gebhart/patrepeval huggingface dataset:
Rhodococcus l-Phenylalanine Dehydrogenase:  Kinetics, Mechanism, and Structural Basis for Catalytic Specifity, (2000)

Phenylalanine dehydrogenase catalyzes the reversible, pyridine nucleotide-dependent oxidative deamination of L-phenylalanine to form phenylpyruvate and ammonia. We have characterized the steady-state kinetic behavior of the enzyme from Rhodococcus sp. M4 and determined the X-ray crystal structures of the recombinant enzyme in the complexes, E.NADH.L-phenylalanine and E.NAD(+). L-3-phenyllactate, to 1.25 and 1.4 A resolution, respectively. Initial velocity, product inhibition, and dead-end inhibition studies indicate the kinetic mechanism is ordered, with NAD(+) binding prior to phenylalanine and the products' being released in the order of ammonia, phenylpyruvate, and NADH. The enzyme shows no activity with NADPH or other 2'-phosphorylated pyridine nucleotides but has broad activity with NADH analogues. Our initial structural analyses of the E.NAD(+).phenylpyruvate and E.NAD(+). 3-phenylpropionate complexes established that Lys78 and Asp118 function as the catalytic residues in the active site [Vanhooke et al. (1999) Biochemistry 38, 2326-2339]. We have studied the ionization behavior of these residues in steady-state turnover and use these findings in conjunction with the structural data described both here and in our first report to modify our previously proposed mechanism for the enzymatic reaction. The structural characterizations also illuminate the mechanism of the redox specificity that precludes alpha-amino acid dehydrogenases from functioning as alpha-hydroxy acid dehydrogenases.
Gene polymorphisms and prostate cancer: the evidence (2009)

The difference between the results of studies on gene polymorphisms in prostate cancer may be explained partly by ethnic differences, limited sample size, and other risk or protective factors modifying these effects. Genome-wide studies are currently performed in developed countries and extensive use of this type of analysis may merit consideration in other countries. Furthermore, future studies are needed to further investigate environmental and diet factors interactions with genetic factors.
Solution structure of the calcium channel antagonist ω‐conotoxin GVIA (1993)

The three-dimensional solution structure is reported for omega-conotoxin GVIA, which is a potent inhibitor of presynaptic calcium channels in vertebrate neuromuscular junctions. Structures were generated by a hybrid distance geometry and restrained molecular dynamics approach using interproton distance, torsion angle, and hydrogen-bonding constraints derived from 1H NMR data. Conformations of GVIA with low constraint violations converged to a common peptide fold. The secondary structure in the peptide is an antiparallel triple-stranded beta-sheet containing a beta-hairpin and three tight turns. The NMR data are consistent with the region of the peptide from residues S9 to C16 being more dynamic than the rest of the peptide. The peptide has an amphiphilic structure with a positively charged hydrophilic side and an opposite side that contains a small hydrophobic region. Residues that are thought to be important in binding and function are located on the hydrophilic face of the peptide.
Fully Convolutional Networks for Semantic Segmentation (2016)

Convolutional networks are powerful visual models that yield hierarchies of features. We show that convolutional networks by themselves, trained end-to-end, pixels-to-pixels, improve on the previous best result in semantic segmentation. Our key insight is to build "fully convolutional" networks that take input of arbitrary size and produce correspondingly-sized output with efficient inference and learning. We define and detail the space of fully convolutional networks, explain their application to spatially dense prediction tasks, and draw connections to prior models. We adapt contemporary classification networks (AlexNet, the VGG net, and GoogLeNet) into fully convolutional networks and transfer their learned representations by fine-tuning to the segmentation task. We then define a skip architecture that combines semantic information from a deep, coarse layer with appearance information from a shallow, fine layer to produce accurate and detailed segmentations. Our fully convolutional networks achieve improved segmentation of PASCAL VOC (30% relative improvement to 67.2% mean IU on 2012), NYUDv2, SIFT Flow, and PASCAL-Context, while inference takes one tenth of a second for a typical image.
Chelator‐Free Synthesis of a Dual‐Modality PET/MRI Agent (2013)

