gebhart/patrepeval huggingface dataset:
Dye Dependent Regeneration Dynamics in Dye Sensitized Nanocrystalline Solar Cells:  Evidence for the Formation of a Ruthenium Bipyridyl Cation/Iodide Intermediate (2007)

We report a transient absorption study of the kinetics of re-reduction of ruthenium bipyridyl dye cations adsorbed to nanocrystalline TiO2 films by iodide ions, employing a series of RuII(dcbpy)2X dyes, where dcpby = 4,4‘-dicarboxy-2,2‘-bipyridyl and X = (NCS)2, (CN)2, DTC (diethyldithiocarbamate), and Cl2. The data indicate that this re-reduction (or ‘regeneration') reaction proceeds via a transient (dye+−iodide) intermediate complex formed by reaction of photogenerated dye cations with one iodide ion. The subsequent reaction of this complex with a second iodide ion, forming I2-, is shown to be the kinetically and thermodynamically limiting step in the overall regeneration reaction. The implications of this reaction scheme for the function of dye sensitized photoelectrochemical cells are discussed, considering in particular the high photovoltaic efficiencies obtained for such devices employing such ruthenium bipyridyl senstiser dyes in combination with iodide/tri-iodide based redox electrolytes.
Endothelin-1 and Endothelin Converting Enzyme-1 in Human Atherosclerosis - Novel Targets for Pharmacotherapy in Atherosclerosis (2004)

The role of chronic inflammation in the pathogenesis of the acute coronary syndromes has received increasing attention since active plaques rich in macrophages (Mphi's) are more prone to rupture whereas plaques rich in myofibroblasts are considered to be stable. Functionally, active plaques show a locally enhanced vasoreactivity. Endothelin-1 (ET-1) a potent vasoconstrictor acts in a paracrine fashion to regulate vascular tone. ET-1 is also produced by inflammatory cells suggesting a role for ET-1 in inflammation. Additionally, ET-1 is a mitogen. Endothelin converting enzyme-1 (ECE-1) activates ET-1 and may thus contribute to the regulation of vascular tone and cell growth during atherosclerosis. We evaluated the presence of ECE-1 and big ET-1/ET-1 and the activity of ECE-1 in different plaque types. Together with ET-1, ECE-1 is present in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and Mphi's. ECE-1 activity and ET-1-immunoreactivity (IR) both are upregulated during the progression of atherosclerosis from a non-inflammatory to an inflammatory stage. Thus, enhanced production of active ET-1 may contribute to cell growth and regulation of vascular tone in advanced plaques and also in very early stages of atherosclerosis. Furthermore, we examined the presence of ET-1 in coronary plaque tissue obtained by directional coronary atherectomy. ET-1 IR localized to plaque components indicative of chronic inflammation. Semiquantitative analysis of ET-1 IR revealed significantly higher staining grades in active coronary lesions compared with nonactive lesions. The increased ET-1 content in active coronary lesions may be beneficial to the stabilization of the vessel wall after plaque rupture and disadvantageous because it may lead to vasospasm and to the progression of atherosclerosis.
Lymph node ratio in melanoma (2009)

The N ratio is increasingly promoted as a better indicator of prognosis than the American Joint Committee on Cancer's N stage in a number of diseases including melanoma. The most likely explanation for these findings is variation of surgical quality that is able to be corrected by applying rigorous quality standards to complete lymph node dissections.
Triterpenes from Salvia glutinosa L. (1967)

D. A. H. Taylor, J. Chem. Soc. C, 1967, 490 DOI: 10.1039/J39670000490
Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy (2010)

