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Sample records for net positive protein

  1. Positive muscle protein net balance and differential regulation of atrogene expression after resistance exercise and milk protein supplementation

    DEFF Research Database (Denmark)

    Reitelseder, Søren; Agergaard, Jakob; Doessing, Simon

    2014-01-01

    body mass), or a non-caloric control after heavy resistance exercise on protein turnover and mRNA expressions of forkhead homeobox type O (FOXO) isoforms, muscle RING finger 1 (MuRF1), and Atrogin1 in young healthy males. Methods Protein turnover was determined by stable isotope-labeled leucine...... and femoral arteriovenous blood samples at rest and during 6-h recovery. Muscle biopsies were collected at −60 min (rest) and at 60, 210, and 360 min in the recovery period. Results During recovery, leucine NB was significantly higher in the protein groups compared to control (P

  2. Protein crystallization image classification with elastic net

    Science.gov (United States)

    Hung, Jeffrey; Collins, John; Weldetsion, Mehari; Newland, Oliver; Chiang, Eric; Guerrero, Steve; Okada, Kazunori

    2014-03-01

    Protein crystallization plays a crucial role in pharmaceutical research by supporting the investigation of a protein's molecular structure through X-ray diffraction of its crystal. Due to the rare occurrence of crystals, images must be manually inspected, a laborious process. We develop a solution incorporating a regularized, logistic regression model for automatically evaluating these images. Standard image features, such as shape context, Gabor filters and Fourier transforms, are first extracted to represent the heterogeneous appearance of our images. Then the proposed solution utilizes Elastic Net to select relevant features. Its L1-regularization mitigates the effects of our large dataset, and its L2- regularization ensures proper operation when the feature number exceeds the sample number. A two-tier cascade classifier based on naïve Bayes and random forest algorithms categorized the images. In order to validate the proposed method, we experimentally compare it with naïve Bayes, linear discriminant analysis, random forest, and their two-tier cascade classifiers, by 10-fold cross validation. Our experimental results demonstrate a 3-category accuracy of 74%, outperforming other models. In addition, Elastic Net better reduces the false negatives responsible for a high, domain specific risk. To the best of our knowledge, this is the first attempt to apply Elastic Net to classifying protein crystallization images. Performance measured on a large pharmaceutical dataset also fared well in comparison with those presented in the previous studies, while the reduction of the high-risk false negatives is promising.

  3. Net foreign asset (com)position : Does financial development matter?

    NARCIS (Netherlands)

    Vermeulen, Robert; de Haan, Jakob

    We investigate the relationship between a country's domestic financial development and the (composition of its) net foreign asset position using a pooled mean group estimator and data for 50 countries for the 1970-2007 period. The results show that financial development reduces a country's long-run

  4. AFM characterization of protein net formation on a fibrous medium

    Directory of Open Access Journals (Sweden)

    Assis O.B.G.

    2000-01-01

    Full Text Available Lysozyme protein net is set on a glass fiber support using the self-assembly technique. Enzymatic film formation is followed by surface imaging via atomic force microscopy (AFM. Change in roughness as a function of deposition time is used as an indirect indicator of film formation. The objective was to form a protein film that would have no effect on the permeability of the medium, aiming at its application as a bioactive membrane or reactor suitable for bacteria and chemical interactions in aqueous media.

  5. Diffusion of Clostridium perfringens NetB positive strains in healthy and diseased chickens

    Directory of Open Access Journals (Sweden)

    Luca Bano

    2010-01-01

    Full Text Available For over 30 years α toxin was considered the key virulence factor responsible for the appearance of necrotic enteritis (NE in chickens but, recently, a new toxin related to the occurrence of NE, called NetB, has been described. The aim of this work was to evaluate the CP toxin-type and the NetB gene presence in strains collected from chickens affected or not by enteric diseases. 107 strains were tested: 30 isolated from chickens affected by NE, 54 from subjects affected by other enteric pathologies and 22 from healthy animals. All strains resulted toxin-type A and 26.17% of these was positive also for β2 toxin gene. No strains were positive for cpe gene. 27% (29/107 of CP was NetB positive and 93% (27/29 of these was isolated from birds affected by intestinal disorders. 16 NetB positive strains were obtained from chickens affected by NE (16/30, 9 from animals affected by other intestinal disorders (9/54 and 4 from healthy animals (4/22. A significant difference between the number of NetB positive strains isolated from animals affected by NE and healthy chickens has been observed (P=0.014. However, the finding that the 17.4% of strains isolated from healthy chickens was also positive for NetB, confirm that other virulence factors could play an important role on NE appearance.

  6. 31 CFR 356.13 - When must I report my net long position and how do I calculate it?

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false When must I report my net long position and how do I calculate it? 356.13 Section 356.13 Money and Finance: Treasury Regulations Relating... net long position and how do I calculate it? (a) Net long position reporting threshold. (1) If you are...

  7. NetPhosBac - A predictor for Ser/Thr phosphorylation sites in bacterial proteins

    DEFF Research Database (Denmark)

    Miller, Martin Lee; Soufi, Boumediene; Jers, Carsten

    2009-01-01

    predictors on bacterial systems. We used these large bacterial datasets and neural network algorithms to create the first bacteria-specific protein phosphorylation predictor: NetPhosBac. With respect to predicting bacterial phosphorylation sites, NetPhosBac significantly outperformed all benchmark predictors....... Moreover, NetPhosBac predictions of phosphorylation sites in E. coli proteins were experimentally verified on protein and site-specific levels. In conclusion, NetPhosBac clearly illustrates the advantage of taxa-specific predictors and we hope it will provide a useful asset to the microbiological community....

  8. Prevalence of netF-positive Clostridium perfringens in foals in southwestern Ontario.

    Science.gov (United States)

    Finley, Abigail; Gohari, Iman Mehdizadeh; Parreira, Valeria R; Abrahams, Miranda; Staempfli, Henry R; Prescott, John F

    2016-07-01

    NetF-producing Clostridium perfringens have recently been identified as a cause of necrotizing enteritis in neonatal foals, but little is known about its prevalence in clinically normal foals. Foals (n = 88) ranging in age from perfringens. Of the foals that tested positive, 5 isolates (n = 675) were examined for the netF and enterotoxin (cpe) genes. Colonization by C. perfringens was most marked in foals perfringens does not colonize young foals with any detectable frequency in Ontario and this organism is not likely to be adapted to the intestine of the horse.

  9. Quantity of dietary protein intake, but not pattern of intake, affects net protein balance primarily through differences in protein synthesis in older adults.

    Science.gov (United States)

    Kim, Il-Young; Schutzler, Scott; Schrader, Amy; Spencer, Horace; Kortebein, Patrick; Deutz, Nicolaas E P; Wolfe, Robert R; Ferrando, Arny A

    2015-01-01

    To examine whole body protein turnover and muscle protein fractional synthesis rate (MPS) following ingestions of protein in mixed meals at two doses of protein and two intake patterns, 20 healthy older adult subjects (52-75 yr) participated in one of four groups in a randomized clinical trial: a level of protein intake of 0.8 g (1RDA) or 1.5 g·kg(-1)·day(-1) (∼2RDA) with uneven (U: 15/20/65%) or even distribution (E: 33/33/33%) patterns of intake for breakfast, lunch, and dinner over the day (1RDA-U, 1RDA-E, 2RDA-U, or 2RDA-E). Subjects were studied with primed continuous infusions of L-[(2)H5]phenylalanine and L-[(2)H2]tyrosine on day 4 following 3 days of diet habituation. Whole body protein kinetics [protein synthesis (PS), breakdown, and net balance (NB)] were expressed as changes from the fasted to the fed states. Positive NB was achieved at both protein levels, but NB was greater in 2RDA vs. 1RDA (94.8 ± 6.0 vs. 58.9 ± 4.9 g protein/750 min; P = 0.0001), without effects of distribution on NB. The greater NB was due to the higher PS with 2RDA vs. 1RDA (15.4 ± 4.8 vs. -18.0 ± 8.4 g protein/750 min; P = 0.0018). Consistent with PS, MPS was greater with 2RDA vs. 1RDA, regardless of distribution patterns. In conclusion, whole body net protein balance was greater with protein intake above recommended dietary allowance (0.8 g protein·kg(-1)·day(-1)) in the context of mixed meals, without demonstrated effects of protein intake pattern, primarily through higher rates of protein synthesis at whole body and muscle levels. Copyright © 2015 the American Physiological Society.

  10. Characterisation and testing of the KM3NeT acoustic positioning system

    Directory of Open Access Journals (Sweden)

    Viola S.

    2016-01-01

    Full Text Available In underwater neutrino telescopes, the search of point-like sources through the Cherenkov detection technique requires a precise knowledge of the positions of thousands of optical sensors, spread in a volume of a few cubic kilometres. In KM3NeT the optical sensors are hosted in 700 m high semi-rigid structures, called detection units, which move under the effects of underwater currents. These movements are continuously monitored through an underwater positioning system based on acoustic emitters and receivers. In this work, the tests performed on the key elements of the positioning system are presented.

  11. MyProteinNet: build up-to-date protein interaction networks for organisms, tissues and user-defined contexts.

    Science.gov (United States)

    Basha, Omer; Flom, Dvir; Barshir, Ruth; Smoly, Ilan; Tirman, Shoval; Yeger-Lotem, Esti

    2015-07-01

    The identification of the molecular pathways active in specific contexts, such as disease states or drug responses, often requires an extensive view of the potential interactions between a subset of proteins. This view is not easily obtained: it requires the integration of context-specific protein list or expression data with up-to-date data of protein interactions that are typically spread across multiple databases. The MyProteinNet web server allows users to easily create such context-sensitive protein interaction networks. Users can automatically gather and consolidate data from up to 11 different databases to create a generic protein interaction network (interactome). They can score the interactions based on reliability and filter them by user-defined contexts including molecular expression and protein annotation. The output of MyProteinNet includes the generic and filtered interactome files, together with a summary of their network attributes. MyProteinNet is particularly geared toward building human tissue interactomes, by maintaining tissue expression profiles from multiple resources. The ability of MyProteinNet to facilitate the construction of up-to-date, context-specific interactomes and its applicability to 11 different organisms and to tens of human tissues, make it a powerful tool in meaningful analysis of protein networks. MyProteinNet is available at http://netbio.bgu.ac.il/myproteinnet. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Experimental induction of necrotic enteritis in chickens by a netB-positive Japanese isolate of Clostridium perfringens.

    Science.gov (United States)

    To, Ho; Suzuki, Takayuki; Kawahara, Fumiya; Uetsuka, Koji; Nagai, Shinya; Nunoya, Tetsuo

    2017-02-28

    Necrotic enteritis (NE) is one of the most important bacterial diseases in terms of economic losses. Clostridium perfringens necrotic enteritis toxin B, NetB, was recently proposed as a new key virulent factor for the development of NE. The goal of this work was to develop a necrotic enteritis model in chickens by using a Japanese isolate of C. perfringens. The Japanese isolate has been found to contain netB gene, which had the same nucleotide and deduced amino acid sequences as those of prototype gene characterized in Australian strain EHE-NE18, and also expressed in vitro a 33-kDa protein identified as NetB toxin by nano-scale liquid chromatographic tandem mass spectrometry. In the challenge experiment, broiler chickens fed a commercial chicken starter diet for 14 days post-hatch were changed to a high protein feed mixed 50:50 with fishmeal for 6 days. At day 21 of age, feed was withheld for 24 hr, and each chicken was orally challenged twice daily with 2 ml each of C. perfringens culture (10 9 to 10 10 CFU) on 5 consecutive days. The gross necrotic lesions were observed in 90 and 12.5% of challenged and control chickens, respectively. To our knowledge, this is the first study that demonstrated that a netB-positive Japanese isolate of C. perfringens is able to induce the clinical signs and lesions characteristic of NE in the experimental model, which may be useful for evaluating the pathogenicity of field isolates, the efficacy of a vaccine or a specific drug against NE.

  13. AN ECONOMETRICAL APPROACH OF THE RELATIONSHIP BETWEEN INNOVATION AND NET OUTWARD INVESTMENT POSITION

    Directory of Open Access Journals (Sweden)

    Viorela IACOVOIU

    2015-02-01

    Full Text Available Starting from the theory of the Investment Development Path (IDP and competitive advantages, this study presents an econometrical approach of the relationship between net outward investment position, given by the net outward investment per capita (NOI, and innovation capabilities, reflected by the global innovation index (GII. The results of the analysis carried out for the worldwide economies, in the year 2013, using five models demonstrate that there is no significant correlation between NOI, as dependent variable, and GII as independent one. Thus, the highest coefficient of determination value was .201 (cubic model, reflecting the fact that only 20.1% of the variation in the NOI is explained by GII. Therefore, the level of country’s innovation capacities is not one of the main forces that determine its NOI position.

  14. Correlated positions in protein evolution and engineering.

    Science.gov (United States)

    Franceus, Jorick; Verhaeghe, Tom; Desmet, Tom

    2017-05-01

    Statistical analysis of a protein multiple sequence alignment can reveal groups of positions that undergo interdependent mutations throughout evolution. At these so-called correlated positions, only certain combinations of amino acids appear to be viable for maintaining proper folding, stability, catalytic activity or specificity. Therefore, it is often speculated that they could be interesting guides for semi-rational protein engineering purposes. Because they are a fingerprint from protein evolution, their analysis may provide valuable insight into a protein's structure or function and furthermore, they may also be suitable target positions for mutagenesis. Unfortunately, little is currently known about the properties of these correlation networks and how they should be used in practice. This review summarises the recent findings, opportunities and pitfalls of the concept.

  15. Urbanization has a positive net effect on soil carbon stocks: modelling outcomes for the Moscow region

    Science.gov (United States)

    Vasenev, Viacheslav; Stoorvogel, Jetse; Leemans, Rik; Valentini, Riccardo

    2016-04-01

    Urbanization is responsible for large environmental changes worldwide. Urbanization was traditionally related to negative environmental impacts, but recent research highlights the potential to store soil carbon (C) in urban areas. The net effect of urbanization on soil C is, however, poorly understood. Negative influences of construction and soil sealing can be compensated by establishing of green areas. We explored possible net effects of future urbanization on soil C-stocks in the Moscow Region. Urbanization was modelled as a function of environmental, socio-economic and neighbourhood factors. This yielded three alternative scenarios: i) including neighbourhood factors; ii) excluding neighbourhood factors and focusing on environmental drivers; and iii) considering the New Moscow Project, establishing 1500km2 of new urbanized area following governmental regulation. All three scenarios showed substantial urbanization on 500 to 2000km2 former forests and arable lands. Our analysis shows a positive net effect on SOC stocks of 5 to 11 TgC. The highest increase occurred on the less fertile Orthic Podzols and Eutric Podzoluvisols, whereas C-storage in Orthic Luvisols, Luvic Chernozems, Dystric Histosols and Eutric Fluvisols increased less. Subsoil C-stocks were much more affected with an extra 4 to 10 TgC than those in the topsoils. The highest increase of both topsoil and subsoil C stocks occurred in the New Moscow scenario with the highest urbanization. Even when the relatively high uncertainties of the absolute C-values are considered, a clear positive net effect of urbanization on C-stocks is apparent. This highlights the potential of cities to enhance C-storage. This will progressively become more important in the future following the increasing world-wide urbanization.

  16. The Cornell Net Carbohydrate and Protein System model for evaluating herd nutrition and nutrient excretion

    National Research Council Canada - National Science Library

    Fox, D.G; Tedeschi, L.O; Tylutki, T.P; Russell, J.B; Van Amburgh, M.E; Chase, L.E; Pell, A.N; Overton, T.R

    2004-01-01

    .... The Cornell Net Carbohydrate and Protein System (CNCPS) is a mathematical model to evaluate diet and animal performance that was developed from basic principles of rumen function, microbial growth, feed digestion and passage and animal physiology. By accounting for farm-specific management, environmental and feed characteristics, more ...

  17. Conserved intron positions in ancient protein modules

    Directory of Open Access Journals (Sweden)

    de Roos Albert DG

    2007-02-01

    Full Text Available Abstract Background The timing of the origin of introns is of crucial importance for an understanding of early genome architecture. The Exon theory of genes proposed a role for introns in the formation of multi-exon proteins by exon shuffling and predicts the presence of conserved splice sites in ancient genes. In this study, large-scale analysis of potential conserved splice sites was performed using an intron-exon database (ExInt derived from GenBank. Results A set of conserved intron positions was found by matching identical splice sites sequences from distantly-related eukaryotic kingdoms. Most amino acid sequences with conserved introns were homologous to consensus sequences of functional domains from conserved proteins including kinases, phosphatases, small GTPases, transporters and matrix proteins. These included ancient proteins that originated before the eukaryote-prokaryote split, for instance the catalytic domain of protein phosphatase 2A where a total of eleven conserved introns were found. Using an experimental setup in which the relation between a splice site and the ancientness of its surrounding sequence could be studied, it was found that the presence of an intron was positively correlated to the ancientness of its surrounding sequence. Intron phase conservation was linked to the conservation of the gene sequence and not to the splice site sequence itself. However, no apparent differences in phase distribution were found between introns in conserved versus non-conserved sequences. Conclusion The data confirm an origin of introns deep in the eukaryotic branch and is in concordance with the presence of introns in the first functional protein modules in an 'Exon theory of genes' scenario. A model is proposed in which shuffling of primordial short exonic sequences led to the formation of the first functional protein modules, in line with hypotheses that see the formation of introns integral to the origins of genome evolution

  18. Dual targeted mitochondrial proteins are characterized by lower MTS parameters and total net charge.

    Science.gov (United States)

    Dinur-Mills, Maya; Tal, Merav; Pines, Ophry

    2008-05-14

    In eukaryotic cells, identical proteins can be located in different subcellular compartments (termed dual-targeted proteins). We divided a reference set of mitochondrial proteins (published single gene studies) into two groups: i) Dual targeted mitochondrial proteins and ii) Exclusive mitochondrial proteins. Mitochondrial proteins were considered dual-targeted if they were also found or predicted to be localized to the cytosol, the nucleus, the endoplasmic reticulum (ER) or the peroxisome. We found that dual localized mitochondrial proteins have i) A weaker mitochondrial targeting sequence (MitoProtII score, hydrophobic moment and number of basic residues) and ii) a lower whole-protein net charge, when compared to exclusive mitochondrial proteins. We have also generated an annotation list of dual-targeted proteins within the predicted yeast mitochondrial proteome. This considerably large group of dual-localized proteins comprises approximately one quarter of the predicted mitochondrial proteome. We supported this prediction by experimental verification of a subgroup of the predicted dual targeted proteins. Taken together, these results establish dual targeting as a widely abundant phenomenon that should affect our concepts of gene expression and protein function. Possible relationships between the MTS/mature sequence traits and protein dual targeting are discussed.

  19. Acute supplementation of amino acids increases net protein accretion in IUGR fetal sheep.

    Science.gov (United States)

    Brown, Laura D; Rozance, Paul J; Thorn, Stephanie R; Friedman, Jacob E; Hay, William W

    2012-08-01

    Placental insufficiency decreases fetal amino acid uptake from the placenta, plasma insulin concentrations, and protein accretion, thus compromising normal fetal growth trajectory. We tested whether acute supplementation of amino acids or insulin into the fetus with intrauterine growth restriction (IUGR) would increase net fetal protein accretion rates. Late-gestation IUGR and control (CON) fetal sheep received acute, 3-h infusions of amino acids (with euinsulinemia), insulin (with euglycemia and euaminoacidemia), or saline. Fetal leucine metabolism was measured under steady-state conditions followed by a fetal muscle biopsy to quantify insulin signaling. In CON, increasing amino acid delivery rates to the fetus by 100% increased leucine oxidation rates by 100%. In IUGR, amino acid infusion completely suppressed fetal protein breakdown rates but increased leucine oxidation rate by only 25%, resulting in increased protein accretion rates by 150%. Acute insulin infusion, however, had very little effect on amino acid delivery rates, fetal leucine disposal rates, or fetal protein accretion rates in CON or IUGR fetuses despite robust signaling of the fetal skeletal muscle insulin-signaling cascade. These results indicate that, when amino acids are given directly into the fetal circulation independently of changes in insulin concentrations, IUGR fetal sheep have suppressed protein breakdown rates, thus increasing net fetal protein accretion.

  20. [Influence of indium net position on 253.7 nm resonance spectra line of electrodeless discharge lamps].

    Science.gov (United States)

    Dong, Jin-Yang; Zhang, Gui-Xin; Wang, Chang-Quan; Zou, Jun; Zhao, Ting

    2012-09-01

    As a kind of new electric light source, electrodeless discharge lamps (EDL) are based on high-frequency electromagnetic induction and nonpolar gas discharge. Visible light is emitted as a result of Hg 253.7 nm resonance spectrum line inspiring phosphor. The influence of indium net position on the Hg 253. 7 nm resonance spectral line was studied experimentally by atomic emission spectral analysis. It was found that the relative intensity of Hg 253.7 nm resonance spectral line is strongest when the indium net is located at both ends of coupling coil, weaker at middle and weakest when far away from coupling coil. It was inferred that there is an optimum indium net position for EDL, and the corresponding lighting effect is maximal. The results were qualitatively analyzed from the standpoint of gas discharge theory, combined with the finite element simulation of Maxwell 3D, which has instructive value for pattern design and parametric optimization of EDL.

  1. NetPhosYeast: prediction of protein phosphorylation sites in yeast

    DEFF Research Database (Denmark)

    Ingrell, C.R.; Miller, Martin Lee; Jensen, O.N.

    2007-01-01

    We here present a neural network-based method for the prediction of protein phosphorylation sites in yeast-an important model organism for basic research. Existing protein phosphorylation site predictors are primarily based on mammalian data and show reduced sensitivity on yeast phosphorylation...... sites compared to those in humans, suggesting the need for an yeast-specific phosphorylation site predictor. NetPhosYeast achieves a correlation coefficient close to 0.75 with a sensitivity of 0.84 and specificity of 0.90 and outperforms existing predictors in the identification of phosphorylation sites...

  2. Dietary Protein and Potassium, Diet–Dependent Net Acid Load, and Risk of Incident Kidney Stones

    Science.gov (United States)

    Mandel, Ernest I.; Curhan, Gary C.; Gambaro, Giovanni; Taylor, Eric N.

    2016-01-01

    Background and objectives Protein and potassium intake and the resulting diet–dependent net acid load may affect kidney stone formation. It is not known whether protein type or net acid load is associated with risk of kidney stones. Design, setting, participants, & measurements We prospectively examined intakes of protein (dairy, nondairy animal, and vegetable), potassium, and animal protein-to-potassium ratio (an estimate of net acid load) and risk of incident kidney stones in the Health Professionals Follow-Up Study (n=42,919), the Nurses’ Health Study I (n=60,128), and the Nurses’ Health Study II (n=90,629). Multivariable models were adjusted for age, body mass index, diet, and other factors. We also analyzed cross-sectional associations with 24-hour urine (n=6129). Results During 3,108,264 person-years of follow-up, there were 6308 incident kidney stones. Dairy protein was associated with lower risk in the Nurses’ Health Study II (hazard ratio for highest versus lowest quintile, 0.84; 95% confidence interval, 0.73 to 0.96; P value for trend <0.01). The hazard ratios for nondairy animal protein were 1.15 (95% confidence interval, 0.97 to 1.36; P value for trend =0.04) in the Health Professionals Follow-Up Study and 1.20 (95% confidence interval, 0.99 to 1.46; P value for trend =0.06) in the Nurses’ Health Study I. Potassium intake was associated with lower risk in all three cohorts (hazard ratios from 0.44 [95% confidence interval, 0.36 to 0.53] to 0.67 [95% confidence interval, 0.57 to 0.78]; P values for trend <0.001). Animal protein-to-potassium ratio was associated with higher risk (P value for trend =0.004), even after adjustment for animal protein and potassium. Higher dietary potassium was associated with higher urine citrate, pH, and volume (P values for trend <0.002). Conclusions Kidney stone risk may vary by protein type. Diets high in potassium or with a relative abundance of potassium compared with animal protein could represent a means of

  3. Dietary Protein and Potassium, Diet-Dependent Net Acid Load, and Risk of Incident Kidney Stones.

    Science.gov (United States)

    Ferraro, Pietro Manuel; Mandel, Ernest I; Curhan, Gary C; Gambaro, Giovanni; Taylor, Eric N

    2016-10-07

    Protein and potassium intake and the resulting diet-dependent net acid load may affect kidney stone formation. It is not known whether protein type or net acid load is associated with risk of kidney stones. We prospectively examined intakes of protein (dairy, nondairy animal, and vegetable), potassium, and animal protein-to-potassium ratio (an estimate of net acid load) and risk of incident kidney stones in the Health Professionals Follow-Up Study (n=42,919), the Nurses' Health Study I (n=60,128), and the Nurses' Health Study II (n=90,629). Multivariable models were adjusted for age, body mass index, diet, and other factors. We also analyzed cross-sectional associations with 24-hour urine (n=6129). During 3,108,264 person-years of follow-up, there were 6308 incident kidney stones. Dairy protein was associated with lower risk in the Nurses' Health Study II (hazard ratio for highest versus lowest quintile, 0.84; 95% confidence interval, 0.73 to 0.96; P value for trend <0.01). The hazard ratios for nondairy animal protein were 1.15 (95% confidence interval, 0.97 to 1.36; P value for trend =0.04) in the Health Professionals Follow-Up Study and 1.20 (95% confidence interval, 0.99 to 1.46; P value for trend =0.06) in the Nurses' Health Study I. Potassium intake was associated with lower risk in all three cohorts (hazard ratios from 0.44 [95% confidence interval, 0.36 to 0.53] to 0.67 [95% confidence interval, 0.57 to 0.78]; P values for trend <0.001). Animal protein-to-potassium ratio was associated with higher risk (P value for trend =0.004), even after adjustment for animal protein and potassium. Higher dietary potassium was associated with higher urine citrate, pH, and volume (P values for trend <0.002). Kidney stone risk may vary by protein type. Diets high in potassium or with a relative abundance of potassium compared with animal protein could represent a means of stone prevention. Copyright © 2016 by the American Society of Nephrology.

  4. Mem-mEN: Predicting Multi-Functional Types of Membrane Proteins by Interpretable Elastic Nets.

    Science.gov (United States)

    Wan, Shibiao; Mak, Man-Wai; Kung, Sun-Yuan

    2016-01-01

    Membrane proteins play important roles in various biological processes within organisms. Predicting the functional types of membrane proteins is indispensable to the characterization of membrane proteins. Recent studies have extended to predicting single- and multi-type membrane proteins. However, existing predictors perform poorly and more importantly, they are often lack of interpretability. To address these problems, this paper proposes an efficient predictor, namely Mem-mEN, which can produce sparse and interpretable solutions for predicting membrane proteins with single- and multi-label functional types. Given a query membrane protein, its associated gene ontology (GO) information is retrieved by searching a compact GO-term database with its homologous accession number, which is subsequently classified by a multi-label elastic net (EN) classifier. Experimental results show that Mem-mEN significantly outperforms existing state-of-the-art membrane-protein predictors. Moreover, by using Mem-mEN, 338 out of more than 7,900 GO terms are found to play more essential roles in determining the functional types. Based on these 338 essential GO terms, Mem-mEN can not only predict the functional type of a membrane protein, but also explain why it belongs to that type. For the reader's convenience, the Mem-mEN server is available online at http://bioinfo.eie.polyu.edu.hk/MemmENServer/.

  5. Accounting for the effects of a ruminal nitrogen deficiency within the structure of the Cornell Net Carbohydrate and Protein System

    National Research Council Canada - National Science Library

    Tedeschi, L. O; Fox, D. G; Russell, J. B

    2000-01-01

    .... The Cornell Net Carbohydrate and Protein System (CNCPS) prediction of fiber digestion and microbial mass production from ruminally degraded carbohydrate has been adjusted to accommodate a ruminal N deficiency...

  6. Accounting for the effects of a ruminal nitrogen deficiency within the structure of the Cornell Net Carbonhydrate and Protein System

    National Research Council Canada - National Science Library

    L O Tedeschi; D G Fox; J B Russell

    2000-01-01

      The Cornell Net Carbohydrate and Protein System (CNCPS) prediction of fiber digestion and microbial mass production from ruminally degraded carbohydrate has been adjusted to accommodate a ruminal N deficiency...

  7. Sex effects on net protein and energy requirements for growth of Saanen goats.

    Science.gov (United States)

    Souza, A P; St-Pierre, N R; Fernandes, M H R M; Almeida, A K; Vargas, J A C; Resende, K T; Teixeira, I A M A

    2017-06-01

    Requirements for growth in the different sexes remain poorly quantified in goats. The objective of this study was to develop equations for estimating net protein (NP G ) and net energy (NE G ) for growth in Saanen goats of different sexes from 5 to 45 kg of body weight (BW). A data set from 7 comparative slaughter studies (238 individual records) of Saanen goats was used. Allometric equations were developed to determine body protein and energy contents in the empty BW (EBW) as dependent variables and EBW as the allometric predictor. Parameter estimates were obtained using a linearized (log-transformation) expression of the allometric equations using the MIXED procedure in SAS software (SAS Institute Inc., Cary, NC). The model included the random effect of the study and the fixed effects of sex (intact male, castrated male, and female; n = 94, 73, and 71, respectively), EBW, and their interactions. Net requirements for growth were estimated as the first partial derivative of the allometric equations with respect to EBW. Additionally, net requirements for growth were evaluated based on the degree of maturity. Monte Carlo techniques were used to estimate the uncertainty of the calculated net requirement values. Sex affected allometric relationships for protein and energy in Saanen goats. The allometric equation for protein content in the EBW of intact and castrated males was log 10 protein (g) = 2.221 (±0.0224) + 1.015 (±0.0165) × log 10 EBW (kg). For females, the relationship was log 10 protein (g) = 2.277 (±0.0288) + 0.958 (±0.0218) × log 10 EBW (kg). Therefore, NP G for males was greater than for females. The allometric equation for the energy content in the EBW of intact males was log 10 energy (kcal) = 2.988 (±0.0323) + 1.240 (±0.0238) × log 10 EBW (kg); of castrated males, log 10 energy (kcal) = 2.873 (±0.0377) + 1.359 (±0.0283) × log 10 EBW (kg); and of females, log 10 energy (kcal) = 2.820 (±0.0377) + 1.442 (±0.0281) × log 10 EBW (kg). The NE G

  8. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins

    Energy Technology Data Exchange (ETDEWEB)

    Miller, L.L.

    1976-01-01

    The isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs--Ringer bicarbonate buffer containing 3% bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of rat serum albumin, fibrinogen, ..cap alpha../sub 1/-acid glycoprotein, ..cap alpha../sub 2/-(acute phase) globulin, and haptoglobin. Quantitative measurement of perfusate glucose, amino acid nitrogen, and urea affords a basis for determining net glucose and nitrogen balance in the perfusion system. Although the dose of dexamethasone (total 1.0 ..mu..g) used was insufficient to induce synthesis of ..cap alpha../sub 2/-acute phase globulin, net syntheses of albumin, fibrinogen, ..cap alpha../sub 1/-acid glycoprotein, and haptoglobin were increased. Glucagon given with dexamethasone depressed albumin and haptoglobin synthesis markedly, but not that of fibrinogen and ..cap alpha../sub 1/-acid glycoprotein. Glucagon with dexamethasone markedly enhanced ureogenesis and glycogenolysis and elicited an exaggerated negative nitrogen balance. The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously. It is emphasized that insulin is essential for positive nitrogen balance.

  9. The positive net radiative greenhouse gas forcing of increasing methane emissions from a thawing boreal forest-wetland landscape.

    Science.gov (United States)

    Helbig, Manuel; Chasmer, Laura E; Kljun, NatasCha; Quinton, William L; Treat, Claire C; Sonnentag, Oliver

    2017-06-01

    At the southern margin of permafrost in North America, climate change causes widespread permafrost thaw. In boreal lowlands, thawing forested permafrost peat plateaus ('forest') lead to expansion of permafrost-free wetlands ('wetland'). Expanding wetland area with saturated and warmer organic soils is expected to increase landscape methane (CH4 ) emissions. Here, we quantify the thaw-induced increase in CH4 emissions for a boreal forest-wetland landscape in the southern Taiga Plains, Canada, and evaluate its impact on net radiative forcing relative to potential long-term net carbon dioxide (CO2 ) exchange. Using nested wetland and landscape eddy covariance net CH4 flux measurements in combination with flux footprint modeling, we find that landscape CH4 emissions increase with increasing wetland-to-forest ratio. Landscape CH4 emissions are most sensitive to this ratio during peak emission periods, when wetland soils are up to 10 °C warmer than forest soils. The cumulative growing season (May-October) wetland CH4 emission of ~13 g CH4  m-2 is the dominating contribution to the landscape CH4 emission of ~7 g CH4  m-2 . In contrast, forest contributions to landscape CH4 emissions appear to be negligible. The rapid wetland expansion of 0.26 ± 0.05% yr-1 in this region causes an estimated growing season increase of 0.034 ± 0.007 g CH4  m-2  yr-1 in landscape CH4 emissions. A long-term net CO2 uptake of >200 g CO2  m-2  yr-1 is required to offset the positive radiative forcing of increasing CH4 emissions until the end of the 21st century as indicated by an atmospheric CH4 and CO2 concentration model. However, long-term apparent carbon accumulation rates in similar boreal forest-wetland landscapes and eddy covariance landscape net CO2 flux measurements suggest a long-term net CO2 uptake between 49 and 157 g CO2  m-2  yr-1 . Thus, thaw-induced CH4 emission increases likely exert a positive net radiative greenhouse gas forcing through the 21st century.

  10. Positive modulator of bone morphogenic protein-2

    Energy Technology Data Exchange (ETDEWEB)

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua; Kazuyuki, Takahashi

    2017-06-06

    Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

  11. Positive modulator of bone morphogenic protein-2

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2009-01-27

    Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

  12. Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults.

    Science.gov (United States)

    Jonker, Renate; Deutz, Nicolaas Ep; Erbland, Marcia L; Anderson, Paula J; Engelen, Mariëlle Pkj

    2017-04-01

    The development of effective nutritional strategies in support of muscle growth for patients with chronic obstructive pulmonary disease (COPD) remains challenging. Dietary essential amino acids (EAAs) are the main driver of postprandial net protein anabolism. In agreement, EAA supplements in healthy older adults are more effective than supplements with the composition of complete proteins. In patients with COPD it is still unknown whether complete protein supplements can be substituted with only EAAs, and whether they are as effective as in healthy older adults. According to a double-blind randomized crossover design, we examined in 23 patients with moderate to very severe COPD (age: 65±2 years, FEV1: 40±2% of predicted) and 19 healthy age-matched subjects (age: 64±2 years), whether a free EAA mixture with a high proportion (40%) of leucine (EAA mixture) stimulated whole body net protein gain more than a similar mixture of balanced free EAAs and non-EAAs as present in whey protein (TAA mixture). Whole body net protein gain and splanchnic extraction of phenylalanine (PHE) were assessed by continuous IV infusion of L-[ring-2H5]-PHE and L-[ring-2H2]-tyrosine, and enteral intake of L-[15N]-PHE (added to the mixtures). Besides an excellent positive linear relationship between PHE intake and net protein gain in both groups (r=0.84-0.91, Panabolism more than free amino acid supplements with the composition of complete proteins. Therefore, free EAA supplements may aid in the prevention and treatment of muscle wasting in this patient population. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Repeatability and reproducibility of the Cornell Net Carbohydrate and Protein System analytical determinations

    Directory of Open Access Journals (Sweden)

    Arianna Buccioni

    2010-01-01

    Full Text Available The increasing use in Italy of the Cornell Net Carbohydrate and Protein System (CNCPS led researchers of five Italianuniversities to carry out a collaborative study to evaluate the precision of the CNCPS chemical analysis and derivate fractions.Each laboratory conducted in duplicate the chemical analyses according to the Weende (dry matter; crude protein;ether extract; crude fibre; ash, Van Soest (neutral and acid detergent fibre, NDF and ADF; acid detergent lignin; ADLand CNCPS (soluble proteins, SP; non-protein nitrogen, NPN; neutral and acid detergent insoluble protein, NDIP andADIP; starch, ST schemes on the same five feeds (barley meal, wheat straw, maize silage, dried lucerne and fieldbeans. Anomalous analytical data were identified and corrected by the “box-plot” graphic tool before the calculation ofthe CNCPS protein (B1, B2 and B3 and carbohydrate (A, B2 and C fractions. Finally, repeatability (chemical analysis andreproducibility (chemical analysis and fractions were calculated and expressed as relative values (repeatability andreproducibility standard deviation as percentage of the corresponding mean, RSDr and RSDR, respectively. Chemicalanalyses of the Weende scheme, together with NDF, ADF and ST analyses, have satisfactory repeatability (0.3-6.2% andreproducibility (0.3-11.2% values. On the contrary the ADL, NPN, NDIP and ADIP analyses showed high variability, bothwithin and between laboratories (RSDr and RSDR between 20 and 45%. The SP analysis had an intermediate value ofprecision (RSDr=10.6%; RSDR=16.4%.Finally, since different combinations of several chemical analyses with scarce (ADL, NPN, NDIP, ADIP, SP or average precision(e.g. NDF and starch are used to calculate CNCPS fractions (excluding B2 protein fraction, also the reproducibilitiesof these fractions are poor and range from 10 to 20%.

  14. Assessment of net postprandial protein utilization of 15N-labelled milk nitrogen in human subjects.

    Science.gov (United States)

    Bos, C; Mahé, S; Gaudichon, C; Benamouzig, R; Gausserès, N; Luengo, C; Ferrière, F; Rautureau, J; Tomé, D

    1999-03-01

    The nutritional quality of milk proteins, evaluated both in terms of digestibility and postprandial oxidation and retention in human subjects, was investigated in this study. Five healthy adult volunteers were given 480 ml 15N-labelled milk (i.e. 190 mmol N). 15N was subsequently determined at the ileal level, using a naso-intestinal intubation technique, as well as at the faecal level. Plasma and urine were sampled for 8 h after meal ingestion. Dietary exogenous N recovered at the terminal ileum after 8 h reached 8.6 (SE 0.8) mmol while the amount collected in the faeces was 6.5 (SE 0.7) mmol after 5 d. The true ileal and faecal digestibilities were 95.5 (SE 0.4)% and 96.6 (SE 0.4)% respectively. The appearance of [15N]amino acids in the plasma was rapid and prolonged. The measurement of 15N in the body urea pool and in the N excreted in the urine allowed us to calculate the deamination occurring after [15N]milk protein absorption. The net postprandial protein utilization (i.e. NPPU = (Nabsorbed-Ndeaminated)/Ningested), calculated as an index of protein quality 8 h after milk ingestion, was 81.0 (SE 1.9)%. Our data confirm that milk protein has a high oro-ileal digestibility in man and demonstrate that milk protein has a high NPPU, an index corresponding to a period in which the dietary protein retention is maximal.

  15. Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes.

    Science.gov (United States)

    Dasmeh, Pouria; Kepp, Kasper P

    2017-08-01

    Positive (adaptive) selection has recently been implied in human superoxide dismutase 1 (SOD1), a highly abundant antioxidant protein with energy signaling and antiaging functions, one of very few examples of direct selection on a human protein product (exon); the molecular drivers of this selection are unknown. We mapped 30 extant SOD1 sequences to the recently established mammalian species tree and inferred ancestors, key substitutions, and signatures of selection during the protein's evolution. We detected elevated substitution rates leading to great apes (Hominidae) at ~1 per 2 million years, significantly higher than in other primates and rodents, although these paradoxically generally evolve much faster. The high evolutionary rate was partly due to relaxation of some selection pressures and partly to distinct positive selection of SOD1 in great apes. We then show that higher stability and net charge and changes at the dimer interface were selectively introduced upon separation from old world monkeys and lesser apes (gibbons). Consequently, human, chimpanzee and gorilla SOD1s have a net charge of -6 at physiological pH, whereas the closely related gibbons and macaques have -3. These features consistently point towards selection against the malicious aggregation effects of elevated SOD1 levels in long-living great apes. The findings mirror the impact of human SOD1 mutations that reduce net charge and/or stability and cause ALS, a motor neuron disease characterized by oxidative stress and SOD1 aggregates and triggered by aging. Our study thus marks an example of direct selection for a particular chemical phenotype (high net charge and stability) in a single human protein with possible implications for the evolution of aging.

  16. Breastfeeding is positively associated with child intelligence even net of parental IQ.

    Science.gov (United States)

    Kanazawa, Satoshi

    2015-12-01

    Some previous reviews conclude that breastfeeding is not significantly associated with increased intelligence in children once mother's IQ is statistically controlled. The conclusion may potentially have both theoretical and methodological problems. The National Child Development Study allows the examination of the effect of breastfeeding on intelligence in two consecutive generations of British children. The analysis of the first generation shows that the effect of breastfeeding on intelligence increases from Age 7 to 16. The analysis of the second generation shows that each month of breastfeeding, net of parental IQ and other potential confounds, is associated with an increase of .16 IQ points. Further analyses suggest that some previous studies may have failed to uncover the effect of breastfeeding on child intelligence because of their reliance on one IQ test. (c) 2015 APA, all rights reserved).

  17. Energy balance of maize production in Brazil: the energetic constraints of a net positive outcome

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Luis Henrique de Barros; Alves, Bruno Jose Rodrigues; Urquiaga, Segundo

    2008-07-01

    Among the factors used to analyze and to establish the sustainability of a whole agricultural production system, the energy balance is one of the most powerful and robust. The maize production in Brazil is surely the reflex of an energy intensive system that demands many field operations and heavy fertilizer applications, notably nitrogen in urea form. This work presents an energy balance of this major crop adjusted to the Brazilian conditions of cultivation. The input components were grouped based on their energy contents, and the possible improvements in the agricultural practices that could improve energy balance and net energy withdrawn from the farming were considered. The replacement of N synthetic fertilizer by biological nitrogen fixation, whether the process is directly carried out by endophytic diazotroph bacteria or by means of a N{sub 2}- fixing legume culture planted before the main crop as a green-manure is also discussed. (author)

  18. The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components.

    Science.gov (United States)

    Borroto-Escuela, Dasiel O; Brito, Ismel; Romero-Fernandez, Wilber; Di Palma, Michael; Oflijan, Julia; Skieterska, Kamila; Duchou, Jolien; Van Craenenbroeck, Kathleen; Suárez-Boomgaard, Diana; Rivera, Alicia; Guidolin, Diego; Agnati, Luigi F; Fuxe, Kjell

    2014-05-14

    G protein-coupled receptors (GPCRs) oligomerization has emerged as a vital characteristic of receptor structure. Substantial experimental evidence supports the existence of GPCR-GPCR interactions in a coordinated and cooperative manner. However, despite the current development of experimental techniques for large-scale detection of GPCR heteromers, in order to understand their connectivity it is necessary to develop novel tools to study the global heteroreceptor networks. To provide insight into the overall topology of the GPCR heteromers and identify key players, a collective interaction network was constructed. Experimental interaction data for each of the individual human GPCR protomers was obtained manually from the STRING and SCOPUS databases. The interaction data were used to build and analyze the network using Cytoscape software. The network was treated as undirected throughout the study. It is comprised of 156 nodes, 260 edges and has a scale-free topology. Connectivity analysis reveals a significant dominance of intrafamily versus interfamily connections. Most of the receptors within the network are linked to each other by a small number of edges. DRD2, OPRM, ADRB2, AA2AR, AA1R, OPRK, OPRD and GHSR are identified as hubs. In a network representation 10 modules/clusters also appear as a highly interconnected group of nodes. Information on this GPCR network can improve our understanding of molecular integration. GPCR-HetNet has been implemented in Java and is freely available at http://www.iiia.csic.es/~ismel/GPCR-Nets/index.html.

  19. The G Protein-Coupled Receptor Heterodimer Network (GPCR-HetNet and Its Hub Components

    Directory of Open Access Journals (Sweden)

    Dasiel O. Borroto-Escuela

    2014-05-01

    Full Text Available G protein-coupled receptors (GPCRs oligomerization has emerged as a vital characteristic of receptor structure. Substantial experimental evidence supports the existence of GPCR-GPCR interactions in a coordinated and cooperative manner. However, despite the current development of experimental techniques for large-scale detection of GPCR heteromers, in order to understand their connectivity it is necessary to develop novel tools to study the global heteroreceptor networks. To provide insight into the overall topology of the GPCR heteromers and identify key players, a collective interaction network was constructed. Experimental interaction data for each of the individual human GPCR protomers was obtained manually from the STRING and SCOPUS databases. The interaction data were used to build and analyze the network using Cytoscape software. The network was treated as undirected throughout the study. It is comprised of 156 nodes, 260 edges and has a scale-free topology. Connectivity analysis reveals a significant dominance of intrafamily versus interfamily connections. Most of the receptors within the network are linked to each other by a small number of edges. DRD2, OPRM, ADRB2, AA2AR, AA1R, OPRK, OPRD and GHSR are identified as hubs. In a network representation 10 modules/clusters also appear as a highly interconnected group of nodes. Information on this GPCR network can improve our understanding of molecular integration. GPCR-HetNet has been implemented in Java and is freely available at http://www.iiia.csic.es/~ismel/GPCR-Nets/index.html.

  20. Temperature-controlled positioning of fusion proteins in microreactors

    NARCIS (Netherlands)

    Teeuwen, R.L.M.; Zuilhof, H.; Wolf, de F.A.; Hest, van J.C.M.

    2009-01-01

    We present a non-covalent immobilization system based on stimulus-responsive elastin-like polypeptides (ELPs) to facilitate the positioning of proteins in microchannels. Two ELP variants were constructed and connected to fluorescent proteins EGFP and DsRed2. These fusion proteins display an inverse

  1. Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein.

    Science.gov (United States)

    Remer, T; Manz, F

    1994-06-01

    The object of this study was to determine whether it is possible to reliably estimate the renal net acid excretion (NAE) produced by adults consuming different amounts of dietary protein. A physiologically based calculation model that corrects for intestinal absorption of minerals and sulfur-containing protein and assumes a rate of urinary excretion of organic acids proportional to body surface area was used to estimate NAE. Urinary excretion of different minerals and NAE was measured during the last 48 h of each of four separate 5-d diet periods in six healthy adults. On the basis of food tables, the four nearly isoenergetic diets (one lacto-vegetarian and one high- and two moderate-protein diets) were estimated to yield the following NAE values: 3.7, 117.5, 62.2, and 102.2 mEq/d, respectively. The analytically determined urinary NAE (24.1 +/- 10.7, 135.5 +/- 16.4, 69.7 +/- 21.4, and 112.6 +/- 10.9 mEq/d) corresponded reasonably well to these estimates, suggesting that the calculation model is appropriate to predict the renal NAE from nutrient intake and anthropometric data.

  2. Positive net movements of amino acids in the hindlimb after overnight food deprivation contribute to sustaining the elevated anabolism of neonatal pigs

    Science.gov (United States)

    During the neonatal period, high protein breakdown rate is a metabolic process inherent to elevated rates of protein accretion in skeletal muscle. To determine the relationship between hindlimb net movements of essential and nonessential amino acids in the regulation of hindlimb protein breakdown du...

  3. A Novel Approach to Head positioning using Fixed Center Interpolation Net with Weight Elimination Algorithm

    OpenAIRE

    Mahmoud Z. Iskandarani

    2011-01-01

    A reliable algorithm for head movements inside a vehicle is designed. The proposed algorithm allowed the adjustment of basic functions such as indicators, mirrors and reverse lights based on the driver final head position. The algorithm system mapped a predefined coordinates for drivers head that resulted in a computable geometry via a sensory system which is fed to the vehicle actuating system. Problem statement: Head position recognition is one of the most common problem...

  4. Net charge per residue modulates conformational ensembles of intrinsically disordered proteins.

    Science.gov (United States)

    Mao, Albert H; Crick, Scott L; Vitalis, Andreas; Chicoine, Caitlin L; Pappu, Rohit V

    2010-05-04

    Intrinsically disordered proteins (IDPs) adopt heterogeneous ensembles of conformations under physiological conditions. Understanding the relationship between amino acid sequence and conformational ensembles of IDPs can help clarify the role of disorder in physiological function. Recent studies revealed that polar IDPs favor collapsed ensembles in water despite the absence of hydrophobic groups--a result that holds for polypeptide backbones as well. By studying highly charged polypeptides, a different archetype of IDPs, we assess how charge content modulates the intrinsic preference of polypeptide backbones for collapsed structures. We characterized conformational ensembles for a set of protamines in aqueous milieus using molecular simulations and fluorescence measurements. Protamines are arginine-rich IDPs involved in the condensation of chromatin during spermatogenesis. Simulations based on the ABSINTH implicit solvation model predict the existence of a globule-to-coil transition, with net charge per residue serving as the discriminating order parameter. The transition is supported by quantitative agreement between simulation and experiment. Local conformational preferences partially explain the observed trends of polymeric properties. Our results lead to the proposal of a schematic protein phase diagram that should enable prediction of polymeric attributes for IDP conformational ensembles using easily calculated physicochemical properties of amino acid sequences. Although sequence composition allows the prediction of polymeric properties, interresidue contact preferences of protamines with similar polymeric attributes suggest that certain details of conformational ensembles depend on the sequence. This provides a plausible mechanism for specificity in the functions of IDPs.

  5. Self-organization and positioning of bacterial protein clusters

    Science.gov (United States)

    Murray, Seán M.; Sourjik, Victor

    2017-10-01

    Many cellular processes require proteins to be precisely positioned within the cell. In some cases this can be attributed to passive mechanisms such as recruitment by other proteins in the cell or by exploiting the curvature of the membrane. However, in bacteria, active self-positioning is likely to play a role in multiple processes, including the positioning of the future site of cell division and cytoplasmic protein clusters. How can such dynamic clusters be formed and positioned? Here, we present a model for the self-organization and positioning of dynamic protein clusters into regularly repeating patterns based on a phase-locked Turing pattern. A single peak in the concentration is always positioned at the midpoint of the model cell, and two peaks are positioned at the midpoint of each half. Furthermore, domain growth results in peak splitting and pattern doubling. We argue that the model may explain the regular positioning of the highly conserved structural maintenance of chromosomes complexes on the bacterial nucleoid and that it provides an attractive mechanism for the self-positioning of dynamic protein clusters in other systems.

  6. International Society of Sports Nutrition position stand: protein and exercise

    Directory of Open Access Journals (Sweden)

    Landis Jamie

    2007-09-01

    Full Text Available Abstract Position Statement The following seven points related to the intake of protein for healthy, exercising individuals constitute the position stand of the Society. They have been approved by the Research Committee of the Society. 1 Vast research supports the contention that individuals engaged in regular exercise training require more dietary protein than sedentary individuals. 2 Protein intakes of 1.4 – 2.0 g/kg/day for physically active individuals is not only safe, but may improve the training adaptations to exercise training. 3 When part of a balanced, nutrient-dense diet, protein intakes at this level are not detrimental to kidney function or bone metabolism in healthy, active persons. 4 While it is possible for physically active individuals to obtain their daily protein requirements through a varied, regular diet, supplemental protein in various forms are a practical way of ensuring adequate and quality protein intake for athletes. 5 Different types and quality of protein can affect amino acid bioavailability following protein supplementation. The superiority of one protein type over another in terms of optimizing recovery and/or training adaptations remains to be convincingly demonstrated. 6 Appropriately timed protein intake is an important component of an overall exercise training program, essential for proper recovery, immune function, and the growth and maintenance of lean body mass. 7 Under certain circumstances, specific amino acid supplements, such as branched-chain amino acids (BCAA's, may improve exercise performance and recovery from exercise.

  7. Net herbage accumulation rate and crude protein content of Urochloa brizantha cultivars under shade intensities

    Directory of Open Access Journals (Sweden)

    Paulo Roberto de Lima Meirelles

    2013-12-01

    Full Text Available The use of silvopastoral systems is a sustainable alternative for animal production in various regions of the Brazil. However to obtain satisfactory results in these systems, the selection of forage species that grows well in the shade should be done. The tolerance of plants to light restriction and the correctly choice of species, considering good nutritional values for these conditions has great importance. The study of artificial shading for forage production helps the clarification of issues related to the behavior of plants under reduced light prior to use in integrations with forests. The aim of the study was to evaluate the net herbage accumulation rate of forage (HAR and crude protein (CP of Urochloa brizantha cultivars (Marandu and Piatã under natural light and shading of 30 and 60%. The experiment was conducted at FMVZ - UNESP, Botucatu. The experimental design was a randomized block in factorial arrangement 3 x 2 (three shading levels: 0, 30 and 60%, two cultivars: Marandu and Piatã with three replications and repeated measures (3 cuts. Sample collection occurred when the cultivars reached 35 cm in height. The treatments with shading showed lower cutting intervals as compared to those subjected to full sunlight, because they have reached in a shorter time to time as determined cut-off criterion (mean of 37, 45 and 61 days for reduction of 60%, reduction of 30% and full sun. Significant effects (P<0.05 interaction cultivar x shade x cut on the net herbage accumulation rate (HAR. Most HAR (P<0.05 was observed for cv. Marandu 60% reduction in lightness (127 kg/ha/day due to increased production of stem during the first growing cycle. The lower HAR also occurred to Marandu, but under natural light in the third cut (34 kg/ha/day due to adverse weather conditions during the growth interval. The shadow effect and the cutting (P<0.05 affected CP. The percentage of CP on cultivars showed the highest values (average value of 9.27% in 60

  8. Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes

    DEFF Research Database (Denmark)

    Dasmeh, Pouria; Kepp, Kasper Planeta

    2017-01-01

    Positive (adaptive) selection has recently been implied in human superoxide dismutase 1 (SOD1), a highly abundant antioxidant protein with energy signaling and antiaging functions, one of very few examples of direct selection on a human protein product (exon); the molecular drivers of this select...... and SOD1 aggregates and triggered by aging. Our study thus marks an example of direct selection for a particular chemical phenotype (high net charge and stability) in a single human protein with possible implications for the evolution of aging.......Positive (adaptive) selection has recently been implied in human superoxide dismutase 1 (SOD1), a highly abundant antioxidant protein with energy signaling and antiaging functions, one of very few examples of direct selection on a human protein product (exon); the molecular drivers...... of this selection are unknown. We mapped 30 extant SOD1 sequences to the recently established mammalian species tree and inferred ancestors, key substitutions, and signatures of selection during the protein's evolution. We detected elevated substitution rates leading to great apes (Hominidae) at ~1 per 2 million...

  9. Protein complex prediction via dense subgraphs and false positive analysis.

    Directory of Open Access Journals (Sweden)

    Cecilia Hernandez

    Full Text Available Many proteins work together with others in groups called complexes in order to achieve a specific function. Discovering protein complexes is important for understanding biological processes and predict protein functions in living organisms. Large-scale and throughput techniques have made possible to compile protein-protein interaction networks (PPI networks, which have been used in several computational approaches for detecting protein complexes. Those predictions might guide future biologic experimental research. Some approaches are topology-based, where highly connected proteins are predicted to be complexes; some propose different clustering algorithms using partitioning, overlaps among clusters for networks modeled with unweighted or weighted graphs; and others use density of clusters and information based on protein functionality. However, some schemes still require much processing time or the quality of their results can be improved. Furthermore, most of the results obtained with computational tools are not accompanied by an analysis of false positives. We propose an effective and efficient mining algorithm for discovering highly connected subgraphs, which is our base for defining protein complexes. Our representation is based on transforming the PPI network into a directed acyclic graph that reduces the number of represented edges and the search space for discovering subgraphs. Our approach considers weighted and unweighted PPI networks. We compare our best alternative using PPI networks from Saccharomyces cerevisiae (yeast and Homo sapiens (human with state-of-the-art approaches in terms of clustering, biological metrics and execution times, as well as three gold standards for yeast and two for human. Furthermore, we analyze false positive predicted complexes searching the PDBe (Protein Data Bank in Europe database in order to identify matching protein complexes that have been purified and structurally characterized. Our analysis shows

  10. International Society of Sports Nutrition Position Stand: protein and exercise.

    Science.gov (United States)

    Jäger, Ralf; Kerksick, Chad M; Campbell, Bill I; Cribb, Paul J; Wells, Shawn D; Skwiat, Tim M; Purpura, Martin; Ziegenfuss, Tim N; Ferrando, Arny A; Arent, Shawn M; Smith-Ryan, Abbie E; Stout, Jeffrey R; Arciero, Paul J; Ormsbee, Michael J; Taylor, Lem W; Wilborn, Colin D; Kalman, Doug S; Kreider, Richard B; Willoughby, Darryn S; Hoffman, Jay R; Krzykowski, Jamie L; Antonio, Jose

    2017-01-01

    The International Society of Sports Nutrition (ISSN) provides an objective and critical review related to the intake of protein for healthy, exercising individuals. Based on the current available literature, the position of the Society is as follows:An acute exercise stimulus, particularly resistance exercise, and protein ingestion both stimulate muscle protein synthesis (MPS) and are synergistic when protein consumption occurs before or after resistance exercise.For building muscle mass and for maintaining muscle mass through a positive muscle protein balance, an overall daily protein intake in the range of 1.4-2.0 g protein/kg body weight/day (g/kg/d) is sufficient for most exercising individuals, a value that falls in line within the Acceptable Macronutrient Distribution Range published by the Institute of Medicine for protein.Higher protein intakes (2.3-3.1 g/kg/d) may be needed to maximize the retention of lean body mass in resistance-trained subjects during hypocaloric periods.There is novel evidence that suggests higher protein intakes (>3.0 g/kg/d) may have positive effects on body composition in resistance-trained individuals (i.e., promote loss of fat mass).Recommendations regarding the optimal protein intake per serving for athletes to maximize MPS are mixed and are dependent upon age and recent resistance exercise stimuli. General recommendations are 0.25 g of a high-quality protein per kg of body weight, or an absolute dose of 20-40 g.Acute protein doses should strive to contain 700-3000 mg of leucine and/or a higher relative leucine content, in addition to a balanced array of the essential amino acids (EAAs).These protein doses should ideally be evenly distributed, every 3-4 h, across the day.The optimal time period during which to ingest protein is likely a matter of individual tolerance, since benefits are derived from pre- or post-workout ingestion; however, the anabolic effect of exercise is long-lasting (at least 24 h), but likely

  11. The Chemorepulsive Protein Semaphorin 3A and Perineuronal Net-Mediated Plasticity

    NARCIS (Netherlands)

    de Winter, F; Kwok, J C F; Fawcett, J W; Vo, T T; Carulli, D; Verhaagen, J

    2016-01-01

    During postnatal development, closure of critical periods coincides with the appearance of extracellular matrix structures, called perineuronal nets (PNN), around various neuronal populations throughout the brain. The absence or presence of PNN strongly correlates with neuronal plasticity. It is not

  12. Physical model of protein cluster positioning in growing bacteria

    Science.gov (United States)

    Wasnik, Vaibhav; Wang, Hui; Wingreen, Ned S.; Mukhopadhyay, Ranjan

    2017-10-01

    Chemotaxic receptors in bacteria form clusters at cell poles and also laterally, and this clustering plays an important role in signal transduction. These clusters were found to be periodically arranged on the surface of the bacterium Escherichia coli, independent of any known positioning mechanism. In this work we extend a model based on diffusion and aggregation to more realistic geometries and present a means based on ‘bursty’ protein production to distinguish spontaneous positioning from an independently existing positioning mechanism. We also consider the case of isotropic cellular growth and characterize the degree of order arising spontaneously. Our model could also be relevant for other examples of periodically positioned protein clusters in bacteria.

  13. Positively selected sites in cetacean myoglobins contribute to protein stability

    DEFF Research Database (Denmark)

    Dasmeh, Pouria; Serohijos, Adrian W R; Kepp, Kasper P

    2013-01-01

    between Mb folding stability and protein abundance, suggesting that a selection pressure for stability acts proportionally to higher expression. We also identify a major divergence event leading to the common ancestor of whales, during which major stabilization occurred. Most of the positively selected...

