccine there is of crucial importance.
Monoclonal antibody treatment of solid tumors: a coming of age. (2000)

Over the past 5 years there has been a renewed interest in the use of monoclonal antibodies and immunoconjugates in the treatment of nonhematologic malignancies. This enthusiasm has stemmed from advances in recombinant technology allowing for the production of chimeric and humanized antibodies, from Food and Drug Administration approval of radioimmunoconjugates for use in diagnosis and staging in colorectal, ovarian, and prostate cancer, from studies demonstrating durable response rates in lymphoma and breast cancer, and from trials demonstrating marked efficacy of radiolabeled antibodies in the treatment of non-Hodgkin's lymphoma. Part of the success of chimeric and humanized antibodies in treating solid tumors relates to the lack of human antimouse antibody formation along with enhanced immunogenic effector mechanisms. The pitfalls underlying early trials of murine monoclonal antibodies in solid tumors and newer antibody approaches using unique antigen targets, bifunctional constructs, and alternative routes of antibody administration will be discussed.
Cross-Resistance Testing of Antihepadnaviral Compounds Using Novel Recombinant Baculoviruses Which Encode Drug-Resistant Strains of Hepatitis B Virus (2001)

Long-term nucleoside analog therapy for hepatitis B virus (HBV)-related disease frequently results in the selection of mutant HBV strains that are resistant to therapy. Molecular studies of such drug-resistant variants are clearly warranted but have been difficult to do because of the lack of convenient and reliable in vitro culture systems for HBV. We previously developed a novel in vitro system for studying HBV replication that relies on the use of recombinant baculoviruses to deliver greater than unit length copies of the HBV genome to HepG2 cells. High levels of HBV replication can be achieved in this system, which has recently been used to assess the effects of lamivudine on HBV replication and covalently closed circular DNA accumulation. The further development of this novel system and its application to determine the cross-resistance profiles of drug-resistant HBV strains are described here. For these studies, novel recombinant HBV baculoviruses which encoded the L526M, M550I, and L526M M550V drug resistance mutations were generated and used to examine the effects of these substitutions on viral sensitivity to lamivudine, penciclovir (the active form of famciclovir), and adefovir, three compounds of clinical importance. The following observations were made: (i) the L526M mutation confers resistance to penciclovir and partial resistance to lamivudine, (ii) the YMDD mutations M550I and L526M M550V confer high levels of resistance to lamivudine and penciclovir, and (iii) adefovir is active against each of these mutants. These findings are supported by the limited amount of clinical data currently available and confirm the utility of the HBV-baculovirus system as an in vitro tool for the molecular characterization of clinically significant HBV strains.
Alcohol-Induced Coagulation Necrosis in Cardiac Tissue: A New Concept in the Surgical Management of Recurrent Ventricular Arrhythmias (1989)

Post myocardial infarction recurrent ventricular arrhythmias are usually coupled with depressed left ventricular function. We have until recently employed the most widely used surgical techniques such as endocardial resection, cryosurgery and isolation. After these methods had failed in a patient with an extensive septal focus, it finally became possible to effectively ablate the arrhythmogenic area by injection of 10 ml 95% alcohol subendocardially. The following experimental studies were carried out to investigate the effect of direct injection of alcohol on the myocardicytes. 95% alcohol, injected into the apex of the left ventricle of Wistar rats weighing between 150 and 200 g caused extensive coagulation necrosis 5 minutes after injection, as was revealed by histological examination. The site of injection showed marked scar formation after 6 months. On the basis of these findings, 4 more patients were treated successfully with alcohol, which was directly injected subendocardially without endocardial resection using a long needle. The advantage of this procedure is that resection can be avoided, particularly in critical areas such as the septum and regions around papillary muscles.
Dendrimers with 1,3,4‐oxadiazole units, 1. Synthesis and characterization (1996)

Abstract The synthesis and characterization of two unsymmetrically substituted star‐shaped oxadiazoles and of a dendrimer of the first generation are described. The key step in the synthesis is the intramolecular ring transformation of aromatic tetrazoles. The well‐defined compounds form stable amorphous glasses with high glass transition temperatures up to 222°C. They are promising candidates for organic light emitting diodes.
A Fully Inkjet-Printed 3-D Honeycomb-Inspired Patch Antenna (2015)

The ability to inkjet print three-dimensional objects with integrated conductive metal provides many opportunities for fabrication of radio frequency electronics and electronics in general. Both a plastic material and silver conductor are deposited by inkjet printing in this work. This is the first demonstration of a fully 3-D multijet printing process with integrated polymer and metal. A 2.4-GHz patch antenna is successfully fabricated with good performance proving the viability of the process. The inkjet-printed plastic surface is very smooth, with less than 100 nm root mean square roughness. The printed silver nanoparticles are laser sintered to achieve adequate conductivity of 1e <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> S/m while keeping the process below 80°C and avoiding damage to the polymer. The antenna is designed with a honeycomb substrate that minimizes material consumption. This reduces the weight, dielectric constant, and dielectric loss, which are all around beneficial. The antenna is entirely inkjet-printed including the ground plane conductor and achieves an impressive 81% efficiency. The honeycomb substrate weighs 20 times less than a solid substrate. For comparison, the honeycomb antenna provides an efficiency nearly 15% greater than a similarly fabricated antenna with a solid substrate.
Isolation and direct complete nucleotide determination of entire genes. Characterization of a gene coding for 16S ribosomal RNA (1989)

Using a set of synthetic oligonucleotides homologous to broadly conserved sequences in-vitro amplification via the polymerase chain reaction followed by direct sequencing results in almost complete nucleotide determination of a gene coding for 16S ribosomal RNA. As a model system the nucleotide sequence of the 16S rRNA gene of M.kansasii was determined and found to be 98.7% homologous to that of M.bovis BCG. This is the first report on a contiguous sequence information of an entire amplified gene spanning 1.5 kb without any subcloning procedures.