Molecular mechanisms underlying renal complications of diabetes remain unclear. We tested whether renal NADPH oxidase (Nox) 4 contributes to increased reactive oxygen species (ROS) generation and hyperactivation of redox-sensitive signaling pathways in diabetic nephropathy. Diabetic mice (db/db) (20 wk) and cultured mouse proximal tubule (MPT) cells exposed to high glucose (25 mmol/l, D-glucose) were studied. Expression (gene and protein) of Nox4, p22(phox), and p47(phox), but not Nox1 or Nox2, was increased in kidney cortex, but not medulla, from db/db vs. control mice (db/m) (P < 0.05). ROS generation, p38 mitogen-activated protein (MAP) kinase phosphorylation, and content of fibronectin and transforming growth factor (TGF)-β1/2 were increased in db/db vs. db/m (P < 0.01). High glucose increased expression of Nox4, but not other Noxes vs. normal glucose (P < 0.05). This was associated with increased NADPH oxidase activation and enhanced ROS production. Nox4 downregulation by small-interfering RNA and inhibition of Nox4 activity by GK-136901 (Nox1/4 inhibitor) attenuated d-glucose-induced NADPH oxidase-derived ROS generation. High d-glucose, but not l-glucose, stimulated phosphorylation of p38MAP kinase and increased expression of TGF-β1/2 and fibronectin, effects that were inhibited by SB-203580 (p38MAP kinase inhibitor). GK-136901 inhibited d-glucose-induced actions. Our data indicate that, in diabetic conditions: 1) renal Nox4 is upregulated in a cortex-specific manner, 2) MPT cells possess functionally active Nox4-based NADPH, 3) Nox4 is a major source of renal ROS, and 4) activation of profibrotic processes is mediated via Nox4-sensitive, p38MAP kinase-dependent pathways. These findings implicate Nox4-based NADPH oxidase in molecular mechanisms underlying fibrosis in type 2 diabetic nephropathy.
Modeling Microseismic Hydraulic Fracture Deformation (2013)

Abstract Microseismic evidence of fracture complexity has lead to the recent development of new modeling tools to simulate the growth of complex fracture networks. Typically these complex fracture models rely on calibration from microseismic location information, although microseismic source mechanics can also provide additional model verification. Modeled geomechanical deformation associated with hydraulic fracture stimulation of a complex hydraulic fracture provides information that can be compared with observed microseismic deformation. Partitioning of modeled strains into shear and dilatational components allows relative comparison of the appropriate displacement mode with observed cumulative microseismic moments. A number of simple fracture geometries are investigated to illustrate the deformation modes of the modeled fracture displacements. A workflow is also described where the input parameters of the simulation are varied to match both the footprint and deformation of the microseismicity, which then results in an estimate of the complete fracture network volume and proppant placement. In this way the effective stimulated volume can be assessed and used as input to a reservoir simulation to investigate well performance and reservoir drainage.
Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons (2016)

Taken together, our results suggest that astrocytes play a central role in the progression of Alzheimer's disease, by accumulating and spreading toxic Aβ species.
Late Breaking Abstract - Danirixin (GSK1325756) improves respiratory symptoms and health status in mild to moderate COPD – results of a 1 year first time in patient study (2017)

<b>Background:</b>Danirixin (DNX) is a competitive, reversible CXCR2 chemokine receptor antagonist. CXCR2 antagonists inhibit neutrophil migration and activation in the lung in experimental medicine models and several respiratory diseases (COPD, severe asthma and bronchiectasis). <b>Methods:</b> Symptomatic mild-moderate COPD patients at risk for exacerbation (on standard inhaled therapies) were randomized to twice daily, oral DNX (75 mg) or placebo (GSK study 200163, NCT02130193) for 52 weeks. Primary endpoints were respiratory symptoms (Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total and subscale scores) and safety. Secondary endpoints included moderate/severe COPD exacerbations and health status (COPD Assessment Test, CAT). <b>Results:</b>Meaningful improvements in E-RS total score and cough &amp; sputum and breathlessness subscales with DNX occurred 2 months after study start and were maintained through 52 wks (Figure). At 52 wks CAT scores improved -2 points with DNX compared to 0.7 point deterioration with placebo. There was a trend for reduction in exacerbations, including number (39 v 32) and duration (19 v14 days) with DNX. Adverse events were not significantly different for DNX v placebo with no reductions in blood neutrophils. <b>Conclusions:</b>DNX was well-tolerated and associated with improvements in respiratory symptoms and health status. The study was sponsored by GSK.
Peptide Substrate Specificity and Properties of the zinc‐endopeptidase Activity of Botulinum Type B Neurotoxin (1994)