  14. Net postprandial utilization of [15N]-labeled milk protein nitrogen is influenced by diet composition in humans.

    Science.gov (United States)

    Gaudichon, C; Mahé, S; Benamouzig, R; Luengo, C; Fouillet, H; Daré, S; Van Oycke, M; Ferrière, F; Rautureau, J; Tomé, D

    1999-04-01

    The aim of this study was to follow the fate of dietary nitrogen to assess the postprandial utilization of purified milk protein and to determine the acute influence of energy nutrients. For this purpose, a [15N]-labeling dietary protein approach was used. Twenty-five subjects swallowed an ileal tube and ingested [15 N]-milk protein alone or supplemented with either milk fat or sucrose. The absorption and postprandial deamination of dietary protein was monitored for 8 h. Sucrose delayed the absorption of protein longer than fat, but the ileal digestibility did not differ among groups (94.5-94.8%). Sucrose, but not fat, significantly reduced the postprandial transfer of [15N]-milk nitrogen to urea. Consequently, the net postprandial protein utilization (NPPU) of milk protein calculated 8 h after meal ingestion was 80% when ingested either alone or supplemented with fat and was significantly greater with sucrose (NPPU = 85%). This study shows that energy nutrients do not affect the nitrogen absorption but modify the metabolic utilization of dietary protein in the phase of nitrogen gain. Our method provides information concerning the deamination kinetics of dietary amino acids and further allows the detection of differences of dietary protein utilization in acute conditions. The diet composition should be carefully considered, and protein quality must be determined under optimal conditions of utilization.

  15. An approach to including protein quality when assessing the net contribution of livestock to human food supply.

    Science.gov (United States)

    Ertl, P; Knaus, W; Zollitsch, W

    2016-11-01

    evaluating the net contribution of livestock to the human food supply. Furthermore, these differences in protein quality might also need to be considered when choosing a functional unit for the assessment of environmental impacts of the production of different proteins.

  16. Positive Selection and Centrality in the Yeast and Fly Protein-Protein Interaction Networks

    Directory of Open Access Journals (Sweden)

    Sandip Chakraborty

    2016-01-01

    Full Text Available Proteins within a molecular network are expected to be subject to different selective pressures depending on their relative hierarchical positions. However, it is not obvious what genes within a network should be more likely to evolve under positive selection. On one hand, only mutations at genes with a relatively high degree of control over adaptive phenotypes (such as those encoding highly connected proteins are expected to be “seen” by natural selection. On the other hand, a high degree of pleiotropy at these genes is expected to hinder adaptation. Previous analyses of the human protein-protein interaction network have shown that genes under long-term, recurrent positive selection (as inferred from interspecific comparisons tend to act at the periphery of the network. It is unknown, however, whether these trends apply to other organisms. Here, we show that long-term positive selection has preferentially targeted the periphery of the yeast interactome. Conversely, in flies, genes under positive selection encode significantly more connected and central proteins. These observations are not due to covariation of genes’ adaptability and centrality with confounding factors. Therefore, the distribution of proteins encoded by genes under recurrent positive selection across protein-protein interaction networks varies from one species to another.

  17. False positive reduction in protein-protein interaction predictions using gene ontology annotations

    Directory of Open Access Journals (Sweden)

    Lin Yen-Han

    2007-07-01

    Full Text Available Abstract Background Many crucial cellular operations such as metabolism, signalling, and regulations are based on protein-protein interactions. However, the lack of robust protein-protein interaction information is a challenge. One reason for the lack of solid protein-protein interaction information is poor agreement between experimental findings and computational sets that, in turn, comes from huge false positive predictions in computational approaches. Reduction of false positive predictions and enhancing true positive fraction of computationally predicted protein-protein interaction datasets based on highly confident experimental results has not been adequately investigated. Results Gene Ontology (GO annotations were used to reduce false positive protein-protein interactions (PPI pairs resulting from computational predictions. Using experimentally obtained PPI pairs as a training dataset, eight top-ranking keywords were extracted from GO molecular function annotations. The sensitivity of these keywords is 64.21% in the yeast experimental dataset and 80.83% in the worm experimental dataset. The specificities, a measure of recovery power, of these keywords applied to four predicted PPI datasets for each studied organisms, are 48.32% and 46.49% (by average of four datasets in yeast and worm, respectively. Based on eight top-ranking keywords and co-localization of interacting proteins a set of two knowledge rules were deduced and applied to remove false positive protein pairs. The 'strength', a measure of improvement provided by the rules was defined based on the signal-to-noise ratio and implemented to measure the applicability of knowledge rules applying to the predicted PPI datasets. Depending on the employed PPI-predicting methods, the strength varies between two and ten-fold of randomly removing protein pairs from the datasets. Conclusion Gene Ontology annotations along with the deduced knowledge rules could be implemented to partially

  18. Positive maternal C-reactive protein predicts neonatal sepsis.

    Science.gov (United States)

    Jeon, Ji Hyun; Namgung, Ran; Park, Min Soo; Park, Koo In; Lee, Chul

    2014-01-01

    To evaluate the diagnostic performance of maternal inflammatory marker: C-reactive protein (CRP) in predicting early onset neonatal sepsis (that occurring within 72 hours after birth). 126 low birth weight newborns (gestation 32±3.2 wk, birth weight 1887±623 g) and their mothers were included. Neonates were divided into sepsis group (n=51) including both proven (positive blood culture) and suspected (negative blood culture but with more than 3 abnormal clinical signs), and controls (n=75). Mothers were subgrouped into CRP positive ≥1.22 mg/dL (n=48) and CRP negative neonatal sepsis according to maternal condition. Maternal CRP was significantly higher in neonatal sepsis group than in control (3.55±2.69 vs. 0.48±0.31 mg/dL, p=0.0001). Maternal CRP (cutoff value >1.22 mg/dL) had sensitivity 71% and specificity 84% for predicting neonatal sepsis. Maternal CRP positive group had more neonatal sepsis than CRP negative group (71% vs. 29%, pneonatal sepsis in maternal CRP positive group versus CRP negative group was 10.68 (95% confidence interval: 4.313-26.428, pneonatal sepsis significantly increased in the case of positive maternal CRP (≥1.22 mg/dL). In newborn of CRP positive mother, the clinician may be alerted to earlier evaluation for possible neonatal infection prior to development of sepsis.

  19. Position-dependent Effects of Polylysine on Sec Protein Transport*

    Science.gov (United States)

    Liang, Fu-Cheng; Bageshwar, Umesh K.; Musser, Siegfried M.

    2012-01-01

    The bacterial Sec protein translocation system catalyzes the transport of unfolded precursor proteins across the cytoplasmic membrane. Using a recently developed real time fluorescence-based transport assay, the effects of the number and distribution of positive charges on the transport time and transport efficiency of proOmpA were examined. As expected, an increase in the number of lysine residues generally increased transport time and decreased transport efficiency. However, the observed effects were highly dependent on the polylysine position in the mature domain. In addition, a string of consecutive positive charges generally had a more significant effect on transport time and efficiency than separating the charges into two or more charged segments. Thirty positive charges distributed throughout the mature domain resulted in effects similar to 10 consecutive charges near the N terminus of the mature domain. These data support a model in which the local effects of positive charge on the translocation kinetics dominate over total thermodynamic constraints. The rapid translocation kinetics of some highly charged proOmpA mutants suggest that the charge is partially shielded from the electric field gradient during transport, possibly by the co-migration of counter ions. The transport times of precursors with multiple positively charged sequences, or “pause sites,” were fairly well predicted by a local effect model. However, the kinetic profile predicted by this local effect model was not observed. Instead, the transport kinetics observed for precursors with multiple polylysine segments support a model in which translocation through the SecYEG pore is not the rate-limiting step of transport. PMID:22367204

  20. Poweo half-year 2006 earnings. Positive net income, implementation of the 1. steps of the industrial plan; Poweo resultats du 1. semestre 2006. Resultat net positif, mise en oeuvre des 1. etapes du plan industriel

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-09-15

    POWEO, the leading independent energy operator in France, presents in this document its key financial data and highlights for the first half of 2006: - Half-year revenue amounts to euro 119.4 m, multiplied by 3.4 compared to the same period last year; - The Energy Management activity has achieved a net margin of euro 34.3 m; - EBIT amounts to euro 6.2 m, compared to euro -2.9 m in the first half of 2005; - Net income amounts to euro 8.9 m, compared to euro -2.9 m in the first half of 2005; - Completion of the preliminary steps to the building of a first thermal power plant (CCGT) is close at hand, two other projects launched; - Strengthening of internal structures in view of the residential market opening up; - Outlook for 2006: total sales expected to reach euro 220 m and positive EBITDA; - LNG terminal building project in Le Havre.

  1. vaccination using profilin and NetB proteins in Montanide IMS adjuvant increases protective immunity against experimentally-induced necrotic enteritis

    Directory of Open Access Journals (Sweden)

    Hyun Soon Lillehoj

    2017-10-01

    Full Text Available Objective The effects of vaccinating 18-day-old chicken embryos with the combination of recombinant Eimeria profilin plus Clostridium perfringens (C. perfringens NetB proteins mixed in the Montanide IMS adjuvant on the chicken immune response to necrotic enteritis (NE were investigated using an Eimeria maxima (E. maxima/C. perfringens co-infection NE disease model that we previously developed. Methods Eighteen-day-old broiler embryos were injected with 100 μL of phosphate-buffered saline, profilin, profilin plus necrotic enteritis B-like (NetB, profilin plus NetB/Montanide adjuvant (IMS 106, and profilin plus Net-B/Montanide adjuvant (IMS 101. After post-hatch birds were challenged with our NE experimental disease model, body weights, intestinal lesions, serum antibody levels to NetB, and proinflammatory cytokine and chemokine mRNA levels in intestinal intraepithelial lymphocytes were measured. Results Chickens in ovo vaccinated with recombinant profilin plus NetB proteins/IMS106 and recombinant profilin plus NetB proteins/IMS101 showed significantly increased body weight gains and reduced gut damages compared with the profilin-only group, respectively. Greater antibody response to NetB toxin were observed in the profilin plus NetB/IMS 106, and profilin plus NetB/IMS 101 groups compared with the other three vaccine/adjuvant groups. Finally, diminished levels of transcripts encoding for proinflammatory cytokines such as lipopolysaccharide-induced tumor necrosis factor-α factor, tumor necrosis factor superfamily 15, and interleukin-8 were observed in the intestinal lymphocytes of chickens in ovo injected with profilin plus NetB toxin in combination with IMS 106, and profilin plus NetB toxin in combination with IMS 101 compared with profilin protein alone bird. Conclusion These results suggest that the Montanide IMS adjuvants potentiate host immunity to experimentally-induced avian NE when administered in ovo in conjunction with the profilin and

  2. Effects of light, temperature and canopy position on net photosynthesis and isoprene emission from sweetgum (Liquidambar styraciflua) leaves.

    Science.gov (United States)

    Harley, P.; Guenther, A.; Zimmerman, P.

    1996-01-01

    In June 1993, net photosynthetic rates, stomatal conductance and isoprene emission rates of sweetgum leaves (Liquidambar styraciflua L.) were measured at the top of the forest canopy (sun leaves) and within the canopy at a height of 8-10 m above ground level (shade leaves). Large differences in net photosynthetic rates and stomatal conductance were found between sun and shade leaves. Mean rates of isoprene emission, expressed on a leaf area basis, were significantly lower in shade leaves than in sun leaves (4.1 versus 17.1 nmol m(-2) s(-1)); however, because specific leaf area of sun leaves was lower than that of shade leaves (0.0121 versus 0.0334 m(2) g(-1)), the difference between sun and shade leaves was less, though still significant, when isoprene emissions were expressed on a dry mass basis (45.5 versus 29.0 micro g C g(-1) h(-1)). Saturation of both net photosynthesis and isoprene emission occurred at lower PPFDs in shade leaves than in sun leaves. The effect of leaf temperature on isoprene emissions also differed between sun and shade leaves. Sun leaves lost a significantly greater percentage of fixed carbon as isoprene than shade leaves. The leaf-level physiological measurements were used to derive parameters for a canopy-level isoprene flux model. The importance of incorporating differences between sun- and shade-leaf properties into existing models is discussed.

  3. Expression and Function of Transmembrane-4 Superfamily (Tetraspanin Proteins in Osteoclasts: Reciprocal Roles of Tspan-5 and NET-6 during Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Kaori Iwai

    2007-01-01

    Conclusions: These data indicate that a diversity of tetraspanins is expressed in osteoclast precursors, and that cell fusion during osteoclastogenesis is regulated by cooperation of distinct tetraspanin family proteins such as Tspan-5 and NET-6. This study indicates that functional alterations of tetraspanin family proteins may have therapeutic potential in diseases where osteoclasts play a major role, such as rheumatoid arthritis and osteoporosis.

  4. Systematic mutagenesis of genes encoding predicted autotransported proteins of Burkholderia pseudomallei identifies factors mediating virulence in mice, net intracellular replication and a novel protein conferring serum resistance.

    Directory of Open Access Journals (Sweden)

    Natalie R Lazar Adler

    Full Text Available Burkholderia pseudomallei is the causative agent of the severe tropical disease melioidosis, which commonly presents as sepsis. The B. pseudomallei K96243 genome encodes eleven predicted autotransporters, a diverse family of secreted and outer membrane proteins often associated with virulence. In a systematic study of these autotransporters, we constructed insertion mutants in each gene predicted to encode an autotransporter and assessed them for three pathogenesis-associated phenotypes: virulence in the BALB/c intra-peritoneal mouse melioidosis model, net intracellular replication in J774.2 murine macrophage-like cells and survival in 45% (v/v normal human serum. From the complete repertoire of eleven autotransporter mutants, we identified eight mutants which exhibited an increase in median lethal dose of 1 to 2-log10 compared to the isogenic parent strain (bcaA, boaA, boaB, bpaA, bpaC, bpaE, bpaF and bimA. Four mutants, all demonstrating attenuation for virulence, exhibited reduced net intracellular replication in J774.2 macrophage-like cells (bimA, boaB, bpaC and bpaE. A single mutant (bpaC was identified that exhibited significantly reduced serum survival compared to wild-type. The bpaC mutant, which demonstrated attenuation for virulence and net intracellular replication, was sensitive to complement-mediated killing via the classical and/or lectin pathway. Serum resistance was rescued by in trans complementation. Subsequently, we expressed recombinant proteins of the passenger domain of four predicted autotransporters representing each of the phenotypic groups identified: those attenuated for virulence (BcaA, those attenuated for virulence and net intracellular replication (BpaE, the BpaC mutant with defects in virulence, net intracellular replication and serum resistance and those displaying wild-type phenotypes (BatA. Only BcaA and BpaE elicited a strong IFN-γ response in a restimulation assay using whole blood from seropositive donors

  5. Petri Net-Based Model of Helicobacter pylori Mediated Disruption of Tight Junction Proteins in Stomach Lining during Gastric Carcinoma

    Directory of Open Access Journals (Sweden)

    Anam Naz

    2017-09-01

    Full Text Available Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins. Furthermore, the signaling pathways disrupted by dysregulated kinases, proteins and post-translational modifications are reviewed to design an abstracted computational model showing the situation-dependent dynamic behaviors of these biological processes and entities. A qualitative hybrid Petri Net model is therefore constructed showing the altered host pathways in the presence of virulence factor cytotoxin-associated gene A, leading to the disruption of tight junction proteins. The model is qualitative logic-based, which does not depend on any kinetic parameter and quantitative data and depends on knowledge derived from experiments. The designed model provides insights into the tight junction disruption and disease progression. Model is then verified by the available experimental data, nevertheless formal in vitro experimentation is a promising way to ensure its validation. The major findings propose that H. pylori activated kinases are responsible to trigger specific post translational modifications within tight junction proteins, at specific sites. These modifications may favor alterations in gastric barrier and provide a route to bacterial invasion into host cells.

  6. Positive effect of protein-supplemented hospital food on protein intake in patients at nutritional risk

    DEFF Research Database (Denmark)

    Munk, T; Beck, A M; Holst, M

    2014-01-01

    BACKGROUND: New evidence indicates that increased dietary protein ingestion promotes health and recovery from illness, and also maintains functionality in older adults. The present study aimed to investigate whether a novel food service concept with protein-supplementation would increase protein ...... of hospital stay did not differ between groups. CONCLUSIONS: The novel food service concept had a significant positive impact on overall protein intake and on weight-adjusted energy intake in hospitalised patients at nutritional risk....... and energy intake in hospitalised patients at nutritional risk. METHODS: A single-blinded randomised controlled trial was conducted. Eighty-four participants at nutritional risk, recruited from the departments of Oncology, Orthopaedics and Urology, were included. The intervention group (IG) received...... the protein-supplemented food service concept. The control group (CG) received the standard hospital menu. Primary outcome comprised the number of patients achieving ≥75% of energy and protein requirements. Secondary outcomes comprised mean energy and protein intake, body weight, handgrip strength and length...

  7. Targeting Neuroblastoma Cell Surface Proteins: Recommendations for Homology Modeling of hNET, ALK, and TrkB.

    Science.gov (United States)

    Haddad, Yazan; Heger, Zbyněk; Adam, Vojtech

    2017-01-01

    Targeted therapy is a promising approach for treatment of neuroblastoma as evident from the large number of targeting agents employed in clinical practice today. In the absence of known crystal structures, researchers rely on homology modeling to construct template-based theoretical structures for drug design and testing. Here, we discuss three candidate cell surface proteins that are suitable for homology modeling: human norepinephrine transporter (hNET), anaplastic lymphoma kinase (ALK), and neurotrophic tyrosine kinase receptor 2 (NTRK2 or TrkB). When choosing templates, both sequence identity and structure quality are important for homology modeling and pose the first of many challenges in the modeling process. Homology modeling of hNET can be improved using template models of dopamine and serotonin transporters instead of the leucine transporter (LeuT). The extracellular domains of ALK and TrkB are yet to be exploited by homology modeling. There are several idiosyncrasies that require direct attention throughout the process of model construction, evaluation and refinement. Shifts/gaps in the alignment between the template and target, backbone outliers and side-chain rotamer outliers are among the main sources of physical errors in the structures. Low-conserved regions can be refined with loop modeling method. Residue hydrophobicity, accessibility to bound metals or glycosylation can aid in model refinement. We recommend resolving these idiosyncrasies as part of "good modeling practice" to obtain highest quality model. Decreasing physical errors in protein structures plays major role in the development of targeting agents and understanding of chemical interactions at the molecular level.

  8. JiffyNet: a web-based instant protein network modeler for newly sequenced species

    OpenAIRE

    Kim, Eiru; Kim, Hanhae; Lee, Insuk

    2013-01-01

    Revolutionary DNA sequencing technology has enabled affordable genome sequencing for numerous species. Thousands of species already have completely decoded genomes, and tens of thousands more are in progress. Naturally, parallel expansion of the functional parts list library is anticipated, yet genome-level understanding of function also requires maps of functional relationships, such as functional protein networks. Such networks have been constructed for many sequenced species including comm...

  9. BMRF-Net: a software tool for identification of protein interaction subnetworks by a bagging Markov random field-based method.

    Science.gov (United States)

    Shi, Xu; Barnes, Robert O; Chen, Li; Shajahan-Haq, Ayesha N; Hilakivi-Clarke, Leena; Clarke, Robert; Wang, Yue; Xuan, Jianhua

    2015-07-15

    Identification of protein interaction subnetworks is an important step to help us understand complex molecular mechanisms in cancer. In this paper, we develop a BMRF-Net package, implemented in Java and C++, to identify protein interaction subnetworks based on a bagging Markov random field (BMRF) framework. By integrating gene expression data and protein-protein interaction data, this software tool can be used to identify biologically meaningful subnetworks. A user friendly graphic user interface is developed as a Cytoscape plugin for the BMRF-Net software to deal with the input/output interface. The detailed structure of the identified networks can be visualized in Cytoscape conveniently. The BMRF-Net package has been applied to breast cancer data to identify significant subnetworks related to breast cancer recurrence. The BMRF-Net package is available at http://sourceforge.net/projects/bmrfcjava/. The package is tested under Ubuntu 12.04 (64-bit), Java 7, glibc 2.15 and Cytoscape 3.1.0. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Total protein, albumin and low-molecular-weight protein excretion in HIV-positive patients

    Directory of Open Access Journals (Sweden)

    Campbell Lucy J

    2012-08-01

    Full Text Available Abstract Background Chronic kidney disease is common in HIV positive patients and renal tubular dysfunction has been reported in those receiving combination antiretroviral therapy (cART. Tenofovir (TFV in particular has been linked to severe renal tubular disease as well as proximal tubular dysfunction. Markedly elevated urinary concentrations of retinal-binding protein (RBP have been reported in patients with severe renal tubular disease, and low-molecular-weight proteins (LMWP such as RBP may be useful in clinical practice to assess renal tubular function in patients receiving TFV. We analysed 3 LMWP as well as protein and albumin in the urine of a sample of HIV positive patients. Methods In a cross-sectional fashion, total protein, albumin, RBP, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL were quantified in random urine samples of 317 HIV positive outpatients and expressed as the ratio-to-creatinine (RBPCR, CCR and NGALCR. Exposure to cART was categorised as none, cART without TFV, and cART containing TFV and a non-nucleoside reverse-transcriptase-inhibitor (TFV/NNRTI or TFV and a protease-inhibitor (TFV/PI. Results Proteinuria was present in 10.4 % and microalbuminuria in 16.7 % of patients. Albumin accounted for approximately 10 % of total urinary protein. RBPCR was within the reference range in 95 % of patients while NGALCR was elevated in 67 % of patients. No overall differences in urine protein, albumin, and LMWP levels were observed among patients stratified by cART exposure, although a greater proportion of patients exposed to TFV/PI had RBPCR >38.8 μg/mmol (343 μg/g (p = 0.003. In multivariate analyses, black ethnicity (OR 0.43, 95 % CI 0.24, 0.77 and eGFR 2 (OR 3.54, 95 % CI 1.61, 7.80 were independently associated with upper quartile (UQ RBPCR. RBPCR correlated well to CCR (r2 = 0.71, but not to NGALCR, PCR or ACR. Conclusions In HIV positive patients, proteinuria was predominantly of

  11. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET)

    DEFF Research Database (Denmark)

    Chan, Arlene; Delaloge, Suzette; Holmes, Frankie A

    2016-01-01

    breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria were amended on Feb 25, 2010, to include patients with stage 2-3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously. Patients were...... randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive [oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen...

  12. Applicability of energy-positive net-zero water management in Alaska: technology status and case study.

    Science.gov (United States)

    Wu, Tingting; Englehardt, James D; Guo, Tianjiao; Gassie, Lucien; Dotson, Aaron

    2017-11-22

    Challenges of water and wastewater management in Alaska include the potential need for above-grade and freeze-protected piping, high unit energy costs and, in many rural areas, low population density and median annual income. However, recently developed net-zero water (NZW), i.e., nearly closed-loop, direct potable water reuse systems, can retain the thermal energy in municipal wastewater, producing warm treated potable water without the need for substantial water re-heating, heat pumping or transfer, or additional energy conversion. Consequently, these systems are projected to be capable of saving more energy than they use in water treatment and conveyance, in the temperate USA. In this paper, NZW technology is reviewed in terms of potential applicability in Alaska by performing a hypothetical case study for the city of Fairbanks, Alaska. Results of this paper study indicate that in municipalities of Alaska with local engineering and road access, the use of NZW systems may provide an energy-efficient water service option. In particular, case study modeling suggests hot water energy savings are equivalent to five times the energy used for treatment, much greater savings than in mid-latitudes, due largely to the substantially higher energy needed for heating water from a conventional treatment system and lack of need for freeze-protected piping. Further study of the applicability of NZW technology in cold regions, with expanded evaluation in terms of system-wide lifecycle cost, is recommended.

  13. A flow cytometry-based screen of nuclear envelope transmembrane proteins identifies NET4/Tmem53 as involved in stress-dependent cell cycle withdrawal.

    Directory of Open Access Journals (Sweden)

    Nadia Korfali

    2011-04-01

    Full Text Available Disruption of cell cycle regulation is one mechanism proposed for how nuclear envelope protein mutation can cause disease. Thus far only a few nuclear envelope proteins have been tested/found to affect cell cycle progression: to identify others, 39 novel nuclear envelope transmembrane proteins were screened for their ability to alter flow cytometry cell cycle/DNA content profiles when exogenously expressed. Eight had notable effects with seven increasing and one decreasing the 4N:2N ratio. We subsequently focused on NET4/Tmem53 that lost its effects in p53(-/- cells and retinoblastoma protein-deficient cells. NET4/TMEM53 knockdown by siRNA altered flow cytometry cell cycle/DNA content profiles in a similar way as overexpression. NET4/TMEM53 knockdown did not affect total retinoblastoma protein levels, unlike nuclear envelope-associated proteins Lamin A and LAP2α. However, a decrease in phosphorylated retinoblastoma protein was observed along with a doubling of p53 levels and a 7-fold increase in p21. Consequently cells withdrew from the cell cycle, which was confirmed in MRC5 cells by a drop in the percentage of cells expressing Ki-67 antigen and an increase in the number of cells stained for ß-galactosidase. The ß-galactosidase upregulation suggests that cells become prematurely senescent. Finally, the changes in retinoblastoma protein, p53, and p21 resulting from loss of NET4/Tmem53 were dependent upon active p38 MAP kinase. The finding that roughly a fifth of nuclear envelope transmembrane proteins screened yielded alterations in flow cytometry cell cycle/DNA content profiles suggests a much greater influence of the nuclear envelope on the cell cycle than is widely held.

  14. Synergistic effect of embryo vaccination with Eimeria profilin and Clostridium perfringens NetB proteins on inducing protective immunity against necrotic enteritis in broiler chickens

    Science.gov (United States)

    The effects of embryo vaccination with Eimeria profilin plus Clostridium perfringens NetB toxin proteins in combination with the Montanide IMS-OVO adjuvant on the chicken immune response to necrotic enteritis were investigated using an E. maxima/C. perfringens co-infection model. Eighteen-day-old br...

  15. Tocilizumab potentially prevents bone loss in patients with anticitrullinated protein antibody-positive rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Yi-Ming Chen

    Full Text Available Rheumatoid arthritis (RA is associated with a high risk of osteoporosis and fracture. Interleukin (IL-6 inhibitors may suppress osteoclast activation. Anticitrullinated protein antibody (ACPA titers are inversely associated with bone mineral density (BMD. However, the differential effect of ACPA on bone turnover marker (BTM and BMD changes after IL-6 inhibition remains unclear. This prospective study recruited patients with active RA with inadequate response to methotrexate or biologics. BMD was measured before and after 2-year tocilizumab (TCZ treatment. Serum osteocalcin, N-terminal propeptide of type I collagen (P1NP, and C-terminal cross-linking telopeptide of type I collagen (CTX levels were assessed at the baseline and after treatment. We enrolled 76 patients with RA (89.5% women, age: 57.2 ± 13.3 years receiving TCZ. The 28-joint disease activity score was negatively correlated with BMD and T-scores of the lumbar spine and bilateral femoral neck. ACPA-positive patients had lower lumbar spine and femoral neck T-scores. After 2-year TCZ treatment, CTX levels significantly decreased (0.32 ± 0.21 vs. 0.26 ± 0.17, p = 0.038. Femoral neck BMD increased significantly (0.71 ± 0.22 vs. 0.69 ± 0.55, p = 0.008. Decreased CTX levels and improved BMD were observed only in ACPA-positive patients. After treatment, femoral neck BMD significantly increased only in patients receiving a glucocorticoid dose of ≥5 mg/day. Two-year TCZ treatment reduced bone resorption and increased femoral BMD in ACPA-positive patients. The net effects of glucocorticoids and IL-6 inhibition on BMD imply that strict inflammation control might affect bone metabolism.

  16. Association of alpha-amylase and the R1 protein with starch granules precedes the initiation of net starch degradation in turions of Spirodela polyrhiza.

    Science.gov (United States)

    Reimann, Rezarta; Ritte, Gerhard; Steup, Martin; Appenroth, Klaus-J

    2002-01-01

    In turions of Spirodela polyrhiza (L.) Schleiden, net degradation of storage starch is controlled by a special low fluence response of phytochrome requiring illumination for several days. This light effect has been used to study protein-starch interactions that occur prior to and during net degradation of starch. Following various pretreatments on S. polyrhiza turions, native starch granules were isolated and two fractions of starch-related proteins were distinguished: proteins enclosed within the starch particles (starch-internalized proteins) and those attached to the surface (starch-associated proteins). The pattern of starch-associated proteins as resolved by SDS-PAGE was more complex than that of starch-internalized proteins and varied depending upon the pretreatment of the turions. Two starch associated proteins were identified immunochemically as alpha-amylase (EC 3.2.1.1) and the R1 protein (Lorberth et al. (1998) Nature Biotechnology 16: 473-477). Dark-pretreatment of non-dormant turions does not induce starch net degradation. Under these conditions, alpha-amylase and R1 were bound to the surface of the starch granules. Continuous illumination with red light induces a rapid degradation of starch. Within the first 24 h of illumination the level of starch-associated alpha-amylase transiently increased and subsequently decreased rapidly. Similarly, the amount of the starch-associated R1 also decreased during illumination. The dissociation of both alpha-amylase and R1 from the starch granules preceded the decrease in starch content. However, binding of the two proteins to starch granules remained unchanged when the turions did not perform net starch degradation (as observed during continuous darkness, orthophosphate deficiency, or dormancy of the turions). Thus, during net starch degradation, so far unidentified changes are postulated to occur at the surface of the starch particles that are relevant for protein binding. This conclusion was supported by in

  17. Accounting for the effects of a ruminal nitrogen deficiency within the structure of the Cornell Net Carbohydrate and Protein System.

    Science.gov (United States)

    Tedeschi, L O; Fox, D G; Russell, J B

    2000-06-01

    The Cornell Net Carbohydrate and Protein System (CNCPS) prediction of fiber digestion and microbial mass production from ruminally degraded carbohydrate has been adjusted to accommodate a ruminal N deficiency. The steps for the adjustment are as follows: 1) the ruminal available peptide and ammonia pools are used to determine the N allowable microbial growth; 2) this value is subtracted from the energy allowable microbial growth to obtain the reduction in microbial mass; 3) this mass reduction is allocated between pools of bacteria digesting fiber (FC) and nonfiber (NFC) carbohydrate according to their original proportions in the energy allowable microbial growth; 4) the reduction in fermented FC is computed as the FC bacterial mass reduction divided by its yield (g bacteria/g FC digested); and 5) this reduction is added to the FC fraction escaping the rumen. Five published studies included information that allowed us to evaluate the response of animals to added dietary N. These evaluations compared observed and CNCPS-predicted ADG with and without this adjustment. The adjustment decreased the CNCPS overprediction of ADG from 19.2 to 4.7%, mean bias declined from .16 to .04 kg/d, and the r2 of the regression between observed and metabolizable energy (ME) or metabolizable protein allowable ADG was increased from .83 to .88 with the adjustment. When the observed dry matter intake was regressed against CNCPS-predicted DMI with an adjustment for reduction in cell wall digestibility, the r2 was increased from .77 to .88. These results indicated the adjustment for ruminal nitrogen deficiency increased the accuracy of the CNCPS model in evaluating diets of growing animals when ruminally degraded N is deficient.

  18. Positive effects of duckweed polycultures on starch and protein accumulation.

    Science.gov (United States)

    Li, Yang; Zhang, Fantao; Daroch, Maurycy; Tang, Jie

    2016-10-01

    The effect of duckweed species composition (Lemna aequinoctialis 5505, Landoltia punctata 5506 and Spirodela polyrhiza 5507) in polyculture and monoculture on biomass and starch/protein content were investigated at different levels of temperature, light intensity, nitrogen and phosphorus concentrations. The three growth parameters significantly affect duckweed biomass accumulation. Different combinations of duckweed species greatly varied in starch/protein content. Although all the polycultures showed a median relative growth rate and the majority of the polycultures showed a median and starch/protein content as compared with their respective monocultures, some of the polycultures were found to promote the accumulation of starch/protein at different growth conditions. These findings indicated that proper combination of duckweed species could facilitate desirable biomass accumulation and improve biomass quality. The present study provides useful references for future large-scale duckweed cultivation. © 2016 The Author(s).

  19. INCREASING PRODUCTION OF PROTEINS IN GRAM-POSITIVE MICROORGANISMS

    NARCIS (Netherlands)

    Quax, Wim; Caldwell, Robert M

    1999-01-01

    The present invention relates to secretion in Gram-positive microorganisms. The present invention provides the nuclei acid and amino acid sequences for the Bacillus subtilis disulfide bond isomerases, Dsb1 and Dsb2. The present invention also provides means for increasing the secretion of

  20. Teaching Tennis for Net Success.

    Science.gov (United States)

    Young, Bryce

    1989-01-01

    A program for teaching tennis to beginners, NET (Net Easy Teaching) is described. The program addresses three common needs shared by tennis students: active involvement in hitting the ball, clearing the net, and positive reinforcement. A sample lesson plan is included. (IAH)

  1. Wyoming: "A Net Positive Session"

    OpenAIRE

    Schuhmann, Robert A.

    2016-01-01

    Wyoming’s general legislative session concluded March 6, 2015 with the passage of 185 bills and nearly $285 million in new spending.[1] Because this was a general session rather than a budget session, very few budget issues were addressed. However, key budgetary matters this year included: (1) addressing a $222 million shortfall brought about by falling oil prices and (2) several new capital construction projects spread across the state and at the University of Wyoming. Wyoming democrats in t...

  2. Net Locality

    DEFF Research Database (Denmark)

    de Souza e Silva, Adriana Araujo; Gordon, Eric

    Provides an introduction to the new theory of Net Locality and the profound effect on individuals and societies when everything is located or locatable. Describes net locality as an emerging form of location awareness central to all aspects of digital media, from mobile phones, to Google Maps...... of emerging technologies, from GeoCities to GPS, Wi-Fi, Wiki Me, and Google Android....

  3. Net Neutrality

    DEFF Research Database (Denmark)

    Savin, Andrej

    2017-01-01

    Repealing “net neutrality” in the US will have no bearing on Internet freedom or security there or anywhere else.......Repealing “net neutrality” in the US will have no bearing on Internet freedom or security there or anywhere else....

  4. Protein intake during hemodialysis maintains a positive whole body protein balance in chronic hemodialysis patients

    NARCIS (Netherlands)

    Veeneman, JM; Kingma, HA; Boer, TS; Stellaard, F; De Jong, PE; Reijngoud, DJ; Huisman, RM

    Protein energy malnutrition is present in 18 to 56% of hemodialysis patients. Because hemodialysis has been regarded as a catabolic event, we studied whether consumption of a protein- and energy-nriched meal improves the whole body protein balance during dialysis in chronic hemodialysis (CHD)

  5. NetTurnP--neural network prediction of beta-turns by use of evolutionary information and predicted protein sequence features.

    Directory of Open Access Journals (Sweden)

    Bent Petersen

    Full Text Available UNLABELLED: β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino acid sequence. The individual β-turn types I, I', II, II', VIII, VIa1, VIa2, VIba and IV have been predicted based on classifications by PROMOTIF, and the two-class prediction of β-turn or not is a superset comprised of all β-turn types. The performance is evaluated using a golden set of non-homologous sequences known as BT426. Our two-class prediction method achieves a performance of: MCC=0.50, Qtotal=82.1%, sensitivity=75.6%, PPV=68.8% and AUC=0.864. We have compared our performance to eleven other prediction methods that obtain Matthews correlation coefficients in the range of 0.17-0.47. For the type specific β-turn predictions, only type I and II can be predicted with reasonable Matthews correlation coefficients, where we obtain performance values of 0.36 and 0.31, respectively. CONCLUSION: The NetTurnP method has been implemented as a webserver, which is freely available at http://www.cbs.dtu.dk/services/NetTurnP/. NetTurnP is the only available webserver that allows submission of multiple sequences.

  6. NetTurnP – Neural Network Prediction of Beta-turns by Use of Evolutionary Information and Predicted Protein Sequence Features

    DEFF Research Database (Denmark)

    Petersen, Bent; Lundegaard, Claus; Petersen, Thomas Nordahl

    2010-01-01

    is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino......β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method...... NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which...

  7. The role of hydrophobic interactions in positioning of peripheral proteins in membranes

    Directory of Open Access Journals (Sweden)

    Lomize Mikhail A

    2007-06-01

    Full Text Available Abstract Background Three-dimensional (3D structures of numerous peripheral membrane proteins have been determined. Biological activity, stability, and conformations of these proteins depend on their spatial positions with respect to the lipid bilayer. However, these positions are usually undetermined. Results We report the first large-scale computational study of monotopic/peripheral proteins with known 3D structures. The optimal translational and rotational positions of 476 proteins are determined by minimizing energy of protein transfer from water to the lipid bilayer, which is approximated by a hydrocarbon slab with a decadiene-like polarity and interfacial regions characterized by water-permeation profiles. Predicted membrane-binding sites, protein tilt angles and membrane penetration depths are consistent with spin-labeling, chemical modification, fluorescence, NMR, mutagenesis, and other experimental studies of 53 peripheral proteins and peptides. Experimental membrane binding affinities of peripheral proteins were reproduced in cases that did not involve a helix-coil transition, specific binding of lipids, or a predominantly electrostatic association. Coordinates of all examined peripheral proteins and peptides with the calculated hydrophobic membrane boundaries, subcellular localization, topology, structural classification, and experimental references are available through the Orientations of Proteins in Membranes (OPM database. Conclusion Positions of diverse peripheral proteins and peptides in the lipid bilayer can be accurately predicted using their 3D structures that represent a proper membrane-bound conformation and oligomeric state, and have membrane binding elements present. The success of the implicit solvation model suggests that hydrophobic interactions are usually sufficient to determine the spatial position of a protein in the membrane, even when electrostatic interactions or specific binding of lipids are substantial. Our

  8. NetSig

    DEFF Research Database (Denmark)

    Horn, Heiko; Lawrence, Michael S; Chouinard, Candace R

    2018-01-01

    Methods that integrate molecular network information and tumor genome data could complement gene-based statistical tests to identify likely new cancer genes; but such approaches are challenging to validate at scale, and their predictive value remains unclear. We developed a robust statistic (Net......Sig) that integrates protein interaction networks with data from 4,742 tumor exomes. NetSig can accurately classify known driver genes in 60% of tested tumor types and predicts 62 new driver candidates. Using a quantitative experimental framework to determine in vivo tumorigenic potential in mice, we found that Net......Sig candidates induce tumors at rates that are comparable to those of known oncogenes and are ten-fold higher than those of random genes. By reanalyzing nine tumor-inducing NetSig candidates in 242 patients with oncogene-negative lung adenocarcinomas, we find that two (AKT2 and TFDP2) are significantly amplified...

  9. Direct effects of TNF-α on local fuel metabolism and cytokine levels in the placebo controlled bilaterally infused human leg; increased insulin sensitivity, increased net protein breakdown and increased IL-6 release

    DEFF Research Database (Denmark)

    Bach, Ermina; Nielsen, Bent Roni Ranghøj; Vendelbo, Mikkel H

    2013-01-01

    . Insulin and protein signaling in muscle biopsies was not affected by TNF-α. TNF-α directly increased net muscle protein loss, which may contribute to cachexia and general protein loss during severe illness. The finding of increased insulin sensitivity, which could relate to IL-6, is of major clinical...

  10. RESTful NET

    CERN Document Server

    Flanders, Jon

    2008-01-01

    RESTful .NET is the first book that teaches Windows developers to build RESTful web services using the latest Microsoft tools. Written by Windows Communication Foundation (WFC) expert Jon Flanders, this hands-on tutorial demonstrates how you can use WCF and other components of the .NET 3.5 Framework to build, deploy and use REST-based web services in a variety of application scenarios. RESTful architecture offers a simpler approach to building web services than SOAP, SOA, and the cumbersome WS- stack. And WCF has proven to be a flexible technology for building distributed systems not necessa

  11. Identification and characterization of nonhistone chromatin proteins: human positive coactivator 4 as a candidate.

    Science.gov (United States)

    Kumari, Sujata; Das, Chandrima; Sikder, Sweta; Kumar, Manoj; Bachu, Mahesh; Ranga, Udaykumar; Kundu, Tapas K

    2015-01-01

    The highly dynamic nucleoprotein structure of eukaryotic genome is organized in an ordered fashion, the unit of which is the nucleosome. The nucleosome is composed of core histones and DNA of variable size wrapped around it. Apart from the histone proteins, several nonhistone proteins also interact with the complex consisting of the DNA, the core and linker histones conferring highly regulated fluidity on the chromatin and permitting fine tuning of its functions. The nonhistone proteins are multifunctional and accentuate diverse cellular outcomes. In spite of the technical challenges, the architectural role of the nonhistone proteins altering the topology of the chromatin has been studied extensively. To appreciate the significance of the chromatin for genome function, it is essential to examine the role of the nonhistone proteins in different physiological conditions. Here, taking the example of a highly abundant chromatin protein, PC4 (Positive coactivator 4), we describe strategies for the identification of the chromatin-associated proteins and their structural and functional characterization.

  12. Translocation of proteins across the cell envelope of Gram-positive bacteria

    NARCIS (Netherlands)

    Wely, Karel H.M. van; Swaving, Jelto; Freudl, Roland; Driessen, Arnold J.M.

    2001-01-01

    In contrast to Gram-negative bacteria, secretory proteins of Gram-positive bacteria only need to traverse a single membrane to enter the extracellular environment. For this reason, Gram-positive bacteria (e.g. various Bacillus species) are often used in industry for the commercial production of

  13. Positive effect of protein-supplemented hospital food on protein intake in patients at nutritional risk: a randomised controlled trial.

    Science.gov (United States)

    Munk, T; Beck, A M; Holst, M; Rosenbom, E; Rasmussen, H H; Nielsen, M A; Thomsen, T

    2014-04-01

    New evidence indicates that increased dietary protein ingestion promotes health and recovery from illness, and also maintains functionality in older adults. The present study aimed to investigate whether a novel food service concept with protein-supplementation would increase protein and energy intake in hospitalised patients at nutritional risk. A single-blinded randomised controlled trial was conducted. Eighty-four participants at nutritional risk, recruited from the departments of Oncology, Orthopaedics and Urology, were included. The intervention group (IG) received the protein-supplemented food service concept. The control group (CG) received the standard hospital menu. Primary outcome comprised the number of patients achieving ≥75% of energy and protein requirements. Secondary outcomes comprised mean energy and protein intake, body weight, handgrip strength and length of hospital stay. In IG, 76% versus 70% CG patients reached ≥75% of their energy requirements (P = 0.57); 66% IG versus 30% CG patients reached ≥75% of their protein requirements (P = 0.001). The risk ratio for achieving ≥75% of protein requirements: 2.2 (95% confidence interval = 1.3-3.7); number needed to treat = 3 (95% confidence interval = 2-6). IG had a higher mean intake of energy and protein when adjusted for body weight (CG: 82 kJ kg(-1) versus IG: 103 kJ kg(-1) , P = 0.013; CG: 0.7 g protein kg(-1) versus 0.9 g protein kg(-1) , P = 0.003). Body weight, handgrip strength and length of hospital stay did not differ between groups. The novel food service concept had a significant positive impact on overall protein intake and on weight-adjusted energy intake in hospitalised patients at nutritional risk. © 2014 The British Dietetic Association Ltd.

  14. Positive selection neighboring functionally essential sites and disease-implicated regions of mammalian reproductive proteins.

    LENUS (Irish Health Repository)

    Morgan, Claire C

    2010-01-01

    ABSTRACT: BACKGROUND: Reproductive proteins are central to the continuation of all mammalian species. The evolution of these proteins has been greatly influenced by environmental pressures induced by pathogens, rival sperm, sexual selection and sexual conflict. Positive selection has been demonstrated in many of these proteins with particular focus on primate lineages. However, the mammalia are a diverse group in terms of mating habits, population sizes and germ line generation times. We have examined the selective pressures at work on a number of novel reproductive proteins across a wide variety of mammalia. RESULTS: We show that selective pressures on reproductive proteins are highly varied. Of the 10 genes analyzed in detail, all contain signatures of positive selection either across specific sites or in specific lineages or a combination of both. Our analysis of SP56 and Col1a1 are entirely novel and the results show positively selected sites present in each gene. Our findings for the Col1a1 gene are suggestive of a link between positive selection and severe disease type. We find evidence in our dataset to suggest that interacting proteins are evolving in symphony: most likely to maintain interacting functionality. CONCLUSION: Our in silico analyses show positively selected sites are occurring near catalytically important regions suggesting selective pressure to maximize efficient fertilization. In those cases where a mechanism of protein function is not fully understood, the sites presented here represent ideal candidates for mutational study. This work has highlighted the widespread rate heterogeneity in mutational rates across the mammalia and specifically has shown that the evolution of reproductive proteins is highly varied depending on the species and interacting partners. We have shown that positive selection and disease are closely linked in the Col1a1 gene.

  15. Petri Nets

    Indian Academy of Sciences (India)

    Associate Professor of. Computer Science and. Automation at the Indian. Institute of Science,. Bangalore. His research interests are broadly in the areas of stochastic modeling and scheduling methodologies for future factories; and object oriented modeling. GENERAL I ARTICLE. Petri Nets. 1. Overview and Foundations.

  16. Petri Nets

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 8. Petri Nets - Overview and Foundations. Y Narahari. General Article Volume 4 Issue 8 August 1999 pp ... Author Affiliations. Y Narahari1. Department ot Computer Science and Automation, Indian Institute of Science, Bangalore 560 012, India.

  17. Effect of pods' position on the protein content in soybean grains at low latitude

    Directory of Open Access Journals (Sweden)

    Paulo Victor Gomes Sales

    2016-12-01

    Full Text Available Soybean grains have a high protein content, which can vary depending on various factors, as the pods' position throughout the plant. In this sense, aiming to study the effect of pods' position on the main stem of the plant for grades of soybean proteins, It has been accomplished in the years 2010 and 2011, a trial with ten soybean cultivars in the experimental area of the Federal University of Tocantins in Palmas. The experimental area was randomized blocks with 30 treatments and three replications. Treatments were arranged in one a split plot, being allocated in Ten cultivars plots (BRS Valuable, P98Y51, P98Y70, P99R03, M8527RR, M8925RR, M9144RR, M8867RR, and TMG103RR, and the sub plots In the pods' position on the plant (upper third, intermediate, and basal third. According to the results, we can conclude that there is variability among the pods' position. The grains located in the median and apical plant showed a trend of higher protein content. Cultivar P98Y70 showed the highest protein value. In the sampling grain for protein quantitation, it is recommended to use grains of pods located at the same position of the plant.

  18. NETS FOR PEACH PROTECTED CULTIVATION

    Directory of Open Access Journals (Sweden)

    Evelia Schettini

    2012-06-01

    Full Text Available The aim of this paper was to investigate the radiometric properties of coloured nets used to protect a peach cultivation. The modifications of the solar spectral distribution, mainly in the R and FR wavelength band, influence plant photomorphogenesis by means of the phytochrome and cryptochrome. The phytochrome response is characterized in terms of radiation rate in the red wavelengths (R, 600-700 nm to that in the farred radiation (FR, 700-800 nm, i.e. the R/FR ratio. The effects of the blue radiation (B, 400-500 nm is investigated by the ratio between the blue radiation and the far-red radiation, i.e. the B/FR ratio. A BLUE net, a RED net, a YELLOW net, a PEARL net, a GREY net and a NEUTRAL net were tested in Bari (Italy, latitude 41° 05’ N. Peach trees were located in pots inside the greenhouses and in open field. The growth of the trees cultivated in open field was lower in comparison to the growth of the trees grown under the nets. The RED, PEARL, YELLOW and GREY nets increased the growth of the trees more than the other nets. The nets positively influenced the fruit characteristics, such as fruit weight and flesh firmness.

  19. Leaving home ain't easy: protein export systems in Gram-positive bacteria.

    Science.gov (United States)

    Freudl, Roland

    2013-01-01

    Transport of proteins into or across biological membranes is catalyzed by membrane-bound transport machineries. In Gram-positive bacteria, the vast majority of proteins are exported out of the cytosol by the conserved general secretion (Sec) system or, alternatively, by the twin-arginine translocation (Tat) system, that closely resemble their well-studied counterparts in Gram-negative bacteria. Besides these common major export routes, additional unique protein export systems (such as accessory Sec2 systems and/or type VII/WXG100 secretion systems) exist in some Gram-positive bacteria that are specifically involved in the secretion of limited subsets of proteins. Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  20. Analysis of Exocyst-Positive Organelle (EXPO)-Mediated Unconventional Protein Secretion (UPS) in Plant Cells.

    Science.gov (United States)

    Ding, Yu; Wang, Juan

    2017-01-01

    Unconventional protein secretion (UPS) together with conventional protein secretion (CPS) is responsible for protein secretion in plants. We have previously identified a novel UPS pathway in plants, which is mediated by exocyst-positive organelle-EXPO. Here, we describe detailed protocols to study UPS in plants by using Arabidopsis protoplasts or transgenic suspension cells, expressing the EXPO marker Exo70E2-XFP, as materials. Via drug and osmotic treatment plus secretion assay, we illustrate several major methods to analyze EXPO-mediated UPS in plant cells, which also supplys mining tools for similar study.

  1. Widespread Positive Selection Drives Differentiation of Centromeric Proteins in the Drosophila melanogaster subgroup.

    Science.gov (United States)

    Beck, Emily A; Llopart, Ana

    2015-11-25

    Rapid evolution of centromeric satellite repeats is thought to cause compensatory amino acid evolution in interacting centromere-associated kinetochore proteins. Cid, a protein that mediates kinetochore/centromere interactions, displays particularly high amino acid turnover. Rapid evolution of both Cid and centromeric satellite repeats led us to hypothesize that the apparent compensatory evolution may extend to interacting partners in the Condensin I complex (i.e., SMC2, SMC4, Cap-H, Cap-D2, and Cap-G) and HP1s. Missense mutations in these proteins often result in improper centromere formation and aberrant chromosome segregation, thus selection for maintained function and coevolution among proteins of the complex is likely strong. Here, we report evidence of rapid evolution and recurrent positive selection in seven centromere-associated proteins in species of the Drosophila melanogaster subgroup, and further postulate that positive selection on these proteins could be a result of centromere drive and compensatory changes, with kinetochore proteins competing for optimal spindle attachment.

  2. Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry Site and Positively Regulates Viral Protein Translation.

    Science.gov (United States)

    Zhang, Hua; Song, Lei; Cong, Haolong; Tien, Po

    2015-10-01

    Enterovirus 71 (EV71) recruits various cellular factors to assist in the replication and translation of its genome. Identification of the host factors involved in the EV71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. In this study, we demonstrated that the cellular factor 68-kDa Src-associated protein in mitosis (Sam68) acts as an internal ribosome entry site (IRES) trans-acting factor (ITAF) that binds specifically to the EV71 5' untranslated region (5'UTR). Interaction sites in both the viral IRES (stem-loops IV and V) and the heterogeneous nuclear ribonucleoprotein K homology (KH) domain of Sam68 protein were further mapped using an electrophoretic mobility shift assay (EMSA) and biotin RNA pulldown assay. More importantly, dual-luciferase (firefly) reporter analysis suggested that overexpression of Sam68 positively regulated IRES-dependent translation of virus proteins. In contrast, both IRES activity and viral protein translation significantly decreased in Sam68 knockdown cells compared with the negative-control cells treated with short hairpin RNA (shRNA). However, downregulation of Sam68 did not have a significant inhibitory effect on the accumulation of the EV71 genome. Moreover, Sam68 was redistributed from the nucleus to the cytoplasm and interacts with cellular factors, such as poly(rC)-binding protein 2 (PCBP2) and poly(A)-binding protein (PABP), during EV71 infection. The cytoplasmic relocalization of Sam68 in EV71-infected cells may be involved in the enhancement of EV71 IRES-mediated translation. Since Sam68 is known to be a RNA-binding protein, these results provide direct evidence that Sam68 is a novel ITAF that interacts with EV71 IRES and positively regulates viral protein translation. The nuclear protein Sam68 is found as an additional new host factor that interacts with the EV71 IRES during infection and could potentially

  3. Computing highly correlated positions using mutual information and graph theory for G protein-coupled receptors.

    Directory of Open Access Journals (Sweden)

    Sarosh N Fatakia

    Full Text Available G protein-coupled receptors (GPCRs are a superfamily of seven transmembrane-spanning proteins involved in a wide array of physiological functions and are the most common targets of pharmaceuticals. This study aims to identify a cohort or clique of positions that share high mutual information. Using a multiple sequence alignment of the transmembrane (TM domains, we calculated the mutual information between all inter-TM pairs of aligned positions and ranked the pairs by mutual information. A mutual information graph was constructed with vertices that corresponded to TM positions and edges between vertices were drawn if the mutual information exceeded a threshold of statistical significance. Positions with high degree (i.e. had significant mutual information with a large number of other positions were found to line a well defined inter-TM ligand binding cavity for class A as well as class C GPCRs. Although the natural ligands of class C receptors bind to their extracellular N-terminal domains, the possibility of modulating their activity through ligands that bind to their helical bundle has been reported. Such positions were not found for class B GPCRs, in agreement with the observation that there are not known ligands that bind within their TM helical bundle. All identified key positions formed a clique within the MI graph of interest. For a subset of class A receptors we also considered the alignment of a portion of the second extracellular loop, and found that the two positions adjacent to the conserved Cys that bridges the loop with the TM3 qualified as key positions. Our algorithm may be useful for localizing topologically conserved regions in other protein families.

  4. Computing highly correlated positions using mutual information and graph theory for G protein-coupled receptors.

    Science.gov (United States)

    Fatakia, Sarosh N; Costanzi, Stefano; Chow, Carson C

    2009-01-01

    G protein-coupled receptors (GPCRs) are a superfamily of seven transmembrane-spanning proteins involved in a wide array of physiological functions and are the most common targets of pharmaceuticals. This study aims to identify a cohort or clique of positions that share high mutual information. Using a multiple sequence alignment of the transmembrane (TM) domains, we calculated the mutual information between all inter-TM pairs of aligned positions and ranked the pairs by mutual information. A mutual information graph was constructed with vertices that corresponded to TM positions and edges between vertices were drawn if the mutual information exceeded a threshold of statistical significance. Positions with high degree (i.e. had significant mutual information with a large number of other positions) were found to line a well defined inter-TM ligand binding cavity for class A as well as class C GPCRs. Although the natural ligands of class C receptors bind to their extracellular N-terminal domains, the possibility of modulating their activity through ligands that bind to their helical bundle has been reported. Such positions were not found for class B GPCRs, in agreement with the observation that there are not known ligands that bind within their TM helical bundle. All identified key positions formed a clique within the MI graph of interest. For a subset of class A receptors we also considered the alignment of a portion of the second extracellular loop, and found that the two positions adjacent to the conserved Cys that bridges the loop with the TM3 qualified as key positions. Our algorithm may be useful for localizing topologically conserved regions in other protein families.

  5. Novel surface display system for proteins on non-genetically modified gram-positive bacteria

    NARCIS (Netherlands)

    Bosma, T; Kanninga, R; Neef, J; Audouy, SAL; van Roosmalen, ML; Steen, A; Buist, G; Kok, J; Kuipers, OP; Robillard, G; Leenhouts, K

    A novel display system is described that allows highly efficient immobilization of heterologous proteins on bacterial surfaces in applications for which the use of genetically modified bacteria is less desirable. This system is based on nonliving and non-genetically modified gram-positive bacterial

  6. Correlation analysis for protein evolutionary family based on amino acid position mutations and application in PDZ domain.

    Directory of Open Access Journals (Sweden)

    Qi-Shi Du

    Full Text Available BACKGROUND: It has been widely recognized that the mutations at specific directions are caused by the functional constraints in protein family and the directional mutations at certain positions control the evolutionary direction of the protein family. The mutations at different positions, even distantly separated, are mutually coupled and form an evolutionary network. Finding the controlling mutative positions and the mutative network among residues are firstly important for protein rational design and enzyme engineering. METHODOLOGY: A computational approach, namely amino acid position conservation-mutation correlation analysis (CMCA, is developed to predict mutually mutative positions and find the evolutionary network in protein family. The amino acid position mutative function, which is the foundational equation of CMCA measuring the mutation of a residue at a position, is derived from the MSA (multiple structure alignment database of protein evolutionary family. Then the position conservation correlation matrix and position mutation correlation matrix is constructed from the amino acid position mutative equation. Unlike traditional SCA (statistical coupling analysis approach, which is based on the statistical analysis of position conservations, the CMCA focuses on the correlation analysis of position mutations. CONCLUSIONS: As an example the CMCA approach is used to study the PDZ domain of protein family, and the results well illustrate the distantly allosteric mechanism in PDZ protein family, and find the functional mutative network among residues. We expect that the CMCA approach may find applications in protein engineering study, and suggest new strategy to improve bioactivities and physicochemical properties of enzymes.

  7. N-acetylgalactosamine positive perineuronal nets in the saccade-related-part of the cerebellar fastigial nucleus do not maintain saccade gain.

    Directory of Open Access Journals (Sweden)

    Adrienne Mueller

    Full Text Available Perineuronal nets (PNNs accumulate around neurons near the end of developmental critical periods. PNNs are structures of the extracellular matrix which surround synaptic contacts and contain chondroitin sulfate proteoglycans. Previous studies suggest that the chondroitin sulfate chains of PNNs inhibit synaptic plasticity and thereby help end critical periods. PNNs surround a high proportion of neurons in the cerebellar nuclei. These PNNs form during approximately the same time that movements achieve normal accuracy. It is possible that PNNs in the cerebellar nuclei inhibit plasticity to maintain the synaptic organization that produces those accurate movements. We tested whether or not PNNs in a saccade-related part of the cerebellar nuclei maintain accurate saccade size by digesting a part of them in an adult monkey performing a task that changes saccade size (long term saccade adaptation. We use the enzyme Chondroitinase ABC to digest the glycosaminoglycan side chains of proteoglycans present in the majority of PNNs. We show that this manipulation does not result in faster, larger, or more persistent adaptation. Our result indicates that intact perineuronal nets around saccade-related neurons in the cerebellar nuclei are not important for maintaining long-term saccade gain.

  8. Proteomic analysis of saliva in HIV-positive heroin addicts reveals proteins correlated with cognition.

    Directory of Open Access Journals (Sweden)

    Stephen S Dominy

    Full Text Available The prevalence of HIV-associated neurocognitive disorders (HAND remains high despite effective antiretroviral therapies. Multiple etiologies have been proposed over the last several years to account for this phenomenon, including the neurotoxic effects of antiretrovirals and co-morbid substance abuse; however, no underlying molecular mechanism has been identified. Emerging evidence in several fields has linked the gut to brain diseases, but the effect of the gut on the brain during HIV infection has not been explored. Saliva is the most accessible gut biofluid, and is therefore of great scientific interest for diagnostic and prognostic purposes. This study presents a longitudinal, liquid chromatography-mass spectrometry-based quantitative proteomics study investigating saliva samples taken from 8 HIV-positive (HIV+, 11 -negative (HIV- heroin addicts. In addition, saliva samples were investigated from 11 HIV-, non-heroin addicted healthy controls. In the HIV+ group, 58 proteins were identified that show significant correlations with cognitive scores, implicating disruption of protein quality control pathways by HIV. Notably, only one protein from the HIV- heroin addict cohort showed a significant correlation with cognitive scores, and no proteins correlated with cognitive scores in the healthy control group. In addition, the majority of correlated proteins have been shown to be associated with exosomes, allowing us to propose that the salivary glands and/or oral epithelium may modulate brain function during HIV infection through the release of discrete packets of proteins in the form of exosomes.

  9. Nature of protein family signatures: insights from singular value analysis of position-specific scoring matrices.

    Directory of Open Access Journals (Sweden)

    Akira R Kinjo

    Full Text Available Position-specific scoring matrices (PSSMs are useful for detecting weak homology in protein sequence analysis, and they are thought to contain some essential signatures of the protein families. In order to elucidate what kind of ingredients constitute such family-specific signatures, we apply singular value decomposition to a set of PSSMs and examine the properties of dominant right and left singular vectors. The first right singular vectors were correlated with various amino acid indices including relative mutability, amino acid composition in protein interior, hydropathy, or turn propensity, depending on proteins. A significant correlation between the first left singular vector and a measure of site conservation was observed. It is shown that the contribution of the first singular component to the PSSMs act to disfavor potentially but falsely functionally important residues at conserved sites. The second right singular vectors were highly correlated with hydrophobicity scales, and the corresponding left singular vectors with contact numbers of protein structures. It is suggested that sequence alignment with a PSSM is essentially equivalent to threading supplemented with functional information. In addition, singular vectors may be useful for analyzing and annotating the characteristics of conserved sites in protein families.