Old technique, new application: A simple and efficient chelator-free strategy for the synthesis of a novel dual-modality PET/MRI agent has been developed. Labeling of radioarsenic (*AsIII and *AsV, *=71, 72, 74, 76) at the surface of superparamagnetic iron oxide nanoparticles (SPIONs) resulted in *As-SPIONs that can be used for simultaneous PET/MRI in cancer diagnosis, lymph-node mapping, and potentially for internal radiotherapy. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Roles of Heparin-Binding Protein in Bacterial Infections (2010)

Infectious diseases remain a major health problem, where sepsis and other severe infectious diseases are common causes of morbidity and mortality. The importance of early and appropriate treatment of sepsis and severe bacterial infections has been underlined by the successes of measures like the Surviving Sepsis Campaign, among others. Thus, there is a need for clinical and laboratory tools to identify a patient with severe infection early and to distinguish between bacterial and non-bacterial conditions. Heparin-binding protein (HBP) is also called azurocidin, or cationic antimicrobial protein of 37 kDa (CAP37). It is a multifunctional granule-associated protein that is rapidly mobilized from migrating polymorphonuclear leukocytes. HBP acts as a chemoattractant, an activator of monocytes and macrophages, and induces vascular leakage and edema formation. The release of HBP is triggered by ligation of neutrophilic beta(2)-integrins, a process that may be initiated by bacterial structures. The overall outcome is powerful vascular leakage. It has been shown that patients with severe sepsis express high levels of HBP in plasma before they develop hypotension. HBP is also involved in the pathophysiology of soft tissue infection. In conclusion, this protein is strongly involved in the pathophysiology of severe bacterial infections, and thus represents a potential diagnostic marker and a target for treatment.
Malignant Mesothelioma: Global Incidence and Relationship with Asbestos (2007)

Mesothelioma incidence varies markedly from one country to another. The highest annual crude incidence rates (about 30 cases per million) are observed in Australia, Belgium, and Great Britain. A lot of data indicate a relationship between mesothelioma and asbestos. The hot areas for mesothelioma exactly correspond to the sites of industries with high asbestos use, such as shipbuilding and asbestos-cement industry. However, in many countries with high asbestos consumption, mesothelioma incidence is low. The reasons for this fact are not clear. The latency periods elapsing between first exposure to asbestos and development of mesothelioma are mostly longer than 40 yr. An inverse relationship exists between intensity of asbestos exposure and length of the latency period. Mesothelioma generally develops after long-time exposures to asbestos. Some recent studies show that the risk increases with the duration of exposure. Possible co-factors in the pathogenesis of asbestos-related mesothelioma include genetic predisposition, diets poor in fruit and vegetables, viruses, immune impairment, recurrent serosal inflammation. The study of co-morbidity in mesothelioma could give an insight into the pathogenesis of the tumor. While a levelling-off in mesothelioma incidence has been registered in some countries, a worsening of the epidemic is predictable in large parts of the world.
Triggering the Sintering of Silver Nanoparticles at Room Temperature (2010)

A new approach to achieve coalescence and sintering of metallic nanoparticles at room temperature is presented. It was discovered that silver nanoparticles behave as soft particles when they come into contact with oppositely charged polyelectrolytes and undergo a spontaneous coalescence process, even without heating. Utilizing this finding in printing conductive patterns, which are composed of silver nanoparticles, enables achieving high conductivities even at room temperature. Due to the sintering of nanoparticles at room temperature, the formation of conductive patterns on plastic substrates and even on paper is made possible. The resulting high conductivity, 20% of that for bulk silver, enabled fabrication of various devices as demonstrated by inkjet printing of a plastic electroluminescent device.
Hot-Melt Coating Technology. I. Influence of Compritol® 888 Ato and Granule Size on Theophylline Release (2000)