Clostridium botulinum type B neurotoxin has been shown to be a zinc endopeptidase specific for vesicle-associated membrane protein (VAMP). A synthetic peptide of human/rat VAMP-2 [VAMP-2-(60-94)] is cleaved by the neurotoxin with the same specificity as that demonstrated for the membrane-associated protein (at the Gln76-Phe77 bond) and has been used to study the properties of the endopeptidase activity of the neurotoxin. Cleavage of the VAMP-2 peptide was demonstrated by both botulinum type B neurotoxin (Km = 3.3 x 10(-4) M) and by its purified light subunit (Km = 3.5 x 10(-4) M). The endopeptidase displayed a pH optimum of 7.0-7.5 and was inhibited by greater than 0.2 M NaCl and greater than 0.05 M sodium phosphate. Neurotoxin which had been inactivated by dialysis against EDTA could be re-activated by incubation with various divalent cations, notably Zn2+ and Cu2+. The substrate specificity of botulinum type B neurotoxin was studied using various analogues of VAMP-2 (60-94). The neurotoxin cleaved selectively to the N-terminal side of phenylalanine and tyrosine; no activity was observed with either leucine, valine or alanine in the P'1 position. The properties of the P1 amino acid were less critical; the neurotoxin cleaving the C-terminus of glutamine, asparagine and alanine. A substrate analogue with valine in the P1 position corresponding to the sequence of rat VAMP-1 was not cleaved. The rate of cleavage of a substrate analogue representing the sequence of human VAMP-1, however, was more than twofold that of the VAMP-2 peptide. The properties and substrate specificity of botulinum type B neurotoxin suggest that the toxin represents a novel class of endopeptidase which requires a specific peptide substrate conformation for the expression of proteolytic activity.
Cathepsin B promotes the progression of pancreatic ductal adenocarcinoma in mice (2011)

These results confirm that cathepsin B plays an important cell autonomous role in the progression of PDA and suggest that the regulation of cathepsin L by cathepsin B may be a means of stimulating cell proliferation in neoplasia.
Assemblies of Titanium Dioxide-Polystyrene Hybrid Nanoparticles for Dielectric Applications (2010)

Macroscopic assemblies of hybrid nanoparticles composed of titanium dioxide core surrounded by covalently grafted polystyrene corona have been prepared by a combination of phosphonate coupling and "click" chemistry. The attached polymer chains existed in the brush regime, with grafting density inversely proportional to the degree of polymerization. Solution casting afforded preparation of robust films of the composite material where all the polymer chains were covalently bound to the uniformly distributed inorganic particles. Inorganic content from 60 to 80 wt % (27 to 50 vol %) was obtained by varying the molecular weight of polystyrene as well as by using the mixture of high and low molecular weight polymer for grafting. The TiO2 grafted with 105 g/mol polystyrene had a volume fraction of nanoparticles of 27% and exhibited glass transition at 110 °C and ∼100% extensibility above Tg. Thin films of this material had a dielectric constant of 6.4 and a dielectric loss of 0.04 at 1 kHz.
Molecular cloning of cDNA for nonhepatic mitochondrial arginase (arginase II) and comparison of its induction with nitric oxide synthase in a murine macrophage‐like cell line (1996)

Arginase exists in two isoforms. Liver-type arginase (arginase I) is expressed almost exclusively in the liver and catalyzes the last step of urea synthesis, whereas the nonhepatic type (arginase II) is expressed in extrahepatic tissues. Arginase II has been proposed to play a role in down-regulation of nitric oxide synthesis. A cDNA for human arginase II was isolated. A polypeptide of 354 amino acid residues including the putative NH2-terminal presequence for mitochondrial import was predicted. It was 59% identical with arginase I. The arginase II precursor synthesized in vitro was imported into isolated mitochondria and proteolytically processed. mRNA for human arginase II was present in the kidney and other tissues, but was not detected in the liver. Arginase II mRNA was coinduced with nitric oxide synthase mRNA in murine macrophage-like RAW 264.7 cells by lipopolysaccharide. This induction was enhanced by dexamethasone and dibutyryl cAMP, and was prevented by interferon-gamma. Possible roles of arginase II in NO synthesis are discussed.
Effect of Pyrrolnitrin on Electron Transport and Oxidative Phosphorylation in Mitochondria Isolated from Neurospora crassa (1972)

Pyrrolnitrin, at low concentrations, uncouples oxidative phosphorylation in Neurospora mitochondria. At higher concentrations, pyrrolnitrin inhibits electron transport both in the flavine region and through cytochrome oxidase.
Mechanism of efficacy of 2-amino oleic acid for inhibition of calcification of glutaraldehyde-pretreated porcine bioprosthetic heart valves. (1994)

AOA covalently binds to glutaraldehyde-pretreated bioprosthetic heart valve tissue, presumably as the result of an aldehyde-amino reaction. Covalently bound AOA diminishes Ca2+ diffusion compared with non-AOA-pretreated bioprosthetic tissues. This may explain in part the anticalcification mechanism of AOA. Furthermore, AOA inhibits calcification of porcine BPHV cusps in the circulation.
Genetic Vaccination against Malaria Infection by Intradermal and Epidermal Injections of a Plasmid Containing the Gene Encoding thePlasmodium bergheiCircumsporozoite Protein (2000)