  10. In vitro digestibility and nutritional characterization of distillers dried grains with solubles according to the Cornell Net Carbohydrate and Protein System

    Directory of Open Access Journals (Sweden)

    Luiz Juliano Valério Geron

    2017-08-01

    Full Text Available We evaluated the fractions of protein and carbohydrates in distillers dried grains with solubles (DDGS, corn grain (CG, soybean meal (SM, and corn silage (CS, as well as the in vitro digestibility (IVD of DDGS, CG, SM, CS, rations containing 0.0, 8.0, 16.0, and 24.0% DDGS, and in vitro fermentation parameters after 24 h of incubation. DDGS were obtained following microbial fermentation for ethanol production from a sugar and alcohol distillery located in the state of Mato Grosso - Brazil. The Cornell Net Carbohydrate and Protein System (CNCPS was used to determine the protein and carbohydrate fractions of experimental diets. For the in vitro nutrient digestion assay using the experimental foods and experimental diets, two sheep with an average body weight of 26 kg were used as inoculum donors. The in vitro digestibility of food and feed was assayed in three replicates. Fraction A of DDGS CP was 88, 71, and 37% lower in relation to fraction A of SM, CG, and CS, respectively. Fraction B2 of DDGS protein contained 21% CP, which represents 78.84% of DDGS protein in fraction B2, and is higher than the SM, which was 70.44%. The B3 fraction of CP, which is partly released during ruminal fermentation, was 18% lower for SM compared to DDGS, and is expressed in %CP. For carbohydrate fractionation, the DDGS presented 8.64% for the A + B1 fraction on a DM basis, which was 62, 86, and 74% lower compared to those obtained for SM, CG. and CS, respectively. The hemicellulose and cellulose contents of DDGS were higher than those of SM, as verified in fraction B2, with a value of 46.92%, expressed in DM. The in vitro digestibility coefficients (IVDC of the DDGS nutrients did not differ (p > 0.05 in relation to those of the other experimental foods. The inclusion of DDGS in rations formulated for sheep did not change (p > 0.05 the IVDC of DM, OM, CP. NDF, or ADF, with mean values of 70.93, 70.64, 59.58, 52.83, and 43.40%, respectively. Therefore, DDGS comprise a

  11. Misannotations of rRNA can now generate 90% false positive protein matches in metatranscriptomic studies

    Science.gov (United States)

    Tripp, H. James; Hewson, Ian; Boyarsky, Sam; Stuart, Joshua M.; Zehr, Jonathan P.

    2011-01-01

    In the course of analyzing 9 522 746 pyrosequencing reads from 23 stations in the Southwestern Pacific and equatorial Atlantic oceans, it came to our attention that misannotations of rRNA as proteins is now so widespread that false positive matching of rRNA pyrosequencing reads to the National Center for Biotechnology Information (NCBI) non-redundant protein database approaches 90%. One conserved portion of 23S rRNA was consistently misannotated often enough to prompt curators at Pfam to create a spurious protein family. Detailed examination of the annotation history of each seed sequence in the spurious Pfam protein family (PF10695, ‘Cw-hydrolase’) uncovered issues in the standard operating procedures and quality assurance programs of major sequencing centers, and other issues relating to the curation practices of those managing public databases such as GenBank and SwissProt. We offer recommendations for all these issues, and recommend as well that workers in the field of metatranscriptomics take extra care to avoid including false positive matches in their datasets. PMID:21771858

  12. Nano-positioning system for structural analysis of functional homomeric proteins in multiple conformations.

    Science.gov (United States)

    Hyde, H Clark; Sandtner, Walter; Vargas, Ernesto; Dagcan, Alper T; Robertson, Janice L; Roux, Benoit; Correa, Ana M; Bezanilla, Francisco

    2012-10-10

    Proteins may undergo multiple conformational changes required for their function. One strategy used to estimate target-site positions in unknown structural conformations involves single-pair resonance energy transfer (RET) distance measurements. However, interpretation of inter-residue distances is difficult when applied to three-dimensional structural rearrangements, especially in homomeric systems. We developed a positioning method using inverse trilateration/triangulation to map target sites within a homomeric protein in all defined states, with simultaneous functional recordings. The procedure accounts for probe diffusion to accurately determine the three-dimensional position and confidence region of lanthanide LRET donors attached to a target site (one per subunit), relative to a single fluorescent acceptor placed in a static site. As first application, the method is used to determine the position of a functional voltage-gated potassium channel's voltage sensor. Our results verify the crystal structure relaxed conformation and report on the resting and active conformations for which crystal structures are not available. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Proteomic Analysis of Saliva in HIV-positive Heroin Addicts Reveals Proteins Correlated with Cognition

    Energy Technology Data Exchange (ETDEWEB)

    Dominy, Stephen; Brown, Joseph N.; Ryder, Mark I.; Gritsenko, Marina A.; Jacobs, Jon M.; Smith, Richard D.

    2014-04-01

    The prevalence of HIV-associated neurocognitive disorders (HAND) remains high despite effective antiretroviral therapies. Multiple etiologies have been proposed over the last few years to account for this phenomenon, including the neurotoxic effects of antiretrovirals and co-morbid substance abuse. However, no underlying molecular mechanism has been identified. Emerging evidence in several fields has linked the gut to brain diseases, but the effect of the gut on the brain during HIV infection has not been explored. Saliva is the most accessible gut biofluid, and is therefore of great scientific interest for diagnostic and prognostic purposes. This study presents a longitudinal, liquid chromatography-mass spectrometry-based quantitative proteomics study investigating saliva samples taken from 8 HIV-positive (HIV+) and 11 -negative (HIV-) heroin addicts. In the HIV+ group, 58 proteins were identified that show significant correlations with cognitive scores and that implicate disruption of protein quality control pathways by HIV. Notably, no proteins from the HIV- heroin addict cohort showed significant correlations with cognitive scores. In addition, the majority of correlated proteins have been shown to be associated with exosomes, allowing us to propose that the salivary glands and/or oral epithelium may modulate brain function during HIV infection through the release of discrete packets of proteins in the form of exosomes.

  14. Electrophysiological findings in patients with low density lipoprotein receptor related protein 4 positive myasthenia gravis.

    Science.gov (United States)

    Nikolic, A V; Bojic, S D; Rakocevic Stojanovic, V M; Basta, I Z; Lavrnic, D V

    2016-11-01

    The aim was to determine the electrophysiological profile of our cohort of low density lipoprotein receptor related protein 4 (LRP4) positive myasthenia gravis (MG) patients. A repetitive nerve stimulation (RNS) test and jitter analysis using a concentric needle electrode were performed in 17 LRP4 positive MG patients. The results were compared to 31 muscle-specific tyrosine kinase (MuSK) positive and 28 acetylcholine receptor (AChR) positive MG patients. The RNS test was negative in almost all patients belonging to the LRP4/seronegative and LRP4/MuSK groups. It was positive most frequently in the AChR MG patients, especially those without anti-LRP4 antibodies. The presence of anti-LRP4 antibodies was connected to lower decrement values, whilst the independent presence of anti-AChR or anti-MuSK antibodies was connected to higher decrement values. Lowest jitter was recorded in patients with LRP4/seronegative MG. The highest percentage of pathological jitter analysis test results was present in MuSK and AChR MG patients. The isolate presence of anti-LRP4 antibodies did not influence the mean consecutive difference values, whilst mean consecutive difference values were higher in the presence of anti-AChR or anti-MuSK antibodies. Low density lipoprotein receptor related protein 4 positive patients make a distinct MG subgroup with rarely detected pathological electrophysiological test results. The lack of influence of anti-LRP4 antibodies on the different electrophysiological parameters brings into question the pathogenic role of anti-LRP4 antibodies in MG. © 2016 EAN.

  15. Positive evolutionary selection of an HD motif on Alzheimer precursor protein orthologues suggests a functional role.

    Directory of Open Access Journals (Sweden)

    István Miklós

    2012-02-01

    Full Text Available HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ and on the carboxy-terminal region of the extracellular domain (CAED of the human amyloid precursor protein (APP and a taxonomically well defined group of APP orthologues (APPOs. In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (p<0.0001. The motif is positively selected along the evolutionary process in the majority of APPOs, despite the fact that HD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the "transcription binding site turnover." CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1 and Amyloid-like protein 2 (APLP2. Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N and English (H6R mutations in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs.

  16. A novel role for the GTPase-activating protein Bud2 in the spindle position checkpoint.

    Directory of Open Access Journals (Sweden)

    Scott A Nelson

    Full Text Available The spindle position checkpoint (SPC ensures correct mitotic spindle position before allowing mitotic exit in the budding yeast Saccharomyces cerevisiae. In a candidate screen for checkpoint genes, we identified bud2Δ as deficient for the SPC. Bud2 is a GTPase activating protein (GAP, and the only known substrate of Bud2 was Rsr1/Bud1, a Ras-like GTPase and a central component of the bud-site-selection pathway. Mutants lacking Rsr1/Bud1 had no checkpoint defect, as did strains lacking and overexpressing Bud5, a guanine-nucleotide exchange factor (GEF for Rsr1/Bud1. Thus, the checkpoint function of Bud2 is distinct from its role in bud site selection. The catalytic activity of the Bud2 GAP domain was required for the checkpoint, based on the failure of the known catalytic point mutant Bud2(R682A to function in the checkpoint. Based on assays of heterozygous diploids, bud2(R682A, was dominant for loss of checkpoint but recessive for bud-site-selection failure, further indicating a separation of function. Tem1 is a Ras-like protein and is the critical regulator of mitotic exit, sitting atop the mitotic exit network (MEN. Tem1 is a likely target for Bud2, supported by genetic analyses that exclude other Ras-like proteins.

  17. The Achilles' Heel of "Ultrastable" Hyperthermophile Proteins: Submillimolar Concentrations of SDS Stimulate Rapid Conformational Change, Aggregation, and Amyloid Formation in Proteins Carrying Overall Positive Charge.

    Science.gov (United States)

    Khan, Javed M; Sharma, Prerna; Arora, Kanika; Kishor, Nitin; Kaila, Pallavi; Guptasarma, Purnananda

    2016-07-19

    Low concentrations (SDS) have been shown to induce the formation of amyloid fibers in more than 20 different mesophile-derived proteins in the cationic state. It is not known whether SDS has similar effects on hyperthermophile-derived proteins, which are otherwise thought to be "ultrastable" and inordinately resistant to structural perturbations at room temperature. Here, we show that low (SDS rapidly induce the formation of aggregates and amyloid fibers in five different ultrastable Pyrococcus furiosus proteins in the cationic state. We also show that amyloid formation is accompanied by the development of a characteristic, negative circular dichroism band at ∼230 nm. These effects are not seen if the proteins have a net negative charge or when higher concentrations of SDS are used (which induce helix formation instead). Our results appear to reveal a potential weakness or "Achilles' heel" in ultrastable proteins from hyperthermophiles. They also provide very strong support for the view that SDS initially interacts with proteins through electrostatic interactions, and not hydrophobic interactions, eliciting similar effects entirely regardless of protein molecular weight, or structural features such as quaternary structure or tertiary structural stability.

  18. Physicochemical evolution and positive selection of the gymnosperm matK proteins.

    Science.gov (United States)

    Hao, Da Cheng; Mu, Jun; Chen, Shi Lin; Xiao, Pei Gen

    2010-04-01

    It is not clear whether matK evolves under Darwinian selection. In this study, the gymnosperm Taxaceae, Cephalotaxaceae and Pinaceae were used to illustrate the physicochemical evolution, molecular adaptation and evolutionary dynamics of gene divergence in matKs. matK sequences were amplified from 27 Taxaceae and 12 Cephalotaxaceae species. matK sequences of 19 Pinaceae species were retrieved from GenBank. The phylogenetic tree was generated using conceptual-translated amino acid sequences. Selective influences were investigated using standard dN/dS ratio methods and more sensitive techniques investigating the amino acid property changes resulting from nonsynonymous replacements in a phylogenetic context. Analyses revealed the presence of positive selection in matKs (N-terminal region, RT domain and domain X) of Taxaceae and Pinaceae,and found positive destabilizing selection in N-terminal region and RT domain of Cephalotaxaceae matK. Moreover, various amino acid properties were found to be influenced by destabilizing positive selection. Amino acid sites relating to these properties and to different secondary structures were found and have the potential to affect group II intron maturase function. Despite the evolutionary constraint on the rapidly evolving matK, this protein evolves under positive selection in gymnosperm. Several regions of matK have experienced molecular adaptation which fine-tunes maturase performance.

  19. Postpartum follow-up of a positive purified protein derivative (PPD) among an indigent population.

    Science.gov (United States)

    Cruz, Carolyn A; Caughey, Aaron B; Jasmer, Robert

    2005-05-01

    This study was undertaken to investigate the rates and predictors of follow-up and treatment for postpartum patients with a positive purified protein derivative (PPD). Retrospective cohort study of all women delivered at San Francisco General Hospital in 2000. All patients with a positive PPD were identified and their demographic and PPD follow-up and treatment data were collected and analyzed. Among the 1331 patients delivered, the prevalence of a positive PPD was 32% (n = 425). Of the 393 patients who had not been previously treated, 42% (n = 167) attended a follow-up visit with 42% of these (n = 71) actually completing 6 months of therapy. Among different ethnicities, Asian patients were more likely to follow-up at a rate of 52% (P = .03). Patients who received care from the same physician both antepartum and postpartum were more likely to attend and complete therapy at rates of 67% (P < .001) and 62% (P = .01), respectively. We found that despite the opportunity given by the interaction with the medical system during pregnancy, only 18% of patients with a positive PPD actually completed therapy.

  20. Functional divergence of the NIP III subgroup proteins involved altered selective constraints and positive selection

    Directory of Open Access Journals (Sweden)

    Zhu Zhujun

    2010-11-01

    Full Text Available Abstract Background Nod26-like intrinsic proteins (NIPs that belong to the aquaporin superfamily are unique to plants. According to homology modeling and phylogenetic analysis, the NIP subfamily can be further divided into three subgroups with distinct biological functions (NIP I, NIP II, and NIP III. In some grasses, the NIP III subgroup proteins (NIP2s were demonstrated to be permeable to solutes with larger diameter, such as silicic acid and arsenous acids. However, to date there is no data-mining or direct experimental evidences for the permeability of such larger solutes for dicot NIP2s, although they exhibit similar three-dimensional structures as those in grasses. It is therefore intriguing to investigate the molecular mechanisms that drive the evolution of plant NIP2s. Results The NIP III subgroup is more ancient with a divergence time that predates the monocot-dicot split. The proliferation of NIP2 genes in modern grass species is primarily attributed to whole genome and segmental chromosomal duplication events. The structure of NIP2 genes is relatively conserved, possessing five exons and four introns. All NIP2s possess an ar/R filter consisting of G, S, G, and R, except for the cucumber CsNIP2;2, where a small G in the H2 is substituted with the bulkier C residue. Our maximum likelihood analysis revealed that NIP2s, especially the loop A (LA region, have undergone strong selective pressure for adaptive evolution. The analysis at the amino acid level provided strong statistical evidences for the functional divergence between monocot and dicot NIP III subgroup proteins. In addition, several SDPs (Specificity Determining Positions responsible for functional specificity were predicted. Conclusions The present study provides the first evidences of functional divergence between dicot and monocot NIP2s, and suggests that positive selection, as well as a radical shift of evolutionary rate at some critical amino acid sites is the primary

  1. Protein Kinase CK2: A Targetable BCR-ABL Partner in Philadelphia Positive Leukemias

    Directory of Open Access Journals (Sweden)

    Alessandro Morotti

    2015-01-01

    Full Text Available BCR-ABL-mediated leukemias, either Chronic Myeloid Leukemia (CML or Philadelphia positive Acute Lymphoblastic Leukemia (ALL, are the paradigm of targeted molecular therapy of cancer due to the impressive clinical responses obtained with BCR-ABL specific tyrosine kinase inhibitors (TKIs. However, BCR-ABL TKIs do not allow completely eradicating both CML and ALL. Furthermore, ALL therapy is associated with much worse responses to TKIs than those observed in CML. The identification of additional pathways that mediate BCR-ABL leukemogenesis is indeed mandatory to achieve synthetic lethality together with TKI. Here, we review the role of BCR-ABL/protein kinase CK2 interaction in BCR-ABL leukemias, with potentially relevant implications for therapy.

  2. The trafficking protein, EHD2, positively regulates cardiac sarcolemmal KATP channel surface expression: role in cardioprotection.

    Science.gov (United States)

    Yang, Hua Qian; Jana, Kundan; Rindler, Michael J; Coetzee, William A

    2017-11-13

    ATP-sensitive K+ (KATP) channels uniquely link cellular energy metabolism to membrane excitability and are expressed in diverse cell types that range from the endocrine pancreas to neurons and smooth, skeletal, and cardiac muscle. A decrease in the surface expression of KATP channels has been linked to various disorders, including dysregulated insulin secretion, abnormal blood pressure, and impaired resistance to cardiac injury. In contrast, up-regulation of KATP channel surface expression may be protective, for example, by mediating the beneficial effect of ischemic preconditioning. Molecular mechanisms that regulate KATP channel trafficking are poorly understood. Here, we used cellular assays with immunofluorescence, surface biotinylation, and patch clamping to demonstrate that Eps15 homology domain-containing protein 2 (EHD2) is a novel positive regulator of KATP channel trafficking to increase surface KATP channel density. EHD2 had no effect on cardiac Na+ channels (Nav1.5). The effect is specific to EHD2 as other members of the EHD family-EHD1, EHD3, and EHD4-had no effect on KATP channel surface expression. EHD2 did not directly affect KATP channel properties as unitary conductance and ATP sensitivity were unchanged. Instead, we observed that the mechanism by which EHD2 increases surface expression is by stabilizing KATP channel-containing caveolar structures, which results in a reduced rate of endocytosis. EHD2 also regulated KATP channel trafficking in isolated cardiomyocytes, which validated the physiologic relevance of these observations. Pathophysiologically, EHD2 may be cardioprotective as a dominant-negative EHD2 mutant sensitized cardiomyocytes to ischemic damage. Our findings highlight EHD2 as a potential pharmacologic target in the treatment of diseases with KATP channel trafficking defects.-Yang, H. Q., Jana, K., Rindler, M. J., Coetzee, W. A. The trafficking protein, EHD2, positively regulates cardiac sarcolemmal KATP channel surface expression

  3. Atrophin protein RERE positively regulates Notch targets in the developing vertebrate spinal cord.

    Science.gov (United States)

    Wang, Hui; Gui, Hongxing; Rallo, Michael S; Xu, Zhiyan; Matise, Michael P

    2017-05-01

    The Notch signaling pathway controls cell fate decision, proliferation, and other biological functions in both vertebrates and invertebrates. Precise regulation of the canonical Notch pathway ensures robustness of the signal throughout development and adult tissue homeostasis. Aberrant Notch signaling results in profound developmental defects and is linked to many human diseases. In this study, we identified the Atrophin family protein RERE (also called Atro2) as a positive regulator of Notch target Hes genes in the developing vertebrate spinal cord. Prior studies have shown that during early embryogenesis in mouse and zebrafish, deficit of RERE causes various patterning defects in multiple organs including the neural tube. Here, we detected the expression of RERE in the developing chick spinal cord, and found that normal RERE activity is needed for proper neural progenitor proliferation and neuronal differentiation possibly by affecting Notch-mediated Hes expression. In mammalian cells, RERE co-immunoprecipitates with CBF1 and Notch intracellular domain (NICD), and is recruited to nuclear foci formed by over-expressed NICD1. RERE is also necessary for NICD to activate the expression of Notch target genes. Our findings suggest that RERE stimulates Notch target gene expression by preventing degradation of NICD protein, thereby facilitating the assembly of a transcriptional activating complex containing NICD, CBF1/RBPjκ in vertebrate, Su(H) in Drosophila melanogaster, Lag1 in C. elegans, and other coactivators. © 2017 International Society for Neurochemistry.

  4. Synthesis of positively charged calcium hydroxyapatite nano-crystals and their adsorption behavior of proteins.

    Science.gov (United States)

    Kandori, Kazuhiko; Oda, Shohei; Fukusumi, Masao; Morisada, Yoshiaki

    2009-10-01

    Positively charged Hap nano-crystals were prepared by using beta-alanine and clarified the adsorption affinity of these surface amide functionalized Hap nano-crystals to proteins. Colloidal surface amide functionalized Hap nano-crystals were prepared by wet method in the presence of various amounts of beta-alanine by changing molar ratio of beta-alanine/Ca (beta/Ca ratio) in the solution. The rod-like nano-crystals were lengthened with addition of beta-alanine though their width did not vary; carboxyl groups of beta-alanine are strongly coordinated to Ca2+ ions exposed on ac and/or bc faces to inhibit particle growth to a- and/or b-axis directions and enhance the particle growth along to the c-axis. No difference can be recognized on the crystal structure among the synthesized Hap nano-crystals by XRD measurements. However, the large difference was recognized by TG-DTA and FTIR measurements. Those measurements revealed that beta-alanine is incorporated on the Hap nano-crystal surface up to the beta/Ca ratio of 1.0, though they are absent in the nano-crystals synthesized at beta/Ca ratio > or = 2.0. The zeta potential (zp) of beta-alanine-Hap nano-crystals prepared at beta/Ca = 0.4 and 1.0 of those incorporating beta-alanine exhibited positive charge at pH crystals were increased 2.3-2.4-fold by their electrostatic attraction force between positively charged beta-alanine-Hap nano-crystals and negatively charged BSA molecules. We were able to control the adsorption affinity of Hap nano-crystal by changing their surface charge.

  5. NA-NET numerical analysis net

    Energy Technology Data Exchange (ETDEWEB)

    Dongarra, J. [Tennessee Univ., Knoxville, TN (United States). Dept. of Computer Science]|[Oak Ridge National Lab., TN (United States); Rosener, B. [Tennessee Univ., Knoxville, TN (United States). Dept. of Computer Science

    1991-12-01

    This report describes a facility called NA-NET created to allow numerical analysts (na) an easy method of communicating with one another. The main advantage of the NA-NET is uniformity of addressing. All mail is addressed to the Internet host ``na-net.ornl.gov`` at Oak Ridge National Laboratory. Hence, members of the NA-NET do not need to remember complicated addresses or even where a member is currently located. As long as moving members change their e-mail address in the NA-NET everything works smoothly. The NA-NET system is currently located at Oak Ridge National Laboratory. It is running on the same machine that serves netlib. Netlib is a separate facility that distributes mathematical software via electronic mail. For more information on netlib consult, or send the one-line message ``send index`` to netlib{at}ornl.gov. The following report describes the current NA-NET system from both a user`s perspective and from an implementation perspective. Currently, there are over 2100 members in the NA-NET. An average of 110 mail messages pass through this facility daily.

  6. NA-NET numerical analysis net

    Energy Technology Data Exchange (ETDEWEB)

    Dongarra, J. (Tennessee Univ., Knoxville, TN (United States). Dept. of Computer Science Oak Ridge National Lab., TN (United States)); Rosener, B. (Tennessee Univ., Knoxville, TN (United States). Dept. of Computer Science)

    1991-12-01

    This report describes a facility called NA-NET created to allow numerical analysts (na) an easy method of communicating with one another. The main advantage of the NA-NET is uniformity of addressing. All mail is addressed to the Internet host na-net.ornl.gov'' at Oak Ridge National Laboratory. Hence, members of the NA-NET do not need to remember complicated addresses or even where a member is currently located. As long as moving members change their e-mail address in the NA-NET everything works smoothly. The NA-NET system is currently located at Oak Ridge National Laboratory. It is running on the same machine that serves netlib. Netlib is a separate facility that distributes mathematical software via electronic mail. For more information on netlib consult, or send the one-line message send index'' to netlib{at}ornl.gov. The following report describes the current NA-NET system from both a user's perspective and from an implementation perspective. Currently, there are over 2100 members in the NA-NET. An average of 110 mail messages pass through this facility daily.

  7. False-Positive Rate Determination of Protein Target Discovery using a Covalent Modification- and Mass Spectrometry-Based Proteomics Platform

    Science.gov (United States)

    Strickland, Erin C.; Geer, M. Ariel; Hong, Jiyong; Fitzgerald, Michael C.

    2014-01-01

    Detection and quantitation of protein-ligand binding interactions is important in many areas of biological research. Stability of proteins from rates of oxidation (SPROX) is an energetics-based technique for identifying the proteins targets of ligands in complex biological mixtures. Knowing the false-positive rate of protein target discovery in proteome-wide SPROX experiments is important for the correct interpretation of results. Reported here are the results of a control SPROX experiment in which chemical denaturation data is obtained on the proteins in two samples that originated from the same yeast lysate, as would be done in a typical SPROX experiment except that one sample would be spiked with the test ligand. False-positive rates of 1.2-2.2 % and replicates can be used to effectively eliminate such false positives that result from this random error, as is demonstrated in a SPROX experiment to identify yeast protein targets of the drug, manassantin A. The impact of ion purity in the tandem mass spectral analyses and of background oxidation on the false-positive rate of protein target discovery using SPROX is also discussed.

  8. Net biosynthesis of Antithrombin III by the isolated rat liver perfused for 12--24 hours. Compared with rat fibrinogen and. cap alpha. -2 (acute phase) globulin, Antithrombin III is not an acute phase protein

    Energy Technology Data Exchange (ETDEWEB)

    Owens, M.R.; Miller, L.L.

    1978-01-01

    Antithrombin III- heparin cofactor has been isolated from normal rat plasma, purified to homogeniety on acrylamide gel electrophoresis and used to prepare a monospecific antiserum in rabbits. Measurements of rat AT-III were made by a single radial immunodiffusion assay. Net synthesis of AT-III was investigated during 12 or 24 hour perfusions of the isolated rat liver. In perfusions performed under basal conditions cumulative synthesis of AT-III was observed to occur at a rate sufficient to replace the total circulating plasma AT-III in about 6 hours. In perfusions performed under full supplementation conditions which greatly enhanced synthesis of fibrinogen and ..cap alpha..-2 (acute phase) globulin (known acute phase reactant proteins) net synthesis of AT-III was not significantly greater than that observed in control perfusions. Although these prolonged perfusion studies conclusively demonstrate net synthesis of AT-III by the isolated rat liver, they afford no evidence that this protein is an acute phase reactant.

  9. ZP domain proteins in the abalone egg coat include a paralog of VERL under positive selection that binds lysin and 18-kDa sperm proteins.

    Science.gov (United States)

    Aagaard, Jan E; Vacquier, Victor D; MacCoss, Michael J; Swanson, Willie J

    2010-01-01

    Identifying fertilization molecules is key to our understanding of reproductive biology, yet only a few examples of interacting sperm and egg proteins are known. One of the best characterized comes from the invertebrate archeogastropod abalone (Haliotis spp.), where sperm lysin mediates passage through the protective egg vitelline envelope (VE) by binding to the VE protein vitelline envelope receptor for lysin (VERL). Rapid adaptive divergence of abalone lysin and VERL are an example of positive selection on interacting fertilization proteins contributing to reproductive isolation. Previously, we characterized a subset of the abalone VE proteins that share a structural feature, the zona pellucida (ZP) domain, which is common to VERL and the egg envelopes of vertebrates. Here, we use additional expressed sequence tag sequencing and shotgun proteomics to characterize this family of proteins in the abalone egg VE. We expand 3-fold the number of known ZP domain proteins present within the VE (now 30 in total) and identify a paralog of VERL (vitelline envelope zona pellucida domain protein [VEZP] 14) that contains a putative lysin-binding motif. We find that, like VERL, the divergence of VEZP14 among abalone species is driven by positive selection on the lysin-binding motif alone and that these paralogous egg VE proteins bind a similar set of sperm proteins including a rapidly evolving 18-kDa paralog of lysin, which may mediate sperm-egg fusion. This work identifies an egg coat paralog of VERL under positive selection and the candidate sperm proteins with which it may interact during abalone fertilization.

  10. Net Ecosystem Carbon Flux

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Net Ecosystem Carbon Flux is defined as the year-over-year change in Total Ecosystem Carbon Stock, or the net rate of carbon exchange between an ecosystem and the...

  11. The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

    Science.gov (United States)

    Chen, Justin L.; Qian, Hongwei; Liu, Yingying; Bernardo, Bianca C.; Beyer, Claudia; Watt, Kevin I.; Thomson, Rachel E.; Connor, Timothy; Turner, Bradley J.; McMullen, Julie R.; Larsson, Lars; McGee, Sean L.; Harrison, Craig A.

    2013-01-01

    Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders. PMID:24145169

  12. Professional Enterprise NET

    CERN Document Server

    Arking, Jon

    2010-01-01

    Comprehensive coverage to help experienced .NET developers create flexible, extensible enterprise application code If you're an experienced Microsoft .NET developer, you'll find in this book a road map to the latest enterprise development methodologies. It covers the tools you will use in addition to Visual Studio, including Spring.NET and nUnit, and applies to development with ASP.NET, C#, VB, Office (VBA), and database. You will find comprehensive coverage of the tools and practices that professional .NET developers need to master in order to build enterprise more flexible, testable, and ext

  13. Pregnancy-associated plasma protein A is positively correlated to first trimester skin microvascular reactivity.

    Science.gov (United States)

    Iacobaeus, C; Kahan, T; Jörneskog, G; Bremme, K; Andolf, E; Thorsell, M

    2017-04-11

    To investigate if there is a correlation between levels of circulating maternal pregnancy-associated plasma protein A (PAPP-A) and first trimester maternal vascular function. A cross-sectional study of 53 healthy non-smoking, pregnant, nulliparous women in Stockholm, Sweden. PAPP-A and vascular function were assessed during gestational week 11-14. Forearm skin microcirculation was investigated by laser Doppler perfusion imaging during iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess endothelium dependent and endothelium independent microvascular vasodilatation, respectively. Vascular endothelial dependent and independent vasodilatation in the brachial artery was evaluated by post-ischemic hyperaemia induced flow mediated vasodilatation (FMD) and by sublingual glyceryl trinatrate (GTN), respectively. PAPP-A related to skin microvascular endothelial function index, i.e. peak Ach/peak SNP (β for PAPP-A 1.008 (0.34 - 1.68), r 2  = 0.17, P = 0.004). PAPP-A also related inversely to FMD (β for PAPP-A = -0.052 (-0.094 - -0.011), r 2  = 0.14, P = 0.014) but did not to FMD/GTN. The results were retained in multivariate analyses including known confounding factors. First trimester endothelium dependent skin microvascular reactivity was positively related to PAPP-A-levels. If confirmed, these novel findings suggest that first trimester skin microvascular reactivity could be a useful early marker for placental function. This article is protected by copyright. All rights reserved.

  14. Peripheral skeleton bone strength is positively correlated with total and dairy protein intakes in healthy postmenopausal women.

    Science.gov (United States)

    Durosier-Izart, Claire; Biver, Emmanuel; Merminod, Fanny; van Rietbergen, Bert; Chevalley, Thierry; Herrmann, François R; Ferrari, Serge L; Rizzoli, René

    2017-02-01

    Bone mineral content (BMC) and bone mineral density (BMD) are positively correlated with dietary protein intakes, which account for 1-8% of BMC and BMD variances. However, the relation between bone strength and microstructure, which are variables that are not captured by areal bone mineral density (aBMD), and dietary protein intakes, particularly from specific dietary sources, has not been clearly established. We investigated the association between the peripheral skeleton-predicted failure load and stiffness, bone microstructure, and dietary protein intakes from various origins (animal, divided into dairy and nondairy, and vegetable origins) in healthy postmenopausal women. In a cross-sectional study in 746 Caucasian women aged 65.0 ± 1.4 y, we measured the aBMD with the use of dual-energy X-ray absorptiometry, the distal radius and tibia bone microstructures with the use of high-resolution peripheral quantitative computerized tomography, and bone strength with the use of a finite element analysis, and we evaluated dietary protein and calcium with the use of a validated food-frequency questionnaire. Mean dietary calcium and protein intakes were greater than recommended amounts for this class of age. The predicted failure load and stiffness at the distal radius and tibia were positively associated with total, animal, and dairy protein intakes but not with vegetable protein intake. Failure load differences were accompanied by modifications of the aBMD and of cortical and trabecular bone microstructures. The associations remained statistically significant after adjustment for weight, height, physical activity, menopause duration, calcium intake, and the interaction between calcium and protein intake. A principal component analysis of the volumetric BMD and bone microstructure indicated that trabecular bone mainly contributed to the positive association between protein intakes and bone strength. These results, which were recorded in a very homogeneous population of

  15. Positively charged amino acids are essential for electron transfer and protein-protein interactions in the soluble methane monooxygenase complex from Methylococcus capsulatus (Bath).

    Science.gov (United States)

    Balendra, Suki; Lesieur, Claire; Smith, Thomas J; Dalton, Howard

    2002-02-26

    The soluble methane monooxygenase (sMMO) complex from Methylococcus capsulatus (Bath) catalyses oxygen- and NAD(P)H-dependent oxygenation of methane, propene, and other substrates. Whole-complex sMMO oxygenase activity requires all three sMMO components: the hydroxylase, the reductase, and protein B. Also, in the presence of hydrogen peroxide, the hydroxylase alone catalyzes substrate oxygenation via the peroxide shunt reaction. We investigated the effect of amine cross-linking on hydroxylase activity to probe the role of a gross conformational change that occurs in the hydroxylase upon binding of the other protein components. The cross-linker inhibited hydroxylase activity in the whole complex, but this effect was due to covalent modification of primary amine groups rather than cross-linking. Covalent modification of arginine side-chains on the hydroxylase had a similar effect, but, most remarkably, neither form of modification affected the activity of the hydroxylase via the peroxide shunt reaction. It was shown that covalent modification of positively charged groups on the hydroxylase, which occurred at multiple sites, interfered with its physical and functional interactions with protein B and with the passage of electrons from the reductase. These results indicate that protein B and the reductase of the sMMO complex interact via positively charged groups on the surface of the hydroxylase to induce a conformational change that is necessary for delivery of electrons into the active site of the hydroxylase. Modification of positively charged groups on protein B had no effect on its function, consistent with the hypothesis that positively charged groups on the hydroxylase interact with negative charges on protein B. Thus, we have discovered a means of specifically inactivating the interactions between the sMMO complex while preserving the catalytic activity of the hydroxylase active site which provides a new method of studying intercomponent interactions within sMMO.

  16. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Martin, Miguel; Holmes, Frankie A; Ejlertsen, Bent; Delaloge, Suzette; Moy, Beverly; Iwata, Hiroji; von Minckwitz, Gunter; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Tomašević, Zorica; Denduluri, Neelima; Šeparović, Robert; Gokmen, Erhan; Bashford, Anna; Ruiz Borrego, Manuel; Kim, Sung-Bae; Jakobsen, Erik Hugger; Ciceniene, Audrone; Inoue, Kenichi; Overkamp, Friedrich; Heijns, Joan B; Armstrong, Anne C; Link, John S; Joy, Anil Abraham; Bryce, Richard; Wong, Alvin; Moran, Susan; Yao, Bin; Xu, Feng; Auerbach, Alan; Buyse, Marc; Chan, Arlene

    2017-12-01

    ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib

  17. Evolution of species-specific major seminal fluid proteins in placental mammals by gene death and positive selection

    NARCIS (Netherlands)

    Meslin, C.; Laurin, M.; Callebaut, I.; Druart, X.; Monget, P.

    2015-01-01

    The seminal fluid is a complex substance composed of a variety of secreted proteins and has been shown to play an important role in the fertilisation process in mammals and also in Drosophila. Several genes under positive selection have been documented in some rodents and primates. Our study

  18. Albumin-based or albumin-linked calibrators cause a positive bias in serum proteins assayed by the biuret method.

    Science.gov (United States)

    Chromý, Vratislav; Sváchová, Lenka; Novosád, Lukás; Jarkovský, Jirí; Sedlák, Pavel; Horák, Petr; Dobrovolná, Hana; Hlavácová, Barbora

    2009-01-01

    Assay of total serum protein by the biuret method calibrated with albumin standards according to the reference method provides results with a positive bias approximately 3%-5% exceeding the total error of 3.4% allowable for total protein in serum analysis made by analysers using two-part reagents and short-term procedures. We used two types of two-part biuret reagents utilised in a short-term measurement in analysers with albumin or serum calibrators, in which protein was attested by the Kjeldahl method. Tests with potentially interfering substances proved that serum blanking used in a short-term biuret procedure is not capable of sufficiently eliminating effects of serum interferents. A short-term blanking is evidently capable of suppressing only an absorbance caused by serum-present coloured and turbid interferents, but its capacity to transform them (oxidise, hydrolyse, saponify, etc.) to some other not-interfering substances is very low compared with a long-term blanking. Lipids and bilirubin are responsible for significant positive bias of total protein in normal serum samples (approximately 3%) and even a greater positive offset in lipaemic and icteric sera (approximately 5%). We verified that interference tests based on a normal serum spiked with endogenous lipids and bilirubin give quite false and misleading results in the biuret reaction. A pure albumin, not depending on its bovine/human origin, gives absorbance responding only to its copper complexes with protein with a biuret regent, while its absorbance with a serum also includes the absorbance of interferents present in serum. The simplest way to improve current short-term biuret procedures is the use of a human serum calibrator with total protein attested by the Kjeldahl method. A serum calibrator, behaving analogously to serum samples, compensates for a positive bias in most normal sera. Reagents with a greater concentration of active biuret components (copper and alkali, reference method included

  19. NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence

    DEFF Research Database (Denmark)

    Nielsen, Morten; Lundegaard, Claus; Blicher, Thomas

    2007-01-01

    surpassed 1500. Characterizing the specificity of each separately would be a major undertaking. PRINCIPAL FINDINGS: Here, we have drawn on a large database of known peptide-HLA-I interactions to develop a bioinformatics method, which takes both peptide and HLA sequence information into account...... to provide new basic insights into HLA structure-function relationships. The method is available at http://www.cbs.dtu.dk/services/NetMHCpan....... successfully validate this method. We further demonstrate that the method can be applied to perform a clustering analysis of MHC specificities and suggest using this clustering to select particularly informative novel MHC molecules for future biochemical and functional analysis. CONCLUSIONS: Encompassing all...

  20. Positive correlation between serum immunoreactivity to Demodex-associated Bacillus proteins and erythematotelangiectatic rosacea.

    Science.gov (United States)

    O'Reilly, N; Menezes, N; Kavanagh, K

    2012-11-01

    Rosacea is a chronic inflammatory condition that affects the skin of the face and the eyes. Erythematotelangiectatic rosacea is characterized by flushing, oedema and telangiectasia. Patients with rosacea demonstrate elevated densities of Demodex mites in their skin compared with controls. A bacterium (Bacillus oleronius) isolated from Demodex mites from a patient with papulopustular rosacea has been demonstrated to produce antigenic proteins that may play a role in papulopustular and ocular rosacea. To establish whether there was a correlation between the reactivity of sera from patients with erythematotelangiectatic rosacea to Bacillus antigens, and to characterize the proteins to which these patients showed reactivity. Serum samples from patients with erythematotelangiectatic rosacea and controls were examined for reactivity to Bacillus proteins by Western blot analysis. Proteins to which the sera reacted were excised from gels, trypsin digested, and putative identities were assigned following liquid chromatography-mass spectrometry (LC-MS) analysis. Eighty per cent (21/26) of patients with erythematotelangiectatic rosacea showed serum reactivity to the 62- and 83-kDa proteins of B. oleronius, compared with 40% (9/22) of controls (P = 0·004). The 62-kDa protein was characterized by LC-MS and showed homology to groEL chaperonin, which provokes a strong immune response in mammals. The 83-kDa protein showed homology to aconitate hydratase, of which expression is increased in bacteria under oxidative stress, and which is highly immunogenic. The majority of patients with erythematotelangiectatic rosacea show serum reactivity to two proteins from B. oleronius, suggesting that this bacterium may play a role in the induction of this condition. The two proteins to which patient sera reacted were found to be similar to a heat shock protein and an enzyme involved in regulating the stress response of the bacterium. © 2012 The Authors. BJD © 2012 British Association of

  1. WaveNet

    Science.gov (United States)

    2015-10-30

    Coastal Inlets Research Program WaveNet WaveNet is a web-based, Graphical-User-Interface ( GUI ) data management tool developed for Corps coastal...generates tabular and graphical information for project planning and design documents. The WaveNet is a web-based GUI designed to provide users with a...data from different sources, and employs a combination of Fortran, Python and Matlab codes to process and analyze data for USACE applications

  2. Coloured Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt

    1991-01-01

    This paper describes how Coloured Petri Nets (CP-nets) have been developed — from being a promising theoretical model to being a full-fledged language for the design, specification, simulation, validation and implementation of large software systems (and other systems in which human beings and...... use of CP-nets — because it means that the function representation and the translations (which are a bit mathematically complex) no longer are parts of the basic definition of CP-nets. Instead they are parts of the invariant method (which anyway demands considerable mathematical skills...

  3. Game Coloured Petri Nets

    DEFF Research Database (Denmark)

    Westergaard, Michael

    2006-01-01

    This paper introduces the notion of game coloured Petri nets. This allows the modeler to explicitly model what parts of the model comprise the modeled system and what parts are the environment of the modeled system. We give the formal definition of game coloured Petri nets, a means of reachability...... analysis of this net class, and an application of game coloured Petri nets to automatically generate easy-to-understand visualizations of the model by exploiting the knowledge that some parts of the model are not interesting from a visualization perspective (i.e. they are part of the environment...

  4. Programming NET Web Services

    CERN Document Server

    Ferrara, Alex

    2007-01-01

    Web services are poised to become a key technology for a wide range of Internet-enabled applications, spanning everything from straight B2B systems to mobile devices and proprietary in-house software. While there are several tools and platforms that can be used for building web services, developers are finding a powerful tool in Microsoft's .NET Framework and Visual Studio .NET. Designed from scratch to support the development of web services, the .NET Framework simplifies the process--programmers find that tasks that took an hour using the SOAP Toolkit take just minutes. Programming .NET

  5. Annotating Coloured Petri Nets

    DEFF Research Database (Denmark)

    Lindstrøm, Bo; Wells, Lisa Marie

    2002-01-01

    -net. An example of such auxiliary information is a counter which is associated with a token to be able to do performance analysis. Modifying colour sets and arc inscriptions in a CP-net to support a specific use may lead to creation of several slightly different CP-nets – only to support the different uses...... a method which makes it possible to associate auxiliary information, called annotations, with tokens without modifying the colour sets of the CP-net. Annotations are pieces of information that are not essential for determining the behaviour of the system being modelled, but are rather added to support...

  6. Prediction of surface exposed proteins in Streptococcus pyogenes, with a potential application to other Gram-positive bacteria.

    Science.gov (United States)

    Barinov, Aleksandr; Loux, Valentin; Hammani, Amal; Nicolas, Pierre; Langella, Philippe; Ehrlich, Dusko; Maguin, Emmanuelle; van de Guchte, Maarten

    2009-01-01

    The in silico prediction of bacterial surface exposed proteins is of growing interest for the rational development of vaccines and in the study of bacteria-host relationships, whether pathogenic or host beneficial. This interest is driven by the increase in the use of DNA sequencing as a major tool in the early characterization of pathogenic bacteria and, more recently, even of complex ecosystems at the host-environment interface in metagenomics approaches. Current protein localization protocols are not suited to this prediction task as they ignore the potential surface exposition of many membrane-associated proteins. Therefore, we developed a new flow scheme, SurfG+, for the processing of protein sequence data with the particular aim of identification of potentially surface exposed (PSE) proteins from Gram-positive bacteria, which was validated for Streptococcus pyogenes. The results of an exploratory case study on closely related lactobacilli of the acidophilus group suggest that the yogurt bacterium Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) dedicates a relatively important fraction of its coding capacity to secreted proteins, while the probiotic gastrointestinal (GI) tract bacteria L. johnsonii and L. gasseri appear to encode a larger variety of PSE proteins, that may play a role in the interaction with the host.

  7. Positional effects of fusion partners on the yield and solubility of MBP fusion proteins.

    Science.gov (United States)

    Raran-Kurussi, Sreejith; Keefe, Karina; Waugh, David S

    2015-06-01

    Escherichia coli maltose-binding protein (MBP) is exceptionally effective at promoting the solubility of its fusion partners. However, there are conflicting reports in the literature claiming that (1) MBP is an effective solubility enhancer only when it is joined to the N-terminus of an aggregation-prone passenger protein, and (2) MBP is equally effective when fused to either end of the passenger. Here, we endeavor to resolve this controversy by comparing the solubility of a diverse set of MBP fusion proteins that, unlike those analyzed in previous studies, are identical in every way except for the order of the two domains. The results indicate that fusion proteins with an N-terminal MBP provide an excellent solubility advantage along with more robust expression when compared to analogous fusions in which MBP is the C-terminal fusion partner. We find that only intrinsically soluble passenger proteins (i.e., those not requiring a solubility enhancer) are produced as soluble fusions when they precede MBP. We also report that even subtle differences in inter-domain linker sequences can influence the solubility of fusion proteins. Published by Elsevier Inc.

  8.  NET and NETosis – new phenomenon in immunology

    Directory of Open Access Journals (Sweden)

    Natalia Matoszka

    2012-06-01

    Full Text Available  Neutrophils are one of the first cells of the immune system recruited to the site of infection, representing the host’s most effective and numerous front-line defenders. Recently, a novel antimicrobial mechanism of neutrophils has been described: upon activation, they release DNA and a subset of their granule content, forming neutrophil extracellular traps (NETs. These extracellular, chromatin structures, which contain histones and neutrophil granule proteins, can trap and kill a broad spectrum of microbes, including Gram-positive and Gram-negative bacteria, fungi, protozoa and viruses. Some of the pathogens, which are trapped and exposed to high local concentrations of antimicrobial compounds, employ strategies against NET binding, including surface modification and/or degradation of NET by DNases. It has been suggested that NETs are formed during active cell death, recently named NETosis. New data indicate that this novel mechanism of cell death requires interaction between three processes – reactive oxygen species generation, histone citrullination and autophagy – and significantly differs from previously known types of cell death, including apoptosis and necrosis. Moreover, the release of nuclear chromatin was also described for other types of cells – mast cells and eosinophils. Mast cells, like neutrophils, under certain conditions release nuclear chromatin and may undergo a similar active cell death program, while eosinophils release only mitochondrial chromatin, and its release does not lead to the death of these cells.

  9. Top-Down LESA Mass Spectrometry Protein Analysis of Gram-Positive and Gram-Negative Bacteria.

    Science.gov (United States)

    Kocurek, Klaudia I; Stones, Leanne; Bunch, Josephine; May, Robin C; Cooper, Helen J

    2017-10-01

    We have previously shown that liquid extraction surface analysis (LESA) mass spectrometry (MS) is a technique suitable for the top-down analysis of proteins directly from intact colonies of the Gram-negative bacterium Escherichia coli K-12. Here we extend the application of LESA MS to Gram-negative Pseudomonas aeruginosa PS1054 and Gram-positive Staphylococcus aureus MSSA476, as well as two strains of E. coli (K-12 and BL21 mCherry) and an unknown species of Staphylococcus. Moreover, we demonstrate the discrimination between three species of Gram-positive Streptococcus (Streptococcus pneumoniae D39, and the viridans group Streptococcus oralis ATCC 35037 and Streptococcus gordonii ATCC35105), a recognized challenge for matrix-assisted laser desorption ionization time-of-flight MS. A range of the proteins detected were selected for top-down LESA MS/MS. Thirty-nine proteins were identified by top-down LESA MS/MS, including 16 proteins that have not previously been observed by any other technique. The potential of LESA MS for classification and characterization of novel species is illustrated by the de novo sequencing of a new protein from the unknown species of Staphylococcus. Graphical Abstract ᅟ.

  10. Top-Down LESA Mass Spectrometry Protein Analysis of Gram-Positive and Gram-Negative Bacteria

    Science.gov (United States)

    Kocurek, Klaudia I.; Stones, Leanne; Bunch, Josephine; May, Robin C.; Cooper, Helen J.

    2017-10-01

    We have previously shown that liquid extraction surface analysis (LESA) mass spectrometry (MS) is a technique suitable for the top-down analysis of proteins directly from intact colonies of the Gram-negative bacterium Escherichia coli K-12. Here we extend the application of LESA MS to Gram-negative Pseudomonas aeruginosa PS1054 and Gram-positive Staphylococcus aureus MSSA476, as well as two strains of E. coli (K-12 and BL21 mCherry) and an unknown species of Staphylococcus. Moreover, we demonstrate the discrimination between three species of Gram-positive Streptococcus ( Streptococcus pneumoniae D39, and the viridans group Streptococcus oralis ATCC 35037 and Streptococcus gordonii ATCC35105), a recognized challenge for matrix-assisted laser desorption ionization time-of-flight MS. A range of the proteins detected were selected for top-down LESA MS/MS. Thirty-nine proteins were identified by top-down LESA MS/MS, including 16 proteins that have not previously been observed by any other technique. The potential of LESA MS for classification and characterization of novel species is illustrated by the de novo sequencing of a new protein from the unknown species of Staphylococcus. [Figure not available: see fulltext.

  11. Fracionamento dos carboidratos pelas equações do Cornell Net Carbohydrate and Protein System de três cultivares de girassol na presença ou não de irrigação Carbohydrate fractionation of three sunflower cultivars in the presence or absence of irrigation using the Cornell Net Carbohydrate and Protein System equations

    Directory of Open Access Journals (Sweden)

    Mário Adriano Ávila Queiroz

    2008-12-01

    Full Text Available Objetivou-se quantificar as frações de carboidratos pelas equações do Cornell Net Carbohydrate and Protein System (CNCPS de três cultivares de girassol (Helianthus annuus L. cultivados na presença ou não de irrigação. A utilização de uma preparação fibrosa, denominada parede celular (PC, nas equações da CNCPS, em substituição à fibra em detergente neutro (FDN não promoveu diferenças nas frações de carboidratos B1 e C, mas influenciou as frações A e B2. Como os valores da fração B1, obtidos pelo modelo CNCPS foram menores que os teores de amido e pectina determinados em laboratório, supõe-se que a pectina e outros oligossacarídeos da parede celular, solubilizados pela solução de detergente neutro (fibra solúvel, nunca fizeram parte da fração B1, e sim da fração A. Apesar de os carboidratos da fibra solúvel apresentarem elevadas taxas de degradação, não parece adequada a caracterização da fibra solúvel na fração A. Parece mais adequado que a fibra solúvel (que inclui a pectina seja alocada a uma fração exclusivamente sua, que pode ser a fração B2, e que seja criada uma nova fração, a B3, para os carboidratos digeríveis da parede celular. Assim, a fração B1 seria composta apenas de amido. A equação da fração C, que estima os carboidratos indigeríveis da parede celular, pode ser simplificada, relacionando a fração indigerível ao teor de lignina na matéria seca, e não à FDN isenta de cinzas e proteína, como atualmente utilizado. Esta proposta tem implicações práticas, uma vez que a fração indigerível da parede celular tem sido expressa em relação à FDN, e não na MS, com base no fato de que os efeitos inibitórios da lignina ocorrem sobre os componentes fibrosos da parede celular vegetal, e não sobre o conteúdo celular.This work aimed to estimate the carbohydrate fractions in three sunflower (Helianthus annuus L. cultivars in the presence or absence of irrigation, using the

  12. Serine-rich protein is a novel positive regulator for silicon accumulation in mangrove.

    Science.gov (United States)

    Sahebi, Mahbod; Hanafi, Mohamed M; Siti Nor Akmar, A; Rafii, Mohd Y; Azizi, Parisa; Idris, A S

    2015-02-10

    Silicon (Si) plays an important role in reducing plant susceptibility against a variety of different biotic and abiotic stresses; and also has an important regulatory role in soil to avoid heavy metal toxicity and providing suitable growing conditions for plants. A full-length cDNAs of 696bp of serine-rich protein was cloned from mangrove plant (Rhizophora apiculata) by amplification of cDNA ends from an expressed sequence tag homologous to groundnut (Arachis hypogaea), submitted to NCBI (KF211374). This serine-rich protein gene encodes a deduced protein of 223 amino acids. The transcript titre of the serine-rich protein was found to be strongly enriched in roots compared with the leaves of two month old mangrove plants and expression level of this serine-rich protein was found to be strongly induced when the mangrove seedlings were exposed to SiO2. Expression of the serine-rich protein transgenic was detected in transgenic Arabidopsis thaliana, where the amount of serine increased from 1.02 to 37.8mg/g. The same trend was also seen in Si content in the roots (14.3%) and leaves (7.4%) of the transgenic A. thaliana compared to the wild-type plants under Si treatment. The biological results demonstrated that the accumulation of the serine amino acid in the vegetative tissues of the transgenic plants enhanced their ability to absorb and accumulate more Si in the roots and leaves and suggests that the serine-rich protein gene has potential for use in genetic engineering of different stress tolerance characteristics. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Net zero water

    CSIR Research Space (South Africa)

    Lindeque, M

    2013-01-01

    Full Text Available Is it possible to develop a building that uses a net zero amount of water? In recent years it has become evident that it is possible to have buildings that use a net zero amount of electricity. This is possible when the building is taken off...

  14. SolNet

    DEFF Research Database (Denmark)

    Jordan, Ulrike; Vajen, Klaus; Bales, Chris

    2014-01-01

    SolNet, founded in 2006, is the first coordinated International PhD education program on Solar Thermal Engineering. The SolNet network is coordinated by the Institute of Thermal Engineering at Kassel University, Germany. The network offers PhD courses on solar heating and cooling, conference...

  15. Kunstige neurale net

    DEFF Research Database (Denmark)

    Hørning, Annette

    1994-01-01

    Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse.......Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse....

  16. Poweo positive net income of 7.4 million euro in 2006. First time in the black since the company's creation; Poweo benefice net de 7,4 millions euro en 2006. 1. exercice beneficiaire depuis la creation de Poweo

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-03-15

    POWEO, leading independent operator of electricity and gas, presents in this document the principal elements of its consolidated results and its highlights for 2006: - Sales turnover reaches 244.4 M euro, multiplied by 2.2 compared to 2005; - Operational result amounts to 9.3 M euro, against a loss of 8.4 M euro in 2005; - Consolidated net income group share reaches 7.4 M euro, against a loss of 4.9 M euro in 2005. The 2006 consolidated revenue amounted to 244.4 million euro against 243.7 million euro announced on January 31, taking into account a revaluation of 0.7 million euro of the Energy Management's performance. The number of transferred customer sites amounted to 80,300 as at December 31, 2006, in progression of 23% compared to the end of 2005. Gross margin reached 33.6 euro million, in strong progression compared to 2005, reflecting the effectiveness of the Energy Management activity which has allowed to very appreciably reduce the cost price for POWEO of the energy delivered to its customers, within the framework of its global sourcing strategy. Operating costs increased in line with the development plan, under the effect in particular of the strengthening of operational teams, the Group head-count having reached 90 people as at December 31, 2006. EBITDA reached 8.1 million euro in 2006, against a negative amount of 5.3 million euro in 2005, allowing POWEO to meet its objective of a positive EBITDA as announced in September 2006. The EBIT amounted to 9.3 million euro, taking into account a profit of dilution of 7.6 million euro related to the issuance premium recognized on POWEO Production by Verbund, the Austrian national electricity operator and reference shareholder of POWEO, within the framework of the partnership announced in January 2006. With a consolidated net income group share of 7.4 million euro, 2006 thus constitutes the first fiscal year in the black since the Company's creation in 2002. The consolidated net equity amounted to 103

  17. Computing highly correlated positions using mutual information and graph theory for G protein-coupled receptors

    National Research Council Canada - National Science Library

    Fatakia, Sarosh N; Costanzi, Stefano; Chow, Carson C

    2009-01-01

    .... A mutual information graph was constructed with vertices that corresponded to TM positions and edges between vertices were drawn if the mutual information exceeded a threshold of statistical significance...

  18. The Escherichia coli L-arabinose operon: binding sites of the regulatory proteins and a mechanism of positive and negative regulation.

    OpenAIRE

    Ogden, S; Haggerty, D.; Stoner, C M; Kolodrubetz, D; Schleif, R

    1980-01-01

    The locations of DNA binding by the proteins involved with positive and negative regulation of transcription initiation of the L-arabinose operon in Escherichia coli have been determined by the DNase I protection method. Two cyclic AMP receptor protein sites were found, at positions -78 to -107 and -121 to -146, an araC protein--arabinose binding site was found at position -40 to -78, and an araC protein-fucose binding site was found at position -106 to -144. These locations, combined with in...

  19. Samira-VP: A simple protein alignment method with rechecking the alphabet vector positions.

    Science.gov (United States)

    Fotoohifiroozabadi, Samira; Mohamad, Mohd Saberi; Deris, Safaai

    2017-04-01

    Protein structure alignment and comparisons that are based on an alphabetical demonstration of protein structure are more simple to run with faster evaluation processes; thus, their accuracy is not as reliable as three-dimension (3D)-based tools. As a 1D method candidate, TS-AMIR used the alphabetic demonstration of secondary-structure elements (SSE) of proteins and compared the assigned letters to each SSE using the [Formula: see text]-gram method. Although the results were comparable to those obtained via geometrical methods, the SSE length and accuracy of adjacency between SSEs were not considered in the comparison process. Therefore, to obtain further information on accuracy of adjacency between SSE vectors, the new approach of assigning text to vectors was adopted according to the spherical coordinate system in the present study. Moreover, dynamic programming was applied in order to account for the length of SSE vectors. Five common datasets were selected for method evaluation. The first three datasets were small, but difficult to align, and the remaining two datasets were used to compare the capability of the proposed method with that of other methods on a large protein dataset. The results showed that the proposed method, as a text-based alignment approach, obtained results comparable to both 1D and 3D methods. It outperformed 1D methods in terms of accuracy and 3D methods in terms of runtime.

  20. DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair

    NARCIS (Netherlands)

    W.L. de Laat (Wouter); E. Appeldoorn (Esther); K. Sugasawa (Kaoru); E.P.W.C. Weterings (Eric); J.H.J. Hoeijmakers (Jan); N.G.J. Jaspers (Nicolaas)

    1998-01-01

    textabstractThe human single-stranded DNA-binding replication A protein (RPA) is involved in various DNA-processing events. By comparing the affinity of hRPA for artificial DNA hairpin structures with 3'- or 5'-protruding single-stranded arms, we found that hRPA binds ssDNA with a

  1. A mode of error: Immunoglobulin binding protein (a subset of anti-citrullinated proteins can cause false positive tuberculosis test results in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Maria Greenwald

    2017-12-01

    Full Text Available Citrullinated Immunoglobulin Binding Protein (BiP is a newly described autoimmune target in rheumatoid arthritis (RA, one of many cyclic citrullinated peptides(CCP or ACPA. BiP is over-expressed in RA patients causing T cell expansion and increased interferon levels during incubation for the QuantiFERON-Gold tuberculosis test (QFT-G TB. The QFT-G TB has never been validated where interferon is increased by underlying disease, as for example RA.Of ACPA-positive RA patients (n = 126, we found a 13% false-positive TB test rate by QFT-G TB. Despite subsequent biologic therapy for 3 years of all 126 RA patients, none showed evidence of TB without INH. Most of the false-positive RA patients after treatment with biologic therapy reverted to a negative QFT-G test. False TB tests correlated with ACPA level (p < 0.02.Three healthy women without arthritis or TB exposure had negative QFT-G TB. In vitro, all three tested positive every time for TB correlating to the dose of BiP or anti-BiP added, at 2 ug/ml, 5 ug/ml, 10 ug/ml, and 20 ug/ml.BiP naturally found in the majority of ACPA-positive RA patients can result in a false positive QFT-G TB. Subsequent undertreatment of RA, if biologic therapy is withheld, and overtreatment of presumed latent TB may harm patients. Keywords: Tuberculosis, IGRA, Rheumatoid arthritis, Interferon, Anti-citrullinated peptide antibody (ACPA, Immunoglobulin binding protein (BiP

  2. Anti-Inflammatory Heat Shock Protein 70 Genes are Positively Associated with Human Survival

    DEFF Research Database (Denmark)

    Singh, Ripudaman; Kølvraa, Steen; Bross, Peter Gerd

    2010-01-01

    with longevity. The involvement of heat shock protein 70 (Hsp70) in cellular maintenance and repair mechanisms, including its role as an anti-inflammatory protein, makes it a suitable candidate for studying such associations. We have studied the association of three single nucleotide polymorphisms, HSPA1A (-110A...... the opportunity to perform survival analysis on these subjects. Haplotype relative risk, and genotype relative risk were calculated to measure the effects of haplotypes and genotypes on human survival in a sex-specific manner. A significant association of HSPA1A-AA (RR=3.864; p=0.016) and HSPA1B-AA (RR=2.764; p=0...... observations from heat shock response (HSR) study where we had shown that after heat stimulation, mononuclear cells from the carriers of genotype HSPA1L-TT had better HSR than cells with the HSPA1L-CC genotype....