The aim of this work was to study the influence of theophylline granule size and the percentage of Compritol 888 Ato on in vitro drug release from granules and tablets. The granules were coated in a fluidized bed apparatus. The dissolution profiles of these granules differed from those of granules coated with classical agents, and there were also differences between the various sieve fractions studied. Drug release was characterized by a rapid-release phase, followed by a slow-release phase. Results indicate that theophylline release can be controlled by controlling granule size. Inspection of the appearance of the tablets at the end of the dissolution test revealed that all tablets containing Compritol 888 Ato remained intact. This indicated that the Compritol 888 Ato used in the tablet formulation created an inert matrix through which the drug diffused. It was found that the Higuchi relationship of linear square root of time was the best model to describe the release kinetics of the drug from tablets. This also confirmed that a matrix diffusion-controlled mechanism was operative. Given the difference between the dissolution profiles of the granules and the tablets, it was concluded that this matrix is formed during compression.
Effects of Intra-Articular Vitamin E and Corticosteroid Injection in Experimental Hemarthrosis in Rabbits (1998)

The effects of intra-articular injections of vitamin E and corticosteroid were investigated in skeletally mature New Zealand white rabbits in which experimental hemarthrosis was induced for 14 days. The rabbits were divided into three groups composed of eight rabbits each: the first group comprised of animals with hemarthrosis, the second group animals with hemarthrosis and intra-articular injections of 20 mg vitamin E, and the third group animals with hemarthrosis and intra-articular injections of 10 mg of triamcinolone acetonide (TCA). Proteoglycan levels in the joint cartilage of the hemarthrosis group were found to be increased significantly compared with the controls (P < .01), whereas in the vitamin E-injected group they were significantly decreased (P < .05). In the TCA-injected group, proteoglycan levels were not found to be significantly different from those in the hemarthrosis group (P > .05). Histopathological evaluation showed that the cartilage structure in the joint of the control limbs was identical to that in the vitamin E- and TCA-injected limbs. In the hemarthrosis group, in comparison with the controls, the joint surface was roughened and fibrillated. In the superficial areas of the cartilage tissue, chondrocytes were decreased in number. These findings suggest that in this model, vitamin E and TCA may be helpful in preventing the joint cartilage changes seen in hemarthrosis.
Facile Diastereoselective Synthesis of 2,6‐Dialkyl‐5‐methylene‐1,3‐dioxan‐4‐ones via α‐Activated Vinyl Esters (1990)

Abstract Vinyl esters such as 2, in the presence of DABCO, undergo intial reaction with aldehydes, followed by nucleophilic attack on a second aldehyde molecule. Subsequent intramolecular transesterification affords the dioxanones 5 in high yields and high diastereomeric excesses.
Phenazine-1-Carboxylic Acid Promotes Bacterial Biofilm Development via Ferrous Iron Acquisition (2011)

