gebhart/patrepeval huggingface dataset:
Inhaled Nitric Oxide in Cardiac Failure: Vascular Versus Ventricular Effects (1996)

Inhaled nitric oxide (INO) is a powerful and selective pulmonary vasodilator in pulmonary hypertension, including that related to cardiac disease. Recently, NO was shown to have a direct negative inotropic action on the myocardium, but whether INO can impair left ventricular (LV) function is not known. We administered INO during right heart catheterisation in 10 subjects with LV failure and secondary pulmonary hypertension. INO was delivered for 10 min at concentrations of 10, 20, and 40 ppm in spontaneous respiration. Average age was 49.9 years (range 19-59 years), and mean LV ejection fraction EF (LVEF) was 19.9% (range 15-27%). INO produced an average decrease in pulmonary vascular resistance (PVR) of 40% as compared with baseline (p < 0.0001) with no significant change in systemic vascular resistance (SVR). There was no significant difference in the haemodynamic response to the three doses of INO. The large decrease in PVR was due mainly to an increase in pulmonary capillary wedge pressure (PCWP). Cardiac index (CI) rose in 7 patients and was unchanged in 2. One patient had a marked increase in PAWP and a marked decrease in CI during administration of INO, which rapidly reversed after discontinuation of INO. This study demonstrates that the administration of INO to patients with impaired cardiac reserve may result in marked increase in ventricular preload with little benefit to pulmonary pressures. In view of the known in vitro effects of NO and the marked haemodynamic changes demonstrated in response to INO in this study, caution should be exercised when using INO in this population.
Human antibody response during sepsis against targets expressed by methicillin resistant Staphylococcus aureus (2000)

The identification of target structures is a prerequisite for the development of new treatment options, like antibody based therapy, against methicillin resistant Staphylococcus aureus (MRSA). In this study we identified immunodominant structures which were expressed in vivo during sepsis caused by MRSA. Using human sera we compared the immune response of humans with MRSA sepsis with the immune response of normal individuals and asymptomatically colonized individuals. We identified and characterized four staphylococcal specific antigenic structures. One target is a staphylococcal protein of 29 kDa that exhibited 29% identity to secreted protein SceA precursor of Staphylococcus carnosus. The putative function of this protein, which was designated IsaA (immunodominant staphylococcal antigen), is unknown. The second target is an immunodominant protein of 17 kDa that showed no homology to any currently known protein. This immunodominant protein was designated IsaB. The third and fourth antigens are both immunodominant proteins of 10 kDa. One of these proteins showed 100% identity to major cold shock protein CspA of S. aureus and the other protein was identified as the phosphocarrier protein Hpr of S. aureus. The identified immunodominant proteins may serve as potential targets for the development of antibody based therapy against MRSA.
Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. (2003)

The antitumor activity of IFN-alpha is well established. However, the role of the plasmacytoid dendritic cell (PDC), the major producer of IFN-alpha upon viral infection, in tumor biology is unknown. We sought to study the presence and function of PDC in a human solid tumor. Here, we demonstrate that PDCs infiltrate tumor tissue of patients with head and neck squamous cell carcinoma (HNSCC). Functional activity of PDC was examined by using CpG motif containing oligonucleotides, a defined microbial stimulus for PDCs (recognized via toll-like receptor 9). We found that HNSCC diminished the ability of PDC to produce IFN-alpha in response to CpG motif containing oligonucleotide. Tumor-induced down-regulation of toll-like receptor 9 was identified as one mechanism likely contributing to impaired PDC function within the tumor environment. In tumor-draining lymph nodes, suppression of CpG-induced IFN-alpha production was less pronounced than in single-cell suspensions of primary tumor tissue. In these lymph nodes, CpG-induced IFN-alpha production was associated with increased levels of interferon-induced protein 10 and IFN-gamma and activation of CD4 and CD8 T cells. These results show for the first time the presence of PDCs in human solid tumor tissue and that tumors suppress the capacity of PDCs to produce IFN-alpha. PDCs, which in the absence of appropriate stimulation are reported to promote regulatory CD8 T cells, may contribute to an impaired T-cell-mediated immune response in HNSCC.
Discovery and Structural Modification of Inhibitors of Methionine Aminopeptidases from Escherichia coli and Saccharomyces cerevisiae (2003)