The circumsporozoite protein (CSP) from the surface of sporozoite stage Plasmodium sp. malaria parasites is among the most important of the malaria vaccine candidates. Gene gun injection of genetic vaccines encoding Plasmodium berghei CSP induces a significant protective effect against sporozoite challenge; however, intramuscular injection does not. In the present study we compared the immune responses and protective effects induced by P. berghei CSP genetic vaccines delivered intradermally with a needle or epidermally with a gene gun. Mice were immunized three times at 4-week intervals and challenged by a single infectious mosquito bite. Although 50 times more DNA was administered by needle than by gene gun, the latter method induced significantly greater protection against infection. Intradermal injection of the CSP genetic vaccine induced a strong Th1-type immune response characterized by a dominant CSP-specific immunoglobulin G2a (IgG2a) humoral response and high levels of gamma interferon produced by splenic T cells. Gene gun injection induced a predominantly Th2-type immune response characterized by a high IgG1/IgG2a ratio and significant IgE production. Neither method generated measurable cytotoxic T lymphocyte activity. The results indicate that a gene gun-mediated CS-specific Th2-type response may be best for protecting against malarial sporozoite infection when the route of parasite entry is via mosquito bite.
Studies on Transfer Ribonucleic Acids and Related Compounds. VII. Synthesis and Properties of Cyclic Oligoadenylic Acids (1974)

N, 2'-O-Dibenzoyladenosine 3'-phosphate was polymerized using dicyclohexylcarbodiimide as the activating reagent to give linear and cyclic oligoadenylic acids. When 5'-O-monomethoxytrityl-N, 2'-O-dibenzoyladenosine 3'-phosphate was added as the chain terminator linear oligoadenylic acids were obtained as major products. Cyclic di- and triadenylic acids were also synthesized by cyclization of the corresponding linear oligonucleotides and were found to be sensitive to RNase M. Their CD spectra were measured in aqueous and methanolic solution.
Factor VIII inhibitors: role of von Willebrand factor on the uptake of factor VIII by dendritic cells (2007)

In patients with haemophilia A, factor VIII (FVIII) therapy leads to the development of anti-FVIII alloantibodies that inhibit FVIII pro-coagulant activity, in up to 25% of the cases. At a time when efficient viral screening procedures are at place, development of inhibitors poses the greatest threat to haemophilia A patients. Various risk factors, both patient and product-related, are responsible for the development of inhibitory antibodies. The role of FVIII-specific CD4+ T lymphocytes in the initiation of the humoral immune response to exogenous FVIII has been well. In view of their capacity to stimulate naïve T cells, dendritic cells (DCs) play a central role in the initiation of the primary immune response. Thus, in the context of a primary alloimmunization against FVIII, i.e. when FVIII-specific B lymphocytes are not there to take up FVIII from the circulation and to serve as antigen presenting cells (APCs), DCs are the only cell type that internalize FVIII, leading to activation of FVIII-specific CD4+ T lymphocytes. von Willebrand factor (VWF) present in plasma-derived FVIII therapeutic concentrates, is known to act as a chaperone molecule for procoagulant FVIII. In addition to its role in reducing the 'antigenicity' of FVIII, the role of VWF in the reduction of the 'immunogenicity' of therapeutic FVIII in patients with haemophilia A has also been suggested. We have recently demonstrated that VWF protects FVIII from being endocytosed by human DCs and subsequently being presented to FVIII-specific T cells. We propose that VWF may reduce the immunogenicity of FVIII by preventing, upstream from the activation of immune effectors, the entry of FVIII in professional antigen presenting cells.
Bovine and rabbit models for the study of a Staphylococcus aureus avirulent mutant strain, RC122. (2002)

Staphylococcus aureus is the main etiological agent of bovine mastitis. Intramammary infections are difficult to cure and vaccination appears to be an alternative to prevent the disease. Research has focused on the development of mutants affected in the synthesis of pathogenicity determinants. We constructed a mutant strain (RC122) after chemical mutagenesis. In a mouse model, the strain was shown to be 1500 times less virulent, showed similar kinetics of disappearance in the kidney as its parental strain, and a good degree of protection against a challenge from homologous and heterologous strains. The objective of the present report was to study the avirulent RC122 S. aureus mutant strain in rabbit and bovine infection models. The results clearly show that RC122 was less virulent than its parental strain in a rabbit skin model, and was also correlated with its avirulence as an udder pathogen. These traits make the RC122 mutant strain interesting as a potential strain for an experimental vaccine trial in dairy herds.
Hydrolysis of glycine‐containing elastin pentapeptides by LasA, a metalloelastase from Pseudomonas aeruginosa (2001)