The opportunistic pathogen Pseudomonas aeruginosa forms biofilms, which render it more resistant to antimicrobial agents. Levels of iron in excess of what is required for planktonic growth have been shown to promote biofilm formation, and therapies that interfere with ferric iron [Fe(III)] uptake combined with antibiotics may help treat P. aeruginosa infections. However, use of these therapies presumes that iron is in the Fe(III) state in the context of infection. Here we report the ability of phenazine-1-carboxylic acid (PCA), a common phenazine made by all phenazine-producing pseudomonads, to help P. aeruginosa alleviate Fe(III) limitation by reducing Fe(III) to ferrous iron [Fe(II)]. In the presence of PCA, a P. aeruginosa mutant lacking the ability to produce the siderophores pyoverdine and pyochelin can still develop into a biofilm. As has been previously reported (P. K. Singh, M. R. Parsek, E. P. Greenberg, and M. J. Welsh, Nature 417:552-555, 2002), biofilm formation by the wild type is blocked by subinhibitory concentrations of the Fe(III)-binding innate-immunity protein conalbumin, but here we show that this blockage can be rescued by PCA. FeoB, an Fe(II) uptake protein, is required for PCA to enable this rescue. Unlike PCA, the phenazine pyocyanin (PYO) can facilitate biofilm formation via an iron-independent pathway. While siderophore-mediated Fe(III) uptake is undoubtedly important at early stages of infection, these results suggest that at later stages of infection, PCA present in infected tissues may shift the redox equilibrium between Fe(III) and Fe(II), thereby making iron more bioavailable.
Biochemical Studies on Vitamin A. XIV. Biopotencies of Geometric Isomers of Vitamin A Acetate in the Rat1 (1955)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiochemical Studies on Vitamin A. XIV. Biopotencies of Geometric Isomers of Vitamin A Acetate in the Rat1Stanley R. Ames, William J. Swanson, and Philip L. HarrisCite this: J. Am. Chem. Soc. 1955, 77, 15, 4134–4136Publication Date (Print):August 1, 1955Publication History Published online1 May 2002Published inissue 1 August 1955https://pubs.acs.org/doi/10.1021/ja01620a047https://doi.org/10.1021/ja01620a047research-articleACS PublicationsRequest reuse permissionsArticle Views60Altmetric-Citations47LEARN 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
Influence of pacing site on canine left ventricular contraction (1986)

We investigated the influence of pacing site on several aspects of left ventricular (LV) performance to test the hypothesis that "effective ventricular muscle mass" is reduced with direct ventricular pacing. All studies were performed on isolated supported canine hearts that were constrained to contract isovolumically. To determine the influence of pacing site on magnitude and time course of isovolumic LV pressure (P) generation, LVP waves were recorded in eight isolated hearts paced at 130 beats/min. Pacing was epicardially from atrium, LV apex, LV free wall, right ventricular free wall (RVF), and endocardially from right ventricular endocardium. In a given heart, peak LVP was greatest with atrial pacing and smallest with RVF pacing, the difference being on average 26 +/- 10% (mean +/- SD) of the former pressure. The other pacing sites produced intermediate peak LVPs. When instantaneous LVP waves, obtained while pacing from each of the five sites, were normalized by their respective amplitudes, they were virtually superimposable up to the time of peak pressure and only slightly different during the remainder of the cardiac cycle. With changes in pacing site there was a linear negative correlation (r = 0.971) between changes in peak pressure and changes in duration of the QRS complex of a bipolar epicardial electrogram with an average slope of -0.51 mmHg/ms. Compared with atrial pacing, the slope of the end-systolic pressure-volume relation, Ees, was decreased with ventricular pacing, but Vo, the volume axis intercept, was relatively constant.(ABSTRACT TRUNCATED AT 250 WORDS)
Nonlinear behavior of piezoelectric lead zinc niobate–lead titanate single crystals under ac electric fields and dc bias (2003)

The nonlinear behaviors of the dielectric and piezoelectric responses of 〈001〉 oriented Pb(Zn1/3Nb2/3)O3-xPbTiO3 (PZN-PT) single crystals for x=4.5% and 8% have been investigated as a function of ac electric fields and dc bias fields. At relatively low applied fields, the polarization and strain of PZN-PT single crystals poled along the 〈001〉 direction show little hysteresis and have a linear dependence on the applied field, which is a consequence of engineered domain stability. Hence the dielectric and piezoelectric coefficients of the material do not exhibit any field dependence. However, when the applied electric field exceeds a threshold value, the strain and dielectric responses become nonlinear. The dielectric and piezoelectric constants are a function of the applied field, and hysteresis loops are observed. The results suggest that the observed nonlinear behavior in the PZN-PT single crystals is caused by domain motion/switching in response to the large ac fields. A positive dc bias effectively stabilizes the domain configuration in the crystals and enhances the linear response. The threshold field, at the onset of nonlinearity, is a linear function of the dc bias field in the field range investigated.
Identification of genes associated with platinum drug sensitivity and resistance in human ovarian cancer cells (2005)