  3. Protein Charge and Mass Contribute to the Spatio-temporal Dynamics of Protein-Protein Interactions in a Minimal Proteome

    Science.gov (United States)

    Xu, Yu; Wang, Hong; Nussinov, Ruth; Ma, Buyong

    2013-01-01

    We constructed and simulated a ‘minimal proteome’ model using Langevin dynamics. It contains 206 essential protein types which were compiled from the literature. For comparison, we generated six proteomes with randomized concentrations. We found that the net charges and molecular weights of the proteins in the minimal genome are not random. The net charge of a protein decreases linearly with molecular weight, with small proteins being mostly positively charged and large proteins negatively charged. The protein copy numbers in the minimal genome have the tendency to maximize the number of protein-protein interactions in the network. Negatively charged proteins which tend to have larger sizes can provide large collision cross-section allowing them to interact with other proteins; on the other hand, the smaller positively charged proteins could have higher diffusion speed and are more likely to collide with other proteins. Proteomes with random charge/mass populations form less stable clusters than those with experimental protein copy numbers. Our study suggests that ‘proper’ populations of negatively and positively charged proteins are important for maintaining a protein-protein interaction network in a proteome. It is interesting to note that the minimal genome model based on the charge and mass of E. Coli may have a larger protein-protein interaction network than that based on the lower organism M. pneumoniae. PMID:23420643

  4. M-protein-positive chronic active Epstein-Barr virus infection: features mimicking HIV-1 infection.

    Science.gov (United States)

    Imashuku, Shinsaku; Azuma, Naoto; Kanegane, Hirokazu; Kasahara, Yoshihito

    2009-09-01

    Chronic active Epstein-Barr virus infection (CAEBV) is a unique and fatal lymphoproliferative disease (LPD), which often shows high serum IgG and/or IgE. The significance of such immunoglobulin abnormalities in CAEBV has not been fully evaluated and discussed. In addition, such clinical features mimic HIV-1 infection. We report here a case of CAEBV with M-protein detected which may shed a new light on the pathogenesis of this disease.

  5. Pro NET Best Practices

    CERN Document Server

    Ritchie, Stephen D

    2011-01-01

    Pro .NET Best Practices is a practical reference to the best practices that you can apply to your .NET projects today. You will learn standards, techniques, and conventions that are sharply focused, realistic and helpful for achieving results, steering clear of unproven, idealistic, and impractical recommendations. Pro .NET Best Practices covers a broad range of practices and principles that development experts agree are the right ways to develop software, which includes continuous integration, automated testing, automated deployment, and code analysis. Whether the solution is from a free and

  6. Getting to Net Zero

    Energy Technology Data Exchange (ETDEWEB)

    2016-09-01

    The technology necessary to build net zero energy buildings (NZEBs) is ready and available today, however, building to net zero energy performance levels can be challenging. Energy efficiency measures, onsite energy generation resources, load matching and grid interaction, climatic factors, and local policies vary from location to location and require unique methods of constructing NZEBs. It is recommended that Components start looking into how to construct and operate NZEBs now as there is a learning curve to net zero construction and FY 2020 is just around the corner.

  7. Instant Lucene.NET

    CERN Document Server

    Heydt, Michael

    2013-01-01

    Filled with practical, step-by-step instructions and clear explanations for the most important and useful tasks. A step-by-step guide that helps you to index, search, and retrieve unstructured data with the help of Lucene.NET.Instant Lucene.NET How-to is essential for developers new to Lucene and Lucene.NET who are looking to get an immediate foundational understanding of how to use the library in their application. It's assumed you have programming experience in C# already, but not that you have experience with search techniques such as information retrieval theory (although there will be a l

  8. MYC Protein-positive Diffuse Large B-Cell Lymphoma Features an Activated B-Cell Receptor Signal Pathway.

    Science.gov (United States)

    Wang, Wei-Ge; Jiang, Xiang-Nan; Liu, Ze-Bing; Zhou, Xiao-Yan; Li, Xiao-Qiu

    2017-04-01

    Components of the B-cell receptor (BCR) signaling pathway represent promising therapeutic targets in diffuse large B-cell lymphoma (DLBCL) and other B-cell malignancies. MYC, a transcriptional factor and oncoprotein, is overexpressed in a fraction of DLBCL and indicates poor prognosis and aggressive clinical course when treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, BCR signaling status in MYC-positive DLBCL cases and the potential efficacy of BCR signal inhibitors in treating this aggressive disease are unknown. To further elucidate the BCR signaling pathway in MYC-positive DLBCL, we analyzed the levels of BCR-associated genes according to MYC gene status, detected phosphorylated protein with primary DLBCL samples, and estimated the patient survival with MYC expression. In addition, we manipulated MYC gene expression and tested its effects on BCR signaling in vitro. We found that CD19, SYK, and BLK were highly expressed in DLBCL with MYC gene overexpression. MYC-positive DLBCL had higher levels of pSYK and pBLK, but only pSYK level correlated with patient survival. The in vitro studies demonstrated that overexpression of the MYC gene augmented BCR signaling, whereas MYC gene knockdown attenuated BCR signaling. Thus, MYC protein-positive DLBCL features highly activated BCR signaling and may represent a potential candidate for BCR inhibitor therapy.

  9. Incorporating deep learning with convolutional neural networks and position specific scoring matrices for identifying electron transport proteins.

    Science.gov (United States)

    Le, Nguyen-Quoc-Khanh; Ho, Quang-Thai; Ou, Yu-Yen

    2017-09-05

    In several years, deep learning is a modern machine learning technique using in a variety of fields with state-of-the-art performance. Therefore, utilization of deep learning to enhance performance is also an important solution for current bioinformatics field. In this study, we try to use deep learning via convolutional neural networks and position specific scoring matrices to identify electron transport proteins, which is an important molecular function in transmembrane proteins. Our deep learning method can approach a precise model for identifying of electron transport proteins with achieved sensitivity of 80.3%, specificity of 94.4%, and accuracy of 92.3%, with MCC of 0.71 for independent dataset. The proposed technique can serve as a powerful tool for identifying electron transport proteins and can help biologists understand the function of the electron transport proteins. Moreover, this study provides a basis for further research that can enrich a field of applying deep learning in bioinformatics. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Increasing production of proteins in gram-positive microorganisms using SecG

    NARCIS (Netherlands)

    Quax, Wilhelmus J.; Caldwell, Robert M

    2003-01-01

    The present invention relates to secretion in Gram-positive microorganisms. The present invention provides the nuclei acid and amino acid sequences for the Bacillus subtilis secretion factor SecG. The present invention also provides means for increasing the secretion of heterologous or homologous

  11. Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides

    NARCIS (Netherlands)

    Sesink, Aloys L. A.; Arts, Ilja C. W.; de Boer, Vincent C. J.; Breedveld, Pauline; Schellens, Jan H. M.; Hollman, Peter C. H.; Russel, Frans G. M.

    2005-01-01

    The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

  12. Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides.

    NARCIS (Netherlands)

    Sesink, A.L.; Arts, I.C.; Boer, V.C. de; Breedveld, P.; Schellens, J.H.M.; Hollman, P.C.H.; Russel, F.G.M.

    2005-01-01

    The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

  13. Net Zero Energy Buildings

    DEFF Research Database (Denmark)

    Marszal, Anna Joanna; Bourrelle, Julien S.; Musall, Eike

    2010-01-01

    and identify possible renewable energy supply options which may be considered in calculations. Finally, the gap between the methodology proposed by each organisation and their respective national building code is assessed; providing an overview of the possible changes building codes will need to undergo......The international cooperation project IEA SHC Task 40 / ECBCS Annex 52 “Towards Net Zero Energy Solar Buildings”, attempts to develop a common understanding and to set up the basis for an international definition framework of Net Zero Energy Buildings (Net ZEBs). The understanding of such buildings...... parameters used in the calculations are discussed and the various renewable supply options considered in the methodologies are summarised graphically. Thus, the paper helps to understand different existing approaches to calculate energy balance in Net ZEBs, highlights the importance of variables selection...

  14. PhysioNet

    Data.gov (United States)

    U.S. Department of Health & Human Services — The PhysioNet Resource is intended to stimulate current research and new investigations in the study of complex biomedical and physiologic signals. It offers free...

  15. M-protein-positive chronic active Epstein-Barr virus infection: features mimicking HIV-1 infection

    OpenAIRE

    Imashuku, Shinsaku; Azuma, Naoto; Kanegane, Hirokazu; Kasahara, Yoshihito

    2009-01-01

    Chronic active Epstein-Barr virus infection (CAEBV) is a unique and fatal lymphoproliferative disease (LPD), which often shows high serum IgG and/or IgE. The significance of such immunoglobulin abnormalities in CAEBV has not been fully evaluated and discussed. In addition, such clinical features mimic HIV-1 infection. We report here a case of CAEBV with M-protein detected which may shed a new light on the pathogenesis of this disease. © 2009 The Japanese Society of Hematology.

  16. The prevalence and predictive value of dipstick urine protein in HIV-positive persons in Europe

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Ryom, Lene; Lapadula, Giuseppe

    2014-01-01

    INTRODUCTION: Proteinuria (PTU) is an important marker for the development and progression of renal disease, cardiovascular disease and death, but there is limited information about the prevalence and factors associated with confirmed PTU in predominantly white European HIV+ persons, especially...... in those with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m(2). PATIENTS AND METHODS: Baseline was defined as the first of two consecutive dipstick urine protein (DPU) measurements during prospective follow-up >1/6/2011 (when systematic data collection began). PTU was defined as two...

  17. TideNet

    Science.gov (United States)

    2015-10-30

    query tide data sources in a desired geographic region of USA and its territories (Figure 1). Users can select a tide data source through the Google Map ...select data sources according to the desired geographic region. It uses the Google Map interface to display data from different sources. Recent...Coastal Inlets Research Program TideNet The TideNet is a web-based Graphical User Interface (GUI) that provides users with GIS mapping tools to

  18. Building Neural Net Software

    OpenAIRE

    Neto, João Pedro; Costa, José Félix

    1999-01-01

    In a recent paper [Neto et al. 97] we showed that programming languages can be translated on recurrent (analog, rational weighted) neural nets. The goal was not efficiency but simplicity. Indeed we used a number-theoretic approach to machine programming, where (integer) numbers were coded in a unary fashion, introducing a exponential slow down in the computations, with respect to a two-symbol tape Turing machine. Implementation of programming languages in neural nets turns to be not only theo...

  19. Interaction Nets in Russian

    OpenAIRE

    Salikhmetov, Anton

    2013-01-01

    Draft translation to Russian of Chapter 7, Interaction-Based Models of Computation, from Models of Computation: An Introduction to Computability Theory by Maribel Fernandez. "In this chapter, we study interaction nets, a model of computation that can be seen as a representative of a class of models based on the notion of 'computation as interaction'. Interaction nets are a graphical model of computation devised by Yves Lafont in 1990 as a generalisation of the proof structures of linear logic...

  20. Programming NET 35

    CERN Document Server

    Liberty, Jesse

    2009-01-01

    Bestselling author Jesse Liberty and industry expert Alex Horovitz uncover the common threads that unite the .NET 3.5 technologies, so you can benefit from the best practices and architectural patterns baked into the new Microsoft frameworks. The book offers a Grand Tour" of .NET 3.5 that describes how the principal technologies can be used together, with Ajax, to build modern n-tier and service-oriented applications. "

  1. Protein Kinase CK2: A Targetable BCR-ABL Partner in Philadelphia Positive Leukemias

    OpenAIRE

    Morotti, Alessandro; Carr?, Giovanna; Panuzzo, Cristina; Crivellaro, Sabrina; Taulli, Riccardo; Guerrasio, Angelo; Saglio, Giuseppe

    2015-01-01

    BCR-ABL-mediated leukemias, either Chronic Myeloid Leukemia (CML) or Philadelphia positive Acute Lymphoblastic Leukemia (ALL), are the paradigm of targeted molecular therapy of cancer due to the impressive clinical responses obtained with BCR-ABL specific tyrosine kinase inhibitors (TKIs). However, BCR-ABL TKIs do not allow completely eradicating both CML and ALL. Furthermore, ALL therapy is associated with much worse responses to TKIs than those observed in CML. The identification of additio...

  2. Organelle positioning in muscles requires cooperation between two KASH proteins and microtubules.

    Science.gov (United States)

    Elhanany-Tamir, Hadas; Yu, Yanxun V; Shnayder, Miri; Jain, Ankit; Welte, Michael; Volk, Talila

    2012-09-03

    Striated muscle fibers are characterized by their tightly organized cytoplasm. Here, we show that the Drosophila melanogaster KASH proteins Klarsicht (Klar) and MSP-300 cooperate in promoting even myonuclear spacing by mediating a tight link between a newly discovered MSP-300 nuclear ring and a polarized network of astral microtubules (aMTs). In either klar or msp-300(ΔKASH), or in klar and msp-300 double heterozygous mutants, the MSP-300 nuclear ring and the aMTs retracted from the nuclear envelope, abrogating this even nuclear spacing. Anchoring of the myonuclei to the core acto-myosin fibrillar compartment was mediated exclusively by MSP-300. This protein was also essential for promoting even distribution of the mitochondria and ER within the muscle fiber. Larval locomotion is impaired in both msp-300 and klar mutants, and the klar mutants were rescued by muscle-specific expression of Klar. Thus, our results describe a novel mechanism of nuclear spacing in striated muscles controlled by the cooperative activity of MSP-300, Klar, and astral MTs, and demonstrate its physiological significance.

  3. DPDR-CPI, a server that predicts Drug Positioning and Drug Repositioning via Chemical-Protein Interactome.

    Science.gov (United States)

    Luo, Heng; Zhang, Ping; Cao, Xi Hang; Du, Dizheng; Ye, Hao; Huang, Hui; Li, Can; Qin, Shengying; Wan, Chunling; Shi, Leming; He, Lin; Yang, Lun

    2016-11-02

    The cost of developing a new drug has increased sharply over the past years. To ensure a reasonable return-on-investment, it is useful for drug discovery researchers in both industry and academia to identify all the possible indications for early pipeline molecules. For the first time, we propose the term computational "drug candidate positioning" or "drug positioning", to describe the above process. It is distinct from drug repositioning, which identifies new uses for existing drugs and maximizes their value. Since many therapeutic effects are mediated by unexpected drug-protein interactions, it is reasonable to analyze the chemical-protein interactome (CPI) profiles to predict indications. Here we introduce the server DPDR-CPI, which can make real-time predictions based only on the structure of the small molecule. When a user submits a molecule, the server will dock it across 611 human proteins, generating a CPI profile of features that can be used for predictions. It can suggest the likelihood of relevance of the input molecule towards ~1,000 human diseases with top predictions listed. DPDR-CPI achieved an overall AUROC of 0.78 during 10-fold cross-validations and AUROC of 0.76 for the independent validation. The server is freely accessible via http://cpi.bio-x.cn/dpdr/.

  4. Wolbachia bacteria reside in host Golgi-related vesicles whose position is regulated by polarity proteins.

    Directory of Open Access Journals (Sweden)

    Kyung-Ok Cho

    Full Text Available Wolbachia pipientis are intracellular symbiotic bacteria extremely common in various organisms including Drosophila melanogaster, and are known for their ability to induce changes in host reproduction. These bacteria are present in astral microtubule-associated vesicular structures in host cytoplasm, but little is known about the identity of these vesicles. We report here that Wolbachia are restricted only to a group of Golgi-related vesicles concentrated near the site of membrane biogenesis and minus-ends of microtubules. The Wolbachia vesicles were significantly mislocalized in mutant embryos defective in cell/planar polarity genes suggesting that cell/tissue polarity genes are required for apical localization of these Golgi-related vesicles. Furthermore, two of the polarity proteins, Van Gogh/Strabismus and Scribble, appeared to be present in these Golgi-related vesicles. Thus, establishment of polarity may be closely linked to the precise insertion of Golgi vesicles into the new membrane addition site.

  5. A positive interaction between inhibitors of protein synthesis and cefepime in the fight against methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Guignard, B; Vouillamoz, J; Giddey, M; Moreillon, P

    2013-07-01

    Quinupristin-dalfopristin (Q-D) synergizes with cefepime for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Here, we studied whether the synergism was restricted to MRSA and if it extended to non-beta-lactam cell wall inhibitors or to other inhibitors of protein synthesis. Three MRSA and two methicillin-susceptible S. aureus (MSSA) strains were tested, including an isogenic pair of mecA (-)/mecA (+) S. aureus Newman. The drug interactions were determined by fractional inhibitory concentration (FIC) indices and population analysis profiles. The antibacterial drugs that we used included beta-lactam (cefepime) and non-beta-lactam cell wall inhibitors (D-cycloserine, fosfomycin, vancomycin, teicoplanin), inhibitors of protein synthesis (Q-D, erythromycin, chloramphenicol, tetracycline, linezolid, fusidic acid), and polynucleotide inhibitors (cotrimoxazole, ciprofloxacin). The addition of each protein inhibitor to cefepime was synergistic (FIC ≤ 0.5) or additive (FIC > 0.5 but synergism was specific to beta-lactam antibiotics. Moreover, the synergism was not lost against fem mutants, indicating that it acted at another level. The restriction of the beneficial effect to MRSA suggests that the functionality of penicillin-binding protein 2A (PBP2A) was affected, either directly or indirectly. Further studies are necessary in order to provide a mechanism for this positive interaction.

  6. The Evolution of the Actin Binding NET Superfamily

    Directory of Open Access Journals (Sweden)

    Tim eHawkins

    2014-06-01

    Full Text Available The arabidopsis Networked protein superfamily are plant-specific actin binding proteins which specifically label different membrane compartments and identify specialized sites of interaction between actin and membranes unique to plants. There are 13 members of the superfamily in arabidopsis which group into 4 distinct clades or subfamilies. NET homologues are absent from the genomes of metazoa and fungi, furthermore in Plantae NET sequences are also absent from the genome of mosses and more ancient extant plant clades. A single subfamily of the NET proteins are found encoded in the club moss genome; an extant species of the earliest vascular plants. Gymnosperms have examples from subfamilies 4 and 3 with a hybrid form of NET1 and 2 which shows characteristics of both NET1 and NET2. In addition to NET3 and 4 subfamilies, the NET1 and pollen-expressed NET2 subfamilies are only found as independent sequences in angiosperms. This is consistent with the divergence of reproductive actin. The four subfamilies are conserved across monocots and eudicots with the numbers of members of each clade expanding at this point due in part to regions of genome duplication. Since the emergence of the NET superfamily at the dawn of vascular plants they have continued to develop and diversify in a manner which has mirrored the divergence and complexity of plant species through evolution in the ‘March of Progress’.

  7. The Net Reclassification Index (NRI)

    DEFF Research Database (Denmark)

    Pepe, Margaret S.; Fan, Jing; Feng, Ziding

    2015-01-01

    The Net Reclassification Index (NRI) is a very popular measure for evaluating the improvement in prediction performance gained by adding a marker to a set of baseline predictors. However, the statistical properties of this novel measure have not been explored in depth. We demonstrate the alarming...... marker is proven to erroneously yield a positive NRI. Some insight into this phenomenon is provided. Since large values for the NRI statistic may simply be due to use of poorly fitting risk models, we suggest caution in using the NRI as the basis for marker evaluation. Other measures of prediction...

  8. Positive Selection in Bone Morphogenetic Protein 15 Targets a Natural Mutation Associated with Primary Ovarian Insufficiency in Human

    Science.gov (United States)

    Meslin, Camille; Monestier, Olivier; Di Pasquale, Elisa; Pascal, Géraldine; Persani, Luca; Fabre, Stéphane

    2013-01-01

    Bone Morphogenetic Protein 15 (BMP15) is a TGFβ-like oocyte-derived growth factor involved in ovarian folliculogenesis as a critical regulator of many granulosa cell processes. Alterations of the BMP15 gene have been found associated with different ovarian phenotypic effects depending on the species, from sterility to increased prolificacy in sheep, slight subfertility in mouse or associated with primary ovarian insufficiency (POI) in women. To investigate the evolving role of BMP15, a phylogenetic analysis of this particular TGFβ family member was performed. A maximum likelihood phylogenetic tree of several TGFβ/BMP family members expressed by the ovary showed that BMP15 has a very strong divergence and a rapid evolution compared to others. Moreover, among 24 mammalian species, we detected signals of positive selection in the hominidae clade corresponding to F146, L189 and Y235 residues in human BMP15. The biological importance of these residues was tested functionally after site directed-mutagenesis in a COV434 cells luciferase assay. By replacing the positively selected amino acid either by alanine or the most represented residue in other studied species, only L189A, Y235A and Y235C mutants showed a significant increase of BMP15 signaling when compared to wild type. Additionally, the Y235C mutant was more potent than wild type in inhibiting progesterone secretion of ovine granulosa cells in primary culture. Interestingly, the Y235C mutation was previously identified in association with POI in women. In conclusion, this study evidences that the BMP15 gene has evolved faster than other members of the TGFß family and was submitted to a positive selection pressure in the hominidae clade. Some residues under positive selection are of great importance for the normal function of the protein and thus for female fertility. Y235 represents a critical residue in the determination of BMP15 biological activity, thus indirectly confirming its role in the onset of POI in

  9. Different amounts of protein-bound citrulline and homocitrulline in foot joint tissues of a patient with anti-citrullinated protein antibody positive erosive rheumatoid arthritis.

    Science.gov (United States)

    Turunen, Sanna; Koivula, Marja-Kaisa; Melkko, Jukka; Alasaarela, Eeva; Lehenkari, Petri; Risteli, Juha

    2013-09-23

    Antibodies binding to citrullinated proteins are a frequent finding in rheumatoid arthritis patients and may precede the onset of clinical symptoms several years. The antibodies are a predisposing factor for bone erosions but their origin is unknown. In this study we analyze in detail the levels of protein bound citrulline and homocitrulline in several tissue samples of a single erosive arthritic surgery patient. Serum antibodies binding to CCP, MCV and citrulline- or homocitrulline-containing type I and II collagen carboxytelopeptides were measured. Tissue samples of a single RA patient, taken in two separate operations performed with two-year time span were hydrolyzed and analyzed for citrulline and homocitrulline content by HPLC. Protein-bound citrulline and homocitrulline were found in several joint tissues of a RA patient with ACPA-positive erosive disease. The amount of homocitrulline stayed relatively constant between the different tissues. The amount of citrulline in erosive tissue was 3-times higher than in non-erosive tissue in the first operation. In the samples of the second operation 3-4-times higher mean amounts of citrulline were found in two out of the six tissues investigated. Homocitrulline is present in rheumatoid nodule together with citrulline. There is more variation in the amount of citrulline than in the amount of homocitrulline between the tissues. The tissue sample containing the most citrulline was the most erosive.

  10. The prevalence and predictive value of dipstick urine protein in HIV-positive persons in Europe

    Directory of Open Access Journals (Sweden)

    Amanda Mocroft

    2014-11-01

    Full Text Available Introduction: Proteinuria (PTU is an important marker for the development and progression of renal disease, cardiovascular disease and death, but there is limited information about the prevalence and factors associated with confirmed PTU in predominantly white European HIV+ persons, especially in those with an estimated glomerular filtration rate (eGFR of 60 mL/min/1.73 m2. Patients and methods: Baseline was defined as the first of two consecutive dipstick urine protein (DPU measurements during prospective follow-up >1/6/2011 (when systematic data collection began. PTU was defined as two consecutive DUP >1+ (>30 mg/dL >3 months apart; persons with eGFR 90 and those with prior abacavir use had lower odds of PTU (Figure 1. There was no significant association between past or current use of tenofovir, lopinavir, atazanvir (boosted or unboosted or any other boosted PI and PTU (p>0.2. During 688.2 person-years of follow up (PYFU, three persons developed chronic kidney disease (CKD; confirmed [>3 months apart] eGFR60 was almost 10 times higher than in those without baseline PTU and eGFR>60 (rate ratio 9.61; 95% CI 0.87–105.9, p=0.065. Conclusions: One in 25 persons with eGFR>60 had confirmed proteinuria at baseline. Factors associated with PTU were similar to those associated with CKD. The lack of association with antiretrovirals, particularly tenofovir, may be due to the cross-sectional design of this study, and additional follow-up is required to address progression to PTU in those without PTU at baseline. It may also suggest other markers are needed to capture the deteriorating renal function associated with antiretrovirals may be needed at higher eGFRs. Our findings suggest PTU is an early marker for impaired renal function.

  11. RTE results 2002: positive net income (+112 million euros), in keeping with forecasts, at the end of a year placed under the sign of quality; Bilan RTE 2002: un resultat net positif (+112 M d'euros), conforme aux previsions, au terme d'une annee placee sous le signe de la qualite

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-03-01

    The results of RTE, the French Transmission System Operator, confirm the company's sound financial position at the end of a year placed under the sign of quality. RTE announces a net income after taxes for 2002 that is in keeping with its forecasts: +112 million euros (versus 250 million euros in 2001) for 3,657 million euros in sales revenue. 616 million euros were devoted to investments for the development and replacement of the company's transmission and interconnection networks. RTE also continued the reduction of its debt by 99 million euros. The year 2001 had experienced a cold spell at year-end, bringing with it higher-than-average revenue (+80 million euros). 2002, which was exceptionally mild at the end of the year, saw revenue fall off by 40 million euros compared with a normal year. In all, the climatic impact goes to explain a drop of 120 million euros in 2002. This drop is partially offset by additional revenue since the adoption on 1/11/02 of the network access tariff (about 30 million euros). This tariff is now substituted for the transitional price scale which was unfavourable to RTE. Operating expenses rose from 3,089 million euros to 3,316 million euros. The most significant increases are to be attributed in particular to: - the contribution of 68 million euros to the 'ETSO Fund', ETSO being the Association of European Transmission System Operators which, since 1/03/02, has ensured the compensation for network utilisation costs related to international transfers, - the gaining in momentum, with more than 80 million euros, of the network mechanical security enhancement programme decided in the wake of the storms of 1999, which aims at adapting RTE infrastructures to the new technical requirements for wind resistance. More than 720 km of power lines were erected or replaced while 12 electrical substations were connected to the RTE network in 2002. Among these projects, mention should be made of the following: the commissioning of

  12. Composição corporal e exigências líquidas proteicas de ovinos Santa Inês em crescimento Body composition and net protein requirements for growing Santa Inês sheep

    Directory of Open Access Journals (Sweden)

    José Gilson Louzada Regadas Filho

    2011-06-01

    protein requirements of 24 Santa Inês non-castrated growing sheep at average age of 50 days and average body weight of 13.00 ± 0.56 kg. After a ten-day adaptation period, four animals were slaughtered to be used as a reference for estimates of empty body weight (EBW and initial body composition of the other animals. The remaining animals were assigned into a randomized block design with diets containg different levels of metabolizable energy (2.08; 2.28; 2.47 and 2.69 Mcal/kg of DM and crude protein (12.74; 14.36, 15.97 and 17.65% CP of DM with five replicates. The N daily excretion was estimated by extrapolating regression equations of N intake (g/kg BW0.75/day in function of retention (g/kg BW0.75/day for zero intake. The derivative regression of the logarithm of protein content in function of the logarithm of EBW enabled the estimation of net protein requirement for empty body weight gain (EBWG. Daily nitrogen excretion was 277 ± 0.05 mg/kg BW0.75/day and net protein requirement for maintenance was 1.73 g/kg BW0.75/day. Protein content of EBW of animals decreased from 157.83 to 144.33 g/kg of EBW when the BW of the animals increased from 15 to 30 kg, respectively. The amount of protein deposited in the gain decreased from 137.47 to 125.71 g/kg of EBWG with the increase of body weight of the animals from 15 to 30 kg, respectively. Nitrogen fecal excretion and protein net requirement for maintenance of Santa Inês growing lambs was lower than the values commonly cited by the main systems of feed evaluation and nutrient requirements for small ruminants.

  13. La plataforma .NET

    OpenAIRE

    Fornas Estrada, Miquel

    2008-01-01

    L'aparició de la plataforma .NET Framework ha suposat un canvi molt important en la forma de crear i distribuir aplicacions, degut a que incorpora una sèrie d'innovacions tècniques i productives que simplifiquen molt les tasques necessàries per desenvolupar un projecte. La aparición de la plataforma. NET Framework ha supuesto un cambio muy importante en la forma de crear y distribuir aplicaciones, debido a que incorpora una serie de innovaciones técnicas y productivas que simplifican mucho...

  14. Biological Petri Nets

    CERN Document Server

    Wingender, E

    2011-01-01

    It was suggested some years ago that Petri nets might be well suited to modeling metabolic networks, overcoming some of the limitations encountered by the use of systems employing ODEs (ordinary differential equations). Much work has been done since then which confirms this and demonstrates the usefulness of this concept for systems biology. Petri net technology is not only intuitively understood by scientists trained in the life sciences, it also has a robust mathematical foundation and provides the required degree of flexibility. As a result it appears to be a very promising approach to mode

  15. Positive selection and increased antiviral activity associated with the PARP-containing isoform of human zinc-finger antiviral protein.

    Directory of Open Access Journals (Sweden)

    Julie A Kerns

    2008-01-01

    Full Text Available Intrinsic immunity relies on specific recognition of viral epitopes to mount a cell-autonomous defense against viral infections. Viral recognition determinants in intrinsic immunity genes are expected to evolve rapidly as host genes adapt to changing viruses, resulting in a signature of adaptive evolution. Zinc-finger antiviral protein (ZAP from rats was discovered to be an intrinsic immunity gene that can restrict murine leukemia virus, and certain alphaviruses and filoviruses. Here, we used an approach combining molecular evolution and cellular infectivity assays to address whether ZAP also acts as a restriction factor in primates, and to pinpoint which protein domains may directly interact with the virus. We find that ZAP has evolved under positive selection throughout primate evolution. Recurrent positive selection is only found in the poly(ADP-ribose polymerase (PARP-like domain present in a longer human ZAP isoform. This PARP-like domain was not present in the previously identified and tested rat ZAP gene. Using infectivity assays, we found that the longer isoform of ZAP that contains the PARP-like domain is a stronger suppressor of murine leukemia virus expression and Semliki forest virus infection. Our study thus finds that human ZAP encodes a potent antiviral activity against alphaviruses. The striking congruence between our evolutionary predictions and cellular infectivity assays strongly validates such a combined approach to study intrinsic immunity genes.

  16. Positive and negative regulation of cell proliferation by E2F-1: influence of protein level and human papillomavirus oncoproteins

    DEFF Research Database (Denmark)

    Melillo, R M; Helin, K; Lowy, D R

    1994-01-01

    that is defective for immortalization and binding of pRB and pRB-related proteins. By contrast, E2F-1 was unable to complement two other E7 mutants, p2PRO and p31/32ARG/PRO, which are also defective in the immortalization assay, although their proteins display wild-type binding of pRB in vitro. Since the binding...... levels of E2F-1, produced by transfection of the E2F-1 cDNA under the control of a strong promoter, reduced colony formation in normal human foreskin keratinocytes (NHFKs). This inhibition could not be overcome by wild-type human papillomavirus type 16 (HPV16) E6 and E7, two proteins which cooperate...... to immortalize NHFKs, or by a transdominant p53 mutant. High levels of E2F-1 also inhibited growth of primary and established fibroblasts. The growth-inhibitory activity required the DNA binding function of E2F-1 but not its transactivation or pRB binding activities. A positive role for lower levels of E2F-1...

  17. A FRET-based study reveals site-specific regulation of spindle position checkpoint proteins at yeast centrosomes

    Science.gov (United States)

    Gryaznova, Yuliya; Caydasi, Ayse Koca; Malengo, Gabriele; Sourjik, Victor; Pereira, Gislene

    2016-01-01

    The spindle position checkpoint (SPOC) is a spindle pole body (SPB, equivalent of mammalian centrosome) associated surveillance mechanism that halts mitotic exit upon spindle mis-orientation. Here, we monitored the interaction between SPB proteins and the SPOC component Bfa1 by FRET microscopy. We show that Bfa1 binds to the scaffold-protein Nud1 and the γ-tubulin receptor Spc72. Spindle misalignment specifically disrupts Bfa1-Spc72 interaction by a mechanism that requires the 14-3-3-family protein Bmh1 and the MARK/PAR-kinase Kin4. Dissociation of Bfa1 from Spc72 prevents the inhibitory phosphorylation of Bfa1 by the polo-like kinase Cdc5. We propose Spc72 as a regulatory hub that coordinates the activity of Kin4 and Cdc5 towards Bfa1. In addition, analysis of spc72∆ cells shows that a mitotic-exit-promoting dominant signal, which is triggered upon elongation of the spindle into the bud, overrides the SPOC. Our data reinforce the importance of daughter-cell-associated factors and centrosome-based regulations in mitotic exit and SPOC control. DOI: http://dx.doi.org/10.7554/eLife.14029.001 PMID:27159239

  18. The FBA motif-containing protein AFBA1 acts as a novel positive regulator of ABA response in Arabidopsis.

    Science.gov (United States)

    Kim, Yun Young; Cui, Mei Hua; Noh, Min Soo; Jung, Kwang Wook; Shin, Jeong Sheop

    2017-03-01

    ABA plays a critical role in regulating seed germination and stomatal movement in response to drought stress. Screening ABA-responsive genes led to the identification of a novel Arabidopsis gene encoding a protein which contained a conserved F-box-associated (FBA) domain, subsequently named ABA-responsive FBA domain-containing protein 1 (AFBA1). Expression of ProAFBA1:GUS revealed that this gene was mainly expressed in guard cells. Expression of AFBA1 increased following the application of exogenous ABA and exposure to salt (NaCl) and drought stresses. Seed germination of the loss-of-function mutant (afba1) was insensitive to ABA, salt or mannitol, whereas AFBA1-overexpressing (Ox) seeds were more sensitive to these stresses than the wild-type seeds. The afba1 plants showed decreased drought tolerance, increased water loss rate and ABA-insensitive stomatal movement compared with the wild-type. In contrast, AFBA1-Ox plants exhibited enhanced drought tolerance and a rapid ABA-induced stomatal closure response. The expression of genes encoding serine/threonine protein phosphatases that are known negative regulators of ABA signaling increased in afba1 plants but decreased in AFBA1-Ox plants. AFBA1 was also found to be localized in the nucleus and to interact with an R2R3-type transcription factor, MYB44, leading to the suggestion that it functions in the stabilization of MYB44. Based on these results, we suggest that AFBA1 functions as a novel positive regulator of ABA responses, regulating the expression of genes involved in ABA signal transduction in Arabidopsis through its interaction with positive regulators of ABA signaling including MYB44, and increasing their stability during ABA-mediated responses. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Double-muscled and conventional cattle have the same net energy requirements if these are related to mature and current body protein mass, and to gain composition.

    Science.gov (United States)

    Schiavon, S; Bittante, G

    2012-11-01

    The hypothesis tested in this paper is that double-muscled (DBM) and conventional cattle, considerably differing in body composition, have similar NE requirements when: a) NE(m) is scaled as a function of current (P(i)) and adult (P(m)) protein mass; and b) ME for gain (ME(g)) is estimated from protein (Pr) and lipid (Lr) retention and their partial ME use efficiencies, the k(p) and k(l) values, respectively. First, 2 databases were examined: 1 was developed combining well known literature information from comparative slaughter trials conducted on British beef steers; the other was based on a trial conducted using extremely lean DBM Piemontese bulls. From the first database, NE(m) was calculated to be 1.625 × P(i) ÷ P(m) × P(m)(0.73) (MJ/kg(0.73)). From the second database, the daily ME(g) was determined as 22.8 MJ × Pr ÷ k(p) + 38.74 MJ × Lr ÷ k(l), assuming (from prior reports) that k(p) = 0.20 and k(l) = 0.75. Thereafter, ME(m) was defined as ME intake minus ME(g), and, hence, NE(m) was predicted as 1.625 × P(i) ÷ P(m) × P(m)(0.73) (where 1.625 was the value obtained from the first dataset). The resulting k(m) (NE(m)/ME(m)) averaged 0.67. This k(m) value did not differ from that (0.65; P = 0.12) predicted by Garrett's equation, which uses dietary ME content as the only predictive variable. Second, the procedure was tested for the ability to detect effects on k(m) caused by increasing BW and dietary factors not estimable from the dietary ME content only. Data were gathered from a trial involving 48 DBM Piemontese bulls divided into 4 groups fed 1 of 4 diets differing in CP content (145 or 108 g/kg DM), with or without addition of 80 g/d of rumen-protected CLA (rpCLA). Bulls were examined at 3 consecutive periods of growth, corresponding to 365, 512 and 631 kg of average BW. All energy balance items were influenced by increasing BW, except k(m) (P = 0.61), in agreement with the expectation that NE(m) requirement depends on the degree of maturity (P

  20. Molecular identification and characterisation of catalase and catalase-like protein genes in urease-positive thermophilic Campylobacter (UPTC).

    Science.gov (United States)

    Nakajima, T; Kuribayashi, T; Moore, J E; Millar, B C; Yamamoto, S; Matsuda, Motoo

    2016-01-01

    Thermophilic Campylobacter are important bacterial pathogens of foodborne diseases worldwide. These organisms' physiology requires a microaerophilic atmosphere. To date, little is known about the protective catalase mechanism in urease-positive thermophilic campylobacters (UPTC); hence, it was the aim of this study to identify and characterise catalase and catalase-like protein genes in these organisms. Catalase (katA) and catalase (Kat)-like protein genes from the Japanese UPTC CF89-12 strain were molecularly analysed and compared with C. lari RM2100 and other C. lari and thermophilic Campylobacter reference isolates. A possible open reading frame of 1,422 base pairs, predicted to encode a peptide of 474 amino acid residues, with calculated molecular weight of 52.7 kilo Daltons for katA, was identified within UPTC CF89-12. A probable ribosome binding site, two putative promoters and a putative ρ-independent transcription terminator were also identified within katA. A similar katA cluster also existed in the C. lari RM2100 strain, except that this strain carries no DcuB genes. However, the Kat-like protein gene or any other homologue(s) were never identified in the C. lari RM2100 strain, or in C. jejuni and C. upsaliensis. This study demonstrates the presence of catalase/catalase-like protein genes in UPTC organisms. These findings are significant in that they suggest that UPTC organisms have the protective genetic capability of helping protect the organisms from toxic oxygen stress, which may help them to survive in physiologically harsh environments, both within human and animal hosts, as well as in the natural environment.

  1. Petri Nets-Applications

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 9. Petri Nets - Applications. Y Narahari. General Article Volume 4 Issue 9 September 1999 pp 44-52. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/004/09/0044-0052. Author Affiliations. Y Narahari ...

  2. Safety nets or straitjackets?

    DEFF Research Database (Denmark)

    Ilsøe, Anna

    2012-01-01

    Does regulation of working hours at national and sector level impose straitjackets, or offer safety nets to employees seeking working time flexibility? This article compares legislation and collective agreements in the metal industries of Denmark, Germany and the USA. The industry has historically...

  3. Coloured Petri Nets

    CERN Document Server

    Jensen, Kurt

    2009-01-01

    Coloured Petri Nets (CPN) is a graphical language for modelling and validating concurrent and distributed systems, and other systems in which concurrency plays a major role. This book introduces the constructs of the CPN modelling language and presents the related analysis methods. It provides a comprehensive road map for the practical use of CPN.

  4. Boom Booom Net Radio

    DEFF Research Database (Denmark)

    Grimshaw, Mark Nicholas; Yong, Louisa; Dobie, Ian

    1999-01-01

    of an existing Internet radio station; Boom Booom Net Radio. Whilst necessity dictates some use of technology-related terminology, wherever possible we have endeavoured to keep such jargon to a minimum and to either explain it in the text or to provide further explanation in the appended glossary....

  5. Game Theory .net.

    Science.gov (United States)

    Shor, Mikhael

    2003-01-01

    States making game theory relevant and accessible to students is challenging. Describes the primary goal of GameTheory.net is to provide interactive teaching tools. Indicates the site strives to unite educators from economics, political and computer science, and ecology by providing a repository of lecture notes and tests for courses using…

  6. Coloured Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kristensen, Lars Michael

    Coloured Petri Nets (CPN) is a graphical language for modelling and validating concurrent and distributed systems, and other systems in which concurrency plays a major role. The development of such systems is particularly challenging because of inherent intricacies like possible nondeterminism...

  7. The Escherichia coli L-arabinose operon: binding sites of the regulatory proteins and a mechanism of positive and negative regulation.

    Science.gov (United States)

    Ogden, S; Haggerty, D; Stoner, C M; Kolodrubetz, D; Schleif, R

    1980-06-01

    The locations of DNA binding by the proteins involved with positive and negative regulation of transcription initiation of the L-arabinose operon in Escherichia coli have been determined by the DNase I protection method. Two cyclic AMP receptor protein sites were found, at positions -78 to -107 and -121 to -146, an araC protein--arabinose binding site was found at position -40 to -78, and an araC protein-fucose binding site was found at position -106 to -144. These locations, combined with in vivo data on induction of the two divergently oriented arabinose promoters, suggest the following regulatory mechanism: induction of the araBAD operon occurs when cyclic AMP receptor protein, araC protein, and RNA polymerase are all present and able to bind to DNA. Negative regulation is accomplished by the repressing form of araC protein binding to a site in the regulatory region such that it stimultaneously blocks access of cyclic AMP receptor protein to two sites on the DNA, one site of which serves each of the two promoters. Thus, from a single operator site, the negative regulator represses the two outwardly oriented ara promoters. This regulatory mechanism explains the known positive and negative regulatory properties of the ara promoters.

  8. Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Viviane F Botosso

    2009-01-01

    Full Text Available Human respiratory syncytial virus (HRSV is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

  9. The Escherichia coli L-Arabinose Operon: Binding Sites of the Regulatory Proteins and a Mechanism of Positive and Negative Regulation

    National Research Council Canada - National Science Library

    Sharon Ogden; Dennis Haggerty; Carol M. Stoner; David Kolodrubetz; Robert Schleif

    1980-01-01

    The locations of DNA binding by the proteins involved with positive and negative regulation of transcription initiation of the L-arabinose operon in Escherichia coli have been determined by the DNase I protection method...

  10. sel-7, a positive regulator of lin-12 activity, encodes a novel nuclear protein in Caenorhabditis elegans.

    Science.gov (United States)

    Chen, Jiabin; Li, Xiajun; Greenwald, Iva

    2004-01-01

    Suppressor genetics in C. elegans has identified key components of the LIN-12/Notch signaling pathway. Here, we describe a genetic and molecular characterization of the suppressor gene sel-7. We show that reducing or eliminating sel-7 activity suppresses the effects of constitutive lin-12 activity, enhances the effects of partially reduced lin-12 activity, and causes a synthetic Lin-12(0) phenotype when combined with a null mutation in the sel-12 presenilin gene. These observations suggest that sel-7 is a positive regulator of lin-12 activity. We also show that SEL-7 encodes a novel nuclear protein. Through yeast two-hybrid screening, we identified an apparent interaction partner, K08E3.8, that also interacts with SEL-8, a known component of the nuclear complex that forms upon LIN-12 activation. Our data suggest potential roles for SEL-7 in the assembly or function of this nuclear complex.

  11. Quinoxaline-substituted chalcones as new inhibitors of breast cancer resistance protein ABCG2: polyspecificity at B-ring position

    Science.gov (United States)

    Winter, Evelyn; Gozzi, Gustavo Jabor; Chiaradia-Delatorre, Louise Domeneghini; Daflon-Yunes, Nathalia; Terreux, Raphael; Gauthier, Charlotte; Mascarello, Alessandra; Leal, Paulo César; Cadena, Silvia M; Yunes, Rosendo Augusto; Nunes, Ricardo José; Creczynski-Pasa, Tania Beatriz; Di Pietro, Attilio

    2014-01-01

    A series of chalcones substituted by a quinoxaline unit at the B-ring were synthesized and tested as inhibitors of breast cancer resistance protein-mediated mitoxantrone efflux. These compounds appeared more efficient than analogs containing other B-ring substituents such as 2-naphthyl or 3,4-methylenedioxyphenyl while an intermediate inhibitory activity was obtained with a 1-naphthyl group. In all cases, two or three methoxy groups had to be present on the phenyl A-ring to produce a maximal inhibition. Molecular modeling indicated both electrostatic and steric positive contributions. A higher potency was observed when the 2-naphthyl or 3,4-methylenedioxyphenyl group was shifted to the A-ring and methoxy substituents were shifted to the phenyl B-ring, indicating preferences among polyspecificity of inhibition. PMID:24920885

  12. Clinicopathological implications of human papilloma virus (HPV) L1 capsid protein immunoreactivity in HPV16-positive cervical cytology.

    Science.gov (United States)

    Lee, Sung-Jong; Lee, Ah-Won; Kang, Chang-Suk; Park, Jong-Sup; Park, Dong-Choon; Ki, Eun-Young; Lee, Keun-Ho; Yoon, Joo-Hee; Hur, Soo-Young; Kim, Tae-Jung

    2014-01-01

    The objective of this study was to investigate the expression of human papilloma virus (HPV) L1 capsid protein in abnormal cervical cytology with HPV16 infection and analyze its association with cervical histopathology in Korean women. We performed immunocytochemistry for HPV L1 in 475 abnormal cervical cytology samples from patients with HPV16 infections using the Cytoactiv(®) HPV L1 screening set. We investigated the expression of HPV L1 in cervical cytology samples and compared it with the results of histopathological examination of surgical specimens. Of a total of 475 cases, 188 (39.6%) were immunocytochemically positive and 287 (60.4%) negative for HPV L1. The immunocytochemical expression rates of HPV L1 in atypical squamous cells of unknown significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and cancer were 21.8%, 59.7%, 19.1%, and 0.0%, respectively. LSIL exhibited the highest rate of HPV L1 positivity. Of a total of 475 cases, the multiple-type HPV infection rate, including HPV16, in HPV L1-negative cytology samples was 27.5%, which was significantly higher than that in HPV L1-positive cytology samples (p = 0.037). The absence of HPV L1 expression in ASCUS and LSIL was significantly associated with high-grade (≥ cervical intraepithelial neoplasia [CIN] 2) than low-grade (≤ CIN1) histopathology diagnoses (p HPV16 single and multiple-type HPV infections (p > 0.05). On the other hand, among 188 HPV L1-positive cases, 30.6% of multiple-type HPV infections showed high-grade histopathology diagnoses (≥ CIN3), significantly higher than the percentage of HPV16 single infections (8.6%) (p = 0.0004) CONCLUSIONS: Our study demonstrates that the expression of HPV L1 is low in advanced dysplasia. Furthermore, the absence of HPV L1 in HPV16-positive low-grade cytology (i.e., ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. The multiplicity of HPV infections

  13. LPS-binding protein-deficient mice have an impaired defense against Gram-negative but not Gram-positive pneumonia

    NARCIS (Netherlands)

    Branger, Judith; Florquin, Sandrine; Knapp, Sylvia; Leemans, Jaklien C.; Pater, Jennie M.; Speelman, Peter; Golenbock, Douglas T.; van der Poll, Tom

    2004-01-01

    LPS-binding protein (LBP) can facilitate the transfer of cell wall components of both Gram-negative bacteria (LPS) and Gram-positive bacteria (lipoteichoic acid) to inflammatory cells. Although LBP is predominantly produced in the liver, recent studies have indicated that this protein is also

  14. Food Safety Nets:

    OpenAIRE

    Haggblade, Steven; Diallo, Boubacar; Staatz, John; Theriault, Veronique; Traoré, Abdramane

    2013-01-01

    Food and social safety nets have a history as long as human civilization. In hunter gatherer societies, food sharing is pervasive. Group members who prove unlucky in the short run, hunting or foraging, receive food from other households in anticipation of reciprocal consideration at a later time (Smith 1988). With the emergence of the first large sedentary civilizations in the Middle East, administrative systems developed specifically around food storage and distribution. The ancient Egyptian...

  15. Net technical assessment

    OpenAIRE

    Wegmann, David G.

    1989-01-01

    Approved for public release; distribution is unlimited. The present and near term military balance of power between the U.S. and the Soviet Union can be expressed in a variety of net assessments. One can examine the strategic nuclear balance, the conventional balance in Europe, the maritime balance, and many others. Such assessments are essential not only for policy making but for arms control purposes and future force structure planning. However, to project the future military balance, on...

  16. Insulin-like growth factors and related proteins in plasma and cerebrospinal fluids of HIV-positive individuals.

    Science.gov (United States)

    Suh, Hyeon-Sook; Lo, Yungtai; Choi, Namjong; Letendre, Scott; Lee, Sunhee C

    2015-04-15

    Clinically significant dysregulation of the insulin-like growth factor (IGF) family proteins occurs in HIV-infected individuals, but the details including whether the deficiencies in IGFs contribute to CNS dysfunction are unknown. We measured the levels of IGF1, IGF2, IGFBP1, IGFBP2, and IGF2 receptor (IGF2R) in matching plasma and cerebrospinal fluid (CSF) samples of 107 HIV+ individuals from CNS HIV Antiretroviral Therapy Effects Research (CHARTER) and analyzed their associations with demographic and disease characteristics, as well as levels of several soluble inflammatory mediators (TNFα, IL-6, IL-10, IL-17, IP-10, MCP-1, and progranulin). We also determined whether IGF1 or IGF2 deficiency is associated with HIV-associated neurocognitive disorder (HAND) and whether the levels of soluble IGF2R (an IGF scavenging receptor, which we also have found to be a cofactor for HIV infection in vitro) correlate with HIV viral load (VL). There was a positive correlation between the levels of IGF-binding proteins (IGFBPs) and those of inflammatory mediators: between plasma IGFBP1 and IL-17 (β coefficient 0.28, P = 0.009), plasma IGFBP2 and IL-6 (β coefficient 0.209, P = 0.021), CSF IGFBP1 and TNFα (β coefficient 0.394, P protein expression/availability in the setting of HIV infection. However, there was no significant association between HAND and the reduced levels of plasma IGF1, IGF2, or CSF IGF1, suggesting a limited power of our study. Interestingly, plasma IGF1 was significantly reduced in subjects on non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) compared to protease inhibitor-based therapy (174.1 ± 59.8 vs. 202.8 ± 47.3 ng/ml, P = 0.008), suggesting a scenario in which ART regimen-related toxicity can contribute to HAND. Plasma IGF2R levels were positively correlated with plasma VL (β coefficient 0.37, P = 0.021) and inversely correlated with current CD4+ T cell counts (β coefficient -0.04, P = 0.021), supporting our

  17. Positive-negative epitope-tagging of beta amyloid precursor protein to identify inhibitors of A beta processing.

    Science.gov (United States)

    Seiffert, D; Mitchell, T; Stern, A M; Roach, A; Zhan, Y; Grzanna, R

    2000-12-08

    In this report, a novel positive-negative epitope tagging approach was developed to study the cellular processing of beta amyloid precursor protein (beta APP). Amino acids centered around the alpha-secretase cleavage site within the A beta sequence were replaced with residues comprising an epitope for which high-affinity monoclonal antibodies are commercially available. The resulting mutant beta APP cDNAs were expressed in human embryonic kidney cells (HEK 293). Cleavage of labeled beta APP by beta- and gamma-secretase(s) results in the release of an epitope-tagged A beta peptide, whereas cleavage by alpha-secretase results in destruction of the epitope. Highly sensitive and specific immunoassays were developed to study processing of this labeled beta APP via the amyloidogenic pathway. Secretion of epitope-tagged A beta was prevented by MDL 28170, a previously described gamma-secretase inhibitor. Confocal microscopic studies revealed that processing and cellular trafficking of epitope-tagged beta APP was not different from wild-type beta APP. These results suggest that positive-negative epitope-tagged beta APP is normally processed within the cell and may be used to identify secretase inhibitors as therapeutics for Alzheimer's disease.

  18. A rice calcium-dependent protein kinase OsCPK9 positively regulates drought stress tolerance and spikelet fertility

    Science.gov (United States)

    2014-01-01

    Background In plants, calcium-dependent protein kinases (CDPKs) are involved in tolerance to abiotic stresses and in plant seed development. However, the functions of only a few rice CDPKs have been clarified. At present, it is unclear whether CDPKs also play a role in regulating spikelet fertility. Results We cloned and characterized the rice CDPK gene, OsCPK9. OsCPK9 transcription was induced by abscisic acid (ABA), PEG6000, and NaCl treatments. The results of OsCPK9 overexpression (OsCPK9-OX) and OsCPK9 RNA interference (OsCPK9-RNAi) analyses revealed that OsCPK9 plays a positive role in drought stress tolerance and spikelet fertility. Physiological analyses revealed that OsCPK9 improves drought stress tolerance by enhancing stomatal closure and by improving the osmotic adjustment ability of the plant. It also improves pollen viability, thereby increasing spikelet fertility. In OsCPK9-OX plants, shoot and root elongation showed enhanced sensitivity to ABA, compared with that of wild-type. Overexpression and RNA interference of OsCPK9 affected the transcript levels of ABA- and stress-responsive genes. Conclusions Our results demonstrated that OsCPK9 is a positive regulator of abiotic stress tolerance, spikelet fertility, and ABA sensitivity. PMID:24884869

  19. Using WordNet for Building WordNets

    CERN Document Server

    Farreres, X; Farreres, Xavier; Rodriguez, Horacio; Rigau, German

    1998-01-01

    This paper summarises a set of methodologies and techniques for the fast construction of multilingual WordNets. The English WordNet is used in this approach as a backbone for Catalan and Spanish WordNets and as a lexical knowledge resource for several subtasks.

  20. A novel {sup 18}F-labeled two-helix scaffold protein for PET imaging of HER2-positive tumor

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Zheng; Ren, Gang; Jiang, Lei; Liu, Hongguang; Cheng, Zhen [Stanford University, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford Cancer Center, Bio-X Program, Stanford, CA (United States); Webster, Jack M.; Zhang, Rong; Syud, Faisal [General Electric Company, Global Research, Niskayuna, NY (United States); Namavari, Mohammad; Gambhir, Sanjiv S. [Stanford University, MIPS, Departments of Radiology and Bioengineering, Stanford Cancer Center, Bio-X Program, Stanford, CA (United States)

    2011-11-15

    Two-helix scaffold proteins ({proportional_to} 5 kDa) against human epidermal growth factor receptor type 2 (HER2) have been discovered in our previous work. In this research we aimed to develop an {sup 18}F-labeled two-helix scaffold protein for positron emission tomography (PET) imaging of HER2-positive tumors. An aminooxy-functionalized two-helix peptide (AO-MUT-DS) with high HER2 binding affinity was synthesized through conventional solid phase peptide synthesis. The purified linear peptide was cyclized by I{sub 2} oxidation to form a disulfide bridge. The cyclic peptide was then conjugated with a radiofluorination synthon, 4-{sup 18}F-fluorobenzyl aldehyde ({sup 18}F-FBA), through the aminooxy functional group at the peptide N terminus (30% yield, non-decay corrected). The binding affinities of the peptides were analyzed by Biacore analysis. Cell uptake assay of the resulting PET probe, {sup 18}F-FBO-MUT-DS, was performed at 37 C. {sup 18}F-FBO-MUT-DS with high specific activity (20-32 MBq/nmol, 88-140 {mu}Ci/{mu}g, end of synthesis) was injected into mice xenograft model bearing SKOV3 tumor. MicroPET and biodistribution and metabolic stability studies were then conducted. Cell uptake assays showed high and specific cell uptake ({proportional_to}12% applied activity at 1 h) by incubation of {sup 18}F-FBO-MUT-DS with HER2 high-expressing SKOV3 ovarian cancer cells. The affinities (K{sub D}) of AO-MUT-DS and FBO-MUT-DS as tested by Biacore analysis were 2 and 1 nM, respectively. In vivo small animal PET demonstrated fast tumor targeting, high tumor accumulation, and good tumor to normal tissue contrast of {sup 18}F-FBO-MUT-DS. Biodistribution studies further revealed that the probe had excellent tumor uptake (6.9%ID/g at 1 h post-injection) and was cleared through both liver and kidneys. Co-injection of the probe with 500 {mu}g of HER2 Affibody protein reduced the tumor uptake (6.9 vs 1.8%ID/g, p < 0.05). F-FBO-MUT-DS displays excellent HER2 targeting ability

  1. The effect of netting solidity ratio and inclined angle on the hydrodynamic characteristics of knotless polyethylene netting

    Science.gov (United States)

    Tang, Hao; Hu, Fuxiang; Xu, Liuxiong; Dong, Shuchuang; Zhou, Cheng; Wang, Xuefang

    2017-10-01

    Knotless polyethylene (PE) netting has been widely used in aquaculture cages and fishing gears, especially in Japan. In this study, the hydrodynamic coefficient of six knotless PE netting panels with different solidity ratios were assessed in a flume tank under various attack angles of netting from 0° (parallel to flow) to 90° (perpendicular to flow) and current speeds from 40 cm s-1 to 130 cm s-1. It was found that the drag coefficient was related to Reynolds number, solidity ratio and attack angle of netting. The solidity ratio was positively related with drag coefficient for netting panel perpendicular to flow, whereas when setting the netting panel parallel to the flow the opposite result was obtained. For netting panels placed at an angle to the flow, the lift coefficient reached the maximum at an attack angle of 50° and then decreased as the attack angle further increased. The solidity ratio had a dual influence on drag coefficient of inclined netting panels. Compared to result in the literature, the normal drag coefficient of knotless PE netting measured in this study is larger than that of nylon netting or Dyneema netting.

  2. Activation of PAD4 in NET formation

    Directory of Open Access Journals (Sweden)

    Amanda eRohrbach

    2012-11-01

    Full Text Available Peptidyl arginine deiminases, or PADs, convert arginine residues to the non-ribosomally encoded amino acid citrulline in a variety of protein substrates. PAD4 is expressed in granulocytes and is essential for the formation of neutrophil extracellular traps (NETs via PAD4-mediated histone citrullination. Citrullination of histones is thought to promote NET formation by inducing chromatin decondensation and facilitating the expulsion of chromosomal DNA that is coated with antimicrobial molecules. Numerous stimuli have been reported to lead to PAD4 activation and NET formation. However, how this signaling process proceeds and how PAD4 becomes activated in cells is largely unknown. Herein, we describe the various stimuli and signaling pathways that have been implicated in PAD4 activation and NET formation, including the role of reactive oxygen species generation. To provide a foundation for the above discussion, we first describe PAD4 structure and function, and how these studies led to the development of PAD-specific inhibitors. A comprehensive survey of the receptors and signaling pathways that regulate PAD4 activation will be important for our understanding of innate immunity, and the identification of signaling intermediates in PAD4 activation may also lead to the generation of pharmaceuticals to target NET-related pathogenesis.

  3. -Net Approach to Sensor -Coverage

    Directory of Open Access Journals (Sweden)

    Fusco Giordano

    2010-01-01

    Full Text Available Wireless sensors rely on battery power, and in many applications it is difficult or prohibitive to replace them. Hence, in order to prolongate the system's lifetime, some sensors can be kept inactive while others perform all the tasks. In this paper, we study the -coverage problem of activating the minimum number of sensors to ensure that every point in the area is covered by at least sensors. This ensures higher fault tolerance, robustness, and improves many operations, among which position detection and intrusion detection. The -coverage problem is trivially NP-complete, and hence we can only provide approximation algorithms. In this paper, we present an algorithm based on an extension of the classical -net technique. This method gives an -approximation, where is the number of sensors in an optimal solution. We do not make any particular assumption on the shape of the areas covered by each sensor, besides that they must be closed, connected, and without holes.

  4. Changes in seed oil and protein contents of maize cultivars at different positions on the ear in response to water limitation

    Directory of Open Access Journals (Sweden)

    Kazem Ghassemi-Golezani

    2016-10-01

    Full Text Available A field experiment was carried out as split-split plot in 2014 to assess the effects of four irrigation treatments (irrigations after 60, 80, 100 and 120 mm evaporation, respectively on oil and protein changes of maize cultivars (SC704, NS640 and DC303: Late, mid and early maturing cultivars, respectively at different seed positions on the ear (upper, middle and lower positions on the ear. Overall, the highest seed yield was obtained from SC704, followed by NS640 and DC303 cultivars. Seed yield of all cultivars was higher at lower seed position on ear than at middle and upper parts of the ear under different irrigation treatments. The highest oil and protein yields were also recorded for seeds at lower position on the ear. Seed yield of all maize cultivars at various seed positions decreased with increasing irrigation intervals. Oil percentage decreased, but protein percentage increased with decreasing water availability. Water limitation decreased oil and protein yields of maize cultivars. Changes in protein and oil yields of maize cultivars at different seed positions and irrigation treatments were attributed to changes in seed yield.