A series of pyridine-2-carboxylic acid derivatives were synthesized according to the leads from the screening, and potent inhibitors have been obtained by structural modification. They have shown submicromolar inhibition of the enzymes (for example, for 9n, IC(50) = 130 nM for EcMetAP1 and IC(50) = 380 nM for ScMetAP1). They represent small-molecule MetAP inhibitors with novel structures different from alkylating fumagillin derivatives and peptidic bestatin-based MetAP inhibitor.
A new vector for recombination-based cloning of large DNA fragments from yeast artificial chromosomes (1995)

The functional analysis of genes frequently requires manipulation of large genomic regions embedded in yeast artificial chromosomes (YACs). We have designed a yeast-bacteria shuttle vector, pClasper, that can be used to clone specific regions of interest from YACs by homologous recombination. The important feature of pClasper is the presence of the mini-F factor replicon. This leads to a significant increase in the size of the plasmid inserts that can be maintained in bacteria after cloning by homologous recombination in yeast. The utility of this vector lies in its ability to maintain large fragments in bacteria and yeast, allowing for mutagenesis in yeast and simplified preparation of plasmid DNA in bacteria. Using PCR-generated recombinogenic fragments in pClasper we cloned a 27 kb region from a YAC containing the Hoxc cluster and a 130 kb region containing the entire Hoxb cluster. No rearrangements were seen when the recombinants in the shuttle vector were transferred to bacteria. We outline the potential uses of pClasper for functional studies of large genomic regions by transgenic and other analyses.
A tyrosinase with an abnormally high tyrosine hydroxylase/dopa oxidase ratio (2005)

The sequencing of the genome of Ralstonia solanacearum[Salanoubat M, Genin S, Artiguenave F, et al. (2002) Nature 415, 497-502] revealed several genes that putatively code for polyphenol oxidases (PPOs). This soil-borne pathogenic bacterium withers a wide range of plants. We detected the expression of two PPO genes (accession numbers NP_518458 and NP_519622) with high similarity to tyrosinases, both containing the six conserved histidines required to bind the pair of type-3 copper ions at the active site. Generation of null mutants in those genes by homologous recombination mutagenesis and protein purification allowed us to correlate each gene with its enzymatic activity. In contrast with all tyrosinases so far studied, the enzyme NP_518458 shows higher monophenolase than o-diphenolase activity and its initial activity does not depend on the presence of l-dopa cofactor. On the other hand, protein NP_519622 is an enzyme with a clear preference to oxidize o-diphenols and only residual monophenolase activity, behaving as a catechol oxidase. These catalytic characteristics are discussed in relation to two other characteristics apart from the six conserved histidines. One is the putative presence of a seventh histidine which interacts with the carboxy group on the substrate and controls the preference for carboxylated and decarboxylated substrates. The second is the size of the residue isosteric with the aromatic F261 reported in sweet potato catechol oxidase which acts as a gate to control accessibility to CuA at the active site.
Genetically‐modified brewing yeasts for the 21st century. Progress to date (1995)

Academic studies and traditional breeding of yeasts depend upon their sporulation lifestyle. The strains used have been specially selected to sporulate readily and to mate producing new yeast types. Unfortunately brewing yeast strains do not behave in this way. They sporulate poorly, any spores which are formed are usually non-viable and any haploid strains produced are invariably non-maters. Only in recent years, with the development of recombinant-DNA techniques, has the specific breeding of new brewing yeast strains become widespread. Strains have been produced with the ability to ferment a wider range of carbohydrates, with altered flocculation properties and which produce beers with modified flavours. Many have been tested on the pilot scale and one, an amylolytic brewing yeast, has received approval for commercial use.
Factor XII Regulates the Pathological Process of Thrombus Formation on Ruptured Plaques (2014)