Pseudomonas aeruginosa is an opportunistic pathogen that causes severe infections in vulnerable hosts. It may produce various virulence factors including proteases. Among them, LasA possesses both elastolytic and staphylolytic (hydrolysis of pentaglycine cross-links in the cell wall peptidoglycan) activities. To understand if its elastolytic activity results from a preference for glycine-rich substrates, we studied its ability to hydrolyse the 65 pentapeptides of human tropoelastin containing at least three glycines. As demonstrated by capillary electrophoresis (CE), 22 of these peptides were hydrolysed by LasA, generally at a single peptide bond and the catalytic ratio kcat/KM was determined for most of them. The highest value was obtained for LGGGA, 59 +/- 9 min(-1) x mmol(-1) x L. The specificity of hydrolysis was elucidated by CE, liquid secondary ion mass spectrometry and, in some cases, collision activated dissociation-mass analysis of ion kinetic energy. The preferred cleavage sites are GG and GA peptide bonds, the sequence GG(cleavage site)A being especially sensitive to hydrolysis. Both positions P2 and P'2 must be occupied for hydrolysis and the presence of an amino acid in P3 (but not in P'3) significantly increases the catalytic ratio. Considering these results, about 30 GGX sequences (X: G, A or Y) of human tropoelastin could be susceptible to LasA elastolysis.
Acid Resistance of Enamel Subsurface Lesions Remineralized by a Sugar-Free Chewing Gum Containing Casein Phosphopeptide-Amorphous Calcium Phosphate (2004)

The aim of this clinical study was to investigate the acid resistance of enamel lesions remineralized in situ by a sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate nanocomplexes (CPP-ACP: Recaldent). The study utilized a double-blind, randomized, crossover design with two treatments: (i) sugar-free gum containing 18.8 mg of CPP-ACP, and (ii) sugar-free gum not containing CPP-ACP as control. Subjects wore removable palatal appliances with insets of human enamel containing demineralized subsurface lesions and chewed the gum for 20 min 4 times per day for 14 days. After each treatment the enamel slabs were removed and half of each lesion challenged with acid in vitro for 8 or 16 h. The level of remineralization was determined using microradiography. The gum containing CPP-ACP produced approximately twice the level of remineralization as the control sugar-free gum. The 8- and 16-hour acid challenge of the lesions remineralized with the control gum resulted in 65.4 and 88.0% reductions, respectively, of deposited mineral, while for the CPP-ACP-remineralized lesions the corresponding reductions were 30.5 and 41.8%. The acid challenge after in situ remineralization for both control and CPP-ACP-treated lesions resulted in demineralization underneath the remineralized zone, indicating that the remineralized mineral was more resistant to subsequent acid challenge. The results show that sugar-free gum containing CPP-ACP is superior to an equivalent gum not containing CPP-ACP in remineralization of enamel subsurface lesions in situ with mineral that is more resistant to subsequent acid challenge.
Endothelin-1 Has a Unique Oxygen-Saving Effect by Increasing Contractile Efficiency in the Isolated Rat Heart (2001)

Agonistic effects of ET-1 on the ET(A) receptor economized the chemomechanical conversion efficiency of the left ventricular unit myocardium by a mechanism independent of the Na(+)/H(+) exchanger. This unique oxygen-saving effect of ET-1 may play an adaptive role in the failing myocardium, in which local accumulation of ET-1 is present.
Study on effective extraction of chicken feather keratins and their films for controlling drug release (2013)

We report the fabrication of keratin films with porosity using keratin, for controlled drug delivery systems. Feathers are currently an important waste product from the poultry industry, however abandoned down products cause an environmentally difficult disposal problem as they are not efficiently extracted and applied. In this paper, feather keratin was extracted using a high-efficiency method. The yield of pure keratin was up to 90%. Its molecular weight was 20 kDa with low dispersity. The films, based on the extracted keratin, were prepared using a simple method, and showed good mechanical properties. Furthermore, the feather keratin films were used to load and release drugs. The resultant feather keratin biopolymer films were pH-responsive and showed controllable drug-release behavior. In summary, we achieved a simple method to reutilize disused feathers. It could be an attractive candidate for applications in the biomedical field.