  5. Proof nets for lingusitic analysis

    NARCIS (Netherlands)

    Moot, R.C.A.

    2002-01-01

    This book investigates the possible linguistic applications of proof nets, redundancy free representations of proofs, which were introduced by Girard for linear logic. We will adapt the notion of proof net to allow the formulation of a proof net calculus which is soundand complete for the

  6. Net4Care Ecosystem Website

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius; Rasmussen, Morten

    2012-01-01

    is a tele-monitoring scenario in which Net4Care clients are deployed in a gateway in private homes. Medical devices then connect to these gateways and transmit their observations to a Net4Care server. In turn the Net4Care server creates valid clinical HL7 documents, stores them in a national XDS repository...

  7. The relationship of C-reactive protein levels and positive culture with quality of life in acute rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Schalek P

    2015-01-01

    Full Text Available Petr Schalek, Zuzana Hornáčková, Aleš Hahn Ear, Nose and Throat department, 3rd Medical Faculty of Charles University, Prague, Czech Republic Background: Acute rhinosinusitis (ARS has been shown to significantly reduce patient quality of life (QoL. While the QoL in patients with chronic rhinosinusitis has been the subject of intensive research over the last decade, studies measuring the impact of ARS on patient QoL have remained relatively scarce. The aim of this study was to determine the relationship between the QoL and parameters suggestive of acute bacterial rhinosinusitis (C-reactive protein [CRP] levels and positive culture and to see if measurement of the QoL could be used as an indicator for antibiotic treatment in ARS.Methods: Eighty patients with ARS were enrolled in the study. A novel QoL instrument for patients with ARS, called Measurement of Acute Rhinosinusitis (MARS questionnaire, was given to patients at the time of diagnosis. We assessed patient QoL, obtained endoscopically guided cultures from the middle meatus, and measured levels of CRP. The relationship between QoL MARS scores (QoL-Mscores and CRP was determined using a correlation coefficient. To compare QoL-Mscores, relative to culture-positive and culture-negative patients, the Student’s t-test was used.Results: No correlation between the QoL, assessed using the MARS questionnaire, and positive middle meatus culture was demonstrated (P=0.332. A weak correlation was found between QoL-Mscores and CRP values, with a correlation coefficient of 0.221 and P=0.0498.Conclusion: No correlation between the QoL in ARS patients and positive culture was found in this study. The clinical significance of the correlation between QoL-Mscores and CRP values in the antibiotic decision making process needs further research. Keywords: endoscopy, quality of life, questionnaires, anti-bacterial agents

  8. Master Robotic Net

    Directory of Open Access Journals (Sweden)

    Vladimir Lipunov

    2010-01-01

    Full Text Available The main goal of the MASTER-Net project is to produce a unique fast sky survey with all sky observed over a single night down to a limiting magnitude of 19-20. Such a survey will make it possible to address a number of fundamental problems: search for dark energy via the discovery and photometry of supernovae (including SNIa, search for exoplanets, microlensing effects, discovery of minor bodies in the Solar System, and space-junk monitoring. All MASTER telescopes can be guided by alerts, and we plan to observe prompt optical emission from gamma-ray bursts synchronously in several filters and in several polarization planes.

  9. Art/Net/Work

    DEFF Research Database (Denmark)

    Andersen, Christian Ulrik; Lindstrøm, Hanne

    2006-01-01

    The seminar Art|Net|Work deals with two important changes in our culture. On one side, the network has become essential in the latest technological development. The Internet has entered a new phase, Web 2.0, including the occurrence of as ‘Wiki’s’, ‘Peer-2-Peer’ distribution, user controlled...... the praxis of the artist. We see different kinds of interventions and activism (including ‘hacktivism’) using the network as a way of questioning the invisible rules that govern public and semi-public spaces. Who ‘owns’ them? What kind of social relationships do they generate? On what principle...

  10. Reconciling catch differences from multiple fishery independent gill net surveys

    Science.gov (United States)

    Kraus, Richard T.; Vandergoot, Christopher; Kocovsky, Patrick M.; Rogers, Mark W.; Cook, H. Andrew; Brenden, Travis O.

    2017-01-01

    Fishery independent gill net surveys provide valuable demographic information for population assessment and resource management, but relative to net construction, the effects of ancillary species, and environmental variables on focal species catch rates are poorly understood. In response, we conducted comparative deployments with three unique, inter-agency, survey gill nets used to assess walleye Sander vitreus in Lake Erie. We used an information-theoretic approach with Akaike’s second-order information criterion (AICc) to evaluate linear mixed models of walleye catch as a function of net type (multifilament and two types of monofilament netting), mesh size (categorical), Secchi depth, temperature, water depth, catch of ancillary species, and interactions among selected variables. The model with the greatest weight of evidence showed that walleye catches were positively associated with potential prey and intra-guild predators and negatively associated with water depth and temperature. In addition, the multifilament net had higher average walleye catches than either of the two monofilament nets. Results from this study both help inform decisions about proposed gear changes to stock assessment surveys in Lake Erie, and advance our understanding of how multispecies associations explain variation in gill net catches. Of broader interest to fishery-independent gill net studies, effects of abiotic variables and ancillary species on focal specie’s catch rates were small in comparison with net characteristics of mesh size or twine type.

  11. Helminth.net: expansions to Nematode.net and an introduction to Trematode.net

    Science.gov (United States)

    Martin, John; Rosa, Bruce A.; Ozersky, Philip; Hallsworth-Pepin, Kymberlie; Zhang, Xu; Bhonagiri-Palsikar, Veena; Tyagi, Rahul; Wang, Qi; Choi, Young-Jun; Gao, Xin; McNulty, Samantha N.; Brindley, Paul J.; Mitreva, Makedonka

    2015-01-01

    Helminth.net (http://www.helminth.net) is the new moniker for a collection of databases: Nematode.net and Trematode.net. Within this collection we provide services and resources for parasitic roundworms (nematodes) and flatworms (trematodes), collectively known as helminths. For over a decade we have provided resources for studying nematodes via our veteran site Nematode.net (http://nematode.net). In this article, (i) we provide an update on the expansions of Nematode.net that hosts omics data from 84 species and provides advanced search tools to the broad scientific community so that data can be mined in a useful and user-friendly manner and (ii) we introduce Trematode.net, a site dedicated to the dissemination of data from flukes, flatworm parasites of the class Trematoda, phylum Platyhelminthes. Trematode.net is an independent component of Helminth.net and currently hosts data from 16 species, with information ranging from genomic, functional genomic data, enzymatic pathway utilization to microbiome changes associated with helminth infections. The databases’ interface, with a sophisticated query engine as a backbone, is intended to allow users to search for multi-factorial combinations of species’ omics properties. This report describes updates to Nematode.net since its last description in NAR, 2012, and also introduces and presents its new sibling site, Trematode.net. PMID:25392426

  12. Protein phosphatase 2A holoenzyme is targeted to peroxisomes by piggybacking and positively affects peroxisomal β-oxidation.

    Science.gov (United States)

    Kataya, Amr R A; Heidari, Behzad; Hagen, Lars; Kommedal, Roald; Slupphaug, Geir; Lillo, Cathrine

    2015-02-01

    The eukaryotic, highly conserved serine (Ser)/threonine-specific protein phosphatase 2A (PP2A) functions as a heterotrimeric complex composed of a catalytic (C), scaffolding (A), and regulatory (B) subunit. In Arabidopsis (Arabidopsis thaliana), five, three, and 17 genes encode different C, A, and B subunits, respectively. We previously found that a B subunit, B'θ, localized to peroxisomes due to its C-terminal targeting signal Ser-Ser-leucine. This work shows that PP2A C2, C5, andA2 subunits interact and colocalize with B'θ in peroxisomes. C and A subunits lack peroxisomal targeting signals, and their peroxisomal import depends on B'θ and appears to occur by piggybacking transport. B'θ knockout mutants were impaired in peroxisomal β-oxidation as shown by developmental arrest of seedlings germinated without sucrose, accumulation of eicosenoic acid, and resistance to protoauxins indole-butyric acid and 2,4-dichlorophenoxybutyric acid. All of these observations strongly substantiate that a full PP2A complex is present in peroxisomes and positively affects β-oxidation of fatty acids and protoauxins. © 2015 American Society of Plant Biologists. All Rights Reserved.

  13. Protein Phosphatase 2A Holoenzyme Is Targeted to Peroxisomes by Piggybacking and Positively Affects Peroxisomal β-Oxidation1[OPEN

    Science.gov (United States)

    Kataya, Amr R.A.; Heidari, Behzad; Hagen, Lars; Kommedal, Roald; Slupphaug, Geir; Lillo, Cathrine

    2015-01-01

    The eukaryotic, highly conserved serine (Ser)/threonine-specific protein phosphatase 2A (PP2A) functions as a heterotrimeric complex composed of a catalytic (C), scaffolding (A), and regulatory (B) subunit. In Arabidopsis (Arabidopsis thaliana), five, three, and 17 genes encode different C, A, and B subunits, respectively. We previously found that a B subunit, B′θ, localized to peroxisomes due to its C-terminal targeting signal Ser-Ser-leucine. This work shows that PP2A C2, C5, andA2 subunits interact and colocalize with B′θ in peroxisomes. C and A subunits lack peroxisomal targeting signals, and their peroxisomal import depends on B′θ and appears to occur by piggybacking transport. B′θ knockout mutants were impaired in peroxisomal β-oxidation as shown by developmental arrest of seedlings germinated without sucrose, accumulation of eicosenoic acid, and resistance to protoauxins indole-butyric acid and 2,4-dichlorophenoxybutyric acid. All of these observations strongly substantiate that a full PP2A complex is present in peroxisomes and positively affects β-oxidation of fatty acids and protoauxins. PMID:25489022

  14. The social patterns of a biological risk factor for disease: race, gender, socioeconomic position, and C-reactive protein.

    Science.gov (United States)

    Herd, Pamela; Karraker, Amelia; Friedman, Elliot

    2012-07-01

    Understand the links between race and C-reactive protein (CRP), with special attention to gender differences and the role of class and behavioral risk factors as mediators. This study utilizes the National Social Life, Health, and Aging Project data, a nationally representative study of older Americans aged 57-85 to explore two research questions. First, what is the relative strength of socioeconomic versus behavioral risk factors in explaining race differences in CRP levels? Second, what role does gender play in understanding race differences? Does the relative role of socioeconomic and behavioral risk factors in explaining race differences vary when examining men and women separately? When examining men and women separately, socioeconomic and behavioral risk factor mediators vary in their importance. Indeed, racial differences in CRP among men aged 57-74 are little changed after adjusting for both socioeconomic and behavioral risk factors with levels 35% higher for black men as compared to white men. For women aged 57-74, however, behavioral risk factors explain 30% of the relationship between race and CRP. The limited explanatory power of socioeconomic position and, particularly, behavioral risk factors, in elucidating the relationship between race and CRP among men, signals the need for research to examine additional mediators, including more direct measures of stress and discrimination.

  15. Effect of rosiglitazone on visfatin and retinol-binding protein-4 plasma concentrations in HIV-positive patients.

    Science.gov (United States)

    Haider, D G; Schindler, K; Mittermayer, F; Müller, M; Nowotny, P; Rieger, A; Luger, A; Ludvik, B; Wolzt, M

    2007-04-01

    Thiazolidinediones (TZD) may improve insulin resistance in patients with diabetes and HIV. The novel adipocytokines visfatin and retinol-binding protein-4 (RBP-4) have been proposed to influence the development of impaired glucose tolerance. The impact of TZD on these cytokines is yet unknown. In this randomized, double-blind, placebo-controlled parallel group study, 37 lean HIV-positive subjects aged 19-50 years were treated with 8 mg/day rosiglitazone (n=20) or placebo (n=17) for 6 months. Insulin sensitivity was estimated from the homeostasis model assessment (HOMA) index. Fasting visfatin, RBP-4, leptin, and adiponectin plasma concentrations were analyzed by immunoassays. Rosiglitazone had no effect on impaired insulin sensitivity, but increased median plasma visfatin from 6.2 ng/ml (95% CI: 5.9; 6.5) to 13.7 ng/ml (12.6; 19.1) (PQuantification of adipocytokines might be useful to assess TZD treatment effectiveness in insulin-resistant subjects with HIV.

  16. The equivalency between logic Petri workflow nets and workflow nets.

    Science.gov (United States)

    Wang, Jing; Yu, ShuXia; Du, YuYue

    2015-01-01

    Logic Petri nets (LPNs) can describe and analyze batch processing functions and passing value indeterminacy in cooperative systems. Logic Petri workflow nets (LPWNs) are proposed based on LPNs in this paper. Process mining is regarded as an important bridge between modeling and analysis of data mining and business process. Workflow nets (WF-nets) are the extension to Petri nets (PNs), and have successfully been used to process mining. Some shortcomings cannot be avoided in process mining, such as duplicate tasks, invisible tasks, and the noise of logs. The online shop in electronic commerce in this paper is modeled to prove the equivalence between LPWNs and WF-nets, and advantages of LPWNs are presented.

  17. Genetic and epigenetic drivers of neuroendocrine tumours (NET).

    Science.gov (United States)

    Di Domenico, Annunziata; Wiedmer, Tabea; Marinoni, Ilaria; Perren, Aurel

    2017-09-01

    Neuroendocrine tumours (NET) of the gastrointestinal tract and the lung are a rare and heterogeneous group of tumours. The molecular characterization and the clinical classification of these tumours have been evolving slowly and show differences according to organs of origin. Novel technologies such as next-generation sequencing revealed new molecular aspects of NET over the last years. Notably, whole-exome/genome sequencing (WES/WGS) approaches underlined the very low mutation rate of well-differentiated NET of all organs compared to other malignancies, while the engagement of epigenetic changes in driving NET evolution is emerging. Indeed, mutations in genes encoding for proteins directly involved in chromatin remodelling, such as DAXX and ATRX are a frequent event in NET. Epigenetic changes are reversible and targetable; therefore, an attractive target for treatment. The discovery of the mechanisms underlying the epigenetic changes and the implication on gene and miRNA expression in the different subgroups of NET may represent a crucial change in the diagnosis of this disease, reveal new therapy targets and identify predictive markers. Molecular profiles derived from omics data including DNA mutation, methylation, gene and miRNA expression have already shown promising results in distinguishing clinically and molecularly different subtypes of NET. In this review, we recapitulate the major genetic and epigenetic characteristics of pancreatic, lung and small intestinal NET and the affected pathways. We also discuss potential epigenetic mechanisms leading to NET development. © 2017 Society for Endocrinology.

  18. Positive expression of p53, c-erbB2 and MRP proteins is correlated with survival rates of NSCLC patients.

    Science.gov (United States)

    Xu, Yujin; Wang, Liancong; Zheng, Xiao; Liu, Guan; Wang, Yuezhen; Lai, Xiaojing; Li, Jianqiang

    2013-05-01

    The incidence of lung cancer is one of the leading causes of mortality. This study aimed to investigate the prognostic and predictive importance of p53, c-erbB2 and multidrug resistance proteins (MRP) expression and its correlation with clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). Expression of p53, c-erbB2 and MRP proteins in 152 tumor samples from resected primary NSCLCs was detected by immunohistochemical staining. The correlation of proteins, survival and clinicopathological characteristics was investigated in 152 patients undergoing potentially curative surgery. The positive rates of p53, c-erbB2 and MRP expression were 53.9 (82/152), 44.1 (67/152) and 43.4% (66/152), respectively. Overall survival rates of patients were markedly correlated with the overexpression of p53, c-erbB2 and MRP proteins. One, 2- and 3-year survival rates of patients exhibiting a positive expression of these proteins were 72.6, 54.8 and 32.2%, respectively. These rates were lower compared with those of patients with a negative expression of these proteins (92.1, 78.5 and 63.4%) (P=0.02, 0.01 or 0.00, respectively). Results of Cox's regression analysis showed that c-erbB2 expression and cell differentiation were independent prognostic factors in patients with NSCLC. These findings suggest that the positive expression of p53, c-erbB2 and MRP proteins is correlated with the survival rates of NSCLC patients. Detection of positive p53, c-erbB2 and MRP expression may be a useful predictive indicator of prognosis. Positive c-erbB2 expression is an independent prognostic factor, with a potential to be used as a predictive indicator of chemotherapy efficacy in NSCLC patients.

  19. Coloured Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kristensen, Lars Michael

    studies that illustrate the practical use of CPN modelling and validation for design, specification, simulation, verification and implementation in various application domains. Their presentation primarily aims at readers interested in the practical use of CPN. Thus all concepts and constructs are first......Coloured Petri Nets (CPN) is a graphical language for modelling and validating concurrent and distributed systems, and other systems in which concurrency plays a major role. The development of such systems is particularly challenging because of inherent intricacies like possible nondeterminism...... and the immense number of possible execution sequences. In this textbook, Jensen and Kristensen introduce the constructs of the CPN modelling language and present the related analysis methods in detail. They also provide a comprehensive road map for the practical use of CPN by showcasing selected industrial case...

  20. Comparative distribution of relaxin-3 inputs and calcium-binding protein-positive neurons in rat amygdala

    Directory of Open Access Journals (Sweden)

    Fabio N Santos

    2016-04-01

    Full Text Available The neural circuits involved in mediating complex behaviors are being rapidly elucidated using various newly developed and powerful anatomical and molecular techniques, providing insights into the neural basis for anxiety disorders, depression, addiction, and dysfunctional social behaviors. Many of these behaviors and associated physiological processes involve the activation of the amygdala in conjunction with cortical and hippocampal circuits. Ascending subcortical projections provide modulatory inputs to the extended amygdala and its related nodes (or ‘hubs’ within these key circuits. One such input arises from the nucleus incertus (NI in the tegmentum, which sends amino acid- and peptide-containing projections throughout the forebrain. Notably, a distinct population of GABAergic NI neurons expresses the highly-conserved neuropeptide, relaxin-3, and relaxin-3 signaling has been implicated in the modulation of reward/motivation and anxiety- and depressive-like behaviors in rodents via actions within the extended amygdala. Thus, a detailed description of the relaxin-3 innervation of the extended amygdala would provide an anatomical framework for an improved understanding of NI and relaxin-3 modulation of these and other specific amygdala-related functions. Therefore, in this study, we examined the distribution of NI projections and relaxin-3-positive elements (axons/fibers/terminals within the amygdala, relative to the distribution of neurons expressing the calcium-binding proteins, parvalbumin, calretinin and/or calbindin. Anterograde tracer injections into the NI revealed a topographic distribution of NI efferents within the amygdala that was near identical to the distribution of relaxin-3-immunoreactive fibers. Highest densities of anterogradely-labeled elements and relaxin-3-immunoreactive fibers were observed in the medial nucleus of the amygdala, medial divisions of the bed nucleus of the stria terminalis (BST and in the endopiriform

  1. Serum liver fatty acid binding protein levels correlate positively with obesity and insulin resistance in Chinese young adults.

    Directory of Open Access Journals (Sweden)

    Juan Shi

    Full Text Available BACKGROUND: Liver fatty acid-binding protein (FABP1 plays an inconclusive role in adiposity. We investigated the association of serum FABP1 levels with obesity and insulin resistance in Chinese young people under 30 years old. METHODOLOGY AND PRINCIPAL FINDINGS: Cross-sectional analysis including 200 obese and 172 normal-weight subjects matched for age and sex, anthropometric measurements were performed and serum FABP1 and biochemical characteristics were measured. Insulin resistance was determined by homeostasis model assessment of insulin resistance (HOMA-IR and by the insulin sensitivity index (S(i derived from Bergman's minimal model. FABP1 levels in obese subjects were significantly higher than those in normal-weight subjects (p<0.001 and the significance remained after adjustment for age, gender, alanine and aspartate aminotransferases (p<0.001. Serum FABP1 levels were significantly correlated with many metabolic-related parameters, with BMI and triglycerides as the independent determinants. FABP1 levels remained an independent risk factor of insulin resistance assessed by binary S(i (OR = 1.868 per SD unit, 95% CI [1.035-3.373], p = 0.038 after adjustment for age, sex, BMI, waist circumference, systolic blood pressure, serum triacylglycerol, total cholesterol, HDL- and LDL-cholesterol,. FABP1 levels were also elevated with an increasing number of components of the metabolic syndrome (p for trend <0.001. Multiple regression modeling for the MetS and its components demonstrated that hypertriglyceridemia and low HDL-cholesterol were significantly correlated to serum FABP1 levels. CONCLUSIONS AND SIGNIFICANCE: Serum FABP1 correlates positively with obesity and insulin resistance in Chinese young adults. Our data supports the fact that FABP1 might be an important mediator participating in fatty acid metabolism and energy balance.

  2. The Parkinson's disease-associated protein DJ-1 plays a positive nonmitochondrial role in endocytosis in Dictyostelium cells

    Directory of Open Access Journals (Sweden)

    Suwei Chen

    2017-10-01

    Full Text Available The loss of function of DJ-1 caused by mutations in DJ1 causes a form of familial Parkinson's disease (PD. However, the role of DJ-1 in healthy and in PD cells is poorly understood. Even its subcellular localization in mammalian cells is uncertain, with both cytosolic and mitochondrial locations having been reported. We show here that DJ-1 is normally located in the cytoplasm in healthy Dictyostelium discoideum cells. With its unique life cycle, straightforward genotype-phenotype relationships, experimental accessibility and genetic tractability, D. discoideum offers an attractive model to investigate the roles of PD-associated genes. Furthermore, the study of mitochondrial biology, mitochondrial genome transcription and AMP-activated protein kinase-mediated cytopathologies in mitochondrial dysfunction have been well developed in this organism. Unlike mammalian systems, Dictyostelium mitochondrial dysfunction causes a reproducible and readily assayed array of aberrant phenotypes: defective phototaxis, impaired growth, normal rates of endocytosis and characteristic defects in multicellular morphogenesis. This makes it possible to study whether the underlying cytopathological mechanisms of familial PD involve mitochondrial dysfunction. DJ-1 has a single homologue in the Dictyostelium genome. By regulating the expression level of DJ-1 in D. discoideum, we show here that in unstressed cells, DJ-1 is required for normal rates of endocytic nutrient uptake (phagocytosis and, to a lesser extent, pinocytosis and thus growth. Reduced expression of DJ-1 had no effect on phototaxis in the multicellular migratory ‘slug’ stage of the life cycle, but resulted in thickened stalks in the final fruiting bodies. This pattern of phenotypes is distinct from that observed in Dictyostelium to result from mitochondrial dyfunction. Direct measurement of mitochondrial respiratory function in intact cells revealed that DJ-1 knockdown stimulates whereas DJ-1

  3. Effect of continuous positive airway pressure on C-reactive protein levels in sleep apnea: a meta-analysis.

    Science.gov (United States)

    Friedman, Michael; Samuelson, Christian G; Hamilton, Craig; Fisher, Michelle; Kelley, Kanwar; Joseph, Ninos J; Wang, Pa-Chun; Lin, Hsin-Ching

    2012-09-01

    Evaluate the effects of continuous positive airway pressure (CPAP) on C-reactive protein (CRP) levels, reported either as a primary or secondary end point among patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) based on a meta-analysis of published studies. English-language searches of PubMed, Ovid, and the Cochrane databases were completed. Reference sections of identified studies were also examined for additional relevant articles to review. Studies of adult patients with OSAHS who reported pre- and post-CPAP treatment CRP were reviewed and analyzed. Two independent reviewers extracted data from 10 peer-reviewed studies, which were combined using a random effects meta-analysis model. The CPAP treatment was found to lead to a significant reduction in CRP levels (17.8%, P = .002). This corresponds to an effect size of -0.485 (-0.731, -0.240). Sensitivity analysis was done to determine the impact of study design. Both case-control studies and case-series studies yielded a significant effect. Sensitivity analysis also yielded a significant effect for studies with average body mass index pressure, and studies treating patients ≤ 3 months. Analysis of publication bias, however, revealed a likelihood of "missing" studies. Although there is a significant lack of high-quality studies addressing this question, this analysis suggests that treatment with CPAP leads to a statistically significant reduction in CRP levels. However, the mean pre- and posttreatment CRP levels observed are considered "high risk" for cardiovascular morbidity. The clinical significance of this finding as it relates to cardiovascular risk reduction and the relationship between CRP and OSAHS requires further study.

  4. Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs.

    Science.gov (United States)

    Zheng, Liufeng; Zuo, Fangrui; Zhao, Shengjun; He, Pingli; Wei, Hongkui; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

    2017-04-01

    Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.

  5. Comparative analysis of twin-arginine (Tat)-dependent protein secretion of a heterologous model protein (GFP) in three different Gram-positive bacteria

    NARCIS (Netherlands)

    Meissner, Daniel; Vollstedt, Angela; van Dijl, Jan Maarten; Freudl, Roland

    In contrast to the general protein secretion (Sec) system, the twin-arginine translocation (Tat) export pathway allows the translocation of proteins across the bacterial plasma membrane in a fully folded conformation. Due to this feature, the Tat pathway provides an attractive alternative to the

  6. Large-scale inference of protein tissue origin in gram-positive sepsis plasma using quantitative targeted proteomics.

    Science.gov (United States)

    Malmström, Erik; Kilsgård, Ola; Hauri, Simon; Smeds, Emanuel; Herwald, Heiko; Malmström, Lars; Malmström, Johan

    2016-01-06

    The plasma proteome is highly dynamic and variable, composed of proteins derived from surrounding tissues and cells. To investigate the complex processes that control the composition of the plasma proteome, we developed a mass spectrometry-based proteomics strategy to infer the origin of proteins detected in murine plasma. The strategy relies on the construction of a comprehensive protein tissue atlas from cells and highly vascularized organs using shotgun mass spectrometry. The protein tissue atlas was transformed to a spectral library for highly reproducible quantification of tissue-specific proteins directly in plasma using SWATH-like data-independent mass spectrometry analysis. We show that the method can determine drastic changes of tissue-specific protein profiles in blood plasma from mouse animal models with sepsis. The strategy can be extended to several other species advancing our understanding of the complex processes that contribute to the plasma proteome dynamics.

  7. NET23/STING Promotes Chromatin Compaction from the Nuclear Envelope

    Science.gov (United States)

    de las Heras, Jose I.; Saiz-Ros, Natalia; Makarov, Alexandr A.; Lazou, Vassiliki; Meinke, Peter; Waterfall, Martin; Kelly, David A.; Schirmer, Eric C.

    2014-01-01

    Changes in the peripheral distribution and amount of condensed chromatin are observed in a number of diseases linked to mutations in the lamin A protein of the nuclear envelope. We postulated that lamin A interactions with nuclear envelope transmembrane proteins (NETs) that affect chromatin structure might be altered in these diseases and so screened thirty-one NETs for those that promote chromatin compaction as determined by an increase in the number of chromatin clusters of high pixel intensity. One of these, NET23 (also called STING, MITA, MPYS, ERIS, Tmem173), strongly promoted chromatin compaction. A correlation between chromatin compaction and endogenous levels of NET23/STING was observed for a number of human cell lines, suggesting that NET23/STING may contribute generally to chromatin condensation. NET23/STING has separately been found to be involved in innate immune response signaling. Upon infection cells make a choice to either apoptose or to alter chromatin architecture to support focused expression of interferon genes and other response factors. We postulate that the chromatin compaction induced by NET23/STING may contribute to this choice because the cells expressing NET23/STING eventually apoptose, but the chromatin compaction effect is separate from this as the condensation was still observed when cells were treated with Z-VAD to block apoptosis. NET23/STING-induced compacted chromatin revealed changes in epigenetic marks including changes in histone methylation and acetylation. This indicates a previously uncharacterized nuclear role for NET23/STING potentially in both innate immune signaling and general chromatin architecture. PMID:25386906

  8. Plasmid Characterization and Chromosome Analysis of Two netF+ Clostridium perfringens Isolates Associated with Foal and Canine Necrotizing Enteritis

    Science.gov (United States)

    Mehdizadeh Gohari, Iman; Kropinski, Andrew M.; Weese, Scott J.; Parreira, Valeria R.; Whitehead, Ashley E.; Boerlin, Patrick; Prescott, John F.

    2016-01-01

    The recent discovery of a novel beta-pore-forming toxin, NetF, which is strongly associated with canine and foal necrotizing enteritis should improve our understanding of the role of type A Clostridium perfringens associated disease in these animals. The current study presents the complete genome sequence of two netF-positive strains, JFP55 and JFP838, which were recovered from cases of foal necrotizing enteritis and canine hemorrhagic gastroenteritis, respectively. Genome sequencing was done using Single Molecule, Real-Time (SMRT) technology-PacBio and Illumina Hiseq2000. The JFP55 and JFP838 genomes include a single 3.34 Mb and 3.53 Mb chromosome, respectively, and both genomes include five circular plasmids. Plasmid annotation revealed that three plasmids were shared by the two newly sequenced genomes, including a NetF/NetE toxins-encoding tcp-conjugative plasmid, a CPE/CPB2 toxins-encoding tcp-conjugative plasmid and a putative bacteriocin-encoding plasmid. The putative beta-pore-forming toxin genes, netF, netE and netG, were located in unique pathogenicity loci on tcp-conjugative plasmids. The C. perfringens JFP55 chromosome carries 2,825 protein-coding genes whereas the chromosome of JFP838 contains 3,014 protein-encoding genes. Comparison of these two chromosomes with three available reference C. perfringens chromosome sequences identified 48 (~247 kb) and 81 (~430 kb) regions unique to JFP55 and JFP838, respectively. Some of these divergent genomic regions in both chromosomes are phage- and plasmid-related segments. Sixteen of these unique chromosomal regions (~69 kb) were shared between the two isolates. Five of these shared regions formed a mosaic of plasmid-integrated segments, suggesting that these elements were acquired early in a clonal lineage of netF-positive C. perfringens strains. These results provide significant insight into the basis of canine and foal necrotizing enteritis and are the first to demonstrate that netF resides on a large and

  9. Plasmid Characterization and Chromosome Analysis of Two netF+ Clostridium perfringens Isolates Associated with Foal and Canine Necrotizing Enteritis.

    Science.gov (United States)

    Mehdizadeh Gohari, Iman; Kropinski, Andrew M; Weese, Scott J; Parreira, Valeria R; Whitehead, Ashley E; Boerlin, Patrick; Prescott, John F

    2016-01-01

    The recent discovery of a novel beta-pore-forming toxin, NetF, which is strongly associated with canine and foal necrotizing enteritis should improve our understanding of the role of type A Clostridium perfringens associated disease in these animals. The current study presents the complete genome sequence of two netF-positive strains, JFP55 and JFP838, which were recovered from cases of foal necrotizing enteritis and canine hemorrhagic gastroenteritis, respectively. Genome sequencing was done using Single Molecule, Real-Time (SMRT) technology-PacBio and Illumina Hiseq2000. The JFP55 and JFP838 genomes include a single 3.34 Mb and 3.53 Mb chromosome, respectively, and both genomes include five circular plasmids. Plasmid annotation revealed that three plasmids were shared by the two newly sequenced genomes, including a NetF/NetE toxins-encoding tcp-conjugative plasmid, a CPE/CPB2 toxins-encoding tcp-conjugative plasmid and a putative bacteriocin-encoding plasmid. The putative beta-pore-forming toxin genes, netF, netE and netG, were located in unique pathogenicity loci on tcp-conjugative plasmids. The C. perfringens JFP55 chromosome carries 2,825 protein-coding genes whereas the chromosome of JFP838 contains 3,014 protein-encoding genes. Comparison of these two chromosomes with three available reference C. perfringens chromosome sequences identified 48 (~247 kb) and 81 (~430 kb) regions unique to JFP55 and JFP838, respectively. Some of these divergent genomic regions in both chromosomes are phage- and plasmid-related segments. Sixteen of these unique chromosomal regions (~69 kb) were shared between the two isolates. Five of these shared regions formed a mosaic of plasmid-integrated segments, suggesting that these elements were acquired early in a clonal lineage of netF-positive C. perfringens strains. These results provide significant insight into the basis of canine and foal necrotizing enteritis and are the first to demonstrate that netF resides on a large and

  10. Plasmid Characterization and Chromosome Analysis of Two netF+ Clostridium perfringens Isolates Associated with Foal and Canine Necrotizing Enteritis.

    Directory of Open Access Journals (Sweden)

    Iman Mehdizadeh Gohari

    Full Text Available The recent discovery of a novel beta-pore-forming toxin, NetF, which is strongly associated with canine and foal necrotizing enteritis should improve our understanding of the role of type A Clostridium perfringens associated disease in these animals. The current study presents the complete genome sequence of two netF-positive strains, JFP55 and JFP838, which were recovered from cases of foal necrotizing enteritis and canine hemorrhagic gastroenteritis, respectively. Genome sequencing was done using Single Molecule, Real-Time (SMRT technology-PacBio and Illumina Hiseq2000. The JFP55 and JFP838 genomes include a single 3.34 Mb and 3.53 Mb chromosome, respectively, and both genomes include five circular plasmids. Plasmid annotation revealed that three plasmids were shared by the two newly sequenced genomes, including a NetF/NetE toxins-encoding tcp-conjugative plasmid, a CPE/CPB2 toxins-encoding tcp-conjugative plasmid and a putative bacteriocin-encoding plasmid. The putative beta-pore-forming toxin genes, netF, netE and netG, were located in unique pathogenicity loci on tcp-conjugative plasmids. The C. perfringens JFP55 chromosome carries 2,825 protein-coding genes whereas the chromosome of JFP838 contains 3,014 protein-encoding genes. Comparison of these two chromosomes with three available reference C. perfringens chromosome sequences identified 48 (~247 kb and 81 (~430 kb regions unique to JFP55 and JFP838, respectively. Some of these divergent genomic regions in both chromosomes are phage- and plasmid-related segments. Sixteen of these unique chromosomal regions (~69 kb were shared between the two isolates. Five of these shared regions formed a mosaic of plasmid-integrated segments, suggesting that these elements were acquired early in a clonal lineage of netF-positive C. perfringens strains. These results provide significant insight into the basis of canine and foal necrotizing enteritis and are the first to demonstrate that netF resides on a

  11. Identification of phosphorylation sites in protein kinase A substrates using artificial neural networks and mass spectrometry

    DEFF Research Database (Denmark)

    Hjerrild, M.; Stensballe, A.; Rasmussen, T.E.

    2004-01-01

    Protein phosphorylation plays a key role in cell regulation and identification of phosphorylation sites is important for understanding their functional significance. Here, we present an artificial neural network algorithm: NetPhosK (http://www.cbs.dtu.dk/services/NetPhosK/) that predicts protein...... kinase A (PKA) phosphorylation sites. The neural network was trained with a positive set of 258 experimentally verified PKA phosphorylation sites. The predictions by NetPhosK were! validated using four novel PKA substrates: Necdin, RFX5, En-2, and Wee 1. The four proteins were phosphorylated by PKA...... in vitro and 13 PKA phosphorylation sites were identified by mass spectrometry. NetPhosK was 100% sensitive and 41% specific in predicting PKA sites in the four proteins. These results demonstrate the potential of using integrated computational and experimental methods for detailed investigations...

  12. [Effects of glutathione on plasma heat shock protein 70 of acute gastric mucosal injury in rats exposed to positive acceleration].

    Science.gov (United States)

    Shao, Ying-tan; Li, Jing; Chen, Ying; Yang, Chun-min; Tang, He-lan; Wang, Jian-chang

    2013-12-01

    To explore the change of plasma heat shock protein 70 (HSP70) in rats exposed to acute gastric mucosal injury under the condition of positive acceleration (+Gz) and elucidate the effects of glutathione (GSH) and the corresponding protective mechanisms. A total of 40 male SD rats were randomly by computer randomization into 4 groups of ethanol control, +5 Gz value exposure, +10 Gz value exposure and GSH protection (n = 10 each). GSH protection group received adaptive feeding for 7 days and then an intraperitoneal injection of GSH for 3 consecutive days. All 4 groups fasted for 24 hours within 10 days, water deprivation for 12 hours and a gastric lavage of anhydrous ethanol (0.4 ml/100 g) for 1 hour, ethanol control group had no acceleration,+5 Gz value exposure group at + 5 Gz and the latter two groups respectively at +10 Gz for around 3 min.Each group underwent anesthesia of pentobarbital after centrifuge immediately. Abdominal aortic blood samples were collected and gastric tissues harvested for observation of mucosal injury. Mucosal damage index was calculated by the GUTH method. And the plasma content of HSP70 was measured by radioimmunoassay. (1) Gastric mucosa of each groups rats were injured. Damage was significantly reduced by GSH pretreatment, ethanol control group had less injury, the injury of +5 Gz value exposure group was aggravated compared with the control group (gastric mucosal injury index: 25.4 (14.0-30.0) vs 10.0 (9.2-13.9), P = 0.001); +10 Gz value exposure group mucosal injury was heaviest (47.2 (41.5-60.1)) . There were diffuse hyperemia, edema and erosion with a large area of bleeding spots and flat mucosal folds.It had statistically significant differences with the first two groups (all P ethanol groups ((6.5 ± 0.5) ng/ml, P = 0.897); HSP70 plasma level ((5.9 ± 0.5) ng/ml) of +10 Gz value exposure was significantly lower than those of the first two groups (P = 0.018,0.014); GSH protection group ((7.0 ± 0.5) ng/ml) was significantly higher

  13. Linear Logic on Petri Nets

    DEFF Research Database (Denmark)

    Engberg, Uffe Henrik; Winskel, Glynn

    This article shows how individual Petri nets form models of Girard's intuitionistic linear logic. It explores questions of expressiveness and completeness of linear logic with respect to this interpretation. An aim is to use Petri nets to give an understanding of linear logic and give some apprai...

  14. Reference Guide Microsoft.NET

    NARCIS (Netherlands)

    Zee M van der; Verspaij GJ; Rosbergen S; IMP; NMD

    2003-01-01

    Developers, administrators and managers can get more understanding of the .NET technology with this report. They can also make better choices how to use this technology. The report describes the results and conclusions of a study of the usability for the RIVM of this new generation .NET development

  15. Net neutrality and audiovisual services

    NARCIS (Netherlands)

    van Eijk, N.; Nikoltchev, S.

    2011-01-01

    Net neutrality is high on the European agenda. New regulations for the communication sector provide a legal framework for net neutrality and need to be implemented on both a European and a national level. The key element is not just about blocking or slowing down traffic across communication

  16. The Significance of Gastric Juice Analysis for a Positive Challenge by a Standard Oral Challenge Test in Typical Cow's Milk Protein-Induced Enterocolitis

    Science.gov (United States)

    Song, Jeong-Yoon; Kang, Yu Na; Kim, Sang Pyo; Suh, Seong-Il; Kam, Sin; Choi, Won Joung

    2008-01-01

    This study was performed to investigate the significance of gastric juice analysis (GJA) as a diagnostic criterion of a positive challenge in a standard oral cow's milk challenge (OCC) to confirm typical cow's milk protein-induced enterocolitis (CMPIE). Data from 16 CMPIE patients (aged 14 to 44 days) were analyzed. A standard OCC was openly executed using 0.15 g/kg of protein. Three symptoms (vomiting, lethargy, and bloody or pus-like stool), and four laboratory findings (GJA [3 hr], changes in peripheral blood absolute neutrophil count [ANC] [6 hr], C-reactive protein [6 hr], and stool smear test for occult blood or leukocytes) were observed after OCC. Before OCC, baseline studies were conducted; a stool smear test, blood sampling, and GJA. Positive OCC results were; vomiting (87.5%) (observed 1-3 hr after OCC), lethargy (62.5%) (1-3 hr), bloody or pus-like stool (43.8%) (6-10 hr), abnormal GJA (93.8%), an ANC rise >3,500 cells/µL (93.8%), and an abnormal stool smear test (75.0%). A single GJA test after a standard OCC is a sensitive diagnostic criterion of a positive challenge, and may provide an early confirmatory diagnosis of CMPIE. An investigation of positive OCC outcomes helps to find out a diagnostic algorithm of criteria of a positive challenge in CMPIE. PMID:18437008

  17. Matrix protein of VSV New Jersey serotype containing methionine to arginine substitutions at positions 48 and 51 allows near-normal host cell gene expression.

    Science.gov (United States)

    Kim, Gyoung Nyoun; Kang, C Yong

    2007-01-05

    The matrix (M) protein of vesicular stomatitis virus (VSV) plays significant roles in the replication of VSV through its involvement in the assembly of virus particles as well as by facilitating the evasion of innate host cell defense mechanisms. The presence of methionine at position 51 (M51) of the matrix (M) protein of the VSV Indiana serotype (VSV(Ind)) has been proven to be crucial for cell rounding and inhibition of host cell gene expression. The M protein of VSV(Ind) with the substitution of M51 with arginine (R:M51R) results in the loss of inhibitory effects on host cell gene expression. The VSV(Ind) expressing the M(M51R) protein became the attractive oncolytic virus which is safer and more tumor-specific because the normal cells can clear the mutant VSV(Ind) easily but tumor cells are susceptible to the virus because a variety of tumor cells lack innate antiviral activities. We have studied the role of the methionines at positions 48 and 51 of the M protein of the New Jersey serotype of VSV (VSV(NJ)) in the induction of cytopathic effects (CPE) and host cell gene expression. We have generated human embryonic kidney 293 cell lines inducibly expressing M proteins with M to R mutations at positions 48 and 51, either separately or together as a double mutant, and examined expression of heat shock protein 70 (HSP70) as an indicator of host cell gene expression. We have also generated recombinant VSV(NJ) encoding the mutant M proteins M(M48R) or M(M48R+M51R) for the first time and tested for the expression of HSP70 in infected cells. Our results demonstrated that the M51 of VSV(NJ) M proteins has a major role in cell rounding and in suppressing the host cell gene expression either when the M protein was expressed alone in inducible cell lines or when expressed together with other VSV proteins by the recombinant VSV(NJ). Amino acid residue M48 may also have some role in cell rounding and in the inhibitory effects of VSV(NJ) M, which was demonstrated by the fact

  18. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Chan, Arlene; Delaloge, Suzette; Holmes, Frankie A; Moy, Beverly; Iwata, Hiroji; Harvey, Vernon J; Robert, Nicholas J; Silovski, Tajana; Gokmen, Erhan; von Minckwitz, Gunter; Ejlertsen, Bent; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Buyse, Marc; Gore, Ira; Smith, John; Harker, Graydon; Masuda, Norikazu; Petrakova, Katarina; Zotano, Angel Guerrero; Iannotti, Nicholas; Rodriguez, Gladys; Tassone, Pierfrancesco; Wong, Alvin; Bryce, Richard; Ye, Yining; Yao, Bin; Martin, Miguel

    2016-03-01

    Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer. We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres in Europe, Asia, Australia, New Zealand, and North and South America. Eligible women (aged ≥18 years, or ≥20 years in Japan) had stage 1-3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria were amended on Feb 25, 2010, to include patients with stage 2-3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously. Patients were randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive [oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen and progesterone receptor-negative]), nodal status (0, 1-3, or ≥4), and trastuzumab adjuvant regimen (sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system. Patients, investigators, and trial sponsors were masked to treatment allocation. The primary outcome was invasive disease-free survival, as defined in the original protocol, at 2 years after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00878709. Between July 9, 2009, and Oct 24, 2011, we randomly assigned 2840 women to receive neratinib (n=1420) or placebo (n=1420). Median follow-up time was 24 months (IQR 20-25) in the neratinib group and 24 months (22-25) in the placebo group. At 2 year follow-up, 70

  19. A Small Universal Petri Net

    Directory of Open Access Journals (Sweden)

    Dmitry A. Zaitsev

    2013-09-01

    Full Text Available A universal deterministic inhibitor Petri net with 14 places, 29 transitions and 138 arcs was constructed via simulation of Neary and Woods' weakly universal Turing machine with 2 states and 4 symbols; the total time complexity is exponential in the running time of their weak machine. To simulate the blank words of the weakly universal Turing machine, a couple of dedicated transitions insert their codes when reaching edges of the working zone. To complete a chain of a given Petri net encoding to be executed by the universal Petri net, a translation of a bi-tag system into a Turing machine was constructed. The constructed Petri net is universal in the standard sense; a weaker form of universality for Petri nets was not introduced in this work.

  20. Bed net ownership in Kenya: the impact of 3.4 million free bed nets

    Directory of Open Access Journals (Sweden)

    Vulule John

    2010-06-01

    Full Text Available Abstract Background In July and September 2006, 3.4 million long-lasting insecticide-treated bed nets (LLINs were distributed free in a campaign targeting children 0-59 months old (CU5s in the 46 districts with malaria in Kenya. A survey was conducted one month after the distribution to evaluate who received campaign LLINs, who owned insecticide-treated bed nets and other bed nets received through other channels, and how these nets were being used. The feasibility of a distribution strategy aimed at a high-risk target group to meet bed net ownership and usage targets is evaluated. Methods A stratified, two-stage cluster survey sampled districts and enumeration areas with probability proportional to size. Handheld computers (PDAs with attached global positioning systems (GPS were used to develop the sampling frame, guide interviewers back to chosen households, and collect survey data. Results In targeted areas, 67.5% (95% CI: 64.6, 70.3% of all households with CU5s received campaign LLINs. Including previously owned nets, 74.4% (95% CI: 71.8, 77.0% of all households with CU5s had an ITN. Over half of CU5s (51.7%, 95% CI: 48.8, 54.7% slept under an ITN during the previous evening. Nearly forty percent (39.1% of all households received a campaign net, elevating overall household ownership of ITNs to 50.7% (95% CI: 48.4, 52.9%. Conclusions The campaign was successful in reaching the target population, families with CU5s, the risk group most vulnerable to malaria. Targeted distribution strategies will help Kenya approach indicator targets, but will need to be combined with other strategies to achieve desired population coverage levels.

  1. Polymorphisms in the tumor necrosis factor-alpha gene at position -308 and the inducible 70 kd heat shock protein gene at position +1267 in multifetal pregnancies and preterm premature rupture of fetal membranes.

    Science.gov (United States)

    Kalish, Robin B; Vardhana, Santosh; Gupta, Meruka; Perni, Sriram C; Chasen, Stephen T; Witkin, Steven S

    2004-10-01

    The purpose of this study was to determine the relationship between preterm premature rupture of membranes, tumor necrosis factor-alpha, and heat shock protein-70 gene polymorphisms in multifetal gestations. Buccal swabs from 101 mother-neonate pairs of multifetal pregnancies were tested for single nucleotide polymorphisms at position -308 of the tumor necrosis factor-alpha gene and +1267 of the heat shock protein-70 gene. Pregnancy outcome data were obtained subsequently. Tumor necrosis factor-alpha allele 2 carriage by the first-born occurred in 10 of 27 pregnancies (37.0%) that resulted in preterm premature rupture of membranes compared with 6 of 67 pregnancies (9.0%) without preterm premature rupture of membranes ( P = .002). The allele frequency of tumor necrosis factor-alpha allele 2 and heat shock protein-70 allele 2 in the first born was higher in pregnancies that were complicated by preterm premature rupture of membranes (18.5% vs 4.5%; P = .003; and 57.7% vs 41.3%; P = .04, respectively). There was no relationship between tumor necrosis factor-alpha allele 2 or heat shock protein-70 allele 2 carriage by the second fetus or mother and preterm premature rupture of membranes. Tumor necrosis factor-alpha allele 2 and/or heat shock protein-70 allele 2 carriage by the first-born fetus is associated with preterm premature rupture of membranes in multifetal pregnancies.

  2. Positively-charged semi-tunnel is a structural and surface characteristic of polyphosphate-binding proteins: an in-silico study.

    Directory of Open Access Journals (Sweden)

    Zheng Zachory Wei

    Full Text Available Phosphate is essential for all major life processes, especially energy metabolism and signal transduction. A linear phosphate polymer, polyphosphate (polyP, linked by high-energy phosphoanhydride bonds, can interact with various proteins, playing important roles as an energy source and regulatory factor. However, polyP-binding structures are largely unknown. Here we proposed a putative polyP binding site, a positively-charged semi-tunnel (PCST, identified by surface electrostatics analyses in polyP kinases (PPKs and many other polyP-related proteins. We found that the PCSTs in varied proteins were folded in different secondary structure compositions. Molecular docking calculations revealed a significant value for binding affinity to polyP in PCST-containing proteins. Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3. The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities. This should greatly enhance the understanding of the many physiological functions of protein-bound polyP and the involvement of polyP and polyP-binding proteins in various human diseases.

  3. High-level Petri Nets

    DEFF Research Database (Denmark)

    High-level Petri nets are now widely used in both theoretical analysis and practical modelling of concurrent systems. The main reason for the success of this class of net models is that they make it possible to obtain much more succinct and manageable descriptions than can be obtained by means...... of low-level Petri nets - while, on the other hand, they still offer a wide range of analysis methods and tools. The step from low-level nets to high-level nets can be compared to the step from assembly languages to modern programming languages with an elaborated type concept. In low-level nets...... there is only one kind of token and this means that the state of a place is described by an integer (and in many cases even by a boolean). In high-level nets each token can carry a complex information/data - which, e.g., may describe the entire state of a process or a data base. Today most practical...

  4. Positive selection drives rapid evolution of certain amino acid residues in an evolutionarily highly conserved interferon-inducible antiviral protein of fishes.

    Science.gov (United States)

    Padhi, Abinash

    2013-01-01

    Viperin, an evolutionarily highly conserved interferon-inducible multifunctional protein, has previously been reported to exhibit antiviral activity against a wide range of DNA and RNA viruses. Utilizing the complete nucleotide coding sequence data of fish viperin antiviral genes, and employing the maximum likelihood-based codon substitution models, the present study reports the pervasive role of positive selection in the evolution of viperin antiviral protein in fishes. The overall rate of nonsynonymous (dN) to synonymous (dS) substitutions (dN/dS) for the three functional domains of viperin (N-terminal, central domain and C-terminal) were 1.1, 0.12, and 0.24, respectively. Codon-by-codon substitution analyses have revealed that while most of the positively selected sites were located at the N-terminal amphipathic α-helix domain, few amino acid residues at the C-terminal domain were under positive selection. However, none of the sites in the central domain were under positive selection. These results indicate that, although viperin is evolutionarily highly conserved, the three functional domains experienced differential selection pressures. Taken together with the results of previous studies, the present study suggests that the persistent antagonistic nature of surrounding infectious viral pathogens might be the likely cause for such adaptive evolutionary changes of certain amino acids in fish viperin antiviral protein.

  5. Structural Basis for Recognizing Phosphoarginine and Evolving Residue-Specific Protein Phosphatases in Gram-Positive Bacteria

    Directory of Open Access Journals (Sweden)

    Jakob Fuhrmann

    2013-06-01

    Full Text Available Many cellular pathways are regulated by the competing activity of protein kinases and phosphatases. The recent identification of arginine phosphorylation as a protein modification in bacteria prompted us to analyze the molecular basis of targeting phospho-arginine. In this work, we characterize an annotated tyrosine phosphatase, YwlE, that counteracts the protein arginine kinase McsB. Strikingly, structural studies of YwlE reaction intermediates provide a direct view on a captured arginine residue. Together with biochemical data, the crystal structures depict the evolution of a highly specific phospho-arginine phosphatase, with the use of a size-and-polarity filter for distinguishing phosphorylated arginine from other phosphorylated side chains. To confirm the proposed mechanism, we performed bioinformatic searches for phosphatases, employing a similar selectivity filter, and identified a protein in Drosophila melanogaster exhibiting robust arginine phosphatase activity. In sum, our findings uncover the molecular framework for specific targeting of phospho-arginine and suggest that protein arginine (dephosphorylation may be relevant in eukaryotes.

  6. Positively charged mini-protein Zbasic2 as a highly efficient silica binding module: opportunities for enzyme immobilization on unmodified silica supports.

    Science.gov (United States)

    Bolivar, Juan M; Nidetzky, Bernd

    2012-07-03

    Silica is a highly attractive support material for protein immobilization in a wide range of biotechnological and biomedical-analytical applications. Without suitable derivatization, however, the silica surface is not generally usable for attachment of proteins. We show here that Z(basic2) (a three α-helix bundle mini-protein of 7 kDa size that exposes clustered positive charges from multiple arginine residues on one side) functions as highly efficient silica binding module (SBM), allowing chimeras of target protein with SBM to become very tightly attached to underivatized glass at physiological pH conditions. We used two enzymes, d-amino acid oxidase and sucrose phosphorylase, to demonstrate direct immobilization of Z(basic2) protein from complex biological samples with extremely high selectivity. Immobilized enzymes displayed full biological activity, suggesting that their binding to the glass surface had occurred in a preferred orientation via the SBM. We also show that charge complementarity was the main principle of affinity between SBM and glass surface, and Z(basic2) proteins were bound in a very strong, yet fully reversible manner, presumably through multipoint noncovalent interactions. Z(basic2) proteins were immobilized on porous glass in a loading of 30 mg protein/g support or higher, showing that attachment via the SBM combines excellent binding selectivity with a technically useful binding capacity. Therefore, Z(basic2) and silica constitute a fully orthogonal pair of binding module and insoluble support for oriented protein immobilization, and this opens up new opportunities for the application of silica-based materials in the development of supported heterogeneous biocatalysts.

  7. Pro asynchronous programming with .NET

    CERN Document Server

    Blewett, Richard; Ltd, Rock Solid Knowledge

    2014-01-01

    Pro Asynchronous Programming with .NET teaches the essential skill of asynchronous programming in .NET. It answers critical questions in .NET application development, such as: how do I keep my program responding at all times to keep my users happy how do I make the most of the available hardware how can I improve performanceIn the modern world, users expect more and more from their applications and devices, and multi-core hardware has the potential to provide it. But it takes carefully crafted code to turn that potential into responsive, scalable applications.With Pro Asynchronous Programming

  8. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-08-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  9. Conditional constitutive expression system of a drug protein in vivo by positive feedback loop using an inducer-independent artificial transcription factor.

    Science.gov (United States)

    Lee, Eun-Bin; Lim, Ho-Dong; You, Sung-Hwan; Cheong, Dae-Eun; Kim, Geun-Joong

    2018-01-22

    Bacterial-mediated drug delivery is a potential and promising strategy for the specific treatment of cancer with therapeutic molecules, especially with genetically encoded proteins. These proteins must be tightly regulated due to cytotoxicity and thus are usually expressed under the control of the P BAD and TetA/TetR promoters in vivo. Since protein expression from these systems is triggered by exogenous inducer, periodic intravenous injection of inducer is necessary. However, these treatments can result in non-homogenous and/or inefficient expression of therapeutic proteins in vivo due to impeded diffusion and dilution of the inducer further from the injection site. To overcome these hurdles, we designed a conditional constitutive expression system equipped with the artificial transcription factor, AraC C , which has two operator-binding domains and simultaneously binds to the I 1 and I 2 operators of the P BAD promoter for gene expression in an arabinose-independent manner. Using this construct and the wild type protein AraC under the control of the P BAD promoter, we constructed a self-positive feedback system to constitutively express the therapeutic protein when the induction of AraC was triggered once using arabinose. This expression system could be useful in various cancer treatment strategies using bacteria to deliver genetically encoded drugs in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Identification of unique SUN-interacting nuclear envelope proteins with diverse functions in plants.

    Science.gov (United States)

    Zhou, Xiao; Graumann, Katja; Wirthmueller, Lennart; Jones, Jonathan D G; Meier, Iris

    2014-06-09

    Although a plethora of nuclear envelope (NE) transmembrane proteins (NETs) have been identified in opisthokonts, plant NETs are largely unknown. The only known NET homologues in plants are Sad1/UNC-84 (SUN) proteins, which bind Klarsicht/ANC-1/Syne-1 homology (KASH) proteins. Therefore, de novo identification of plant NETs is necessary. Based on similarities between opisthokont KASH proteins and the only known plant KASH proteins, WPP domain-interacting proteins, we used a computational method to identify the KASH subset of plant NETs. Ten potential plant KASH protein families were identified, and five candidates from four of these families were verified for their NE localization, depending on SUN domain interaction. Of those, Arabidopsis thaliana SINE1 is involved in actin-dependent nuclear positioning in guard cells, whereas its paralogue SINE2 contributes to innate immunity against an oomycete pathogen. This study dramatically expands our knowledge of plant KASH proteins and suggests that plants and opisthokonts have recruited different KASH proteins to perform NE regulatory functions. © 2014 Zhou et al.

  11. Human immunodeficiency virus integrase protein requires a subterminal position of its viral DNA recognition sequence for efficient cleavage

    NARCIS (Netherlands)

    C. Vink (Cornelis); D.C. van Gent (Dik); Y. Elgersma (Ype); R.H. Plassterk

    1991-01-01

    textabstractRetroviral integration requires cis-acting sequences at the termini of linear double-stranded viral DNA and a product of the retroviral pol gene, the integrase protein (IN). IN is required and sufficient for generation of recessed 3' termini of the viral DNA (the first

  12. Bacterial mitosis: partitioning protein ParA oscillates in spiral-shaped structures and positions plasmids at mid-cell

    DEFF Research Database (Denmark)

    Ebersbach, Gitte; Gerdes, Kenn; Charbon, Gitte Ebersbach

    2004-01-01

    The par2 locus of Escherichia coli plasmid pB171 encodes oscillating ATPase ParA, DNA binding protein ParB and two cis-acting DNA regions to which ParB binds (parC1 and parC2). Three independent techniques were used to investigate the subcellular localization of plasmids carrying par2. In cells w...

  13. Petri Net Tool Overview 1986

    DEFF Research Database (Denmark)

    Jensen, Kurt; Feldbrugge, Frits

    1987-01-01

    This paper provides an overview of the characteristics of all currently available net based tools. It is a compilation of information provided by tool authors or contact persons. A concise one page overview is provided as well....

  14. Understanding Net Zero Energy Buildings

    DEFF Research Database (Denmark)

    Salom, Jaume; Widén, Joakim; Candanedo, José

    2011-01-01

    Although several alternative definitions exist, a Net-Zero Energy Building (Net ZEB) can be succinctly described as a grid-connected building that generates as much energy as it uses over a year. The “net-zero” balance is attained by applying energy conservation and efficiency measures...... and by incorporating renewable energy systems. While based on annual balances, a complete description of a Net ZEB requires examining the system at smaller time-scales. This assessment should address: (a) the relationship between power generation and building loads and (b) the resulting interaction with the power grid....... This paper presents and categorizes quantitative indicators suitable to describe both aspects of the building’s performance. These indicators, named LMGI - Load Matching and Grid Interaction indicators, are easily quantifiable and could complement the output variables of existing building simulation tools...

  15. PolicyNet Publication System

    Data.gov (United States)

    Social Security Administration — The PolicyNet Publication System project will merge the Oracle-based Policy Repository (POMS) and the SQL-Server CAMP system (MSOM) into a new system with an Oracle...

  16. KM3NeT

    CERN Multimedia

    KM3NeT is a large scale next-generation neutrino telescope located in the deep waters of the Mediterranean Sea, optimized for the discovery of galactic neutrino sources emitting in the TeV energy region.

  17. Net Neutrality: Background and Issues

    National Research Council Canada - National Science Library

    Gilroy, Angele A

    2006-01-01

    .... The move to place restrictions on the owners of the networks that compose and provide access to the Internet, to ensure equal access and nondiscriminatory treatment, is referred to as "net neutrality...

  18. Differential profiles of salivary proteins with affinity to Streptococcus mutans lipoteichoic acid in caries-free and caries-positive human subjects.