The FVIIa- and FXIIa-triggered coagulation pathways have distinct but complementary roles in atherothrombus formation. The tissue factor-FVIIa pathway contributes to initial thrombus buildup, whereas FXIIa bound to thrombi ensures thrombus stability.
Capacitation of Bovine Sperm by Heparin: Inhibitory Effect of Glucose and Role of Intracellular pH1 (1989)

Bovine sperm incubated with heparin for 7.5-8.5 h underwent an acrosome reaction in the absence but not the presence of glucose (5 mM). When sperm were incubated under capacitating conditions with heparin for 4 h, glucose inhibited sperm penetration of oocytes (p less than 0.01) and lysophosphatidylcholine (LC) induced acrosome reactions. Addition of glucose for the last 0.25 h of a 4.25-h incubation with heparin had no effect on ability of sperm to acrosome-react in response to LC. Nonmetabolizable sugars 3-O-methyl glucose, 2-deoxyglucose, sucrose, and sorbitol did not inhibit capacitation as judged by sperm sensitivity to LC or fertilization (p greater than 0.05), but capacitation was inhibited by the glycolyzable substrates glucose, mannose, and fructose (p less than 0.05). The glycolytic inhibitor, fluoride, reversed glucose inhibition of capacitation in a dose-dependent manner similar to its effect on glucose uptake by sperm. Extracellular pH declined from 7.4 to 7.2 during a 4-h incubation of sperm with heparin and glucose. The decline of extracellular pH during sperm incubation with glucose did not affect capacitation, since only an extracellular pH below 7.02 inhibited capacitation. The intracellular pH (pHi) of sperm increased 0.40 units over a 5-h incubation under capacitating conditions. The change in pHi was inhibited by glucose. Incubation of sperm with heparin and glucose for 12 h resulted in capacitated sperm as judged by both LC sensitivity and fertilizing ability. These studies demonstrate that glycolyzable substrates delay capacitation of bovine sperm and suggest the effect is in delaying an alkalinization of pHi.
Immunity to pathogenic free-living amoebae: role of humoral antibody (1980)

Pathogenic free-living amoebae are common in nature, but few clinical infections by these amoebae have been reported. This has prompted studies of host susceptibility factors in humans. A survey of normal human sera from three New Zealand Health Districts was made; antibodies to pathogenic free-living amoebae were found in all sera, with titers ranging from 1:5 to 1:20 for Naegleria spp. and from 1:20 to 1:80 for Acanthamoeba spp. The antibodies belonged mainly to immunoglobulin G and immunoglobulin M classes. The presence of a specific neutralizing factor against Acanthamoeba spp. but not Naegleria spp. was demonstrated. Possible protective mechanisms are discussed.
Annexin 1: An Endogenous Anti-Inflammatory Protein (2003)

A hallmark of inflammation is the mobilization of blood-borne leukocytes across microvessels to kill and remove the invading pathogen. For its damaging potential, leukocyte movement is finely regulated, and endogenous pathways exist to ensure the time dependency of this process. Annexin 1 and its receptor(s) are one example of these pathways.
Vascular endothelial growth factor is an essential molecule for mouse kidney development: glomerulogenesis and nephrogenesis. (1997)

Homeostasis of body fluid is maintained by the kidneys, which contain two million glomeruli for blood filtration. A glomerulus is formed by growth of Bowman's capsule harmonized with a capillary during kidney development. The vascular endothelial growth factor (VEGF) is an essential angiogenic cytokine, and VEGF deficiency is known to be fatal in mice in early embryonic stages. As secretions of VEGF from cultured kidneys vary according to developmental stages, the role of VEGF in kidney development was studied in vivo by blocking the endogenous VEGF activity with antibody in newborn mice, in which most organs are already developed but kidneys are still developing. The antibody-treated animals showed normal growth but systemic edema. Vessel formation in the superficial renal cortex was disturbed, nephrogenic areas were diminished, and the number of developing nephrons decreased significantly. Many abnormal glomeruli, lacking capillary tufts, were observed in the antibody-treated mice, and VEGF expression in their Bowman's capsule showed a compensatory increase. These results suggest that VEGF mediates communication between the Bowman's capsule and capillary endothelial cells for developing a glomerulus as well as promoting nephrogenesis. In conclusion, VEGF is likely to be an essential molecule for kidney development, and especially for glomerulogenesis.
Beneficial Influence of Glycemic Control Upon the Growth and Function of Transplanted Islets (1994)