Platinum-based chemotherapeutic regimens are ultimately unsuccessful due to intrinsic or acquired drug resistance. Understanding the molecular basis for platinum drug sensitivity/resistance is necessary for the development of new drugs and therapeutic regimens. In an effort to identify such determinants, we evaluated the expression of approximately 4000 genes using cDNA microarray screening in a panel of 14 unrelated human ovarian cancer cell lines derived from patients who were either untreated or treated with platinum-based chemotherapy. These data were analysed relative to the sensitivities of the cells to four platinum drugs (cis-diamminedichloroplatinum (cisplatin), carboplatin, DACH-(oxalato)platinum (II) (oxaliplatin) and cis-diamminedichloro (2-methylpyridine) platinum (II) (AMD473)) as well as the proliferation rate of the cells. Correlation analysis of the microarray data with respect to drug sensitivity and resistance revealed a significant association of Stat1 expression with decreased sensitivity to cisplatin (r=0.65) and AMD473 (r=0.76). These results were confirmed by quantitative RT-PCR and Western blot analyses. To study the functional significance of these findings, the full-length Stat1 cDNA was transfected into drug-sensitive A2780 human ovarian cancer cells. The resulting clones that exhibited increased Stat1 expression were three- to five-fold resistant to cisplatin and AMD473 as compared to the parental cells. The effect of inhibiting Jak/Stat signalling on platinum drug sensitivity was investigated using the Janus kinase inhibitor, AG490. Pretreatment of platinum-resistant cells with AG490 resulted in significant increased sensitivity to AMD473, but not to cisplatin or oxaliplatin. Overall, the results indicate that cDNA microarray analysis may be used successfully to identify determinants of drug sensitivity/resistance and future functional studies of other candidate genes from this database may lead to an increased understanding of the drug resistance phenotype.
An Iron-containing Phosphatase Induced by Progesterone in the Uterine Fluids of Pigs (1974)

A basic, progesterone-induced, intrauterine glycoprotein with a purple coloration can be purified from the uterine fluids of ovariectomized female pigs given daily doses of progesterone, by successive chromatography on columns of CM-cellulose and Sephadex G-100.The protein contains 1 atom of iron per 32,000 molecular weight polypeptide and shows phosphatase activity toward p-nitrophenylphosphate as substrate.The pH optimum of the enzyme is 4.9 and the apparent K, is 2.2 rnM at 30".Activity is enhanced 2-to 4-fold in presence of /3-mercaptoethanol, although the K,,, remains unchanged.Under such optimal conditions 1 molecule of enzyme can hydrolyze approximately 5 x lo3 molecules of substrate per min.Activity is inhibited by fluoride, arsenate, phosphate, and molybdate.To a lesser extent, the enzyme will catalyze the hydrolysis of ATP and pyrophosphate, but has very low activity toward /3-glycerophosphate and n-glucose 6-phosphate.The activation of the enzyme by P-mercaptoethanol is accompanied by a shift in the extinction maximum from 545 nm to around 510 nm.Sodium dithionite causes loss of color and inactivates the enzymatic activity completely.The precise role of the protein in the early pregnant uterus, however, remains unknown.A progesterone-induced, basic glycoprotein was recently purified from the uterine fluids of pigs by a simple two-step procedure (1).This glycoprotein, which had a natural purple color, was one of a group of at least eight proteins which were unique to the luteal phase of the estrous cycle when plasma progesterone levels were high (2-4).The same group of proteins could also be induced in ovariectomized animals given daily doses of progesterone (5) sufficient to maintain pregnancy in the fertilized pig (6).