    Science.gov (United States)

    Hong, S W; Seo, D-G; Baik, J E; Cho, K; Yun, C-H; Han, S H

    2014-10-01

    Streptococcus mutans is a representative oral pathogen that causes dental caries and pulpal inflammation. Its lipoteichoic acid (Sm.LTA) is known to be an important cell-wall virulence factor involved in bacterial adhesion and induction of inflammation. Since Sm.LTA-binding proteins (Sm.LTA-BPs) might play an important role in pathogenesis and host immunity, we identified the Sm.LTA-BPs in the saliva of caries-free and caries-positive human subjects using Sm.LTA-conjugated beads and LTQ-Orbitrap hybrid Fourier transform mass spectrometry. Sm.LTA was conjugated to N-hydroxysuccinimidyl-Sepharose(®) 4 Fast Flow beads (Sm.LTA-beads). Sm.LTA retained its biological properties during conjugation, as determined by the expression of nitric oxide and interferon-γ-inducible protein 10 in a murine macrophage cell line and activation of Toll-like receptor 2 (TLR2) in CHO/CD14/TLR2 cells. Sm.LTA-BPs were isolated from pooled saliva prepared from 10 caries-free or caries-positive human subjects each, electrophoresed to see their differential expression in each group, and further identified by high-resolution mass spectrometry. A total of 8 and 12 Sm.LTA-BPs were identified with statistical significance in the pooled saliva from the caries-free and caries-positive human subjects, respectively. Unique Sm.LTA-BPs found in caries-free saliva included histone H4, profilin-1 and neutrophil defensin-1, and those in caries-positive saliva included cystatin-C, cystatin-SN, cystatin-S, cystatin-D, lysozyme C, calmodulin-like protein 3 and β-actin. The Sm.LTA-BPs found in both groups were hemoglobin subunits α and β, prolactin-inducible protein, protein S100-A9, and SPLUNC2. Collectively, we identified Sm.LTA-BPs in the saliva of caries-free and caries-positive subjects, which exhibit differential protein profiles. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Petri Nets in Cryptographic Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico; Winskel, Glynn

    2001-01-01

    A process language for security protocols is presented together with a semantics in terms of sets of events. The denotation of process is a set of events, and as each event specifies a set of pre and postconditions, this denotation can be viewed as a Petri net. By means of an example we illustrate...... how the Petri-net semantics can be used to prove security properties....

  20. The Economics of Net Neutrality

    OpenAIRE

    Hahn, Robert W.; Wallsten, Scott

    2006-01-01

    This essay examines the economics of "net neutrality" and broadband Internet access. We argue that mandating net neutrality would be likely to reduce economic welfare. Instead, the government should focus on creating competition in the broadband market by liberalizing more spectrum and reducing entry barriers created by certain local regulations. In cases where a broadband provider can exercise market power the government should use its antitrust enforcement authority to police anticompetitiv...

  1. Expression of contactin associated protein-like 2 in a subset of hepatic progenitor cell compartment identified by gene expression profiling in hepatitis B virus-positive cirrhosis.

    Science.gov (United States)

    Wang, Huafeng; Gao, Yabo; Jin, Xiaolong; Xiao, Jiacheng

    2010-01-01

    Hepatic progenitor cells (HPC), a cell compartment capable of differentiating into hepatocytic and biliary lineages, may give rise to the formation of intermediate hepatobiliary cells (IHBC) or ductular reactions (DR). The aim of this study was to analyse the gene expression profiles of DR in cirrhosis and further investigate novel proteins expressed by HPC and their intermediate progeny. DR in hepatitis B virus (HBV)-positive cirrhotic liver tissues adjacent to hepatocellular carcinoma and interlobular bile ducts (ILBDs) in normal liver tissues were isolated by laser capture microdissection and then subjected to microarray analysis. Differential gene expression patterns were verified by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry on serial sections. HPC and their intermediate progeny were recognized by immunostaining with hepatocytic and biliary markers [HepPar1, cytokeratin (CK)7, CK19, neural cell adhesion molecule (NCAM), epithelial cell adhesion molecule (EpCAM)]. A total of 88 genes showed upregulation in DR compared with ILBDs. Gene ontology analyses revealed that these upregulated genes were mostly associated with cell adhesion, immune response and the metabolic process. Contactin associated protein-like 2 (CNTNAP2) was first confirmed to be a novel protein expressed in a subpopulation of DR that was positive for CK7, NCAM or EpCAM. In addition, immunoreactivity for CNTNAP2 was also noted in a subset of isolated CK7-positive HPC as well as some ductular IHBC positive for CK19 and HepPar1 in DR. CNTNAP2 is specifically associated with the emergence of ductular populations and may be identified as a novel protein for defining a subset of HPC and their intermediate progeny in cirrhosis.

  2. Anti-citrullinated protein antibody positive rheumatoid arthritis is primarily determined by rheumatoid factor titre and the shared epitope rather than smoking per se.

    Science.gov (United States)

    Murphy, Dan; Mattey, Derek; Hutchinson, David

    2017-01-01

    To analyse the relationship between rheumatoid factor (RF) titre, smoking and HLA-DRB1 alleles coding a "shared epitope" (SE) in relation to anti-citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA). RA patients (n = 658) attending rheumatology clinics in Cornwall, UK (cohort 1) were stratified according to RF and ACPA titre, and smoking pack years at diagnosis. A further 409 RA patients from North Staffordshire, UK (cohort 2) were studied to confirm the relationship between RF levels, smoking and ACPA positivity in relation to SE status. In cohort 1 there was a trend (p20 pack years conferred an increased risk of anti-CCP positive RA (158/200 (79%)), compared to having never smoked (146/235 (62%), p = <0.01), but this increased risk correlated with smokers' RF positivity as the principal determinant on subsequent regression analysis of cohort 2. In cohort 2, ACPA positivity rates significantly increased with RF positivity and carriage of 1 or 2 SE alleles (p<0.01). Little or no relationship was observed in patients lacking SE. ACPA positivity in RA strongly associates with increasing RF titre independent of smoking. This relationship is dependent on carriage of SE alleles. There is no relationship between ACPA and smoking in RF negative patients.

  3. iRPIS-PseNNC: identifying RNA-protein interaction sites by incorporating the position-specific dinucleotide propensity into ensemble random forest approach

    Science.gov (United States)

    Li, Long; Chen, Guojin; Jin, Tingdu

    2017-06-01

    As the pile of RNA-Protein complexes sequences mounted, in order to overcome time-consuming problem of the traditional identify RNA-Protein interaction sites (RPIS) method, it is urgent need develop intelligent recognition approach for quickly and reliable recognition of the RNA-Protein interaction sites (RPIS). To settle the question, we developed a new method named iRPIS-PseNNC, in which each sample is a nineteen nucleotides segment that for positive the centre of the segments is RPIS and for negative the segments centre is non-RPIS, and the sample was obtained by sliding window. The RNA sample was formulated by combining the dipeptide position-specific propensity into random forest approach, and by using the random sampling to balance the training dataset. According the voting system, we combine eleven random forest together to construct an ensemble classifier. It is shown that via the rigorous cross validations that the new predictor “iRPIS-PseNNC” achieved very high percentage of accuracy than any other existing algorithms in this field, indicating that the iRPIS-PseNNC predictor will be an effective tool for prediction RNA-Protein interaction sites.

  4. The role of positively charged amino acids and electrostatic interactions in the complex of U1A protein and U1 hairpin II RNA.

    Science.gov (United States)

    Law, Michael J; Linde, Michael E; Chambers, Eric J; Oubridge, Chris; Katsamba, Phinikoula S; Nilsson, Lennart; Haworth, Ian S; Laird-Offringa, Ite A

    2006-01-01

    Previous kinetic investigations of the N-terminal RNA recognition motif (RRM) domain of spliceosomal protein U1A, interacting with its RNA target U1 hairpin II, provided experimental evidence for a 'lure and lock' model of binding in which electrostatic interactions first guide the RNA to the protein, and close range interactions then lock the two molecules together. To further investigate the 'lure' step, here we examined the electrostatic roles of two sets of positively charged amino acids in U1A that do not make hydrogen bonds to the RNA: Lys20, Lys22 and Lys23 close to the RNA-binding site, and Arg7, Lys60 and Arg70, located on 'top' of the RRM domain, away from the RNA. Surface plasmon resonance-based kinetic studies, supplemented with salt dependence experiments and molecular dynamics simulation, indicate that Lys20 predominantly plays a role in association, while nearby residues Lys22 and Lys23 appear to be at least as important for complex stability. In contrast, kinetic analyses of residues away from the RNA indicate that they have a minimal effect on association and stability. Thus, well-positioned positively charged residues can be important for both initial complex formation and complex maintenance, illustrating the multiple roles of electrostatic interactions in protein-RNA complexes.

  5. Muscle Mass Index and Animal Source of Dietary Protein Are Positively Associated with Insulin Resistance in Participants of the NuAge Study.

    Science.gov (United States)

    Matta, J; Mayo, N; Dionne, I J; Gaudreau, P; Fulop, T; Tessier, D; Gray-Donald, K; Shatenstein, B; Morais, J A

    2016-02-01

    Contribute evidence towards the complex interrelationships of body composition, insulin sensitivity and protein intake independently from adiposity in an older population. This is a cross-sectional analysis of an existing dataset in which a literature-supported model linking together the variables of interest is tested using path analysis. The loss of muscle mass has been implicated in the development of insulin resistance. We propose to test associations of muscle mass with insulin sensitivity and their respective associations with animal and vegetable sources of protein intake, independently from adiposity. Non-diabetic participants aged 68-82 years from the NuAge study with all available measures (n=441) were included. A model considering age, sex, chronic diseases, physical activity; smoking and sources of protein intake influencing body composition components and insulin sensitivity was created and tested with Path Analysis for their independent associations. Muscle mass index (MMI; kg/height in m2) and % body fat were derived from DXA and BIA. Insulin resistance was estimated by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score and physical activity by the Physical Activity Scale for the Elderly (PASE) questionnaire. Protein intakes were obtained from three non-consecutive 24h-diet recalls. In the final model, direct positive associations were observed between HOMA-IR score and MMI (ß=0.42; 95%CI: 0.24; 0.6) and % body fat (ß=0.094; 95%CI: 0.07; 0.11). There were no direct associations between animal protein intake and MMI or with HOMA-IR. There was a significant direct negative association between plant protein intake and MMI (ß= -0.068; 95%CI: -0.13; -0.003) and significant indirect associations mediated through MMI and % body fat between HOMA-IR and animal protein intake (ß=0.0321; 95%CI: 0.01; 0.05), as well as plant protein intake (ß= -0.07; 95%CI: -0.1; 0.0). Our final model indicated that MMI and HOMA score were significantly

  6. HER-2 protein concentrations in breast cancer cells increase before immunohistochemical and fluorescence in situ hybridization analysis turn positive

    DEFF Research Database (Denmark)

    Olsen, Dorte A; Østergaard, Birthe; Bokmand, Susanne

    2007-01-01

    BACKGROUND: The level of HER-2/neu in breast cancer cells is normally measured by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). It determines whether patients should be treated with trastuzumab (Herceptin). In this study, HER-2 protein in breast cancer tissue...... was measured using a quantitative method. METHODS: Tissue samples of malignant and adjacent benign breast tissue were collected from 118 consecutive women admitted for surgical treatment of breast cancer. The HER-2 protein concentration was determined by 2 HER-2 assays: ELISA and the Bayer ADVIA Centaur assay....... Paraffin-embedded tissue sections of the corresponding tumors were analyzed by IHC and FISH. RESULTS: Increased HER-2 concentrations in cancer tissue were found compared to autologous reference tissue (p

  7. 26 CFR 1.904(f)-3 - Allocation of net operating losses and net capital losses.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Allocation of net operating losses and net....904(f)-3 Allocation of net operating losses and net capital losses. For rules relating to the allocation of net operating losses and net capital losses, see § 1.904(g)-3T. ...

  8. 29 CFR 4204.13 - Net income and net tangible assets tests.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Net income and net tangible assets tests. 4204.13 Section....13 Net income and net tangible assets tests. (a) General. The criteria under this section are that either— (1) Net income test. The purchaser's average net income after taxes for its three most recent...

  9. Maintenance of energy expenditure on high-protein vs. high-carbohydrate diets at a constant body weight may prevent a positive energy balance.

    Science.gov (United States)

    Martens, E A; Gonnissen, H K; Gatta-Cherifi, B; Janssens, P L; Westerterp-Plantenga, M S

    2015-10-01

    Relatively high-protein diets are effective for body weight loss, and subsequent weight maintenance, yet it remains to be shown whether these diets would prevent a positive energy balance. Therefore, high-protein diet studies at a constant body weight are necessary. The objective was to determine fullness, energy expenditure, and macronutrient balances on a high-protein low-carbohydrate (HPLC) diet compared with a high-carbohydrate low-protein (HCLP) diet at a constant body weight, and to assess whether effects are transient or sustained after 12 weeks. A randomized parallel study was performed in 14 men and 18 women [mean ± SD age: 24 ± 5 y; BMI (in kg/m(2)): 22.8 ± 2.0] on diets containing 30/35/35 (HPLC) or 5/60/35 (HCLP) % of energy from protein/carbohydrate/fat. Significant interactions between dietary intervention and time on total energy expenditure (TEE) (P = 0.013), sleeping metabolic rate (SMR) (P = 0.040), and diet-induced thermogenesis (DIT) (P = 0.027) appeared from baseline to wk 12. TEE was maintained in the HPLC diet group, while it significantly decreased throughout the intervention period in the HCLP diet group (wk 1: P = 0.002; wk 12: P = 0.001). Energy balance was maintained in the HPLC diet group, and became positive in the HCLP diet group at wk 12 (P = 0.008). Protein balance varied directly according to the amount of protein in the diet, and diverged significantly between the diets (P = 0.001). Fullness ratings were significantly higher in the HPLC vs. the HCLP diet group at wk 1 (P = 0.034), but not at wk 12. Maintenance of energy expenditure on HPLC vs. HCLP diets at a constant body weight may prevent development of a positive energy balance, despite transiently higher fullness. The study was registered on clinicaltrials.gov with Identifier: NCT01551238. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  10. Lactobacillus plantarum gene clusters encoding putative cell-surface protein complexes for carbohydrate utilization are conserved in specific gram-positive bacteria

    Directory of Open Access Journals (Sweden)

    Muscariello Lidia

    2006-05-01

    Full Text Available Abstract Background Genomes of gram-positive bacteria encode many putative cell-surface proteins, of which the majority has no known function. From the rapidly increasing number of available genome sequences it has become apparent that many cell-surface proteins are conserved, and frequently encoded in gene clusters or operons, suggesting common functions, and interactions of multiple components. Results A novel gene cluster encoding exclusively cell-surface proteins was identified, which is conserved in a subgroup of gram-positive bacteria. Each gene cluster generally has one copy of four new gene families called cscA, cscB, cscC and cscD. Clusters encoding these cell-surface proteins were found only in complete genomes of Lactobacillus plantarum, Lactobacillus sakei, Enterococcus faecalis, Listeria innocua, Listeria monocytogenes, Lactococcus lactis ssp lactis and Bacillus cereus and in incomplete genomes of L. lactis ssp cremoris, Lactobacillus casei, Enterococcus faecium, Pediococcus pentosaceus, Lactobacillius brevis, Oenococcus oeni, Leuconostoc mesenteroides, and Bacillus thuringiensis. These genes are neither present in the genomes of streptococci, staphylococci and clostridia, nor in the Lactobacillus acidophilus group, suggesting a niche-specific distribution, possibly relating to association with plants. All encoded proteins have a signal peptide for secretion by the Sec-dependent pathway, while some have cell-surface anchors, novel WxL domains, and putative domains for sugar binding and degradation. Transcriptome analysis in L. plantarum shows that the cscA-D genes are co-expressed, supporting their operon organization. Many gene clusters are significantly up-regulated in a glucose-grown, ccpA-mutant derivative of L. plantarum, suggesting catabolite control. This is supported by the presence of predicted CRE-sites upstream or inside the up-regulated cscA-D gene clusters. Conclusion We propose that the CscA, CscB, CscC and Csc

  11. Fermentative biohydrogen production: Evaluation of net energy gain

    Energy Technology Data Exchange (ETDEWEB)

    Perera, Karnayakage Rasika J.; Ketheesan, Balachandran; Nirmalakhandan, Nagamany [Civil Engineering Department, New Mexico State University, Las Cruces, NM 88011 (United States); Gadhamshetty, Venkataramana [Civil and Environmental Engineering Dept., Rensselaer Polytechnic Institute, Troy, NY 12180 (United States)

    2010-11-15

    Most dark fermentation (DF) studies had resorted to above-ambient temperatures to maximize hydrogen yield, without due consideration of the net energy gain. In this study, literature data on fermentative hydrogen production from glucose, sucrose, and organic wastes were compiled to evaluate the benefit of higher fermentation temperatures in terms of net energy gain. This evaluation showed that the improvement in hydrogen yield at higher temperatures is not justified as the net energy gain not only declined with increase of temperature, but also was mostly negative when the fermentation temperature exceeded 25 C. To maximize the net energy gain of DF, the following two options for recovering additional energy from the end products and to determine the optimal fermentation temperature were evaluated: methane production via anaerobic digestion (AD); and direct electricity production via microbial fuel cells (MFC). Based on net energy gain, it is concluded that DF has to be operated at near-ambient temperatures for the net energy gain to be positive; and DF + MFC can result in higher net energy gain at any temperature than DF or DF + AD. (author)

  12. The serum concentration of the calcium binding protein S100B is positively associated with cognitive performance in older adults

    Directory of Open Access Journals (Sweden)

    Virginie eLam

    2013-09-01

    Full Text Available S100B is a calcium-binding peptide produced predominantly by astroglial cells in the central nervous system. S100B paradoxically has neurotrophic and apoptotic effects, dependent on extracellular concentration. This study investigated the relationship between serum S100B levels and neuropsychological performance across a range of cognitive domains in healthy older aged adults. A cohort of 219 participants between the ages of 43 and 84 years (141 female were recruited. Subjects provided a fasting blood sample for S100B measurement (Mean = 0.24 ng/mL, SD = 0.14 and completed a battery of neuropsychological tests. S100B concentrations (both with and without the covariates of age and sex were positively associated with the following measures of cognitive performance: digit symbol coding, Stroop test and measures of verbal ability. The results from this study show that serum S100B is positively associated with better cognitive performance in healthy older adults.

  13. Drastic shift from positive to negative estrogen effect on bone morphogenetic protein signaling in pulmonary arterial endothelial cells under hypoxia.

    Science.gov (United States)

    Ichimori, Hiroaki; Kogaki, Shigetoyo; Takahashi, Kunihiko; Ishida, Hidekazu; Narita, Jun; Nawa, Nobutoshi; Baden, Hiroki; Uchikawa, Toshiki; Okada, Yoko; Ozono, Keiichi

    2013-01-01

    To investigate the possible role of sex hormones in the pathogenesis of pulmonary arterial hypertension (PAH), the effect of β-estradiol (E2) on bone morphogenetic protein (BMP) signaling, a key signaling pathway involved in PAH, was studied in human pulmonary arterial endothelial cells (HPAEC). BMP signaling molecules, including BMP receptor, Smad1/5/8 and Id1, were studied in HPAEC under 1% O2 (hypoxia) and 21% O2 (normoxia) as well as the effect of hypoxia-inducible factor (HIF)-1α expression in the presence of E2 on BMP signaling. The effects of an estrogen receptor (ER) antagonist (ICI 182,780) and cycloheximide, and the interaction of ER with Smad or HIF-1α were also studied. In the presence of E2, BMP signaling was augmented under normoxia but suppressed under hypoxia. HIF-1α accumulation suppressed BMP signaling, whereas HIF-1α inhibition augmented signaling. These effects were cancelled by ICI 182,780. Moreover, binding between ER, HIF-1α and phosphorylated (p)-Smad1/5/8 proteins occurred only under hypoxia. On inhibition of de novo synthesis with cycloheximide, however, p-Smad1/5/8 expression was suppressed only under normoxia. The effects of E2 on BMP signaling in HPAEC altered depending on O2 concentration and different mechanisms may be involved. BMP and sex hormones may play an important role in PAH development.

  14. Anti–citrullinated protein antibody positivity correlates with cartilage damage and proteoglycan levels in patients with rheumatoid arthritis in the hand joints.

    Science.gov (United States)

    Renner, Nina; Krönke, Gerhard; Rech, Jürgen; Uder, Michael; Janka, Rolf; Lauer, Lars; Paul, Dominik; Herz, Barbara; Schlechtweg, Philipp; Hennig, Friedrich Frank; Schett, Georg; Welsch, Götz

    2014-12-01

    Objective: To investigate the factors associated with cartilage proteoglycan content in patients with rheumatoid arthritis (RA) Methods: 32 RA patients received high-field 3 Tesla Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) for determining cartilage proteoglycan content. Measurements were performed in three individual cartilage regions (medial, central, lateral) of the metacarpophalangeal joints 2 and 3. dGEMRIC values were then related to disease duration, disease activity, anti-citrullinated protein antibody (ACPA) status, rheumatoid factor status and C-reactive protein level. Results: dGEMRIC values were not significantly different between the MCP2 and MCP3 joint. Inter-class correlations were high (>0.92) for all three (medial, central and lateral) cartilage compartments. dGEMRIC values were significantly lower in RA patients with longer disease duration (≥3 years) and those with ACPA positivity than those with a short disease duration (proteoglycan content and disease activity, C-reactive protein level and rheumatoid factor status was found. Conclusion: Decreased cartilage proteoglycan content in RA patients is associated with disease duration and ACPA positivity but not with the actual disease activity, CRP level or rheumatoid factor status. These data suggest that the cumulative burden of inflammation as well as ACPA are the determinants for cartilage damage in RA.

  15. Recognition of interaction interface residues in low-resolution structures of protein assemblies solely from the positions of C(alpha atoms.

    Directory of Open Access Journals (Sweden)

    Rupali A Gadkari

    Full Text Available BACKGROUND: The number of available structures of large multi-protein assemblies is quite small. Such structures provide phenomenal insights on the organization, mechanism of formation and functional properties of the assembly. Hence detailed analysis of such structures is highly rewarding. However, the common problem in such analyses is the low resolution of these structures. In the recent times a number of attempts that combine low resolution cryo-EM data with higher resolution structures determined using X-ray analysis or NMR or generated using comparative modeling have been reported. Even in such attempts the best result one arrives at is the very course idea about the assembly structure in terms of trace of the C(alpha atoms which are modeled with modest accuracy. METHODOLOGY/PRINCIPAL FINDINGS: In this paper first we present an objective approach to identify potentially solvent exposed and buried residues solely from the position of C(alpha atoms and amino acid sequence using residue type-dependent thresholds for accessible surface areas of C(alpha. We extend the method further to recognize potential protein-protein interface residues. CONCLUSION/ SIGNIFICANCE: Our approach to identify buried and exposed residues solely from the positions of C(alpha atoms resulted in an accuracy of 84%, sensitivity of 83-89% and specificity of 67-94% while recognition of interfacial residues corresponded to an accuracy of 94%, sensitivity of 70-96% and specificity of 58-94%. Interestingly, detailed analysis of cases of mismatch between recognition of interface residues from C(alpha positions and all-atom models suggested that, recognition of interfacial residues using C(alpha atoms only correspond better with intuitive notion of what is an interfacial residue. Our method should be useful in the objective analysis of structures of protein assemblies when positions of only (alpha positions are available as, for example, in the cases of integration of cryo

  16. TimeNET Optimization Environment

    Directory of Open Access Journals (Sweden)

    Christoph Bodenstein

    2015-12-01

    Full Text Available In this paper a novel tool for simulation-based optimization and design-space exploration of Stochastic Colored Petri nets (SCPN is introduced. The working title of this tool is TimeNET Optimization Environment (TOE. Targeted users of this tool are people modeling complex systems with SCPNs in TimeNET who want to find parameter sets that are optimal for a certain performance measure (fitness function. It allows users to create and simulate sets of SCPNs and to run different optimization algorithms based on parameter variation. The development of this tool was motivated by the need to automate and speed up tests of heuristic optimization algorithms to be applied for SCPN optimization. A result caching mechanism is used to avoid recalculations.

  17. Redução da proteína da dieta com base no conceito de proteína ideal para tilápias-do-nilo (Oreochromis niloticus criadas em tanques-rede Dietary protein reduction based on ideal protein concept for Nile Tilapia (Oreochromis niloticus cultured in net pens

    Directory of Open Access Journals (Sweden)

    Daniele Botaro

    2007-06-01

    Full Text Available Avaliou-se o desempenho de tilápias-do-nilo (Oreochromis niloticus criadas em tanques-rede e alimentadas com dietas contendo 27,0 (controle; 25,2; 24,3 e 22,7% de proteína digestível. Aminoácidos cristalinos (L-lisina, DL-metionina e L-treonina foram adicionados à dieta considerando o conceito de proteína ideal e simulando o perfil de aminoácidos da dieta controle. Os peixes (34,63±19 g foram alimentados manualmente com dietas isoenergéticas (3.075 kcal de energia digestível/kg de dieta até saciedade aparente, três vezes ao dia, durante 91 dias. Utilizou-se um delineamento inteiramente casualizado, com quatro tratamentos, três repetições e 25 peixes/unidade experimental. Não foram observados efeitos dos níveis de proteína digestível sobre o ganho de peso, a conversão alimentar, a taxa de eficiência protéica, o peso da carcaça eviscerada, o rendimento de carcaça, o peso e o rendimento de filé, a sobrevivência e o hematócrito. Houve efeito quadrático dos níveis de proteína digestível sobre o consumo; o maior valor foi estimado para a dieta contendo 24,41% de proteína digestível e excreção de nitrogênio, na qual o melhor resultado estimado foi obtido com peixes que receberam a dieta contendo 24,92% de PD. Com a redução nos níveis de proteína digestível, observou-se aumento linear na retenção de nitrogênio. É possível reduzir o nível de proteína digestível, de 27 (29,1% de PB para 24,3% (26,6% de PB, em dietas para tilápias-do-nilo criadas em tanques-rede. Essa redução deve ser feita por meio da suplementação de aminoácidos (com base no conceito de proteína ideal, considerando o desempenho e o custo da dieta/kg ganho em filé.This study was carried out to evaluate the performance of Nile tilapia, cultured in net pens, and fed diets containing 27.0 (control, 25.2, 24.3, and 22.7% of digestible protein. Crystalline amino acids (L-lysine, DL-methionine and L-threonine were added to keep amino acid

  18. ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

    Science.gov (United States)

    Abreu, Rui M. V.; Bastos, Estela; Amorim, Irina; Gut, Ivo G.; Gärtner, Fátima; Chaves, Raquel

    2013-01-01

    Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC

  19. Heterochromatin protein 1 (HP1a positively regulates euchromatic gene expression through RNA transcript association and interaction with hnRNPs in Drosophila.

    Directory of Open Access Journals (Sweden)

    Lucia Piacentini

    2009-10-01

    Full Text Available Heterochromatin Protein 1 (HP1a is a well-known conserved protein involved in heterochromatin formation and gene silencing in different species including humans. A general model has been proposed for heterochromatin formation and epigenetic gene silencing in different species that implies an essential role for HP1a. According to the model, histone methyltransferase enzymes (HMTases methylate the histone H3 at lysine 9 (H3K9me, creating selective binding sites for itself and the chromodomain of HP1a. This complex is thought to form a higher order chromatin state that represses gene activity. It has also been found that HP1a plays a role in telomere capping. Surprisingly, recent studies have shown that HP1a is present at many euchromatic sites along polytene chromosomes of Drosophila melanogaster, including the developmental and heat-shock-induced puffs, and that this protein can be removed from these sites by in vivo RNase treatment, thus suggesting an association of HP1a with the transcripts of many active genes. To test this suggestion, we performed an extensive screening by RIP-chip assay (RNA-immunoprecipitation on microarrays, and we found that HP1a is associated with transcripts of more than one hundred euchromatic genes. An expression analysis in HP1a mutants shows that HP1a is required for positive regulation of these genes. Cytogenetic and molecular assays show that HP1a also interacts with the well known proteins DDP1, HRB87F, and PEP, which belong to different classes of heterogeneous nuclear ribonucleoproteins (hnRNPs involved in RNA processing. Surprisingly, we found that all these hnRNP proteins also bind heterochromatin and are dominant suppressors of position effect variegation. Together, our data show novel and unexpected functions for HP1a and hnRNPs proteins. All these proteins are in fact involved both in RNA transcript processing and in heterochromatin formation. This suggests that, in general, similar epigenetic mechanisms

  20. Triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Heng [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Guo, Wei [Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Long, Cong; Wang, Huan; Wang, Jingchao [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Sun, Xiaoping, E-mail: xsun6@whu.edu.cn [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); State Key Laboratory of Virology, Wuhan University, Wuhan 430072 (China)

    2015-01-16

    Highlights: • Triptolide inhibits proliferation of EBV-positive lymphoma cells in vitro and in vivo. • Triptolide reduces expression of LMP1 by decreasing its transcription level. • Triptolide inhibits ED-L1 promoter activity. - Abstract: Epstein–Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities. In this study, it is determined whether triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes. The CCK-8 assays were performed to examine cell viabilities of EBV-positive B95-8 and P3HR-1 cells treated by triptolide. The mRNA and protein levels of LMP1 were examined by real time-PCR and Western blotting, respectively. The activities of two LMP1 promoters (ED-L1 and TR-L1) were determined by Dual luciferase reportor assay. The results showed that triptolide inhibited the cell viability of EBV-positive B lymphocytes, and the over-expression of LMP1 attenuated this inhibitory effect. Triptolide decreased the LMP1 expression and transcriptional levels in EBV-positive B cells. The activity of LMP1 promoter ED-L1 in type III latent infection was strongly suppressed by triptolide treatment. In addition, triptolide strongly reduced growth of B95-8 induced B lymphoma in BALB/c nude mice. These results suggest that triptolide decreases proliferation of EBV-induced B lymphocytes possibly by a mechanism related to down-regulation of the LMP1 expression.

  1. Implementing NetScaler VPX

    CERN Document Server

    Sandbu, Marius

    2014-01-01

    An easy-to-follow guide with detailed step-by step-instructions on how to implement the different key components in NetScaler, with real-world examples and sample scenarios.If you are a Citrix or network administrator who needs to implement NetScaler in your virtual environment to gain an insight on its functionality, this book is ideal for you. A basic understanding of networking and familiarity with some of the different Citrix products such as XenApp or XenDesktop is a prerequisite.

  2. Net4Care PHMR Library

    DEFF Research Database (Denmark)

    2014-01-01

    The Net4Care PHMR library contains a) A GreenCDA approach for constructing a data object representing a PHMR document: SimpleClinicalDocument, and b) A Builder which can produce a XML document representing a valid Danish PHMR (following the MedCom profile) document from the SimpleClinicalDocument......The Net4Care PHMR library contains a) A GreenCDA approach for constructing a data object representing a PHMR document: SimpleClinicalDocument, and b) A Builder which can produce a XML document representing a valid Danish PHMR (following the MedCom profile) document from the Simple...

  3. Pro DLR in NET 4

    CERN Document Server

    Wu, Chaur

    2011-01-01

    Microsoft's Dynamic Language Runtime (DLR) is a platform for running dynamic languages such as Ruby and Python on an equal footing with compiled languages such as C#. Furthermore, the runtime is the foundation for many useful software design and architecture techniques you can apply as you develop your .NET applications. Pro DLR in .NET 4 introduces you to the DLR, showing how you can use it to write software that combines dynamic and static languages, letting you choose the right tool for the job. You will learn the core DLR components such as LINQ expressions, call sites, binders, and dynami

  4. Hierarchies in Coloured Petri Nets

    DEFF Research Database (Denmark)

    Huber, Peter; Jensen, Kurt; Shapiro, Robert M.

    1991-01-01

    The paper shows how to extend Coloured Petri Nets with a hierarchy concept. The paper proposes five different hierarchy constructs, which allow the analyst to structure large CP-nets as a set of interrelated subnets (called pages). The paper discusses the properties of the proposed hierarchy...... constructs, and it illustrates them by means of two examples. The hierarchy constructs can be used for theoretical considerations, but their main use is to describe and analyse large real-world systems. All of the hierarchy constructs are supported by the editing and analysis facilities in the CPN Palette...

  5. Arabidopsis Small Rubber Particle Protein Homolog SRPs Play Dual Roles as Positive Factors for Tissue Growth and Development and in Drought Stress Responses.

    Science.gov (United States)

    Kim, Eun Yu; Park, Ki Youl; Seo, Young Sam; Kim, Woo Taek

    2016-04-01

    Lipid droplets (LDs) act as repositories for fatty acids and sterols, which are used for various cellular processes such as energy production and membrane and hormone synthesis. LD-associated proteins play important roles in seed development and germination, but their functions in postgermination growth are not well understood. Arabidopsis (Arabidopsis thaliana) contains three SRP homologs (SRP1, SRP2, and SRP3) that share sequence identities with small rubber particle proteins of the rubber tree (Hevea brasiliensis). In this report, the possible cellular roles of SRPs in postgermination growth and the drought tolerance response were investigated. Arabidopsis SRPs appeared to be LD-associated proteins and displayed polymerization properties in vivo and in vitro. SRP-overexpressing transgenic Arabidopsis plants (35S:SRP1, 35S:SRP2, and 35S:SRP3) exhibited higher vegetative and reproductive growth and markedly better tolerance to drought stress than wild-type Arabidopsis. In addition, constitutive over-expression of SRPs resulted in increased numbers of large LDs in postgermination seedlings. In contrast, single (srp1, 35S:SRP2-RNAi, and srp3) and triple (35S:SRP2-RNAi/srp1srp3) loss-of-function mutant lines exhibited the opposite phenotypes. Our results suggest that Arabidopsis SRPs play dual roles as positive factors in postgermination growth and the drought stress tolerance response. The possible relationships between LD-associated proteins and the drought stress response are discussed. © 2016 American Society of Plant Biologists. All Rights Reserved.

  6. Rapid Assessment of Resistance to Antibiotic Inhibitors of Protein Synthesis in the Gram-Positive Pathogens, Enterococcus faecalis and Streptococcus pneumoniae, Based on Evaluation of the Lytic Response.

    Science.gov (United States)

    Otero, Fátima; Tamayo, María; Santiso, Rebeca; Gosálvez, Jaime; Bou, Germán; Fernández, José Luis

    2017-04-01

    A novel assay for rapid determination of resistance to antibiotic inhibitors of protein synthesis was developed for the gram-positive pathogens, Enterococcus faecalis and Streptococcus pneumoniae. To this purpose, a lytic response was obtained by a brief incubation with lysozyme or a mixture of lysozyme, Triton X-100, and EDTA for E. faecalis (n = 82) and S. pneumoniae (n = 51), respectively. Lysis was quantified by visualizing the released nucleoids. Antibiotic-susceptible bacteria treated with Clinical and Laboratory Standards Institute (CLSI) breakpoint doses of erythromycin, azithromycin, or doxycycline that inhibited protein synthesis demonstrated a large reduction of lysed cells with respect to the control, that is, without antibiotics. However, cell lysis prevention was much lower in nonsusceptible strains, with unsuccessful inhibition of protein synthesis. ROC analysis showed that a reduction value of ≥35.6% and ≥40.4% discriminates susceptible and nonsusceptible strains for erythromycin and for doxycycline, respectively, in E. faecalis, whereas ≥20.0% is adequate for both macrolides and doxycycline in S. pneumoniae. Resistant stains were identified in 90-120 min with sensitivity and specificity between 91.7% and 100%. This is a proof of concept that evaluation of the lytic response may be a rapid and efficient test for determination of resistance to antibiotic inhibitors of protein synthesis.

  7. Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

    Directory of Open Access Journals (Sweden)

    Lu Kun

    2008-12-01

    Full Text Available Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7% stained positive for Her2 (IHC 3+, and 54% (122/223 of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5% were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2

  8. High calcium and dobutamine positive inotropy in the perfused mouse heart: myofilament calcium responsiveness, energetic economy, and effects of protein kinase C inhibition

    Directory of Open Access Journals (Sweden)

    Du Congwu

    2001-08-01

    Full Text Available Abstract Background In perfused hearts, high calcium-induced inotropy results in less developed pressure relative to myocardial oxygen consumption compared to the β-adrenergic agonist dobutamine. Calcium handling is an important determinant of myocardial oxygen consumption. Therefore, we hypothesized that this phenomenon was due to reduced myofilament responsiveness to calcium, related to protein kinase C activation. Results Developed pressure was significantly higher with dobutamine compared to high perfusate calcium of 3.5 mM (73 ± 10 vs 63 ± 10 mmHg, p Conclusions By measuring intracellular calcium, developed pressures and myocardial oxygen consumption in perfused mouse hearts, these results demonstrate that high perfusate calcium positive inotropy compared to dobutamine results in reduced myofilament responsiveness to intracellular calcium, which is associated with energetic inefficiency and evidence of protein kinase C activation.

  9. The onset of the progression of acute phase response mechanisms induced by extreme impacts can be followed by the decrease in blood levels of positive acute phase proteins.

    Science.gov (United States)

    Larina, Olga; Bekker, Anna

    Studies performed at space flights and earth-based simulation models detected the plasma indices of acute phase reaction (APR), i.e. the increase of APR cytokine mediators and alterations in the production of blood acute phase proteins (APP) at the initial stages of adaptation to altered gravity conditions. Acute phase response is the principal constituent of the functional activity of innate immunity system. Changes in plasma APPs contents are considered to serve the restoration of homeostasis state. According to trends of their concentration shifts at the evolving of acute phase reaction APPs are denoted as positive, neutral, or negative. Plasma concentrations of positive acute phase proteins α1-acid glycoprotein (α1-AGP), α1-antitrypsin (α1-AT), and neutral α2-macroglobulin (α2-M) were measured in human study at 12-hour antiorthostatic position (AOP) with 15° head down tilt and hypoxia experiments at 14% oxygen in pressure chamber. Both of these impacts were shown to produce alterations in the APP levels indicative for acute phase response. Nevertheless, in AOP experiment noticeable decrease in α1-AGP concentration occurred by hour 12, and even more pronounced decline of α1-AGP and α1-AT were found on hypoxia hours 12 and 36. Acute phase proteins α1-AGP and α2-M possess the features of proteinase inhibitors. This function is implemented by the formation of complexes with the molecules of proteolytic enzymes which subsequently are removed from the blood flow. Transient decrease in plasma concentrations of protease inhibitors on early phases of APR development was reported to result from the growth of plasma protease activity due to cathepsin release from activated leukocytes, which had not yet been compensated by enhanced APP synthesis. Being a carrier protein for positively charged and neutral substances, α1-AGP shows pronounced elevation in its blood content during APR development. As assumed, it is required for the transportation of the increased

  10. Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with Gram-positive antibacterial activity.

    Science.gov (United States)

    O'Daniel, Peter I; Peng, Zhihong; Pi, Hualiang; Testero, Sebastian A; Ding, Derong; Spink, Edward; Leemans, Erika; Boudreau, Marc A; Yamaguchi, Takao; Schroeder, Valerie A; Wolter, William R; Llarrull, Leticia I; Song, Wei; Lastochkin, Elena; Kumarasiri, Malika; Antunes, Nuno T; Espahbodi, Mana; Lichtenwalter, Katerina; Suckow, Mark A; Vakulenko, Sergei; Mobashery, Shahriar; Chang, Mayland

    2014-03-05

    Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin- and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.

  11. Increasing body condition score is positively associated interleukin-6 and monocyte chemoattractant protein-1 in Labrador retrievers.

    Science.gov (United States)

    Frank, Lauren; Mann, Sabine; Levine, Corri B; Cummings, Bethany P; Wakshlag, Joseph J

    2015-10-15

    The accumulation of excess body fat is a growing problem in dogs as well as people. Contrary to prior understanding of adipose tissue, fat is now considered to be an active endocrine organ that promotes a chronic low-grade inflammatory state often characterized by an increase in pro-inflammatory cytokines and chemokines. These have been implicated in several obesity-related disorders such as insulin resistance, cardiovascular disease, and neoplasia. The purpose of this study was to characterize fasting plasma cytokine concentrations in ninety-two healthy client-owned Labrador retriever dogs of various ages and body condition scores. The dogs were grouped according to body condition score (BCS) into three categories, lean, overweight and obese. The following cytokines and chemokines were evaluated; tumor necrosis factor-alpha, interleukin-2, interleukin-6, interleukin-8, and monocyte chemotactic protein-1 (TNF-α, IL-2, IL-6, IL-8, MCP-1). Our results indicated that fasting plasma IL-6 and MCP-1 concentrations are associated with increasing BCS. This data suggest that certain markers of inflammation increase with increasing body condition score, and that dogs, similar to humans, may be fostering a chronic inflammatory state due to obesity. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Identification of nucleosome assembly protein 1 (NAP1) as an interacting partner of plant ribosomal protein S6 (RPS6) and a positive regulator of rDNA transcription

    Energy Technology Data Exchange (ETDEWEB)

    Son, Ora [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Kim, Sunghan [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Department of Plant Science, Plant Genomics and Breeding Institute, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921 (Korea, Republic of); Shin, Yun-jeong [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Kim, Woo-Young [College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Koh, Hee-Jong, E-mail: heejkoh@snu.ac.kr [Department of Plant Science, Plant Genomics and Breeding Institute, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921 (Korea, Republic of); Cheon, Choong-Ill, E-mail: ccheon@sookmyung.ac.kr [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of)

    2015-09-18

    The ribosomal protein S6 (RPS6) is a downstream component of the signaling mediated by the target of rapamycin (TOR) kinase that acts as a central regulator of the key metabolic processes, such as protein translation and ribosome biogenesis, in response to various environmental cues. In our previous study, we identified a novel role of plant RPS6, which negatively regulates rDNA transcription, forming a complex with a plant-specific histone deacetylase, AtHD2B. Here we report that the Arabidopsis RPS6 interacts additionally with a histone chaperone, nucleosome assembly protein 1(AtNAP1;1). The interaction does not appear to preclude the association of RPS6 with AtHD2B, as the AtNAP1 was also able to interact with AtHD2B as well as with an RPS6-AtHD2B fusion protein in the BiFC assay and pulldown experiment. Similar to a positive effect of the ribosomal S6 kinase 1 (AtS6K1) on rDNA transcription observed in this study, overexpression or down regulation of the AtNAP1;1 resulted in concomitant increase and decrease, respectively, in rDNA transcription suggesting a positive regulatory role played by AtNAP1 in plant rDNA transcription, possibly through derepression of the negative effect of the RPS6-AtHD2B complex. - Highlights: • Nucleosome assembly protein 1 (AtNAP1) interacts with RPS6 as well as with AtHD2B. • rDNA transcription is regulated S6K1. • Overexpression or down regulation of AtNAP1 results in concomitant increase or decrease in rDNA transcription.

  13. D.NET case study

    International Development Research Centre (IDRC) Digital Library (Canada)

    lremy

    developing products, marketing tools and building capacity of the grass root telecentre workers. D.Net recognized that it had several ideas worth developing into small interventions that would make big differences, but resource constraints were a barrier for scaling-up these initiatives. More demands, limited resources.

  14. Surgery for GEP-NETs

    DEFF Research Database (Denmark)

    Knigge, Ulrich; Hansen, Carsten Palnæs

    2012-01-01

    Surgery is the only treatment that may cure the patient with gastroentero-pancreatic (GEP) neuroendocrine tumours (NET) and neuroendocrine carcinomas (NEC) and should always be considered as first line treatment if R0/R1 resection can be achieved. The surgical and interventional procedures for GEP...

  15. Net Neutrality in the Netherlands

    NARCIS (Netherlands)

    van Eijk, N.

    2014-01-01

    The Netherlands is among the first countries that have put specific net neutrality standards in place. The decision to implement specific regulation was influenced by at least three factors. The first was the prevailing social and academic debate, partly due to developments in the United States. The

  16. Complexity Metrics for Workflow Nets

    DEFF Research Database (Denmark)

    Lassen, Kristian Bisgaard; van der Aalst, Wil M.P.

    2009-01-01

    Process modeling languages such as EPCs, BPMN, flow charts, UML activity diagrams, Petri nets, etc.\\ are used to model business processes and to configure process-aware information systems. It is known that users have problems understanding these diagrams. In fact, even process engineers and system...

  17. C11ORF24 is a novel type I membrane protein that cycles between the Golgi apparatus and the plasma membrane in Rab6-positive vesicles.

    Science.gov (United States)

    Fraisier, Vincent; Kasri, Amal; Miserey-Lenkei, Stéphanie; Sibarita, Jean-Baptiste; Nair, Deepak; Mayeux, Adeline; Bardin, Sabine; Toyoda, Yusuke; Poser, Ina; Poznyakovskiy, Andrei; Goud, Bruno; Hyman, Anthony A; Dimitrov, Ariane

    2013-01-01

    The Golgi apparatus is an intracellular compartment necessary for post-translational modification, sorting and transport of proteins. It plays a key role in mitotic entry through the Golgi mitotic checkpoint. In order to identify new proteins involved in the Golgi mitotic checkpoint, we combine the results of a knockdown screen for mitotic phenotypes and a localization screen. Using this approach, we identify a new Golgi protein C11ORF24 (NP_071733.1). We show that C11ORF24 has a signal peptide at the N-terminus and a transmembrane domain in the C-terminal region. C11ORF24 is localized on the Golgi apparatus and on the trans-Golgi network. A large part of the protein is present in the lumen of the Golgi apparatus whereas only a short tail extends into the cytosol. This cytosolic tail is well conserved in evolution. By FRAP experiments we show that the dynamics of C11ORF24 in the Golgi membrane are coherent with the presence of a transmembrane domain in the protein. C11ORF24 is not only present on the Golgi apparatus but also cycles to the plasma membrane via endosomes in a pH sensitive manner. Moreover, via video-microscopy studies we show that C11ORF24 is found on transport intermediates and is colocalized with the small GTPase RAB6, a GTPase involved in anterograde transport from the Golgi to the plasma membrane. Knocking down C11ORF24 does not lead to a mitotic phenotype or an intracellular transport defect in our hands. All together, these data suggest that C11ORF24 is present on the Golgi apparatus, transported to the plasma membrane and cycles back through the endosomes by way of RAB6 positive carriers.

  18. Comparison of Superparamagnetic and Ultrasmall Superparamagnetic Iron Oxide Cell Labeling for Tracking Green Fluorescent Protein Gene Marker with Negative and Positive Contrast Magnetic Resonance Imaging

    Science.gov (United States)

    Zhang, Zhuoli; Dharmakumar, Rohan; Mascheri, Nicole; Fan, Zhaoyang; Wu, Shengyong; Li, Debiao

    2010-01-01

    The objectives of this study were to investigate the feasibility of imaging green fluorescent protein (GFP)-expressing cells labeled with iron oxide nanoparticles with the fast low-angle positive contrast steady-state free precession (FLAPS) method and to compare them with the traditional negative contrast technique. The GFP-R3230Ac cell line (GFP cell) was incubated for 24 hours using 20 μg Fe/mL concentration of superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. Cell samples were prepared for iron content analysis and cell function evaluation. The labeled cells were imaged using positive contrast with FLAPS imaging, and FLAPS images were compared with negative contrast T2*-weighted images. The results demonstrated that SPIO and USPIO labeling of GFP cells had no effect on cell function or GFP expression. Labeled cells were successfully imaged with both positive and negative contrast magnetic resonance imaging (MRI). The labeled cells were observed as a narrow band of signal enhancement surrounding signal voids in FLAPS images and were visible as signal voids in T2*-weighted images. Positive contrast and negative contrast imaging were both valuable for visualizing labeled GFP cells. MRI of labeled cells with GFP expression holds potential promise for monitoring the temporal and spatial migration of gene markers and cells, thereby enhancing the understanding of cell- and gene-based therapeutic strategies. PMID:19723472

  19. Kidney specific protein-positive cells derived from embryonic stem cells reproduce tubular structures in vitro and differentiate into renal tubular cells.

    Science.gov (United States)

    Morizane, Ryuji; Monkawa, Toshiaki; Fujii, Shizuka; Yamaguchi, Shintaro; Homma, Koichiro; Matsuzaki, Yumi; Okano, Hideyuki; Itoh, Hiroshi

    2014-01-01

    Embryonic stem cells and induced pluripotent stem cells have the ability to differentiate into various organs and tissues, and are regarded as new tools for the elucidation of disease mechanisms as well as sources for regenerative therapies. However, a method of inducing organ-specific cells from pluripotent stem cells is urgently needed. Although many scientists have been developing methods to induce various organ-specific cells from pluripotent stem cells, renal lineage cells have yet to be induced in vitro because of the complexity of kidney structures and the diversity of kidney-component cells. Here, we describe a method of inducing renal tubular cells from mouse embryonic stem cells via the cell purification of kidney specific protein (KSP)-positive cells using an anti-KSP antibody. The global gene expression profiles of KSP-positive cells derived from ES cells exhibited characteristics similar to those of cells in the developing kidney, and KSP-positive cells had the capacity to form tubular structures resembling renal tubular cells when grown in a 3D culture in Matrigel. Moreover, our results indicated that KSP-positive cells acquired the characteristics of each segment of renal tubular cells through tubular formation when stimulated with Wnt4. This method is an important step toward kidney disease research using pluripotent stem cells, and the development of kidney regeneration therapies.

  20. Down syndrome candidate region-1 protein interacts with Tollip and positively modulates interleukin-1 receptor-mediated signaling.

    Science.gov (United States)

    Lee, Jae Youn; Lee, Hyun Jung; Lee, Eun Jung; Jang, Sung Hee; Kim, Hyeyoung; Yoon, Joo-Heon; Chung, Kwang Chul

    2009-12-01

    The Down syndrome candidate region-1 gene (DSCR1, also known as RCAN1) is situated close to the Down Syndrome Critical Region (DSCR), which contains genes responsible for many features of Down syndrome. DSCR1 modulates calcineurin phosphatase activity, though its functional role is incompletely understood. Here we investigated the role of DSCR1-1S isoform in IL-1 receptor (IL-1R)-mediated signaling by analyzing interaction between DSCR1-1S and the IL-1R pathway components Tollip, IRAK-1, and TRAF6. Co-immunoprecipitation analyses of HEK293 cells revealed that DSCR1-1S interacted with Tollip, an IRAK-1 inhibitor, leading to the dissociation of IRAK-1 from Tollip. Similarly, both DSCR1-1S and Tollip interacted with TRAF6, with DSCR1 reducing interaction between Tollip and TRAF6. DSCR1-1S also stimulated IL-1R-mediated signaling pathways, TAK1 activation, NF-kappaB transactivation, and IL-8 production, all downstream consequences of IL-1R activation. Together, these results suggest that DSCR1-1S isoform positively modulates IL-1R-mediated signaling pathways by regulating Tollip/IRAK-1/TRAF6 complex formation.

  1. Economic Burden of Rheumatoid Arthritis in Italy: Possible Consequences on Anti-Citrullinated Protein Antibody-Positive Patients.

    Science.gov (United States)

    Mennini, Francesco Saverio; Marcellusi, Andrea; Gitto, Lara; Iannone, Florenzo

    2017-04-01

    Rheumatoid arthritis (RA) is an autoimmune disease with a substantial medical and economic burden. In Italy, it affects approximately 280,000 people, therefore representing the musculoskeletal disease with the highest economic impact in terms of costs for the National Health Service and the social security system. The aim of this study was to estimate the annual economic burden of RA in Italy and determine the potential cost reduction considering the most effective biologic treatment for early rapidly progressing RA (ERPRA) patients. The model developed considers both direct costs that are mainly due to the pharmacological treatments, and indirect costs, which also include the productivity lost because of the disease. A systematic literature review provided the epidemiological and economic data used to inform the model. A one-way probabilistic sensitivity analysis based on 5000 Monte Carlo simulations was performed. Furthermore, specific scenario analyses were developed for those patients presenting an ERPRA, with the aim of evaluating the effectiveness of different biologic treatments for this subgroup of patients and estimating potential cost reduction. The total economic burden associated with RA was estimated to be €2.0 billion per year (95% confidence interval [CI] €1.8-2.3 billion). Forty-five percent of the expenditure was due to indirect costs (95% CI €0.8-1.0 billion); 45% depended on direct medical costs (95% CI €0.7-1.1 billion), and the residual 10% was determined by direct non-medical costs (95% CI €0.16-0.25 billion). In particular, the costs estimated for ERPRA patients totalled €76,171,181, of which approximately €18 million was associated with patients with a high level of anti-citrullinated protein antibodies (ACPA). The results of the analysis outline how it is possible to obtain a cost reduction for ERPRA patients of between €1 and €3 million by varying the number of patients with a high level of immunoglobulin

  2. Caught in the Net: Perineuronal Nets and Addiction

    Directory of Open Access Journals (Sweden)

    Megan Slaker

    2016-01-01

    Full Text Available Exposure to drugs of abuse induces plasticity in the brain and creates persistent drug-related memories. These changes in plasticity and persistent drug memories are believed to produce aberrant motivation and reinforcement contributing to addiction. Most studies have explored the effect drugs of abuse have on pre- and postsynaptic cells and astrocytes; however, more recently, attention has shifted to explore the effect these drugs have on the extracellular matrix (ECM. Within the ECM are unique structures arranged in a net-like manner, surrounding a subset of neurons called perineuronal nets (PNNs. This review focuses on drug-induced changes in PNNs, the molecules that regulate PNNs, and the expression of PNNs within brain circuitry mediating motivation, reward, and reinforcement as it pertains to addiction.

  3. Fe-S cluster biogenesis in Gram-positive bacteria: SufU is a zinc-dependent sulfur transfer protein.

    Science.gov (United States)

    Selbach, Bruna P; Chung, Alexander H; Scott, Aubrey D; George, Simon J; Cramer, Stephen P; Dos Santos, Patricia C

    2014-01-14

    The biosynthesis of Fe-S clusters in Bacillus subtilis and other Gram-positive bacteria is catalyzed by the SufCDSUB system. The first step in this pathway involves the sulfur mobilization from the free amino acid cysteine to a sulfur acceptor protein SufU via a PLP-dependent cysteine desulfurase SufS. In this reaction scheme, the formation of an enzyme S-covalent intermediate is followed by the binding of SufU. This event leads to the second half of the reaction where a deprotonated thiol of SufU promotes the nucleophilic attack onto the persulfide intermediate of SufS. Kinetic analysis combined with spectroscopic methods identified that the presence of a zinc atom tightly bound to SufU (Ka = 10(17) M(-1)) is crucial for its structural and catalytic competency. Fe-S cluster assembly experiments showed that despite the high degree of sequence and structural similarity to the ortholog enzyme IscU, the B. subtilis SufU does not act as a standard Fe-S cluster scaffold protein. The involvement of SufU as a dedicated agent of sulfur transfer, rather than as an assembly scaffold, in the biogenesis of Fe-S clusters in Gram-positive microbes indicates distinct strategies used by bacterial systems to assemble Fe-S clusters.

  4. Army Net Zero Prove Out. Army Net Zero Training Report

    Science.gov (United States)

    2014-11-20

    sensors were strategically placed throughout the installation by magnetically attaching them to water main valve stems. The sensors check sound...Recycle Wrap  Substitutes for Packaging Materials  Re-Use of Textiles and Linens  Setting Printers to Double-Sided Printing Net Zero Waste...can effectively achieve source reduction. Clean and Re-Use Shop Rags - Shop rags represent a large textile waste stream at many installations. As a

  5. Army Net Zero Prove Out. Net Zero Waste Best Practices

    Science.gov (United States)

    2014-11-20

    Anaerobic Digesters – Although anaerobic digestion is not a new technology and has been used on a large-scale basis in wastewater treatment , the...technology and has been used on a large-scale basis in wastewater treatment , the use of the technology should be demonstrated with other...approaches can be used for cardboard and cellulose -based packaging materials. This approach is in line with the Net Zero Waste hierarchy in terms of

  6. Lah is a transmembrane protein and requires Spa10 for stable positioning of Woronin bodies at the septal pore of Aspergillus fumigatus.

    Science.gov (United States)

    Leonhardt, Yannik; Kakoschke, Sara Carina; Wagener, Johannes; Ebel, Frank

    2017-03-10

    Woronin bodies are specialized, fungal-specific organelles that enable an immediate closure of septal pores after injury to protect hyphae from excessive cytoplasmic bleeding. In most Ascomycetes, Woronin bodies are tethered at the septal pore by so-called Lah proteins. Using the pathogenic mold Aspergillus fumigatus as a model organism, we show that the C-terminal 288 amino acids of Lah (LahC288) bind to the rim of the septal pore. LahC288 essentially consists of a membrane spanning region and a putative extracellular domain, which are both required for the targeting to the septum. In an A. fumigatus rho4 deletion mutant that has a severe defect in septum formation, LahC288 is recruited to spot-like structures in or at the lateral membrane. This suggests that LahC is recruited before Rho4 starts to govern the septation process. Accordingly, we found that in wild type hyphae Lah is bound before a cross-wall emerges and thus enables a tethering of Woronin bodies at the site of the newly formed septum. Finally, we identified Spa10, a member of a recently described family of septal pore-associated proteins, as a first protein that directly or indirectly interacts with LahC to allow a stable positioning of Woronin bodies at the mature septum.

  7. An intriguing shift occurs in the novel protein phosphatase 1 binding partner, TCTEX1D4: evidence of positive selection in a pika model.

    Directory of Open Access Journals (Sweden)

    Luís Korrodi-Gregório

    Full Text Available T-complex testis expressed protein 1 domain containing 4 (TCTEX1D4 contains the canonical phosphoprotein phosphatase 1 (PPP1 binding motif, composed by the amino acid sequence RVSF. We identified and validated the binding of TCTEX1D4 to PPP1 and demonstrated that indeed this protein is a novel PPP1 interacting protein. Analyses of twenty-one mammalian species available in public databases and seven Lagomorpha sequences obtained in this work showed that the PPP1 binding motif 90RVSF93 is present in all of them and is flanked by a palindromic sequence, PLGS, except in three species of pikas (Ochotona princeps, O. dauurica and O. pusilla. Furthermore, for the Ochotona species an extra glycosylation site, motif 96NLS98, and the loss of the palindromic sequence were observed. Comparison with other lagomorphs suggests that this event happened before the Ochotona radiation. The dN/dS for the sequence region comprising the PPP1 binding motif and the flanking palindrome highly supports the hypothesis that for Ochotona species this region has been evolving under positive selection. In addition, mutational screening shows that the ability of pikas TCTEX1D4 to bind to PPP1 is maintained, although the PPP1 binding motif is disrupted, and the N- and C-terminal surrounding residues are also abrogated. These observations suggest pika as an ideal model to study novel PPP1 complexes regulatory mechanisms.

  8. Preferential binding of positive nanoparticles on cell membranes is due to electrostatic interactions: A too simplistic explanation that does not take into account the nanoparticle protein corona.

    Science.gov (United States)

    Forest, Valérie; Pourchez, Jérémie

    2017-01-01

    The internalization of nanoparticles by cells (and more broadly the nanoparticle/cell interaction) is a crucial issue both for biomedical applications (for the design of nanocarriers with enhanced cellular uptake to reach their intracellular therapeutic targets) and in a nanosafety context (as the internalized dose is one of the key factors in cytotoxicity). Many parameters can influence the nanoparticle/cell interaction, among them, the nanoparticle physico-chemical features, and especially the surface charge. It is generally admitted that positive nanoparticles are more uptaken by cells than neutral or negative nanoparticles. It is supposedly due to favorable electrostatic interactions with negatively charged cell membrane. However, this theory seems too simplistic as it does not consider a fundamental element: the nanoparticle protein corona. Indeed, once introduced in a biological medium nanoparticles adsorb proteins at their surface, forming a new interface defining the nanoparticle "biological identity". This adds a new level of complexity in the interactions with biological systems that cannot be any more limited to electrostatic binding. These interactions will then influence cell behavior. Based on a literature review and on an example of our own experience the parameters involved in the nanoparticle protein corona formation as well as in the nanoparticle/cell interactions are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Re-directed T cells for the treatment of fibroblast activation protein (FAP-positive malignant pleural mesothelioma (FAPME-1

    Directory of Open Access Journals (Sweden)

    Petrausch Ulf

    2012-12-01

    Full Text Available Abstract Background Asbestos is the main cause of MPM in industrialized countries. Even since asbestos is banned in most developed countries, the peak wave of MPM incidence is anticipated for the next years due to the long latency of asbestos induced MPM. MPM patients not eligible for surgical procedures like decortication or pleuro-pneumectomie have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. Methods/design This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x106 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor recognizing FAP which serves as target structure in MPM. At day 0 of the protocol, re-directed T cells will be injected in the pleural effusion and patients will be monitored for 48h under intermediate care conditions. AE, SAE, SADR and SUSAR will be monitored for 35 days and evaluated by an independent safety board to define any dose limiting toxicity (DLT. No further patient can be treated before the previous patient passed day 14 after T cell transfer. The protocol will be judged as save when no DLT occurred in the first 3 patients, or 1 DLT in 6 patients. Secondary objectives are feasibility and immune monitoring. Discussion Adoptive T cell transfer is a new and rapidly expanding branch of immunotherapies focusing on cancer treatment. Recently, objective responses could be observed in patients with chronic lymphatic leukemia treated with adoptively transferred CD19-specific re-directed T cells. The choice of the target antigen determines the possible on-target off-tissue toxicity of such approaches. There are reports of

  10. Mycobacterial and HIV infections up-regulated human zinc finger protein 134, a novel positive regulator of HIV-1 LTR activity and viral propagation.