Syngeneic transplantation of 200 mouse islets under the kidney capsule usually fails to cure streptozocin-induced diabetes. We hypothesized that this number of islets, if engrafted in a normoglycemic environment, could expand their mass and improve their function to restore normoglycemia. Therefore, 200 freshly isolated mouse islets were transplanted under the capsule of each kidney of diabetic mice. Two weeks after transplantation, the recipients were normoglycemic, and one of the two grafts was removed. Removal of the graft was followed by transient hyperglycemia. At day 14 after graft removal, the beta-cell mass and insulin content of the remaining graft had increased 2.3- and 2.1-fold, respectively. At day 3 after graft removal, the replication rate of beta-cells increased threefold, and the mean individual beta-cell cross-sectional area, an indicator of cell size, was also increased. Perfusion of the kidney bearing the remaining graft showed biphasic insulin responses to high glucose and arginine 14 days after one graft removal. These data indicate that maintaining a period of near-normoglycemia after islet transplantation enhances the performance of an islet graft that would otherwise be expected to fail.
Monoclonal antibodies targeted to a-oligonucleotides. Characterisation and application in nucleic acid detection (1994)

The aim of the present study was to test the antigenicity of alpha-deoxyribonucleotides in order to develop a new tool for the detection of nucleic acid sequences for use in diagnostic applications. We describe four monoclonal antibodies (Mabs) which recognize alpha-deoxyribonucleotides. Two were raised against a poly(alpha-dT) sequence and specifically recognized the alpha-dT nucleotide. Two were raised against a sequence containing all four common nucleotides as alpha-nucleotides and, surprisingly, only recognized the alpha-dG nucleotide. For all four Mabs, no cross reactivity was observed with beta-oligonucleotides. These Mabs were reactive with alpha-oligonucleotide sequences whether these sequences were single-stranded or hybridized to DNA or RNA. The four Mabs were tested in a sandwich hybridization assay that consisted of an alpha-oligonucleotide (for target sequence recognition), one of the four Mabs (for recognition of the hybridized alpha-oligonucleotide), and goat anti-mouse antibody conjugated to horse radish peroxidase (HRP) (for detection). One of the monoclonal antibodies, Mab 2E11D7, was directly conjugated to HRP and used in sandwich hybridization to detect PCR fragments of HPV 18 DNA. The sensitivity of this reaction was 1 pg of plasmid DNA containing the HPV 18 fragment. The specificity of the detection was demonstrated using HPV 6/11 and 16 DNA sequences.
Sequence determinants of protein phase behavior from a coarse-grained model (2018)

Membraneless organelles important to intracellular compartmentalization have recently been shown to comprise assemblies of proteins which undergo liquid-liquid phase separation (LLPS). However, many proteins involved in this phase separation are at least partially disordered. The molecular mechanism and the sequence determinants of this process are challenging to determine experimentally owing to the disordered nature of the assemblies, motivating the use of theoretical and simulation methods. This work advances a computational framework for conducting simulations of LLPS with residue-level detail, and allows for the determination of phase diagrams and coexistence densities of proteins in the two phases. The model includes a short-range contact potential as well as a simplified treatment of electrostatic energy. Interaction parameters are optimized against experimentally determined radius of gyration data for multiple unfolded or intrinsically disordered proteins (IDPs). These models are applied to two systems which undergo LLPS: the low complexity domain of the RNA-binding protein FUS and the DEAD-box helicase protein LAF-1. We develop a novel simulation method to determine thermodynamic phase diagrams as a function of the total protein concentration and temperature. We show that the model is capable of capturing qualitative changes in the phase diagram due to phosphomimetic mutations of FUS and to the presence or absence of the large folded domain in LAF-1. We also explore the effects of chain-length, or multivalency, on the phase diagram, and obtain results consistent with Flory-Huggins theory for polymers. Most importantly, the methodology presented here is flexible so that it can be easily extended to other pair potentials, be used with other enhanced sampling methods, and may incorporate additional features for biological systems of interest.
A protease assay for two-photon crosscorrelation and FRET analysis based solely on fluorescent proteins (2002)