    Directory of Open Access Journals (Sweden)

    Ronald Benjamin

    Full Text Available BACKGROUND: Concurrent occurrence of HIV and Tuberculosis (TB infections influence the cellular environment of the host for synergistic existence. An elementary approach to understand such coalition at the molecular level is to understand the interactions of the host and the viral factors that subsequently effect viral replication. Long terminal repeats (LTR of HIV genome serve as a template for binding trans-acting viral and cellular factors that regulate its transcriptional activity, thereby, deciding the fate of HIV pathogenesis, making it an ideal system to explore the interplay between HIV and the host. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using biotinylated full length HIV-1 LTR sequence as bait followed by MALDI analyses, we identified and further characterized human-Zinc-finger-protein-134 (hZNF-134 as a novel positive regulator of HIV-1 that promoted LTR-driven transcription and viral production. Over-expression of hZNF-134 promoted LTR driven luciferase activity and viral transcripts, resulting in increased virus production while siRNA mediated knockdown reduced both the viral transcripts and the viral titers, establishing hZNF-134 as a positive effector of HIV-1. HIV, Mycobacteria and HIV-TB co-infections increased hZNF-134 expressions in PBMCs, the impact being highest by mycobacteria. Corroborating these observations, primary TB patients (n = 22 recorded extraordinarily high transcript levels of hZNF-134 as compared to healthy controls (n = 16. CONCLUSIONS/SIGNIFICANCE: With these observations, it was concluded that hZNF-134, which promoted HIV-1 LTR activity acted as a positive regulator of HIV propagation in human host. High titers of hZNF-134 transcripts in TB patients suggest that up-regulation of such positive effectors of HIV-1 upon mycobacterial infection can be yet another mechanism by which mycobacteria assists HIV-1 propagation during HIV-TB co-infections. hZNF-134, an uncharacterized host protein, thus

  11. HANPP Collection: Human Appropriation of Net Primary Productivity as a Percentage of Net Primary Productivity

    Data.gov (United States)

    National Aeronautics and Space Administration — The Human Appropriation of Net Primary Productivity (HANPP) as a Percentage of Net Primary Productivity (NPP) portion of the Human Appropriation of Net Primary...

  12. Hydrodynamic characteristics of plane netting used for aquaculture net cages in uniform current

    National Research Council Canada - National Science Library

    DONG, SHUCHUANG; HU, FUXIANG; KUMAZAWA, TAISEI; SIODE, DAISUKE; TOKAI, TADASHI

    2016-01-01

      The hydrodynamic characteristics of polyethylene (PE) netting and chain link wire netting with different types of twine diameter and mesh size for aquaculture net cages were examined by experiments in a flume tank...

  13. Alternative BCR/ABL splice variants in Philadelphia chromosome-positive leukemias result in novel tumor-specific fusion proteins that may represent potential targets for immunotherapy approaches.

    Science.gov (United States)

    Volpe, Gisella; Cignetti, Alessandro; Panuzzo, Cristina; Kuka, Mirela; Vitaggio, Katiuscia; Brancaccio, Mara; Perrone, Giuseppe; Rinaldi, Monica; Prato, Giuseppina; Fava, Milena; Geuna, Massimo; Pautasso, Marisa; Casnici, Claudia; Signori, Emanuela; Tonon, Giancarlo; Tarone, Guido; Marelli, Ornella; Fazio, Vito M; Saglio, Giuseppe

    2007-06-01

    Imatinib currently represents the standard treatment in the early chronic phase of chronic myelogenous leukemia (CML), thanks to the high percentage of cytogenetic complete remission achieved, but it is yet unclear to what extent it can eradicate leukemia. Therefore, different vaccination strategies have been suggested, mainly based on the exploitment of the junctional peptides spanning the fusion region of the Bcr/Abl proteins. To identify new potential immunologic targets, 63 Philadelphia chromosome-positive patients and 6 BCR/ABL-positive cell lines were tested in nested reverse transcriptase PCR to detect the presence of BCR/ABL transcripts arising from the alternative splicing of the main BCR/ABL transcripts. We could detect BCR/ABL transcripts with junctions between BCR exon 1, 13, or 14 and ABL exon 4 in approximately 80% of patients and 84% of cell lines, beside the main fusion transcripts. Translation products of these transcripts were characterized at their COOH terminus by a large amino acid portion derived from the out of frame (OOF) reading of ABL gene. These proteins were detected in BCR/ABL-positive cell lines by immunoprecipitation and immunohistochemistry. Finally, we determined whether OOF-specific CD8+ T cells could be found in the peripheral blood of CML patients and whether they could acquire effector function following in vitro sensitization with OOF-derived peptides predicted to bind to human leucocyte antigen (HLA)-A2 and HLA-A3 molecules. We detected the presence of OOF-specific CD8+ T cells in four of four patients studied, and in one case, these T cells exhibited specific cytotoxic activity against both peptide-pulsed targets and autologous primary CML cells.

  14. The Influence of Colour on Radiometric Performances of Agricultural Nets

    NARCIS (Netherlands)

    Castellano, S.; Hemming, S.; Russo, G.

    2008-01-01

    The whole construction parameters of the net, combined with the shape of the structure, the position of the sun and the sky conditions affect the radiometric performance of the permeable covering system. The radiometric properties of the permeable membrane influence the quality of the agricultural

  15. Comparative Study of Different Gill Net Mesh Sizes in the ...

    African Journals Online (AJOL)

    Bioline

    indiv). The coefficient of variation between the size classes was high (93.9%) and showed slight positive skewness (0.58)and kurtosis of -0.43 (Table 1). The comparison of mean within the gill net mesh sizes using student t-test (t -test=145 > 0.890.5) showed significance variation between the size classes caught (Table 1).

  16. Determinants of net return among fish marketers in Port Harcourt ...

    African Journals Online (AJOL)

    The ordinary least squares multiple regression technique was also used to estimate the determinants of net returns of the marketers. The result showed that fish marketing in the area is profitable and has a return on investment of N1.17. Educational level and marketing experience positively and significantly influenced the ...

  17. iHyd-PseAAC: Predicting Hydroxyproline and Hydroxylysine in Proteins by Incorporating Dipeptide Position-Specific Propensity into Pseudo Amino Acid Composition

    Directory of Open Access Journals (Sweden)

    Yan Xu

    2014-05-01

    Full Text Available Post-translational modifications (PTMs play crucial roles in various cell functions and biological processes. Protein hydroxylation is one type of PTM that usually occurs at the sites of proline and lysine. Given an uncharacterized protein sequence, which site of its Pro (or Lys can be hydroxylated and which site cannot? This is a challenging problem, not only for in-depth understanding of the hydroxylation mechanism, but also for drug development, because protein hydroxylation is closely relevant to major diseases, such as stomach and lung cancers. With the avalanche of protein sequences generated in the post-genomic age, it is highly desired to develop computational methods to address this problem. In view of this, a new predictor called “iHyd-PseAAC” (identify hydroxylation by pseudo amino acid composition was proposed by incorporating the dipeptide position-specific propensity into the general form of pseudo amino acid composition. It was demonstrated by rigorous cross-validation tests on stringent benchmark datasets that the new predictor is quite promising and may become a useful high throughput tool in this area. A user-friendly web-server for iHyd-PseAAC is accessible at http://app.aporc.org/iHyd-PseAAC/. Furthermore, for the convenience of the majority of experimental scientists, a step-by-step guide on how to use the web-server is given. Users can easily obtain their desired results by following these steps without the need of understanding the complicated mathematical equations presented in this paper just for its integrity.

  18. FosPeg® PDT alters the EBV miRNAs and LMP1 protein expression in EBV positive nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Wu, Ricky W K; Chu, Ellie S M; Huang, Zheng; Xu, C S; Ip, C W; Yow, Christine M N

    2013-10-05

    Nasopharyngeal carcinoma (NPC) is one of the top ten cancers highly prevalent in Hong Kong and South China. Epstein-Barr virus (EBV) infection contributes to the tumorigenesis of NPC through the expression of different viral proteins. Among these, Latent Membrane Protein 1(LMP1) is the major oncoprotein expressed by EBV. Foscan® (Biolitec AG), m-tetrahydroxyphenylchlorin (mTHPC)-based photosensitizing drug, has been used in the photodynamic therapy (PDT) for head and neck cancers. FosPeg® (Biolitec AG) is a new formulation of mTHPC contained in PEGylated liposomes with optimized distribution properties. In this in vitro study, the potential of FosPeg®-PDT on human EBV positive NPC cell (c666-1) and EBV negative cells (HK1 and CNE2) were investigated. Effects of FosPeg®-PDT on the expression of EBV BART miRNAs (EBV miRNA BART 1-5p, BART 16, and BART 17-5p), LMP1 mRNA and proteins on c666-1 cells were also elucidated. The killing efficacy of FosPeg®-PDT on NPC cells were determined by MTT assay after LED activation. Effects of FosPeg®-PDT on the expression of LMP1 mRNA and protein were examined by real time PCR and western blot analysis. FosPeg®-PDT demonstrated its antitumor effect on c666-1 cells in a drug and light dose dependent manner. LD30, LD50 and LD70 were achieved by applying LED activation (3J/cm(2)) at 4h post incubated cells with 0.05μg/ml, 0.07μg/ml and 0.3μg/ml FosPeg®, respectively. Up-regulation of both LMP1 mRNA and protein were observed after FosPeg®-PDT in a dose dependent manner. FosPeg®-PDT exerted antitumor effect on c666-1 cells through up-regulation of LMP1 protein. Understanding the mechanism of FosPeg®-PDT may help to develop better strategies for the treatment of NPC. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Lineage-specific positive selection at the merozoite surface protein 1 (msp1 locus of Plasmodium vivax and related simian malaria parasites

    Directory of Open Access Journals (Sweden)

    Kawai Satoru

    2010-02-01

    Full Text Available Abstract Background The 200 kDa merozoite surface protein 1 (MSP-1 of malaria parasites, a strong vaccine candidate, plays a key role during erythrocyte invasion and is a target of host protective immune response. Plasmodium vivax, the most widespread human malaria parasite, is closely related to parasites that infect Asian Old World monkeys, and has been considered to have become a parasite of man by host switch from a macaque malaria parasite. Several Asian monkey parasites have a range of natural hosts. The same parasite species shows different disease manifestations among host species. This suggests that host immune responses to P. vivax-related malaria parasites greatly differ among host species (albeit other factors. It is thus tempting to invoke that a major immune target parasite protein such as MSP-1 underwent unique evolution, depending on parasite species that exhibit difference in host range and host specificity. Results We performed comparative phylogenetic and population genetic analyses of the gene encoding MSP-1 (msp1 from P. vivax and nine P. vivax-related simian malaria parasites. The inferred phylogenetic tree of msp1 significantly differed from that of the mitochondrial genome, with a striking displacement of P. vivax from a position close to P. cynomolgi in the mitochondrial genome tree to an outlier of Asian monkey parasites. Importantly, positive selection was inferred for two ancestral branches, one leading to P. inui and P. hylobati and the other leading to P. vivax, P. fieldi and P. cynomolgi. This ancestral positive selection was estimated to have occurred three to six million years ago, coinciding with the period of radiation of Asian macaques. Comparisons of msp1 polymorphisms between P. vivax, P. inui and P. cynomolgi revealed that while some positively selected amino acid sites or regions are shared by these parasites, amino acid changes greatly differ, suggesting that diversifying selection is acting species

  20. Isolated unit tests in .Net

    OpenAIRE

    Haukilehto, Tero

    2013-01-01

    In this thesis isolation in unit testing is studied to get a precise picture of the isolation frameworks available for .Net environment. At the beginning testing is discussed in theory with the benefits and the problems it may have been linked with. The theory includes software development in general in connection with testing. Theory of isolation is also described before the actual isolation frameworks are represented. Common frameworks are described in more detail and comparable informa...

  1. Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer.

    Science.gov (United States)

    Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N; Dean, Michelle; Lees-Miller, Susan P; Riabowol, Karl; Magliocco, Anthony M; Morris, Don; Watson, Peter H; Enwere, Emeka K; Bebb, Gwyn; Paterson, Alexander

    2016-12-27

    This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC.

  2. Event hierarchies in DanNet

    DEFF Research Database (Denmark)

    Pedersen, Bolette Sandford; Nimb, Sanni

    2008-01-01

    Artiklen omhandler udarbejdelsen af et verbumshierarki i det leksikalsk-semantiske ordnet, DanNet.......Artiklen omhandler udarbejdelsen af et verbumshierarki i det leksikalsk-semantiske ordnet, DanNet....

  3. The Uniframe .Net Web Service Discovery Service

    National Research Council Canada - National Science Library

    Berbeco, Robert W

    2003-01-01

    Microsoft .NET allows the creation of distributed systems in a seamless manner Within NET small, discrete applications, referred to as Web services, are utilized to connect to each other or larger applications...

  4. Long Term RadNet Quality Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — This RadNet Quality Data Asset includes all data since initiation and when ERAMS was expanded to become RadNet, name changed to reflect new mission. This includes...

  5. Use of a Spreadsheet to Calculate the Net Charge of Peptides and Proteins as a Function of pH: An Alternative to Using "Canned" Programs to Estimate the Isoelectric Point of These Important Biomolecules

    Science.gov (United States)

    Sims, Paul A.

    2010-01-01

    An approach is presented that utilizes a spreadsheet to allow students to explore different means of calculating and visualizing how the charge on peptides and proteins varies as a function of pH. In particular, the concept of isoelectric point is developed to allow students to compare the results of their spreadsheet calculations with those of…

  6. Procalcitonin and C-reactive protein in early diagnosis of sepsis caused by either Gram-negative or Gram-positive bacteria.

    Science.gov (United States)

    Liu, H H; Zhang, M W; Guo, J B; Li, J; Su, L

    2017-02-01

    Sepsis is the most frequent cause of systemic inflammatory response syndrome (SIRS). Procalcitonin (PCT) and C-reactive protein (CRP) are well-known predictors of sepsis. Serum PCT levels are associated with blood culture positivity in patients with sepsis, but the magnitude of elevation of PCT and CRP levels at the onset of sepsis is unknown in Gram-negative (GN) bacteremia and in Gram-positive (GP) bacteremia. To evaluate the PCT and CRP levels in 72 h at the onset of sepsis in GN and GP bacteremia. We retrospectively analyzed the data from 648 blood-positive specimens from three integrated teaching hospitals in Xiamen, China. One hundred and forty-seven adult patients with sepsis within 72 h enrolled in the study. Serum PCT and CRP level were assessed according GN or GP bacteremia. A total of 147 (22.68 %) patients were eligible for inclusion in the study, including 56 GP sepsis and 91 GN sepsis. PCT, but not CRP levels, was significantly higher in patients in the GP group than in the GN group (23.64 vs 6.18 ng/mL, p < 0.001). The area under the receiver-operating characteristic (ROC) curve of PCT was 0.73 (95 % confidence interval 0.65-0.81) and that under the ROC curve of CRP was 0.52 (95 % confidence interval 0.43-0.62). A positive predictive value of 72.5 % and a negative predictive value of 67.9 % were achieved with a PCT cutoff value of 2.1 ng/ml. Serum PCT levels are higher in GN sepsis than GP sepsis in 72 h. There are not differences in CRP. The separation of PCT and CRP phenomenon is helpful for early diagnosis of GP sepsis.

  7. PsychoNet: a psycholinguistc commonsense ontology

    OpenAIRE

    Mohtasseb, Haytham; Ahmed, Amr

    2010-01-01

    Ontologies have been widely accepted as the most advanced knowledge representation model. This paper introduces PsychoNet, a new knowledgebase that forms the link between psycholinguistic taxonomy, existing in LIWC, and its semantic textual representation in the form of commonsense semantic ontology, represented by ConceptNet. The integration of LIWC and ConceptNet and the added functionalities facilitate employing ConceptNet in psycholinguistic studies. Furthermore, it simplifies utilization...

  8. 78 FR 72451 - Net Investment Income Tax

    Science.gov (United States)

    2013-12-02

    ... Revenue Service 26 CFR Part 1 RIN 1545-BL74 Net Investment Income Tax AGENCY: Internal Revenue Service...). These regulations provide guidance on the computation of net investment income. The regulations affect... lesser of: (A) The individual's net investment income for such taxable year, or (B) the excess (if any...

  9. 47 CFR 69.302 - Net investment.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Net investment. 69.302 Section 69.302... Apportionment of Net Investment § 69.302 Net investment. (a) Investment in Accounts 2001, 1220 and Class B Rural...) Investment in Accounts 2002, 2003 and to the extent such inclusions are allowed by this Commission, Account...

  10. 47 CFR 65.450 - Net income.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Net income. 65.450 Section 65.450... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Exchange Carriers § 65.450 Net income. (a) Net income shall consist of all revenues derived from the provision of interstate telecommunications services...

  11. 47 CFR 65.500 - Net income.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Net income. 65.500 Section 65.500... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Interexchange Carriers § 65.500 Net income. The net income methodology specified in § 65.450 shall be utilized by all interexchange carriers that are...

  12. NetBeans IDE 8 cookbook

    CERN Document Server

    Salter, David

    2014-01-01

    If you're a Java developer of any level using NetBeans and want to learn how to get the most out of NetBeans, then this book is for you. Learning how to utilize NetBeans will provide a firm foundation for your Java application development.

  13. Characterizing behavioural congruences for Petri nets

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Priese, Lutz; Sassone, Vladimiro

    1995-01-01

    We exploit a notion of interface for Petri nets in order to design a set of net combinators. For such a calculus of nets, we focus on the behavioural congruences arising from four simple notions of behaviour, viz., traces, maximal traces, step, and maximal step traces, and from the corresponding...

  14. 27 CFR 4.37 - Net contents.

    Science.gov (United States)

    2010-04-01

    ... the volume of wine within the container, except that the following tolerances shall be allowed: (1... THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.37 Net contents. (a) Statement of net contents. The net contents of wine for which a standard of fill is...

  15. Changes in gene expression, protein content and morphology of chondrocytes cultured on a 3D Random Positioning Machine and 2D rotating clinostat

    Science.gov (United States)

    Aleshcheva, Ganna; Hauslage, Jens; Hemmersbach, Ruth; Infanger, Manfred; Bauer, Johann; Grimm, Daniela; Sahana, Jayashree

    Chondrocytes are the only cell type found in human cartilage consisting of proteoglycans and type II collagen. Several studies on chondrocytes cultured either in Space or on a ground-based facility for simulation of microgravity revealed that these cells are very resistant to adverse effects and stress induced by altered gravity. Tissue engineering of chondrocytes is a new strategy for cartilage regeneration. Using a three-dimensional Random Positioning Machine and a 2D rotating clinostat, devices designed to simulate microgravity on Earth, we investigated the early effects of microgravity exposure on human chondrocytes of six different donors after 30 min, 2 h, 4 h, 16 h, and 24 h and compared the results with the corresponding static controls cultured under normal gravity conditions. As little as 30 min of exposure resulted in increased expression of several genes responsible for cell motility, structure and integrity (beta-actin); control of cell growth, cell proliferation, cell differentiation and apoptosis; and cytoskeletal components such as microtubules (beta-tubulin) and intermediate filaments (vimentin). After 4 hours disruptions in the vimentin network were detected. These changes were less dramatic after 16 hours, when human chondrocytes appeared to reorganize their cytoskeleton. However, the gene expression and protein content of TGF-β1 was enhanced for 24 h. Based on the results achieved, we suggest that chondrocytes exposed to simulated microgravity seem to change their extracellular matrix production behavior while they rearrange their cytoskeletal proteins prior to forming three-dimensional aggregates.

  16. Reverse phase protein array based tumor profiling identifies a biomarker signature for risk classification of hormone receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Johanna Sonntag

    2014-03-01

    Full Text Available A robust subclassification of luminal breast cancer, the most common molecular subtype of human breast cancer, is crucial for therapy decisions. While a part of patients is at higher risk of recurrence and requires chemo-endocrine treatment, the other part is at lower risk and also poorly responds to chemotherapeutic regimens. To approximate the risk of cancer recurrence, clinical guidelines recommend determining histologic grading and abundance of a cell proliferation marker in tumor specimens. However, this approach assigns an intermediate risk to a substantial number of patients and in addition suffers from a high interobserver variability. Therefore, the aim of our study was to identify a quantitative protein biomarker signature to facilitate risk classification. Reverse phase protein arrays (RPPA were used to obtain quantitative expression data for 128 breast cancer relevant proteins in a set of hormone receptor-positive tumors (n = 109. Proteomic data for the subset of histologic G1 (n = 14 and G3 (n = 22 samples were used for biomarker discovery serving as surrogates of low and high recurrence risk, respectively. A novel biomarker selection workflow based on combining three different classification methods identified caveolin-1, NDKA, RPS6, and Ki-67 as top candidates. NDKA, RPS6, and Ki-67 were expressed at elevated levels in high risk tumors whereas caveolin-1 was observed as downregulated. The identified biomarker signature was subsequently analyzed using an independent test set (AUC = 0.78. Further evaluation of the identified biomarker panel by Western blot and mRNA profiling confirmed the proteomic signature obtained by RPPA. In conclusion, the biomarker signature introduced supports RPPA as a tool for cancer biomarker discovery.

  17. Waterscape determinants of net mercury methylation in a tropical wetland.

    Science.gov (United States)

    Lázaro, Wilkinson L; Díez, Sergi; da Silva, Carolina J; Ignácio, Áurea R A; Guimarães, Jean R D

    2016-10-01

    The periphyton associated with freshwater macrophyte roots is the main site of Hg methylation in different wetland environments in the world. The aim of this study was to test the use of connectivity metrics of water bodies, in the context of patches, in a tropical waterscape wetland (Guapore River, Amazonia, Brazil) as a predictor of potential net methylmercury (MeHg) production by periphyton communities. We sampled 15 lakes with different patterns of lateral connectivity with the main river channel, performing net mercury methylation potential tests in incubations with local water and Eichhornia crassipes root-periphyton samples, using (203)HgCl2 as a tracer. Physico-chemical variables, landscape data (morphological characteristics, land use, and lateral connection type of water bodies) using GIS resources and field data were analyzed with Generalized Additive Models (GAM). The net Me(203)Hg production (as % of total added (203)Hg) was expressive (6.2-25.6%) showing that periphyton is an important matrix in MeHg production. The model that best explained the variation in the net Me(203)Hg production (76%) was built by the variables: connection type, total phosphorus and dissolved organic carbon (DOC) in water (AICc=48.324, p=0.001). Connection type factor was the best factor to model fit (r(2)=0.32; p=0.008) and temporarily connected lakes had higher rates of net mercury methylation. Both DOC and total phosphorus showed positive significant covariation with the net methylation rates (r(2)=0.26; p=0.008 and r(2)=0.21; p=0.012 respectively). Our study suggests a strong relationship between rates of net MeHg production in this tropical area and the type of water body and its hydrological connectivity within the waterscape. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. NetF-producing Clostridium perfringens: Clonality and plasmid pathogenicity loci analysis.

    Science.gov (United States)

    Mehdizadeh Gohari, Iman; Kropinski, Andrew M; Weese, Scott J; Whitehead, Ashley E; Parreira, Valeria R; Boerlin, Patrick; Prescott, John F

    2017-04-01

    Clostridium perfringens is an important cause of foal necrotizing enteritis and canine acute hemorrhagic diarrhea. A major virulence determinant of the strains associated with these diseases appears to be a beta-sheet pore-forming toxin, NetF, encoded within a pathogenicity locus (NetF locus) on a large tcp-conjugative plasmid. Strains producing NetF also produce the putative toxin NetE, encoded within the same pathogenicity locus, as well as CPE enterotoxin and CPB2 on a second plasmid, and sometimes the putative toxin NetG within a pathogenicity locus (NetG locus) on another separate large conjugative plasmid. Previous genome sequences of two netF-positive C. perfringens showed that they both shared three similar plasmids, including the NetF/NetE and CPE/CPB2 toxins-encoding plasmids mentioned above and a putative bacteriocin-encoding plasmid. The main purpose of this study was to determine whether all NetF-producing strains share this common plasmid profile and whether their distinct NetF and CPE pathogenicity loci are conserved. To answer this question, 15 equine and 15 canine netF-positive isolates of C. perfringens were sequenced using Illumina Hiseq2000 technology. In addition, the clonal relationships among the NetF-producing strains were evaluated by core genome multilocus sequence typing (cgMLST). The data obtained showed that all NetF-producing strains have a common plasmid profile and that the defined pathogenicity loci on the plasmids are conserved in all these strains. cgMLST analysis showed that the NetF-producing C. perfringens strains belong to two distinct clonal complexes. The pNetG plasmid was absent from isolates of one of the clonal complexes, and there were minor but consistent differences in the NetF/NetE and CPE/CPB2 plasmids between the two clonal complexes. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The synthetic heat shock protein 90 (Hsp90) inhibitor EC141 induces degradation of Bcr-Abl p190 protein and apoptosis of Ph-positive acute lymphoblastic leukemia cells.

    Science.gov (United States)

    Tong, Wei-Gang; Estrov, Zeev; Wang, Yongtao; O'Brien, Susan; Faderl, Stefan; Harris, David M; Van Pham, Quin; Hazan-Halevy, Inbal; Liu, Zhiming; Koch, Patricia; Kantarjian, Hagop; Keating, Michael J; Ferrajoli, Alessandra

    2011-12-01

    The prognosis of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is poor. Chemotherapy is rarely curative and tyrosine kinase inhibitors (TKIs) induce only transient responses. Heat shock protein 90 (Hsp90) is a chaperone protein that is important in signal transduction, cell cycle control, and transcription regulation in both normal and leukemia cells. In the current study, we tested the growth inhibitory and apoptotic effects of a novel Hsp90 inhibitor, EC141 on the Ph+ ALL lines Z-119, Z-181, and Z-33, as well as primary bone marrow-derived blasts from patients with newly diagnosed Ph+ ALL. We found that EC141 inhibited the growth of Ph+ ALL cells in a concentration-dependent manner with IC(50) ranged from 1 to 10 nM. EC141 also inhibited the proliferation of primary bone marrow-derived blasts using the ALL blast colony assay. EC141 down-regulated Hsp90 and up-regulated Hsp70 protein levels, inhibited CrkL phosphorylation, and induced degradation of Bcr-Abl p190 protein through ubiquitin-dependent proteasomal pathway. Furthermore, exposure of Ph+ ALL cells to EC141 resulted in activation of caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and induction of apoptosis. In conclusion, our data suggest that EC141 is a potent Hsp90 inhibitor with activity against Ph+ ALL. Further studies to investigate the anticancer effect of EC141 either as a single agent, or in combination in Ph+ ALL and other hematological malignancies are warranted.

  20. NET 40 Generics Beginner's Guide

    CERN Document Server

    Mukherjee, Sudipta

    2012-01-01

    This is a concise, practical guide that will help you learn Generics in .NET, with lots of real world and fun-to-build examples and clear explanations. It is packed with screenshots to aid your understanding of the process. This book is aimed at beginners in Generics. It assumes some working knowledge of C# , but it isn't mandatory. The following would get the most use out of the book: Newbie C# developers struggling with Generics. Experienced C++ and Java Programmers who are migrating to C# and looking for an alternative to other generic frameworks like STL and JCF would find this book handy.

  1. Plasma concentrations of copeptin, C-reactive protein and procalcitonin are positively correlated with APACHE II scores in patients with sepsis.

    Science.gov (United States)

    Jiang, Li; Feng, Bing; Gao, Dongna; Zhang, Yu

    2015-04-01

    To evaluate the correlation between Acute Physiology and Chronic Health Evaluation II (APACHE II) score and plasma concentrations of copeptin, C-reactive protein (CRP) and procalcitonin in patients with sepsis. Patients with sepsis were prospectively enrolled. APACHE II scores were determined during the first 24 h after admission to the intensive care unit. Plasma copeptin, CRP and procalcitonin were quantified at admission, 24 h, 48 h, and 72 h. Survival at 28 days after admission was recorded. APACHE II score was significantly positively correlated with plasma copeptin, CRP and procalcitonin concentrations. Survivors (n = 15) had significantly lower APACHE II scores and copeptin, CRP and procalcitonin concentrations than nonsurvivors (n = 26). APACHE II score, copeptin at 72 h, CRP at 48 h and procalcitonin at 24 h were independent risk factors for death. Plasma copeptin, CRP and procalcitonin concentrations were positively correlated with APACHE II score in patients with sepsis, and reflected disease severity. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  2. The Hydroxyl at Position C1 of Genipin Is the Active Inhibitory Group that Affects Mitochondrial Uncoupling Protein 2 in Panc-1 Cells.

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available Genipin (GNP effectively inhibits uncoupling protein 2 (UCP2, which regulates the leakage of protons across the inner mitochondrial membrane. UCP2 inhibition may induce pancreatic adenocarcinoma cell death by increasing reactive oxygen species (ROS levels. In this study, the hydroxyls at positions C10 (10-OH and C1 (1-OH of GNP were hypothesized to be the active groups that cause these inhibitory effects. Four GNP derivatives in which the hydroxyl at position C10 or C1 was replaced with other chemical groups were synthesized and isolated. Differences in the inhibitory effects of GNP and its four derivatives on pancreatic carcinoma cell (Panc-1 proliferation were assessed. The effects of GNP and its derivatives on apoptosis, UCP2 inhibition and ROS production were also studied to explore the relationship between GNP's activity and its structure. The derivatives with 1-OH substitutions, geniposide (1-GNP1 and 1-ethyl-genipin (1-GNP2 lacked cytotoxic effects, while the other derivatives that retained 1-OH, 10-piv-genipin (10-GNP1 and 10-acetic acid-genipin (10-GNP2 exerted biological effects similar to those of GNP, even in the absence of 10-OH. Thus, 1-OH is the key functional group in the structure of GNP that is responsible for GNP's apoptotic effects. These cytotoxic effects involve the induction of Panc-1 cell apoptosis through UCP2 inhibition and subsequent ROS production.

  3. Testing Benjamin Graham’s net current asset value model

    Directory of Open Access Journals (Sweden)

    Chongsoo An

    2015-02-01

    Full Text Available The objective of this paper is to empirically test one of Graham’s investment methods based on the net current asset value (NCAV. The NCAV is truly unique, and conservative, and commonly known as the net-net method.  The ratio of the net current asset value to market value (NCAV/MV was employed in this study to test a stock’s performance comparing to the performance of S&P 500 as the market index. We used all stocks in Portfolio123 whose raw data were supplied by Compustat, Standard & Poors, Capital IQ, and Reuters for the period of January 2, 1999 to August 31, 2012. The overall results show that the firms with high net current asset values outperform the market. These results are strong in the up market. It can be argued that the firms with a high NCAV/MV ratio are likely to move toward their fundamental value and generate high excess return because its stock prices are now undervalued. The implications of the study are: (a a positive NCAV/MV ratio may be a good indicator of the underpriced security; (b investing in the growth period and avoiding the downturn period leads investors to earn much higher returns from the firms with a high NCAV/MV ratio; and (c The NCAV/MV strategy requires a longer holding period of the portfolio in order to generate excess returns.

  4. VitisNet: "Omics" integration through grapevine molecular networks.

    Directory of Open Access Journals (Sweden)

    Jérôme Grimplet

    Full Text Available BACKGROUND: Genomic data release for the grapevine has increased exponentially in the last five years. The Vitis vinifera genome has been sequenced and Vitis EST, transcriptomic, proteomic, and metabolomic tools and data sets continue to be developed. The next critical challenge is to provide biological meaning to this tremendous amount of data by annotating genes and integrating them within their biological context. We have developed and validated a system of Grapevine Molecular Networks (VitisNet. METHODOLOGY/PRINCIPAL FINDINGS: The sequences from the Vitis vinifera (cv. Pinot Noir PN40024 genome sequencing project and ESTs from the Vitis genus have been paired and the 39,424 resulting unique sequences have been manually annotated. Among these, 13,145 genes have been assigned to 219 networks. The pathway sets include 88 "Metabolic", 15 "Genetic Information Processing", 12 "Environmental Information Processing", 3 "Cellular Processes", 21 "Transport", and 80 "Transcription Factors". The quantitative data is loaded onto molecular networks, allowing the simultaneous visualization of changes in the transcriptome, proteome, and metabolome for a given experiment. CONCLUSIONS/SIGNIFICANCE: VitisNet uses manually annotated networks in SBML or XML format, enabling the integration of large datasets, streamlining biological functional processing, and improving the understanding of dynamic processes in systems biology experiments. VitisNet is grounded in the Vitis vinifera genome (currently at 8x coverage and can be readily updated with subsequent updates of the genome or biochemical discoveries. The molecular network files can be dynamically searched by pathway name or individual genes, proteins, or metabolites through the MetNet Pathway database and web-portal at http://metnet3.vrac.iastate.edu/. All VitisNet files including the manual annotation of the grape genome encompassing pathway names, individual genes, their genome identifier, and chromosome

  5. Effects of dietary soybean oil on pig growth performance, retention of protein, lipids, and energy, and the net energy of corn in diets fed to growing or finishing pigs.

    Science.gov (United States)

    Kil, D Y; Ji, F; Stewart, L L; Hinson, R B; Beaulieu, A D; Allee, G L; Patience, J F; Pettigrew, J E; Stein, H H

    2013-07-01

    The objectives of this experiment were 1) to determine if dietary soybean oil (SBO) affects the NE of corn when fed to growing or finishing pigs, 2) to determine if possible effects of dietary SBO on the NE of corn differ between growing and finishing pigs, and 3) to determine effects of SBO on pig growth performance and retention of energy, protein, and lipids. Forty-eight growing (initial BW: 27.3 ± 2.5 kg) and 48 finishing (initial BW: 86.0 ± 3.0 kg) barrows were used, and within each stage of growth, pigs were allotted to 1 of 6 groups. Two groups at each stage of growth served as an initial slaughter group. The remaining 4 groups were randomly assigned to 4 dietary treatments and pigs in these groups were harvested at the conclusion of the experiment. A low-lipid basal diet containing corn, soybean meal, and no added SBO and a high-lipid basal diet containing corn, soybean meal, and 8% SBO were formulated at each stage of growth. Two additional diets at each stage of growth were formulated by mixing 25% corn and 75% of the low-lipid basal diet or 25% corn and 75% of the high-lipid basal diet. Results indicated that addition of SBO had no effects on growth performance, carcass composition, or retention of energy, protein, and lipids but increased (P growth performance and retention of energy, protein, and lipids than growing pigs. A greater (P < 0.05) DE and NE of diets was observed for finishing pigs than for growing pigs and the DE and NE of corn was also greater (P < 0.05) for finishing pigs than for growing pigs. In conclusion, addition of SBO increases the DE and NE of diets but has no impact on the DE and NE of corn. Diets fed to finishing pigs have greater DE and NE values than diets fed to growing pigs and the DE and NE of corn are greater for finishing pigs than for growing pigs.

  6. Proteína e energia na dieta de jundiás criados em tanques-rede Protein and energy in diet for catsfish raised in net cages

    Directory of Open Access Journals (Sweden)

    Jakeline Marcela Azambuja de Freitas

    2011-12-01

    Full Text Available Objetivou-se com este trabalho avaliar a influência de dois níveis de energia digestível (3.250 e 3.500 kcal kg-1 em combinação a três níveis de proteína bruta (25, 30 e 35% sobre o desempenho produtivo de juvenis de jundiá (Rhamdia voulezi. Utilizaram-se 240 juvenis de jundiá com peso inicial de 95,55±6,70 g e 20,43±1,13 cm de comprimento total, distribuídos ao acaso em 24 tanques-rede (370 L cada em delineamento fatorial com seis tratamentos e quatro repetições. O arraçoamento foi realizado quatro vezes ao dia, à vontade. Ao final do período experimental, a análise fatorial de variância evidenciou influência significativa nos parâmetros zootécnicos avaliados. Foram observados melhor ganho de peso e comprimento final médios e menor deposição de gordura visceral nos peixes alimentados com a dieta contendo 30% de proteína bruta e 3.250 kcal de energia digestível kg-1. Portanto, recomendam-se para juvenis de jundiá dietas que contenham no mínimo 30% de proteína bruta e 3.250 kcal de energia digestível kg-1 de ração.The objective of this study was to evaluate the influence of two levels of digestible energy (3250 and 3500 kcal kg-1 in conjunction with three levels of crude protein (25, 30 and 35% on the productive performance of catfish (Rhamdia voulezi juveniles. Two-hundred and forty catfish juveniles with 95.55±6.70 g average weight and 20.43±1.13 cm total length were randomly assigned into twenty-four 370 L-cages, in a factorial arrangement with six treatments and four reptitions. Feeding was performed four times a day, ad libitum. At end of experimental period, the factorial analysis of variance showed significant influence with respect to the different parameters evaluated. The fish fed with diets of 30% crude protein and 3,250 kcal digestible energy kg-1 of diet presented the best results. Therefore, diets with at least 30% crude protein and 3,250 kcal digestible energy kg-1 are recommend for catfish

  7. Cdc5 influences phosphorylation of Net1 and disassembly of the RENT complex.

    Science.gov (United States)

    Shou, Wenying; Azzam, Ramzi; Chen, Susan L; Huddleston, Michael J; Baskerville, Christopher; Charbonneau, Harry; Annan, Roland S; Carr, Steve A; Deshaies, Raymond J

    2002-04-17

    In S. cerevisiae, the mitotic exit network (MEN) proteins, including the Polo-like protein kinase Cdc5 and the protein phosphatase Cdc14, are required for exit from mitosis. In pre-anaphase cells, Cdc14 is sequestered to the nucleolus by Net1 as a part of the RENT complex. When cells are primed to exit mitosis, the RENT complex is disassembled and Cdc14 is released from the nucleolus. Here, we show that Cdc5 is necessary to free nucleolar Cdc14 in late mitosis, that elevated Cdc5 activity provokes ectopic release of Cdc14 in pre-anaphase cells, and that the phosphorylation state of Net1 is regulated by Cdc5 during anaphase. Furthermore, recombinant Cdc5 and Xenopus Polo-like kinase can disassemble the RENT complex in vitro by phosphorylating Net1 and thereby reducing its affinity for Cdc14. Surprisingly, although RENT complexes containing Net1 mutants (Net1(7m) and Net1(19m') lacking sites phosphorylated by Cdc5 in vitro are refractory to disassembly by Polo-like kinases in vitro, net1(7m) and net1(19m') cells grow normally and exhibit only minor defects in releasing Cdc14 during anaphase. However, net1(19m') cells exhibit a synergistic growth defect when combined with mutations in CDC5 or DBF2 (another MEN gene). We propose that although Cdc5 potentially disassembles RENT by directly phosphorylating Net1, Cdc5 mediates exit from mitosis primarily by phosphorylating other targets. Our study suggests that Cdc5/Polo is unusually promiscuous and highlights the need to validate Cdc5/Polo in vitro phosphorylation sites by direct in vivo mapping experiments.

  8. Long-term protection against human papillomavirus e7-positive tumor by a single vaccination of adeno-associated virus vectors encoding a fusion protein of inactivated e7 of human papillomavirus 16/18 and heat shock protein 70.

    Science.gov (United States)

    Zhou, Liqiao; Zhu, Tong; Ye, Xiaojing; Yang, Lin; Wang, Bing; Liang, Xiaoyan; Lu, Lina; Tsao, Yeou-Ping; Chen, Show-Li; Li, Juan; Xiao, Xiao

    2010-01-01

    We investigated a gene vaccine strategy against human papillomavirus (HPV)-induced cancer and premalignant diseases, using adeno-associated virus (AAV) vector encoding the viral E7 oncoproteins as the tumor antigens from HPV serotypes 16 (HPV16) and 18 (HPV18). Genetically inactivated E7 proteins were fused with a heat shock protein 70 (hsp70) to minimize the risk of cell transformation and enhance immune responses. The fusion protein gene was packaged in AAV serotype 1 or 2 (AAV1 or 2) for efficient in vivo gene expression. Our results showed that after a single intramuscular injection, the AAV1 vector elicited stronger HPV-specific cytotoxic T lymphocyte (CTL) responses and interferon-gamma secretion when compared with the AAV2 vector. Prophylactic immunization with AAV1 protected 100% of the mice from tumor growth for more than 1 year, whereas all the control mice immunized with either a LacZ vector or saline grew large tumors and died within 6 weeks after inoculation of E7-positive tumor cell line TC-1. In addition, this single-dose AAV1 vaccination completely protected the mice against second and third challenges with higher numbers of TC-1 cells. Despite lower CTL responses against the E7 antigens, AAV2 vector prophylactic immunization was also sufficient to protect 100% of the mice against the initial and second tumor challenges and 70% of the mice against the third challenge. In addition, therapeutic immunization with AAV1 after palpable tumor formation inhibited tumor growth and caused tumor regression in some mice. Thus, our studies support the potential of AAV vectors as a genetic vaccine for the prevention and treatment of HPV-induced malignancies.

  9. A Mutant of Hepatitis B Virus X Protein (HBxΔ127 Promotes Cell Growth through A Positive Feedback Loop Involving 5-Lipoxygenase and Fatty Acid Synthase

    Directory of Open Access Journals (Sweden)

    Qi Wang

    2010-02-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common malignant tumors worldwide. Hepatitis B virus X protein (HBx contributes to the development of HCC, whereas HBx with COOH-terminal deletion is a frequent event in the HCC tissues. Previously, we identified a natural mutant of HBx-truncated 27 amino acids at the COOH-terminal (termed HBxΔ127, which strongly enhanced cell growth. In the present study, we focused on investigating the mechanism. Accordingly, fatty acid synthase (FAS plays a crucial role in cancer cell survival and proliferation; thus, we examined the signaling pathways involving FAS. Our data showed that HBxΔ127 strongly increased the transcriptional activities of FAS in human hepatoma HepG2 and H7402 cells. Moreover, we found that 5-lipoxygenase (5-LOX was responsible for the up-regulation of FAS by using MK886 (an inhibitor of 5-LOX and 5-LOX small interfering RNA. We observed that HBxΔ127 could upregulate 5-LOX through phosphorylated extracellular signal-regulated protein kinases 1/2 and thus resulted in the increase of released leukotriene B4 (LTB4, a metabolite of 5-LOX by ELISA. The additional LTB4 could upregulate the expression of FAS in the cells as well. Interestingly, we found that FAS was able to upregulate the expression of 5-LOX in a feedback manner by using cerulenin (an inhibitor of FAS. Collectively, HBxΔ127 promotes cell growth through a positive feedback loop involving 5-LOX and FAS, in which released LTB4 is involved in the up-regulation of FAS. Thus, our finding provides a new insight into the mechanism involving the promotion of cell growth mediated by HBxΔ127.

  10. Sry HMG box protein 9-positive (Sox9+) epithelial cell adhesion molecule-negative (EpCAM-) biphenotypic cells derived from hepatocytes are involved in mouse liver regeneration.

    Science.gov (United States)

    Tanimizu, Naoki; Nishikawa, Yuji; Ichinohe, Norihisa; Akiyama, Haruhiko; Mitaka, Toshihiro

    2014-03-14

    It has been shown that mature hepatocytes compensate tissue damages not only by proliferation and/or hypertrophy but also by conversion into cholangiocyte-like cells. We found that Sry HMG box protein 9-positive (Sox9(+)) epithelial cell adhesion molecule-negative (EpCAM(-)) hepatocyte nuclear factor 4α-positive (HNF4α(+)) biphenotypic cells showing hepatocytic morphology appeared near EpCAM(+) ductular structures in the livers of mice fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing diet. When Mx1-Cre:ROSA mice, which were injected with poly(I:C) to label mature hepatocytes, were fed with the DDC diet, we found LacZ(+)Sox9(+) cells near ductular structures. Although Sox9(+)EpCAM(-) cells adjacent to expanding ducts likely further converted into ductular cells, the incidence was rare. To know the cellular characteristics of Sox9(+)EpCAM(-) cells, we isolated them as GFP(+)EpCAM(-) cells from DDC-injured livers of Sox9-EGFP mice. Sox9(+)EpCAM(-) cells proliferated and could differentiate to functional hepatocytes in vitro. In addition, Sox9(+)EpCAM(-) cells formed cysts with a small central lumen in collagen gels containing Matrigel® without expressing EpCAM. These results suggest that Sox9(+)EpCAM(-) cells maintaining biphenotypic status can establish cholangiocyte-type polarity. Interestingly, we found that some of the Sox9(+) cells surrounded luminal spaces in DDC-injured liver while they expressed HNF4α. Taken together, we consider that in addition to converting to cholangiocyte-like cells, Sox9(+)EpCAM(-) cells provide luminal space near expanded ductular structures to prevent deterioration of the injuries and potentially supply new hepatocytes to repair damaged tissues.

  11. High-throughput system for the presentation of secreted and surface-exposed proteins from Gram-positive bacteria in functional metagenomics studies.

    Directory of Open Access Journals (Sweden)

    Dragana Dobrijevic

    Full Text Available Complex microbial ecosystems are increasingly studied through the use of metagenomics approaches. Overwhelming amounts of DNA sequence data are generated to describe the ecosystems, and allow to search for correlations between gene occurrence and clinical (e.g. in studies of the gut microbiota, physico-chemical (e.g. in studies of soil or water environments, or other parameters. Observed correlations can then be used to formulate hypotheses concerning microbial gene functions in relation to the ecosystem studied. In this context, functional metagenomics studies aim to validate these hypotheses and to explore the mechanisms involved. One possible approach is to PCR amplify or chemically synthesize genes of interest and to express them in a suitable host in order to study their function. For bacterial genes, Escherichia coli is often used as the expression host but, depending on the origin and nature of the genes of interest and the test system used to evaluate their putative function, other expression systems may be preferable. In this study, we developed a system to evaluate the role of secreted and surface-exposed proteins from Gram-positive bacteria in the human gut microbiota in immune modulation. We chose to use a Gram-positive host bacterium, Bacillus subtilis, and modified it to provide an expression background that behaves neutral in a cell-based immune modulation assay, in vitro. We also adapted an E. coli-B. subtilis shuttle expression vector for use with the Gateway high-throughput cloning system. Finally, we demonstrate the functionality of this host-vector system through the cloning and expression of a flagellin-coding sequence, and show that the expression-clone elicits an inflammatory response in a human intestinal epithelial cell line. The expression host can easily be adapted to assure neutrality in other assay systems, allowing the use of the presented presentation system in functional metagenomics of the gut and other

  12. High-throughput system for the presentation of secreted and surface-exposed proteins from Gram-positive bacteria in functional metagenomics studies.

    Science.gov (United States)

    Dobrijevic, Dragana; Di Liberto, Gaetana; Tanaka, Kosei; de Wouters, Tomas; Dervyn, Rozenn; Boudebbouze, Samira; Binesse, Johan; Blottière, Hervé M; Jamet, Alexandre; Maguin, Emmanuelle; van de Guchte, Maarten

    2013-01-01

    Complex microbial ecosystems are increasingly studied through the use of metagenomics approaches. Overwhelming amounts of DNA sequence data are generated to describe the ecosystems, and allow to search for correlations between gene occurrence and clinical (e.g. in studies of the gut microbiota), physico-chemical (e.g. in studies of soil or water environments), or other parameters. Observed correlations can then be used to formulate hypotheses concerning microbial gene functions in relation to the ecosystem studied. In this context, functional metagenomics studies aim to validate these hypotheses and to explore the mechanisms involved. One possible approach is to PCR amplify or chemically synthesize genes of interest and to express them in a suitable host in order to study their function. For bacterial genes, Escherichia coli is often used as the expression host but, depending on the origin and nature of the genes of interest and the test system used to evaluate their putative function, other expression systems may be preferable. In this study, we developed a system to evaluate the role of secreted and surface-exposed proteins from Gram-positive bacteria in the human gut microbiota in immune modulation. We chose to use a Gram-positive host bacterium, Bacillus subtilis, and modified it to provide an expression background that behaves neutral in a cell-based immune modulation assay, in vitro. We also adapted an E. coli-B. subtilis shuttle expression vector for use with the Gateway high-throughput cloning system. Finally, we demonstrate the functionality of this host-vector system through the cloning and expression of a flagellin-coding sequence, and show that the expression-clone elicits an inflammatory response in a human intestinal epithelial cell line. The expression host can easily be adapted to assure neutrality in other assay systems, allowing the use of the presented presentation system in functional metagenomics of the gut and other ecosystems.

  13. NETS - Danish participation. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Alsen, S. (Grontmij - Carl Bro, Glostrup (Denmark)); Theel, C. (Baltic Sea Solutions, Holeby (Denmark))

    2008-12-15

    Within the NICe-funded project 'Nordic Environmental Technology Solutions (NETS)' a new type of networking at the Nordic level was organized in order to jointly exploit the rapidly growing market potential in the environmental technology sector. The project aimed at increased and professionalized commercialization of Nordic Cleantech in energy and water business segments through 1) closer cooperation and joint marketing activities, 2) a website, 3) cleantech product information via brochures and publications 4) and participating in relevant trade fairs and other industry events. Facilitating business-to-business activities was another core task for the NETS project partners from Norway, Sweden, Finland and Denmark with the aim to encourage total solutions for combined Cleantech system offers. The project has achieved to establish a Cleantech register of 600 Nordic Cleantech companies, a network of 86 member enterprises, produced several publications and brochures for direct technology promotion and a website for direct access to company profiles and contact data. The project partners have attended 14 relevant international Cleantech trade fairs and conferences and facilitated business-to-business contacts added by capacity building offers through two company workshops. The future challenge for the project partners and Nordic Cleantech will be to coordinate the numerous efforts within the Nordic countries in order to reach concerted action and binding of member companies for reliable services, an improved visibility and knowledge exchange. With Cleantech's growing market influence and public awareness, the need to develop total solutions is increasing likewise. Marketing efforts should be encouraged cross-sectional and cross-border among the various levels of involved actors from both the public and the private sector. (au)

  14. HAMS: High-Affinity Mass Spectrometry Screening. A High-Throughput Screening Method for Identifying the Tightest-Binding Lead Compounds for Target Proteins with No False Positive Identifications

    Science.gov (United States)

    Imaduwage, Kasun P.; Go, Eden P.; Zhu, Zhikai; Desaire, Heather

    2016-11-01

    A major challenge in drug discovery is the identification of high affinity lead compounds that bind a particular target protein; these leads are typically identified by high throughput screens. Mass spectrometry has become a detection method of choice in drug screening assays because the target and the ligand need not be modified. Label-free assays are advantageous because they can be developed more rapidly than assays requiring labels, and they eliminate the risk of the label interfering with the binding event. However, in commonly used MS-based screening methods, detection of false positives is a major challenge. Here, we describe a detection strategy designed to eliminate false positives. In this approach, the protein and the ligands are incubated together, and the non-binders are separated for detection. Hits (protein binders) are not detectable by MS after incubation with the protein, but readily identifiable by MS when the target protein is not present in the incubation media. The assay was demonstrated using three different proteins and hundreds of non-inhibitors; no false positive hits were identified in any experiment. The assay can be tuned to select for ligands of a particular binding affinity by varying the quantity of protein used and the immobilization method. As examples, the method selectively detected inhibitors that have Ki values of 0.2 μM, 50 pM, and 700 pM. These findings demonstrate that the approach described here compares favorably with traditional MS-based screening methods.

  15. Selection, purification, and characterization of a HER2-targeting soluble designed ankyrin repeat protein by E. coli surface display using HER2-positive melanoma cells.

    Science.gov (United States)

    Chen, Xiaofei; Yu, Xiaoxiao; Song, Xiaoda; Liu, Li; Yi, Yuting; Yao, Wenbing; Gao, Xiangdong

    2018-01-09

    Human epidermal growth factor receptor 2 (HER2) is a powerful target for cancer immune therapy. The development of anti-HER2 monoclonal antibodies targeting different domains of HER2 is quite effective. However, the selection and production of multivalent antibodies are complicated. In this study, a mimivirus-based designed ankyrin repeat protein (DARPin) targeting HER2 was selected from an artificial library by bacteria surface display. The selection was performed on HER2-positive B16BL6/E2 melanoma cells and HER2-nagative cells. DARPin selected from the library could be expressed in soluble form with a yield of 70 mg/L. After purified by two continuous and easy steps, the purity of DARPin was 90% as established by SDS-PAGE and RP-HPLC. Selected DARPin showed significant HER2-targeting ability with an affinity of 1.05 ± 0.47 µM. MTT assay demonstrated that at the concentration of 640 nM, the selected DARPin dimer could inhibit the SK-BR-3 growth at a rate of 36.63 and 46.34% in 48 and 72 hr incubation separately, which was similar to trastuzumab (43.12 and 49.14% separately). These findings suggested that it was an effective method to select antibody mimetic DARPin by bacteria surface display combined with live cells sorting and provided a drug candidate for cancer therapy.

  16. Application and Theory of Petri Nets

    DEFF Research Database (Denmark)

    This volume contains the proceedings of the 13th International Conference onApplication and Theory of Petri Nets, held in Sheffield, England, in June 1992. The aim of the Petri net conferences is to create a forum for discussing progress in the application and theory of Petri nets. Typically....... Balbo and W. Reisig, 18 submitted papers, and seven project papers. The submitted papers and project presentations were selectedby the programme committee and a panel of referees from a large number of submissions....

  17. Are You Neutral About Net Neutrality

    Science.gov (United States)

    2007-06-20

    Information Resources Management College National Defense University Are You Neutral About Net Neutrality ? A presentation for Systems & Software...author uses Verizon FiOS for phone, TV, and internet service 3 Agenda Net Neutrality —Through 2 Lenses Who Are the Players & What Are They Saying...Medical Treatment Mini-Case Studies Updates Closing Thoughts 4 Working Definitions of Net Neutrality "Network Neutrality" is the concept that

  18. Texture Based Image Analysis With Neural Nets

    Science.gov (United States)

    Ilovici, Irina S.; Ong, Hoo-Tee; Ostrander, Kim E.

    1990-03-01

    In this paper, we combine direct image statistics and spatial frequency domain techniques with a neural net model to analyze texture based images. The resultant optimal texture features obtained from the direct and transformed image form the exemplar pattern of the neural net. The proposed approach introduces an automated texture analysis applied to metallography for determining the cooling rate and mechanical working of the materials. The results suggest that the proposed method enhances the practical applications of neural nets and texture extraction features.

  19. Factors associated with mosquito net use by individuals in households owning nets in Ethiopia

    Directory of Open Access Journals (Sweden)

    Graves Patricia M

    2011-12-01

    Full Text Available Abstract Background Ownership of insecticidal mosquito nets has dramatically increased in Ethiopia since 2006, but the proportion of persons with access to such nets who use them has declined. It is important to understand individual level net use factors in the context of the home to modify programmes so as to maximize net use. Methods Generalized linear latent and mixed models (GLLAMM were used to investigate net use using individual level data from people living in net-owning households from two surveys in Ethiopia: baseline 2006 included 12,678 individuals from 2,468 households and a sub-sample of the Malaria Indicator Survey (MIS in 2007 included 14,663 individuals from 3,353 households. Individual factors (age, sex, pregnancy; net factors (condition, age, net density; household factors (number of rooms [2006] or sleeping spaces [2007], IRS, women's knowledge and school attendance [2007 only], wealth, altitude; and cluster level factors (rural or urban were investigated in univariate and multi-variable models for each survey. Results In 2006, increased net use was associated with: age 25-49 years (adjusted (a OR = 1.4, 95% confidence interval (CI 1.2-1.7 compared to children U5; female gender (aOR = 1.4; 95% CI 1.2-1.5; fewer nets with holes (Ptrend = 0.002; and increasing net density (Ptrend [all nets in HH good] = 1.6; 95% CI 1.2-2.1; increasing net density (Ptrend [per additional space] = 0.6, 95% CI 0.5-0.7; more old nets (aOR [all nets in HH older than 12 months] = 0.5; 95% CI 0.3-0.7; and increasing household altitude (Ptrend Conclusion In both surveys, net use was more likely by women, if nets had fewer holes and were at higher net per person density within households. School-age children and young adults were much less likely to use a net. Increasing availability of nets within households (i.e. increasing net density, and improving net condition while focusing on education and promotion of net use, especially in school-age children

  20. Pro Agile NET Development with Scrum

    CERN Document Server

    Blankenship, Jerrel; Millett, Scott

    2011-01-01

    Pro Agile .NET Development with SCRUM guides you through a real-world ASP.NET project and shows how agile methodology is put into practice. There is plenty of literature on the theory behind agile methodologies, but no book on the market takes the concepts of agile practices and applies these in a practical manner to an end-to-end ASP.NET project, especially the estimating, requirements and management aspects of a project. Pro Agile .NET Development with SCRUM takes you through the initial stages of a project - gathering requirements and setting up an environment - through to the development a

  1. Pro ASP.NET MVC 4

    CERN Document Server

    Freeman, Adam

    2012-01-01

    The ASP.NET MVC 4 Framework is the latest evolution of Microsoft's ASP.NET web platform. It provides a high-productivity programming model that promotes cleaner code architecture, test-driven development, and powerful extensibility, combined with all the benefits of ASP.NET. ASP.NET MVC 4 contains a number of significant advances over previous versions. New mobile and desktop templates (employing adaptive rendering) are included together with support for jQuery Mobile for the first time. New display modes allow your application to select views based on the browser that's making the request whi

  2. Professional Visual Basic 2010 and .NET 4

    CERN Document Server

    Sheldon, Bill; Sharkey, Kent

    2010-01-01

    Intermediate and advanced coverage of Visual Basic 2010 and .NET 4 for professional developers. If you've already covered the basics and want to dive deep into VB and .NET topics that professional programmers use most, this is your book. You'll find a quick review of introductory topics-always helpful-before the author team of experts moves you quickly into such topics as data access with ADO.NET, Language Integrated Query (LINQ), security, ASP.NET web programming with Visual Basic, Windows workflow, threading, and more. You'll explore all the new features of Visual Basic 2010 as well as all t

  3. NASA Net Zero Energy Buildings Roadmap

    Energy Technology Data Exchange (ETDEWEB)

    Pless, S.; Scheib, J.; Torcellini, P.; Hendron, B.; Slovensky, M.

    2014-10-01

    In preparation for the time-phased net zero energy requirement for new federal buildings starting in 2020, set forth in Executive Order 13514, NASA requested that the National Renewable Energy Laboratory (NREL) to develop a roadmap for NASA's compliance. NASA detailed a Statement of Work that requested information on strategic, organizational, and tactical aspects of net zero energy buildings. In response, this document presents a high-level approach to net zero energy planning, design, construction, and operations, based on NREL's first-hand experience procuring net zero energy construction, and based on NREL and other industry research on net zero energy feasibility. The strategic approach to net zero energy starts with an interpretation of the executive order language relating to net zero energy. Specifically, this roadmap defines a net zero energy acquisition process as one that sets an aggressive energy use intensity goal for the building in project planning, meets the reduced demand goal through energy efficiency strategies and technologies, then adds renewable energy in a prioritized manner, using building-associated, emission- free sources first, to offset the annual energy use required at the building; the net zero energy process extends through the life of the building, requiring a balance of energy use and production in each calendar year.

  4. Towards a Standard for Modular Petri Nets

    DEFF Research Database (Denmark)

    Kindler, Ekkart; Petrucci, Laure

    2009-01-01

    When designing complex systems, mechanisms for structuring, composing, and reusing system components are crucial. Today, there are many approaches for equipping Petri nets with such mechanisms. In the context of defining a standard interchange format for Petri nets, modular PNML was defined....... Moreover, we present and discuss some more advanced features of modular Petri nets that could be included in the standard. This way, we provide a formal foundation and a basis for a discussion of features to be included in the upcoming standard of a module concept for Petri nets in general and for high...