GFP and the red fluorescent protein, DsRed, have been combined to design a protease assay that allows not only for fluorescence resonance energy transfer (FRET) studies but also for dual-color crosscorrelation analysis, a single-molecule-based method that selectively probes the concomitant movement of two distinct tags. The measurement principle is based on a spectrally resolved detection of single molecules diffusing in and out of a diffraction-limited laser focus. Double-labeled substrate molecules are separated into two single-labeled products by specific cleavage at a protease cleavage site between the two flanking tags, DsRed and GFP, thus disrupting joint fluctuations in the two detection channels and terminating FRET between the two labels. In contrast to enzyme assays based solely on FRET, this method of dual-color crosscorrelation is not limited to a certain range of distances between the fluorophores and is much more versatile with respect to possible substrate design. To simplify the measurement setup, two-photon excitation was used, allowing for simultaneous excitation of both tags with a single infrared laser wavelength. The general concept was experimentally verified with a GFP-peptide-DsRed construct containing the cleavage site for tobacco etch virus protease. Two-photon excitation in the infrared and the use of cloneable tags make this assay easily adaptable to intracellular applications. Moreover, the combination of FRET and crosscorrelation analysis in a single-molecule-based approach promises exciting perspectives for miniaturized high-throughput screening based on fluorescence spectroscopy.
Antiepileptic drugs (2016)

Antiepileptic drugs (AEDs) are the main treatment for seizures in people with epilepsy. The first AED, phenobarbital, was discovered in 1912 and the company that developed it gave it the brand name Luminal. Between 1938 and 2016, 25 more brand name AEDs were approved by the US Food and Drug Administration (FDA). The generic name is the chemical name for the medication. The brand name is created by the company that first discovers and patents the medication. A patent gives that company the right to be the only one that sells that drug for many years. After the patent expires, other companies can sell the generic drug. Generic drugs are usually less expensive. Today, all AEDs approved by the FDA before 2005 are available as generics.
Synthesis of oximes. III. Iodine dimethyl sulfoxide reaction with methylpyridines (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of oximes. III. Iodine dimethyl sulfoxide reaction with methylpyridinesAnica Markovac, Calvin Lee Stevens, Arthur B. Ash, and Brennie E. Hackley Jr.Cite this: J. Org. Chem. 1970, 35, 3, 841–843Publication Date (Print):March 1, 1970Publication History Published online1 May 2002Published inissue 1 March 1970https://pubs.acs.org/doi/10.1021/jo00828a074https://doi.org/10.1021/jo00828a074research-articleACS PublicationsRequest reuse permissionsArticle Views534Altmetric-Citations32LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The Chemistry of Borylstannanes:  Oxidative Addition to Palladium Species and Its Application to Palladium-Catalyzed Borylstannation of Alkynes (1996)

cis addition of the borylstannanes Me3SnB[NMe(CH2CH2)NMe] (1) and Me3SnB(NEt2)2 (4) across alkynes was efficiently catalyzed at room temperature or 80 °C by Pd(PPh3)4, Pd(dba)2, Cl2Pd(PPh3)2, or Me2Pd[PMe2(CH2CH2)PMe2] to give (β-stannylalkenyl)boranes in high yields. Treatments of 1 with Me2Pd[PMe2(CH2CH2)PMe2] and of 4 with cis-Me2Pd(PPh2Me)2 gave [{MeN(CH2CH2)MeN}B](Me3Sn)Pd[PMe2(CH2CH2)PMe2] (5) and [(Et2N)2B](Me3Sn)Pd(PPh2Me)2 (6), respectively, with the former characterized by X-ray analysis. Complex 5, when treated with 1-octyne, formed the corresponding (β-stannyl-1-octen-1-yl)borane and could catalyze the addition reaction of 1 with 1-octyne.