  5. An analytical method for well-formed workflow/Petri net verification of classical soundness

    Directory of Open Access Journals (Sweden)

    Clempner Julio

    2014-12-01

    Full Text Available In this paper we consider workflow nets as dynamical systems governed by ordinary difference equations described by a particular class of Petri nets. Workflow nets are a formal model of business processes. Well-formed business processes correspond to sound workflow nets. Even if it seems necessary to require the soundness of workflow nets, there exist business processes with conditional behavior that will not necessarily satisfy the soundness property. In this sense, we propose an analytical method for showing that a workflow net satisfies the classical soundness property using a Petri net. To present our statement, we use Lyapunov stability theory to tackle the classical soundness verification problem for a class of dynamical systems described by Petri nets. This class of Petri nets allows a dynamical model representation that can be expressed in terms of difference equations. As a result, by applying Lyapunov theory, the classical soundness property for workflow nets is solved proving that the Petri net representation is stable. We show that a finite and non-blocking workflow net satisfies the sound property if and only if its corresponding PN is stable, i.e., given the incidence matrix A of the corresponding PN, there exists a Փ strictly positive m vector such that AՓ≤ 0. The key contribution of the paper is the analytical method itself that satisfies part of the definition of the classical soundness requirements. The method is designed for practical applications, guarantees that anomalies can be detected without domain knowledge, and can be easily implemented into existing commercial systems that do not support the verification of workflows. The validity of the proposed method is successfully demonstrated by application examples.

  6. Experiments and simulation of a net closing mechanism for tether-net capture of space debris

    Science.gov (United States)

    Sharf, Inna; Thomsen, Benjamin; Botta, Eleonora M.; Misra, Arun K.

    2017-10-01

    This research addresses the design and testing of a debris containment system for use in a tether-net approach to space debris removal. The tether-net active debris removal involves the ejection of a net from a spacecraft by applying impulses to masses on the net, subsequent expansion of the net, the envelopment and capture of the debris target, and the de-orbiting of the debris via a tether to the chaser spacecraft. To ensure a debris removal mission's success, it is important that the debris be successfully captured and then, secured within the net. To this end, we present a concept for a net closing mechanism, which we believe will permit consistently successful debris capture via a simple and unobtrusive design. This net closing system functions by extending the main tether connecting the chaser spacecraft and the net vertex to the perimeter and around the perimeter of the net, allowing the tether to actuate closure of the net in a manner similar to a cinch cord. A particular embodiment of the design in a laboratory test-bed is described: the test-bed itself is comprised of a scaled-down tether-net, a supporting frame and a mock-up debris. Experiments conducted with the facility demonstrate the practicality of the net closing system. A model of the net closure concept has been integrated into the previously developed dynamics simulator of the chaser/tether-net/debris system. Simulations under tether tensioning conditions demonstrate the effectiveness of the closure concept for debris containment, in the gravity-free environment of space, for a realistic debris target. The on-ground experimental test-bed is also used to showcase its utility for validating the dynamics simulation of the net deployment, and a full-scale automated setup would make possible a range of validation studies of other aspects of a tether-net debris capture mission.

  7. Avaliação do modelo CNCPS na predição do consumo de matéria seca em vacas da raça Holandesa em pastejo Evaluation of the Cornell Net Carbohydrate and Protein System on the prediction of dry matter intake of grazing lactating Holstein cows

    Directory of Open Access Journals (Sweden)

    Ana Cristina Wyllie Elyas

    2009-06-01

    Full Text Available Este trabalho foi realizado com o objetivo de avaliar o modelo Cornell Net Carbohydrate and Protein System (CNCPS, versão 5.0, na predição do consumo de matéria seca de vacas da raça Holandesa, lactantes, em pastagem de capim coast-cross suplementada com silagem de milho e concentrado (3 ou 6 kg/vaca.dia. Foram realizados seis ensaios experimentais, cada um com 12 vacas. Em três das avaliações, os animais receberam, além do concentrado, 17 kg de silagem de milho/dia (base natural. As coletas de forragem selecionada na pastagem para análise da composição química foram realizadas por uma vaca com fístula esofágica. A estimativa do consumo voluntário foi realizada com sesquióxido de cromo (Cr2O3, administrado em doses de 5 g, duas vezes ao dia. Foram fornecidos ao programa dados (inputs referentes aos animais (peso vivo corporal, escore corporal, idade, produção e composição do leite e tipo racial, ao ambiente (temperatura, umidade relativa do ar e manejo e à composição do alimento em cada período experimental. Os valores preditos pelo CNCPS para a ingestão voluntária de matéria seca foram próximos àqueles estimados, havendo pequena tendência do modelo em subestimar o valor determinado com o indicador.The aim of this work was to evaluate the ability of the Cornell Net Carbohydrate and Protein System (CNCPS version 5.0 to estimate the dry matter intake (DMI of grazing lactating Holstein cows, grazing coast-cross pasture supplemented with corn silage and concentrate (3 or 6 kg/cow/day. Six experiments were carried out, with 12 cows each. The cows were fed 17 kg/cow/day of corn ensilage in three experiments. The chemical composition of extrusa samples of forage was determined, obtained using an esophageous fistulated cow. The intake estimates were obtained using 5 g of chromium oxide (Cr2O3 methodology supplied two times a day. Data corresponding to animals (body weight, age, milk yield and composition and racial type

  8. HANPP Collection: Human Appropriation of Net Primary Productivity as a Percentage of Net Primary Productivity

    Data.gov (United States)

    National Aeronautics and Space Administration — The Human Appropriation of Net Primary Productivity (HANPP) as a Percentage of Net Primary Product (NPP) portion of the HANPP Collection represents a map identifying...

  9. Price smarter on the Net.

    Science.gov (United States)

    Baker, W; Marn, M; Zawada, C

    2001-02-01

    Companies generally have set prices on the Internet in two ways. Many start-ups have offered untenably low prices in a rush to capture first-mover advantage. Many incumbents have simply charged the same prices on-line as they do off-line. Either way, companies are missing a big opportunity. The fundamental value of the Internet lies not in lowering prices or making them consistent but in optimizing them. After all, if it's easy for customers to compare prices on the Internet, it's also easy for companies to track customers' behavior and adjust prices accordingly. The Net lets companies optimize prices in three ways. First, it lets them set and announce prices with greater precision. Different prices can be tested easily, and customers' responses can be collected instantly. Companies can set the most profitable prices, and they can tap into previously hidden customer demand. Second, because it's so easy to change prices on the Internet, companies can adjust prices in response to even small fluctuations in market conditions, customer demand, or competitors' behavior. Third, companies can use the clickstream data and purchase histories that it collects through the Internet to segment customers quickly. Then it can offer segment-specific prices or promotions immediately. By taking full advantage of the unique possibilities afforded by the Internet to set prices with precision, adapt to changing circumstances quickly, and segment customers accurately, companies can get their pricing right. It's one of the ultimate drivers of e-business success.

  10. Minimal Edge-Transitive Nets for the Design and Construction of Metal-Organic Frameworks

    KAUST Repository

    Eddaoudi, Mohamed

    2017-04-05

    Highly-connected and minimal edge-transitive nets (with one or two kinds of edge) can be regarded as ideal blueprints for the rational design and construction of metal-organic frameworks (MOFs). Here we report and affirm the prominence of highly-connected nets as suitable targets in reticular chemistry for the design and synthesis of MOFs. Of special interest are augmented highly-connected binodal edge-transitive nets embedding a unique and precise positioning and connectivity of the net vertex figures, regarded as net-coded building units (net-cBUs). Explicitly, a definite net-cBU encompasses precise geometrical information that codes uniquely and matchlessly a selected net, a compelling perquisite for the rational design of MOFs. Interestingly, the double six-membered ring (d6R) building unit offers great prospective to be deployed as a net-cBU for the deliberate reticulation of the sole two edge-transitive nets with a vertex figure as a d6R, namely the (4,12)-coordinated shp net (square and hexagonal prism) and the (6,12)-coordinated alb net (aluminium diboride, hexagonal prism and trigonal prism). Conceivably, we envisioned and proposed various MOF structures based on the derived shp and alb nets. Gaining access to the requisite net-cBUs is essential for the successful practice of reticular chemistry; correspondingly organic and organic chemistries were deployed to afford concomitant molecular building blocks (MBBs) with the looked-for shape and connectivity. Practically, the combination of the 12-connected (12-c) rare-earth (RE) polynuclear, points of extension matching the 12 vertices of the hexagonal prism (d6R) with a 4-connected tetracarboxylate ligand or a 6-connected hexacarboxylate ligand afforded the targeted shp-MOF or alb-MOF, respectively. Intuitively, a dodecacarboxylate ligand can be conceived and purported as a compatible 12-c MBB, plausibly affording the positioning of the carbon centers of the twelve carboxylate groups on the vertices of the

  11. SpectralNET – an application for spectral graph analysis and visualization

    Directory of Open Access Journals (Sweden)

    Schreiber Stuart L

    2005-10-01

    Full Text Available Abstract Background Graph theory provides a computational framework for modeling a variety of datasets including those emerging from genomics, proteomics, and chemical genetics. Networks of genes, proteins, small molecules, or other objects of study can be represented as graphs of nodes (vertices and interactions (edges that can carry different weights. SpectralNET is a flexible application for analyzing and visualizing these biological and chemical networks. Results Available both as a standalone .NET executable and as an ASP.NET web application, SpectralNET was designed specifically with the analysis of graph-theoretic metrics in mind, a computational task not easily accessible using currently available applications. Users can choose either to upload a network for analysis using a variety of input formats, or to have SpectralNET generate an idealized random network for comparison to a real-world dataset. Whichever graph-generation method is used, SpectralNET displays detailed information about each connected component of the graph, including graphs of degree distribution, clustering coefficient by degree, and average distance by degree. In addition, extensive information about the selected vertex is shown, including degree, clustering coefficient, various distance metrics, and the corresponding components of the adjacency, Laplacian, and normalized Laplacian eigenvectors. SpectralNET also displays several graph visualizations, including a linear dimensionality reduction for uploaded datasets (Principal Components Analysis and a non-linear dimensionality reduction that provides an elegant view of global graph structure (Laplacian eigenvectors. Conclusion SpectralNET provides an easily accessible means of analyzing graph-theoretic metrics for data modeling and dimensionality reduction. SpectralNET is publicly available as both a .NET application and an ASP.NET web application from http://chembank.broad.harvard.edu/resources/. Source code is

  12. SpectralNET--an application for spectral graph analysis and visualization.

    Science.gov (United States)

    Forman, Joshua J; Clemons, Paul A; Schreiber, Stuart L; Haggarty, Stephen J

    2005-10-19

    Graph theory provides a computational framework for modeling a variety of datasets including those emerging from genomics, proteomics, and chemical genetics. Networks of genes, proteins, small molecules, or other objects of study can be represented as graphs of nodes (vertices) and interactions (edges) that can carry different weights. SpectralNET is a flexible application for analyzing and visualizing these biological and chemical networks. Available both as a standalone .NET executable and as an ASP.NET web application, SpectralNET was designed specifically with the analysis of graph-theoretic metrics in mind, a computational task not easily accessible using currently available applications. Users can choose either to upload a network for analysis using a variety of input formats, or to have SpectralNET generate an idealized random network for comparison to a real-world dataset. Whichever graph-generation method is used, SpectralNET displays detailed information about each connected component of the graph, including graphs of degree distribution, clustering coefficient by degree, and average distance by degree. In addition, extensive information about the selected vertex is shown, including degree, clustering coefficient, various distance metrics, and the corresponding components of the adjacency, Laplacian, and normalized Laplacian eigenvectors. SpectralNET also displays several graph visualizations, including a linear dimensionality reduction for uploaded datasets (Principal Components Analysis) and a non-linear dimensionality reduction that provides an elegant view of global graph structure (Laplacian eigenvectors). SpectralNET provides an easily accessible means of analyzing graph-theoretic metrics for data modeling and dimensionality reduction. SpectralNET is publicly available as both a .NET application and an ASP.NET web application from http://chembank.broad.harvard.edu/resources/. Source code is available upon request.

  13. Leucine-rich repeat-containing G-protein-coupled receptor 5-positive cells in the endometrial stem cell niche.

    Science.gov (United States)

    Cervelló, Irene; Gil-Sanchis, Claudia; Santamaría, Xavier; Faus, Amparo; Vallvé-Juanico, Julia; Díaz-Gimeno, Patricia; Genolet, Oriana; Pellicer, Antonio; Simón, Carlos

    2017-02-01

    To study, isolate and characterize leucine-rich repeat-containing heterotrimeric guanine nucleotide-binding protein-coupled receptor 5 (LGR5)-positive cells from human endometrium to determine their functional relevance. Prospective experimental animal study. University research laboratories. Nonobese diabetic mice (NOD-SCID) (strain code 394; NOD.CB17-Prkdc(scid)/NcrCrl). Human LGR5(+) cells were labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and injected under the kidney capsule in immunocompromised mice. Epithelial and stromal LGR5(+) cells were isolated from human endometrium by means of fluorescence-activated cell sorting, and phenotypic characterization was performed by means of flow cytometry with the use of hematopoietic and mesenchymal markers. Engrafted SPIO-labeled LGR5(+) cells were localized with the use of Prussian blue staining and immunohistochemistry against CD9 and Vimentin. Deep transcriptomic profiling of LGR5(+) cells was performed with the use of microarrays and RNA sequencing. The percentage of LGR5(+) cells in human endometrium represented 1.08 ± 0.73% and 0.82 ± 0.76% of total cells in the epithelial and stromal compartments, respectively. LGR5(+) cells were phenotypically characterized by abundant expression of CD45 hematopoietic marker and no expression of surface markers CD31, CD34, CD133, CD73, and CD90. Coexpression with the macrophage marker CD163 was detected. Xenotransplantation of labeled LGR5(+) cells into the kidney capsules of immunocompromised mice resulted in a weak endometrial reconstitution from this cell of origin. Transcriptomic profiling revealed new attributes for LGR5(+) cells related to their putative hematopoietic origin. These data suggest that endometrial LGR5 is not an endogenous stem cell marker. Instead, LGR5(+) cells appear to be recruited from blood to be part of the stem cell niche at the perivascular microenvironment to activate the endogenous niche. Copyright © 2016 American Society for

  14. Dynamics of C-reactive protein and white blood cell count in critically ill patients with nosocomial Gram positive vs. Gram negative bacteremia: a historical cohort study

    Directory of Open Access Journals (Sweden)

    Depuydt Pieter O

    2007-09-01

    Full Text Available Abstract Background Nosocomial bacteremia is associated with a poor prognosis. Early adequate therapy has been shown to improve outcome. Consequently, rapid detection of a beginning sepsis is therefore of the utmost importance. This historical cohort study was designed to evaluate if different patterns can be observed in either C-reactive protein (CRP and white blood cell count (WCC between Gram positive bacteremia (GPB vs. Gram negative bacteremia (GNB, and to assess the potential benefit of serial measurements of both biomarkers in terms of early antimicrobial therapy initiation. Methods A historical study (2003–2004 was conducted, including all adult intensive care unit patients with a nosocomial bacteremia. CRP and WCC count measurements were recorded daily from two days prior (d-2 until one day after onset of bacteremia (d+1. Delta (Δ CRP and Δ WCC levels from the level at d-2 onward were calculated. Results CRP levels and WCC counts were substantially higher in patients with GNB. Logistic regression analysis demonstrated that GNB and Acute Physiology and Chronic Health Evaluation (APACHE II score were independently associated with a CRP increase of 5 mg/dL from d-2 to d+1, and both were also independently associated with an increase of WCC levels from d-2 to d+1 of 5,000 × 103 cells/mm3. Conclusion Increased levels of CRP and WCC are suggestive for GNB, while almost unchanged CRP and WCC levels are observed in patients with GPB. However, despite the different patterns observed, antimicrobial treatment as such cannot be guided based on both biomarkers.

  15. The albinism of the feral Asinara white donkeys (Equus asinus) is determined by a missense mutation in a highly conserved position of the tyrosinase (TYR) gene deduced protein.

    Science.gov (United States)

    Utzeri, V J; Bertolini, F; Ribani, A; Schiavo, G; Dall'Olio, S; Fontanesi, L

    2016-02-01

    A feral donkey population (Equus asinus), living in the Asinara National Park (an island north-west of Sardinia, Italy), includes a unique white albino donkey subpopulation or colour morph that is a major attraction of this park. Disrupting mutations in the tyrosinase (TYR) gene are known to cause recessive albinisms in humans (oculocutaneous albinism Type 1; OCA1) and other species. In this study, we analysed the donkey TYR gene as a strong candidate to identify the causative mutation of the albinism of these donkeys. The TYR gene was sequenced from 13 donkeys (seven Asinara white albino and six coloured animals). Seven single nucleotide polymorphisms were identified. A missense mutation (c.604C>G; p.His202Asp) in a highly conserved amino acid position (even across kingdoms), which disrupts the first copper-binding site (CuA) of functional protein, was identified in the homozygous condition (G/G or D/D) in all Asinara white albino donkeys and in the albino son of a trio (the grey parents had genotype C/G or H/D), supporting the recessive mode of inheritance of this mutation. Genotyping 82 donkeys confirmed that Asinara albino donkeys had genotype G/G whereas all other coloured donkeys had genotype C/C or C/G. Across-population association between the c.604C>G genotypes and the albino coat colour was highly significant (P = 6.17E-18). The identification of the causative mutation of the albinism in the Asinara white donkeys might open new perspectives to study the dynamics of this putative deleterious allele in a feral population and to manage this interesting animal genetic resource. © 2015 Stichting International Foundation for Animal Genetics.

  16. A Proposed Role for Neutrophil Extracellular Traps (NETs in Ewing Sarcoma Cancer Immunoediting

    Directory of Open Access Journals (Sweden)

    Sivan eBerger-Achituv

    2013-03-01

    Full Text Available Upon activation, neutrophils release fibers composed of chromatin and neutrophil proteins termed neutrophil extracellular traps (NETs. NETs trap and kill microbes, activate dendritic cells and T-cells, and are implicated in auto-immune and vascular diseases. Given the growing interest in the role of neutrophils in cancer immunoediting and the diverse function of NETs, we searched for NETs release by tumor associated neutrophils (TANs. Using pediatric Ewing sarcoma (ES as a model, we retrospectively examined histopathological material from diagnostic biopsies of 8 patients (mean ± SD age of 11.5 ± 4.7 years. TANs were found in 6 patients and in 2 of those we identified NETs. These 2 patients presented with metastatic disease and despite entering complete remission after intensive chemotherapy had an early relapse. NETs were not identified in the diagnostic biopsies of 2 patients with localized disease and 2 with metastatic disease. This study is the first to show that TANs in ES are activated to make NETs, pointing to a possible role of NETs in cancer.

  17. Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners

    OpenAIRE

    Uversky Vladimir N; Yang Mary Qu; Yang Jack Y; Meng Jingwei; Oldfield Christopher J; Dunker A Keith

    2008-01-01

    Abstract Background Proteins are involved in many interactions with other proteins leading to networks that regulate and control a wide variety of physiological processes. Some of these proteins, called hub proteins or hubs, bind to many different protein partners. Protein intrinsic disorder, via diversity arising from structural plasticity or flexibility, provide a means for hubs to associate with many partners (Dunker AK, Cortese MS, Romero P, Iakoucheva LM, Uversky VN: Flexible Nets: The r...

  18. 78 FR 72393 - Net Investment Income Tax

    Science.gov (United States)

    2013-12-02

    ... Investment Income Tax; Final and Proposed Rules #0;#0;Federal Register / Vol. 78, No. 231 / Monday, December... Parts 1 and 602 RIN 1545-BK44 Net Investment Income Tax AGENCY: Internal Revenue Service (IRS), Treasury... Investment Income Tax and the computation of Net Investment Income. The regulations affect individuals...

  19. 77 FR 72611 - Net Investment Income Tax

    Science.gov (United States)

    2012-12-05

    ... December 5, 2012 Part V Department of the Treasury Internal Revenue Service 26 CFR Part 1 Net Investment... Investment Income Tax AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of proposed rulemaking...) the individual's net investment income for such taxable year, or (B) the excess (if any) of (i) the...

  20. Net analyte signal based statistical quality control

    NARCIS (Netherlands)

    Skibsted, E.T.S.; Boelens, H.F.M.; Westerhuis, J.A.; Smilde, A.K.; Broad, N.W.; Rees, D.R.; Witte, D.T.

    2005-01-01

    Net analyte signal statistical quality control (NAS-SQC) is a new methodology to perform multivariate product quality monitoring based on the net analyte signal approach. The main advantage of NAS-SQC is that the systematic variation in the product due to the analyte (or property) of interest is

  1. Asynchronous stream processing with S-Net

    NARCIS (Netherlands)

    Grelck, C.; Scholz, S.-B.; Shafarenko, A.

    2010-01-01

    We present the rationale and design of S-Net, a coordination language for asynchronous stream processing. The language achieves a near-complete separation between the application code, written in any conventional programming language, and the coordination/communication code written in S-Net. Our

  2. Using the MVC architecture on . NET platform

    OpenAIRE

    Ježek, David

    2011-01-01

    This thesis deals with usage of MVC (Model View Controller) technology in web development on ASP.NET platform from Microsoft. Mainly it deals with latest version of framework ASP.NET MVC 3. First part describes MVC architecture and the second describes usage of MVC in certain parts of web application an comparing with PHP.

  3. Analysis of Petri Nets and Transition Systems

    Directory of Open Access Journals (Sweden)

    Eike Best

    2015-08-01

    Full Text Available This paper describes a stand-alone, no-frills tool supporting the analysis of (labelled place/transition Petri nets and the synthesis of labelled transition systems into Petri nets. It is implemented as a collection of independent, dedicated algorithms which have been designed to operate modularly, portably, extensibly, and efficiently.

  4. 27 CFR 7.27 - Net contents.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Net contents. 7.27 Section 7.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF... the net contents are displayed by having the same blown, branded, or burned in the container in...

  5. Petri nets and other models of concurrency

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Sassone, Vladimiro

    1998-01-01

    This paper retraces, collects, and summarises contributions of the authors - in collaboration with others - on the theme of Petri nets and their categorical relationships to other models of concurrency.......This paper retraces, collects, and summarises contributions of the authors - in collaboration with others - on the theme of Petri nets and their categorical relationships to other models of concurrency....

  6. Delta Semantics Defined By Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kyng, Morten; Madsen, Ole Lehrmann

    This report is identical to an earlier version of May 1978 except that Chapter 5 has been revised. A new paper: "A Petri Net Definition of a System Description Language", DAIMI, April 1979, 20 pages, extends the Petri net model to include a data state representing the program variables. Delta...

  7. Net neutrality and inflation of traffic

    NARCIS (Netherlands)

    Peitz, M.; Schütt, Florian

    Under strict net neutrality Internet service providers (ISPs) are required to carry data without any differentiation and at no cost to the content provider. We provide a simple framework with a monopoly ISP to evaluate the short-run effects of different net neutrality rules. Content differs in its

  8. Net Neutrality and Inflation of Traffic

    NARCIS (Netherlands)

    Peitz, M.; Schütt, F.

    2015-01-01

    Under strict net neutrality Internet service providers (ISPs) are required to carry data without any differentiation and at no cost to the content provider. We provide a simple framework with a monopoly ISP to evaluate different net neutrality rules. Content differs in its sensitivity to delay.

  9. The Net Neutrality Debate: The Basics

    Science.gov (United States)

    Greenfield, Rich

    2006-01-01

    Rich Greenfield examines the basics of today's net neutrality debate that is likely to be an ongoing issue for society. Greenfield states the problems inherent in the definition of "net neutrality" used by Common Cause: "Network neutrality is the principle that Internet users should be able to access any web content they choose and…

  10. Dynamic response of the thermometric net radiometer

    Science.gov (United States)

    J. D. Wilson; W. J. Massman; G. E. Swaters

    2009-01-01

    We computed the dynamic response of an idealized thermometric net radiometer, when driven by an oscillating net longwave radiation intended roughly to simulate rapid fluctuations of the radiative environment such as might be expected during field use of such devices. The study was motivated by curiosity as to whether non-linearity of the surface boundary conditions...

  11. Teaching and Learning with the Net Generation

    Science.gov (United States)

    Barnes, Kassandra; Marateo, Raymond C.; Ferris, S. Pixy

    2007-01-01

    As the Net Generation places increasingly greater demands on educators, students and teachers must jointly consider innovative ways of teaching and learning. In this, educators are supported by the fact that the Net Generation wants to learn. However, these same educators should not fail to realize that this generation learns differently from…

  12. Verification of Timed-Arc Petri Nets

    DEFF Research Database (Denmark)

    Jacobsen, Lasse; Jacobsen, Morten; Møller, Mikael Harkjær

    2011-01-01

    Timed-Arc Petri Nets (TAPN) are an extension of the classical P/T nets with continuous time. Tokens in TAPN carry an age and arcs between places and transitions are labelled with time intervals restricting the age of tokens available for transition firing. The TAPN model posses a number...

  13. A Brief Introduction to Coloured Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt

    1997-01-01

    Coloured Petri Nets (CP-nets or CPN) is a graphical oriented language for design, specification, simulation and verification of systems. It is in particular well- suited for systems in which communication, synchronisation and resource sharing are important. Typical examples of application areas a...

  14. Gill net and trammel net selectivity in the northern Aegean Sea, Turkey

    Directory of Open Access Journals (Sweden)

    F. Saadet Karakulak

    2008-09-01

    Full Text Available Fishing trials were carried out with gill nets and trammel nets in the northern Aegean Sea from March 2004 to February 2005. Four different mesh sizes for the gill nets and the inner panel of trammel nets (16, 18, 20 and 22 mm bar length were used. Selectivity parameters for the five most economically important species, bogue (Boops boops, annular sea bream (Diplodus annularis, striped red mullet (Mullus surmuletus, axillary sea bream (Pagellus acarne and blotched picarel (Spicara maena, caught by the two gears were estimated. The SELECT method was used to estimate the selectivity parameters of a variety of models. Catch composition and catch proportion of several species were different in gill and trammel nets. The length frequency distributions of the species caught by the two gears were significantly different. The bi-modal model selectivity curve gave the best fit for gill net and trammel net data, and there was little difference between the modal lengths of these nets. However, a clear difference was found in catching efficiency. The highest catch rates were obtained with the trammel net. Given that many discard species and small fish are caught by gill nets and trammel nets with a mesh size of 16 mm, it is clear that these nets are not appropriate for fisheries. Consequently, the best mesh size for multispecies fisheries is 18 mm. This mesh size will considerably reduce the numbers of small sized individuals and discard species in the catch.

  15. Discrete, continuous, and hybrid petri nets

    CERN Document Server

    David, René

    2004-01-01

    Petri nets do not designate a single modeling formalism. In fact, newcomers to the field confess sometimes to be a little puzzled by the diversity of formalisms that are recognized under this "umbrella". Disregarding some extensions to the theoretical modeling capabilities, and looking at the level of abstraction of the formalisms, Condition/Event, Elementary, Place/Transition, Predicate/Transition, Colored, Object Oriented... net systems are frequently encountered in the literature. On the other side, provided with appropriate interpretative extensions, Controled Net Systems, Marking Diagrams (the Petri net generalization of State Diagrams), or the many-many variants in which time can be explicitly incorporated -Time(d), Deterministic, (Generalized) Stochastic, Fuzzy...- are defined. This represents another way to define practical formalisms that can be obtained by the "cro- product" of the two mentioned dimensions. Thus Petri nets constitute a modeling paradigm, understandable in a broad sense as "the total...

  16. Body composition and net requirements of protein and energy for weight gain of Nellore and crossbreed steers finished under grazing Composição corporal e exigências líquidas de proteína e energia para ganho de peso de novilhos nelores e mestiços terminados a pasto

    Directory of Open Access Journals (Sweden)

    N.F. Sant´Ana

    2011-04-01

    Full Text Available The objective of this work was to evaluate body composition and net requirements of protein and energy for weight gain of Nellore and crossbred F1 Limousin-Nellore steers finished on Mombasa grass pastures. Mombasa grass (Panicum maximum pastures were managed under intermitent stocking during the rainy season, with a forage offer of 8% of the body weight (BW based on the dry matter of green leaves. Twenty-four steers were used: 12 were Nellore (386 kg SBW and 12 were F1 Limousin-Nellore (397 kg SBW. Changes in body composition in a 104-day experimental period were evaluated according to the comparative slaughter method. After slaughter, all body components were weighed and representative samples of carcass (HH section and non-carcass tissues were collected, processed and chemically analyzed to determine body contents of protein, fat and energy in each animal. Linearized allometric equations were fitted to describe the pattern of growth of body components as a function of empty body weight of the animals. The obtained equations were derived to predict net requirements of protein and energy for weight gain. There were no differences between Nellore and crossbreed steers regarding to protein deposition. Nellore animals tended to a greater deposition of energy on weight compared to crossbred animals. It is possible to obtain well finished carcass in Nellore and crossbred steers with a greater weight on tropical pastures with an adequate supply of leaves.Este trabalho foi conduzido com o objetivo de avaliar a composição corporal e as exigências líquidas de proteína e energia para ganho de peso de novilhos Nelore e mestiços ½Limousin-Nelore terminados em pastagem de capim-mombaça. A pastagem de capim-mombaça (Panicum maximum foi manejada em regime de lotação intermitente durante a época chuvosa, com oferta de forragem de 8% do peso corporal (PC, com base na matéria seca de folhas verdes. Foram utilizados 24 novilhos: 12 da raça Nelore

  17. TarNet: An Evidence-Based Database for Natural Medicine Research.

    Directory of Open Access Journals (Sweden)

    Ruifeng Hu

    Full Text Available Complex diseases seriously threaten human health. Drug discovery approaches based on "single genes, single drugs, and single targets" are limited in targeting complex diseases. The development of new multicomponent drugs for complex diseases is imperative, and the establishment of a suitable solution for drug group-target protein network analysis is a key scientific problem that must be addressed. Herbal medicines have formed the basis of sophisticated systems of traditional medicine and have given rise to some key drugs that remain in use today. The search for new molecules is currently taking a different route, whereby scientific principles of ethnobotany and ethnopharmacognosy are being used by chemists in the discovery of different sources and classes of compounds.In this study, we developed TarNet, a manually curated database and platform of traditional medicinal plants with natural compounds that includes potential bio-target information. We gathered information on proteins that are related to or affected by medicinal plant ingredients and data on protein-protein interactions (PPIs. TarNet includes in-depth information on both plant-compound-protein relationships and PPIs. Additionally, TarNet can provide researchers with network construction analyses of biological pathways and protein-protein interactions (PPIs associated with specific diseases. Researchers can upload a gene or protein list mapped to our PPI database that has been manually curated to generate relevant networks. Multiple functions are accessible for network topological calculations, subnetwork analyses, pathway analyses, and compound-protein relationships.TarNet will serve as a useful analytical tool that will provide information on medicinal plant compound-affected proteins (potential targets and system-level analyses for systems biology and network pharmacology researchers. TarNet is freely available at http://www.herbbol.org:8001/tarnet, and detailed tutorials on the

  18. Pro visual C++/CLI and the net 35 platform

    CERN Document Server

    Fraser, Stephen

    2008-01-01

    Pro Visual C++/CLI and the .NET 3.5 Platform is about writing .NET applications using C++/CLI. While readers are learning the ins and outs of .NET application development, they will also be learning the syntax of C++, both old and new to .NET. Readers will also gain a good understanding of the .NET architecture. This is truly a .NET book applying C++ as its development language not another C++ syntax book that happens to cover .NET.

  19. Spring Hydrology Determines Summer Net Carbon Uptake in Northern Ecosystems

    Science.gov (United States)

    Yi, Yonghong; Kimball, John; Reichle, Rolf H.

    2014-01-01

    Increased photosynthetic activity and enhanced seasonal CO2 exchange of northern ecosystems have been observed from a variety of sources including satellite vegetation indices (such as the Normalized Difference Vegetation Index; NDVI) and atmospheric CO2 measurements. Most of these changes have been attributed to strong warming trends in the northern high latitudes (greater than or equal to 50N). Here we analyze the interannual variation of summer net carbon uptake derived from atmospheric CO2 measurements and satellite NDVI in relation to surface meteorology from regional observational records. We find that increases in spring precipitation and snow pack promote summer net carbon uptake of northern ecosystems independent of air temperature effects. However, satellite NDVI measurements still show an overall benefit of summer photosynthetic activity from regional warming and limited impact of spring precipitation. This discrepancy is attributed to a similar response of photosynthesis and respiration to warming and thus reduced sensitivity of net ecosystem carbon uptake to temperature. Further analysis of boreal tower eddy covariance CO2 flux measurements indicates that summer net carbon uptake is positively correlated with early growing-season surface soil moisture, which is also strongly affected by spring precipitation and snow pack based on analysis of satellite soil moisture retrievals. This is attributed to strong regulation of spring hydrology on soil respiration in relatively wet boreal and arctic ecosystems. These results document the important role of spring hydrology in determining summer net carbon uptake and contrast with prevailing assumptions of dominant cold temperature limitations to high-latitude ecosystems. Our results indicate potentially stronger coupling of boreal/arctic water and carbon cycles with continued regional warming trends.

  20. EgoNet identifies differential ego-modules and pathways related to prednisolone resistance in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Jiang, Jian; Yin, Xiang-Yun; Song, Xue-Wen; Xie, Dong; Xu, Hui-Juan; Yang, Jing; Sun, Li-Rong

    2017-10-11

    To extract feature ego-modules and pathways in childhood acute lymphoblastic leukemia (ALL) resistant to prednisolone treatment, and further to explore the mechanisms behind prednisolone resistance. EgoNet algorithm was used to identify candidate ego-network modules, mainly via constructing differential co-expression network (DCN); selecting ego genes; collecting ego-network modules; refining candidate modules. Afterwards, statistical significance was calculated for these candidate modules. Biological functions of differential ego-network modules were identified using Reactome database. To verify this proposed method can lead to truly positive findings in clinical settings, support vector machine (SVM) was utilized to compute the AUC values for each significant pathway using 3-fold cross-validation method. To predict the reliability of our findings, another established method (attract) was used to identify the differential attractor modules using the same microarray profile. After eliminating the modules with classification accuracy calculation, module 30 was significant. Module 30 was enriched in APC/C-mediated degradation of cell cycle proteins. The AUC for the significant pathway of APC/C-mediated degradation of cell cycle proteins was 0.915. Although the attract method obtained more modules, the module identified by our proposed method owned more gene nodes, and had more classification ability (AUC = 0.915). One differential ego-network module identified in childhood ALL resistance to prednisolone based on DCN and EgoNet, might be helpful to reveal the mechanisms underlying prednisolone resistance in childhood ALL.

  1. Composição do ganho e exigências de energia e proteína para ganho de peso em bovinos Nelore puros e mestiços Gain composition and net energy and protein requirements for weight gain in Nellore and crossbred cattle

    Directory of Open Access Journals (Sweden)

    José Antônio de Freitas

    2006-06-01

    the four genetic groups were fed diets containing: 30, 40, 60 and 70% of concentrate. Three animals from each genetic group were slaughtered at the beginning of the trial and used as reference for initial body composition. The net protein and energy requirements for gain of 1 kg of empty body weight (EBW were estimated by the equation Y' = a. b. X (b-1, where a and b are the parameters of the regression equations and X is the EBW of the animals. The identity test of the models indicated no significant differences among genetic groups for the net energy and protein requirements for weight gain. It was observed a decrease of 10.6% and an increase of 37.8%, respectively, in the protein and energy requirements for body weight gain between 250 and 550 kg. These changes are result of the increase in the content of fat and reduction in that of protein as EBW increased. The net requirements of protein and energy for body weight gain were estimated as 143.5 g and 4.7 Mcal, respectively, for a body weight of 450 kg.

  2. Cartilage oligomeric matrix protein associates differentially with erosions and synovitis and has a different temporal course in cyclic citrullinated peptide antibody (anti-CCP)-positive versus anti-CCP-negative early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Christensen, Anne F; Lindegaard, Hanne; Hørslev-Petersen, Kim

    2011-01-01

    . We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings....

  3. Cartilage oligomeric matrix protein associates differentially with erosions and synovitis and has a different temporal course in cyclic citrullinated peptide antibody (anti-CCP)-positive versus anti-CCP-negative early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Christensen, Anne F; Lindegaard, Hanne; Hørslev-Petersen, Kim

    2011-01-01

    -suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings...

  4. Presence of inclusions positive for polyglycine containing protein, FMRpolyG, indicates that repeat-associated non-AUG translation plays a role in fragile X-associated primary ovarian insufficiency

    NARCIS (Netherlands)

    R.A.M. Buijsen (Ronald); J.A. Visser (Jenny); P. Kramer (Piet); E.A.W.F.M. Severijnen (Lies-Anne); M. Gearing (Marla); N. Charlet-Berguerand (Nicolas); S.L. Sherman (Stephanie L); R.F. Berman (Robert); R. Willemsen (Rob); R.K. Hukema (Renate)

    2016-01-01

    textabstractSTUDY QUESTION: Does repeat-associated non-AUG (RAN) translation play a role in fragile X-associated primary ovarian insufficiency (FXPOI), leading to the presence of polyglycine containing protein (FMRpolyG)-positive inclusions in ovarian tissue? SUMMARY ANSWER: Ovaries of a woman with

  5. COEXPRESSION OF FOS IMMUNOREACTIVITY IN PROTEIN-KINASE (PKC-GAMMA)-POSITIVE NEURONS - QUANTITATIVE-ANALYSIS OF A BRAIN REGION INVOLVED IN LEARNING

    NARCIS (Netherlands)

    AMBALAVANAR, R; VANDERZEE, EA; BOLHUIS, JJ; MCCABE, BJ; HORN, G

    1993-01-01

    The expression of the gamma protein kinase C isoenzyme (PKCgamma) and of the c-fos immediate early gene protein product Fos in the intermediate and medial hyperstriatum ventrale (IMHV) of day-old chicks was determined immunocytochemically. Previous research has shown that (a) there is a

  6. GsLRPK, a novel cold-activated leucine-rich repeat receptor-like protein kinase from Glycine soja, is a positive regulator to cold stress tolerance.

    Science.gov (United States)

    Yang, Liang; Wu, Kangcheng; Gao, Peng; Liu, Xiaojuan; Li, Guangpu; Wu, Zujian

    2014-02-01

    Plant LRR-RLKs serve as protein interaction platforms, and as regulatory modules of protein activation. Here, we report the isolation of a novel plant-specific LRR-RLK from Glycine soja (termed GsLRPK) by differential screening. GsLRPK expression was cold-inducible and shows Ser/Thr protein kinase activity. Subcellular localization studies using GFP fusion protein indicated that GsLRPK is localized in the plasma membrane. Real-time PCR analysis indicated that temperature, salt, drought, and ABA treatment can alter GsLRPK gene transcription in G. soja. However, just protein induced by cold stress not by salinity and ABA treatment in tobacco was found to possess kinase activity. Furthermore, we found that overexpression of GsLRPK in yeast and Arabidopsis can enhance resistance to cold stress and increase the expression of a number of cold responsive gene markers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. KONVERGENSI DALAM PROGRAM NET CITIZEN JOURNALISM

    Directory of Open Access Journals (Sweden)

    Rhafidilla Vebrynda

    2017-06-01

    Full Text Available Di dalam artikel ini, peneliti ingin melihat perkembangan teknologi di Indonesia sebagai sebuah peluang untuk menjalankan sebuah program berita berbasis video kiriman masyarakat. Perkembangan teknologi tersebut adalah teknologi penyiaran, teknologi sosial media dan teknologi dalam proses produksi sebuah video. Di Indonesia, jumlah televisi semakin banyak. Setiap stasiun televisi harus bersaing untuk dapat bertahan hidup. Net TV merupakan sebuah stasiun televisi baru di Indonesia yang harus memiliki berbagai program unggulan baru agar dapat bersaing dengan televisi lainnya yang sudah ada. Net TV menggunakan berbagai platform media untuk menjalankan program Net Citizen Journalism (Net CJ. Penggunaan berbagai platform media dikenal dengan istilah multiplatform dan secara teoritis dikenal dengan istilah konvergensi. Konvergensi yaitu saat meleburnya domain-domain dalam berbagai media komunikasi. Artikel ini menggunakan metode studi kasus untuk melihat bagaimana konvergensi terjadi dalam proses pengelolaan program Net CJ. Teknik pengumpulan data adalah dengan wawancara mendalam, observasi dan studi dokumen. Wawancara mendalam dilakukan dari tiga sudut pandang yaitu dari pengelola program, pengguna/audience dan pengamat media. Penelitian ini menemukan bahwa dengan menggunakan berbagai platform media yang fungsinya berbeda, memiliki satu tujuan yang sama yaitu untuk menjalankan program Net CJ. Adapun berbagai platform dalam proses produksi program yaitu tayangan TV konvensional, streaming TV, website, aplikasi Net CJ, facebook, twitter, instagram dan path. Konvergensi media dijalankan dalam dua proses, yaitu proses produksi dan proses promosi program berita.

  8. Net Neutrality: Media Discourses and Public Perception

    Directory of Open Access Journals (Sweden)

    Christine Quail

    2010-01-01

    Full Text Available This paper analyzes media and public discourses surrounding net neutrality, with particular attention to public utility philosophy, from a critical perspective. The article suggests that further public education about net neutrality would be beneficial. The first portion of this paper provides a survey of the existing literature surrounding net neutrality, highlighting the contentious debate between market-based and public interest perspectives. In order to contextualize the debate, an overview of public utility philosophy is provided, shedding light on how the Internet can be conceptualized as a public good. Following this discussion, an analysis of mainstream media is presented, exploring how the media represents the issue of net neutrality and whether or not the Internet is discussed through the lens of public utility. To further examine how the net neutrality debate is being addressed, and to see the potential impacts of media discourses on the general public, the results of a focus group are reported and analyzed. Finally, a discussion assesses the implications of the net neutrality debate as presented through media discourses, highlighting the future of net neutrality as an important policy issue.

  9. Cutaneous and mucosal human papillomaviruses differ in net surface charge, potential impact on tropism

    Directory of Open Access Journals (Sweden)

    Wibom Carl

    2008-10-01

    Full Text Available Abstract Papillomaviruses can roughly be divided into two tropism groups, those infecting the skin, including the genus beta PVs, and those infecting the mucosa, predominantly genus alpha PVs. The L1 capsid protein determines the phylogenetic separation between beta types and alpha types and the L1 protein is most probably responsible for the first interaction with the cell surface. Virus entry is a known determinant for tissue tropism and to study if interactions of the viral capsid with the cell surface could affect HPV tropism, the net surface charge of the HPV L1 capsid proteins was analyzed and HPV-16 (alpha and HPV-5 (beta with a mucosal and cutaneous tropism respectively were used to study heparin inhibition of uptake. The negatively charged L1 proteins were all found among HPVs with cutaneous tropism from the beta- and gamma-PV genus, while all alpha HPVs were positively charged at pH 7.4. The linear sequence of the HPV-5 L1 capsid protein had a predicted isoelectric point (pI of 6.59 and a charge of -2.74 at pH 7.4, while HPV-16 had a pI of 7.95 with a charge of +2.98, suggesting no interaction between HPV-5 and the highly negative charged heparin. Furthermore, 3D-modelling indicated that HPV-5 L1 exposed more negatively charged amino acids than HPV-16. Uptake of HPV-5 (beta and HPV-16 (alpha was studied in vitro by using a pseudovirus (PsV assay. Uptake of HPV-5 PsV was not inhibited by heparin in C33A cells and only minor inhibition was detected in HaCaT cells. HPV-16 PsV uptake was significantly more inhibited by heparin in both cells and completely blocked in C33A cells.

  10. Knowledge base verification based on enhanced colored petri net

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Hyun; Seong, Poong Hyun [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1997-12-31

    Verification is a process aimed at demonstrating whether a system meets it`s specified requirements. As expert systems are used in various applications, the knowledge base verification of systems takes an important position. The conventional Petri net approach that has been studied recently in order to verify the knowledge base is found that it is inadequate to verify the knowledge base of large and complex system, such as alarm processing system of nuclear power plant. Thus, we propose an improved method that models the knowledge base as enhanced colored Petri net. In this study, we analyze the reachability and the error characteristics of the knowledge base and apply the method to verification of simple knowledge base. 8 refs., 4 figs. (Author)

  11. Near-Net Shape Powder Metallurgy Rhenium Thruster

    Science.gov (United States)

    Leonhardt, Todd; Hamister, Mark; Carlen, Jan C.; Biaglow, James; Reed, Brian

    2001-01-01

    This paper describes the development of a method to produce a near-net shape (NNS) powder metallurgy (PM) rhenium combustion chamber of the size 445 N (100 lbf) used in a high performance liquid apogee engine. These engines are used in low earth Orbit and geostationary orbit for satellite positioning systems. The developments in near-net shape powder metallurgy rhenium combustion chambers reported in this paper will reduce manufacturing cost of the rhenium chambers by 25 percent, and reduce the manufacturing time by 30 to 40 percent. The quantity of rhenium metal powder used to produce a rhenium chamber is reduced by approximately 70 percent and the subsequent reduction in machining schedule and costs is nearly 50 percent.

  12. Approximation methods for stochastic petri nets

    Science.gov (United States)

    Jungnitz, Hauke Joerg

    1992-01-01

    Stochastic Marked Graphs are a concurrent decision free formalism provided with a powerful synchronization mechanism generalizing conventional Fork Join Queueing Networks. In some particular cases the analysis of the throughput can be done analytically. Otherwise the analysis suffers from the classical state explosion problem. Embedded in the divide and conquer paradigm, approximation techniques are introduced for the analysis of stochastic marked graphs and Macroplace/Macrotransition-nets (MPMT-nets), a new subclass introduced herein. MPMT-nets are a subclass of Petri nets that allow limited choice, concurrency and sharing of resources. The modeling power of MPMT is much larger than that of marked graphs, e.g., MPMT-nets can model manufacturing flow lines with unreliable machines and dataflow graphs where choice and synchronization occur. The basic idea leads to the notion of a cut to split the original net system into two subnets. The cuts lead to two aggregated net systems where one of the subnets is reduced to a single transition. A further reduction leads to a basic skeleton. The generalization of the idea leads to multiple cuts, where single cuts can be applied recursively leading to a hierarchical decomposition. Based on the decomposition, a response time approximation technique for the performance analysis is introduced. Also, delay equivalence, which has previously been introduced in the context of marked graphs by Woodside et al., Marie's method and flow equivalent aggregation are applied to the aggregated net systems. The experimental results show that response time approximation converges quickly and shows reasonable accuracy in most cases. The convergence of Marie's method and flow equivalent aggregation are applied to the aggregated net systems. The experimental results show that response time approximation converges quickly and shows reasonable accuracy in most cases. The convergence of Marie's is slower, but the accuracy is generally better. Delay

  13. Visual Studio 2010 and NET 4 Six-in-One

    CERN Document Server

    Novak, Istvan; Granicz, Adam

    2010-01-01

    Complete coverage of all key .NET 4 and Visual Studio 2010 languages and technologies. .NET 4 is Microsoft's latest version of their core programming platform, and Visual Studio 2010 is the toolset that helps write .NET 4 applications. This comprehensive resource offers one-stop shopping for all you need to know to get productive with .NET 4. Experienced author and .NET guru Mitchel Sellers reviews all the important new features of .NET 4, including .NET charting and ASP.NET charting, ASP.NET dynamic data and jQuery, and the addition of F# as a supported package language. The expansive coverag

  14. Diet-dependent net acid load and risk of incident hypertension in United States women.

    Science.gov (United States)

    Zhang, Luxia; Curhan, Gary C; Forman, John P

    2009-10-01

    Animal and human studies suggest a potential link between acid-base status and blood pressure. Contemporary Western diets yield a daily systemic acid load of varying amounts, yet the association with hypertension has never been explored. We prospectively examined the association between the diet-dependent net acid load (also known as the estimated net endogenous acid production) and the risk of incident hypertension among 87 293 women without a history of hypertension in the Nurses' Health Study II. We also used the ratio of animal protein intake to potassium intake as an alternative evaluation of diet-dependent net acid load. We identified 15 385 incident cases of hypertension during 995 239 person-years of follow-up. After adjusting for potential confounders, women in the top decile of estimated diet-dependent net acid load had an increased risk of hypertension (relative risk: 1.14; 95% CI: 1.05 to 1.24; P for trend=0.01) compared with women in the bottom decile. To test whether the association between estimated diet-dependent net acid load and hypertension is independent of its individual components, an additional adjustment for intakes of protein and potassium was made and resulted in a relative risk of 1.23 (95% CI: 1.08 to 1.41; P for trend=0.003) for the top decile of estimated diet-dependent net acid load. Results of the ratio of animal protein intake to potassium intake were similar with those of estimated diet-depend net acid load. In conclusion, a high diet-dependent net acid load is independently associated with a higher risk of incident hypertension.

  15. Expression of an endotoxin-free S-layer/allergen fusion protein in gram-positive Bacillus subtilis 1012 for the potential application as vaccines for immunotherapy of atopic allergy

    Directory of Open Access Journals (Sweden)

    Egelseer Eva

    2011-02-01

    Full Text Available Abstract Background Genetic fusion of the major birch pollen allergen (Bet v1 to bacterial surface-(S-layer proteins resulted in recombinant proteins exhibiting reduced allergenicity as well as immunomodulatory capacity. Thus, S-layer/allergen fusion proteins were considered as suitable carriers for new immunotherapeutical vaccines for treatment of Type I hypersensitivity. Up to now, endotoxin contamination of the fusion protein which occurred after isolation from the gram-negative expression host E. coli had to be removed by an expensive and time consuming procedure. In the present study, in order to achieve expression of pyrogen-free, recombinant S-layer/allergen fusion protein and to study the secretion of a protein capable to self-assemble, the S-layer/allergen fusion protein rSbpA/Bet v1 was produced in the gram-positive organism Bacillus subtilis 1012. Results The chimaeric gene encoding the S-layer protein SbpA of Lysinibacillus sphaericus CCM 2177 as well as Bet v1 was cloned and expressed in B. subtilis 1012. For that purpose, the E. coli-B. subtilis shuttle vectors pHT01 for expression in the B. subtilis cytoplasm and pHT43 for secretion of the recombinant fusion protein into the culture medium were used. As shown by western blot analysis, immediately after induction of expression, B. subtilis 1012 was able to secret rSbpA/Bet v1 mediated by the signal peptide amyQ of Bacillus amyloliquefaciens. Electron microscopical investigation of the culture medium revealed that the secreted fusion protein was able to form self-assembly products in suspension but did not recrystallize on the surface of the B. subtilis cells. The specific binding mechanism between the N-terminus of the S-layer protein and a secondary cell wall polymer (SCWP, located in the peptidoglycan-containing sacculi of Ly. sphaericus CCM 2177, could be used for isolation and purification of the secreted fusion protein from the culture medium. Immune reactivity of rSbpA/Bet v1

  16. Biological Evaluation of the Protein Quality Sponge Guord ( Luffa ...

    African Journals Online (AJOL)

    Clinical performance of the test animals was determined. The faecal and urinal Nitrogen content were recorded. The True Protein Digestibility (TD); Biological value (BV); Net Protein Utilization (NPU); Net Protein Retention (NPR); and Protein Efficiency Ratio (PER) were determined for the various diets used. Results: There ...

  17. Rendimento corporal e composição química de jundiás alimentados com diferentes níveis de proteína e energia na dieta, criados em tanques-rede Catfish (jundia body yield and chemical composition fed different protein and energy level in the diet, reared in net-tanks

    Directory of Open Access Journals (Sweden)

    Adilson Reidel

    2010-02-01

    Full Text Available Objetivou-se analisar o rendimento corporal e a composição química de jundiás, Rhamdia quelen, alimentados com rações contendo diferentes níveis de proteína e energia e criados em sistema de tanques-rede. Utilizou-se a densidade inicial de 70 peixes/m³, em 18 tanques-rede (5,0 m³, durante 324 dias. O delineamento experimental foi inteiramente casualizado com dois fatores - níveis de proteína bruta (PB, 25, 30 ou 35%; e níveis de energia digestível (ED: 3.250 e 3.500 kcal - e três repetições. A dieta foi fornecida à vontade, mas mensurada diariamente. No início, um lote de peixes foi sacrificado para determinação dos parâmetros corporais e químicos. A cada 28 dias, dois peixes de cada unidade experimental foram abatidos para determinação dos comprimentos total e padrão, do peso total e dos pesos de fígado, gônadas, cabeça, tronco limpo e gordura visceral, respectivamente. Posteriormente, foram realizados cálculos dos índices hepatossomático e gonadossomático, da porcentagem de cabeça e do rendimento de carcaça e do rendimento de tronco limpo. A partir do mês de junho de 2006, também foram registrados o rendimento de filé e o sexo dos indivíduos. Para determinação da composição da carne do jundiá, foram realizadas as análises químicas de umidade, proteína bruta, lipídios e matéria mineral. O fornecimento da ração com 30% de PB resultou em maior rendimento de tronco limpo. A composição do músculo não foi influenciada pelas dietas testadas. Os melhores resultados foram obtidos com a utilização de dietas contendo 30% de PB e 3.250 kcal de energia digestível/kg.The objective of this study was to analyze the body yield and the chemical composition of catfish (jundia, Rhamdia quelen, reared in net-tanks and fed with diets containing different levels of protein and energy. An initial density of 70 fish/m³, in 18 net-tanks (5.0 m³ was used, for 324 days. A randomized complete design was used

  18. Application and Theory of Petri Nets

    DEFF Research Database (Denmark)

    , the conferences have 150-200 participants, one third of these coming from industry and the rest from universities and research institutions. The 1992 conference was organized by the School of Computing and Management Sciences at Sheffield City Polytechnic, England. The volume contains twoinvited papers, by G......This volume contains the proceedings of the 13th International Conference onApplication and Theory of Petri Nets, held in Sheffield, England, in June 1992. The aim of the Petri net conferences is to create a forum for discussing progress in the application and theory of Petri nets. Typically...

  19. Performance Analysis using Coloured Petri Nets

    DEFF Research Database (Denmark)

    Wells, Lisa Marie

    an explicit separation between modelling the behaviour of a system and monitoring the behaviour of the model. As a result, cleaner and more understandable models can be created. The third paper presents a novel method for adding auxiliary information to coloured Petri net models. Coloured Petri nets models...... in a very limited and predictable manner, and it is easy to enable and disable the auxiliary information. The fourth paper is a case study in which the performance of a web server was analysed using coloured Petri nets. This case study has shown that it is relatively easy to analyse the performance...

  20. The KM3NeT project

    Energy Technology Data Exchange (ETDEWEB)

    Katz, U.F., E-mail: katz@physik.uni-erlangen.d [Erlangen Centre for Astroparticle Physics (ECAP), University of Erlangen-Nuernberg, Erwin-Rommel-Str. 1, 91058 Erlangen (Germany)

    2011-01-21

    The KM3NeT research infrastructure in the deep Mediterranean Sea will host a multi-cubic-kilometre neutrino telescope and provide connectivity for continuous, long-term measurements of earth and sea sciences, such as geology, marine biology and oceanography. The KM3NeT neutrino telescope will complement the IceCube telescope currently being installed at the South Pole in its field of view and surpass its sensitivity by a substantial factor. In this document the major aspects of the KM3NeT technical design are described and the expected physics sensitivity is discussed. Finally, the expected time line towards construction is presented.

  1. The net neutrality debate on Twitter

    Directory of Open Access Journals (Sweden)

    Wolf J. Schünemann

    2015-12-01

    Full Text Available The internet has been seen as a medium that empowers individual political actors in relation to established political elites and media gatekeepers. The present article discusses this “net empowerment hypothesis” and tests it empirically by analysing Twitter communication on the regulation of net neutrality. We extracted 503.839 tweets containing #NetNeutrality posted between January and March 2015 and analysed central developments and the network structure of the debate. The empirical results show that traditional actors from media and politics still maintain a central role.

  2. RAR1 positively controls steady state levels of barley MLA resistance proteins and enables sufficient MLA6 accumulation for effective resistance.

    Science.gov (United States)

    Bieri, Stéphane; Mauch, Stefan; Shen, Qian-Hua; Peart, Jack; Devoto, Alessandra; Casais, Catarina; Ceron, Francesca; Schulze, Sabine; Steinbiss, Hans-Henning; Shirasu, Ken; Schulze-Lefert, Paul

    2004-12-01

    The polymorphic barley (Hordeum vulgare) Mla locus harbors allelic race-specific resistance (R) genes to the powdery mildew fungus Blumeria graminis f sp hordei. The highly sequence-related MLA proteins contain an N-terminal coiled-coil structure, a central nucleotide binding (NB) site, a Leu-rich repeat (LRR) region, and a C-terminal non-LRR region. Using transgenic barley lines expressing epitope-tagged MLA1 and MLA6 derivatives driven by native regulatory sequences, we show a reversible and salt concentration-dependent distribution of the intracellular MLA proteins in soluble and membrane-associated pools. A posttranscriptional process directs fourfold greater accumulation of MLA1 over MLA6. Unexpectedly, in rar1 mutant plants that are compromised for MLA6 but not MLA1 resistance, the steady state level of both MLA isoforms is reduced. Furthermore, differential steady state levels of MLA1/MLA6 hybrid proteins correlate with their requirement for RAR1; the RAR1-independent hybrid protein accumulates to higher levels and the RAR1-dependent one to lower levels. Interestingly, yeast two-hybrid studies reveal that the LRR domains of RAR1-independent but not RAR1-dependent MLA isoforms interact with SGT1, a RAR1 interacting protein required for the function of many NB-LRR type R proteins. Our findings implicate the existence of a conserved mechanism to reach minimal NB-LRR R protein thresholds that are needed to trigger effective resistance responses.

  3. 'a'-Position-mutated and G4-mutated hemagglutinin-neuraminidase proteins of Newcastle disease virus impair fusion and hemagglutinin-neuraminidase-fusion interaction by different mechanisms.

    Science.gov (United States)

    Chu, Fu-lu; Wen, Hong-ling; Zhang, Wen-qiang; Lin, Bin; Zhang, Yan; Sun, Cheng-xi; Ren, Gui-jie; Song, Yan-yan; Wang, Zhiyu

    2013-01-01

    To determine the effects of heptad repeat regions (HRs) and N-linked carbohydrate sites of the Newcastle disease virus hemagglutinin-neuraminidase (HN) protein on fusion of HN and fusion (F) proteins and HN-F interaction. We mutated six 'a' residues in the HRs and four asparagines in N-linked carbohydrate sites to alanine in the HN protein. A vaccinia-T7 RNA polymerase expression system was used to express HN cDNAs in BHK-21 cells to determine the HN functions. Deglycosylation was treated with PGNase F digestion. The formation of HN-F protein complexes was determined by the coimmunoprecipitation assay. Each HR-mutated protein interfered with fusion and the HN-F interaction. The G4-mutated protein not only impaired fusion and HN-F interaction but also decreased activities in cell fusion promotion, hemadsorption and neuraminidase. It is assumed that two different mechanisms for mutations in these two regions are responsible for the decreased fusion promotion activity and the reduced ability of interaction with F protein. Mutations in the HRs impair fusion and HN-F interaction by altering the transmission of a signal from the globular domain to the F-specific region in the stalk, but the G4 mutation modulates fusion and HN-F interaction by the misfolding of some important structures. Copyright © 2012 S. Karger AG, Basel.

  4. Planning long lasting insecticide treated net campaigns: should households' existing nets be taken into account?

    Science.gov (United States)

    Yukich, Joshua; Bennett, Adam; Keating, Joseph; Yukich, Rudy K; Lynch, Matt; Eisele, Thomas P; Kolaczinski, Kate

    2013-06-14

    Mass distribution of long-lasting insecticide treated bed nets (LLINs) has led to large increases in LLIN coverage in many African countries. As LLIN ownership levels increase, planners of future mass distributions face the challenge of deciding whether to ignore the nets already owned by households or to take these into account and attempt to target individuals or households without nets. Taking existing nets into account would reduce commodity costs but require more sophisticated, and potentially more costly, distribution procedures. The decision may also have implications for the average age of nets in use and therefore on the maintenance of universal LLIN coverage over time. A stochastic simulation model based on the NetCALC algorithm was used to determine the scenarios under which it would be cost saving to take existing nets into account, and the potential effects of doing so on the age profile of LLINs owned. The model accounted for variability in timing of distributions, concomitant use of continuous distribution systems, population growth, sampling error in pre-campaign coverage surveys, variable net 'decay' parameters and other factors including the feasibility and accuracy of identifying existing nets in the field. Results indicate that (i) where pre-campaign coverage is around 40% (of households owning at least 1 LLIN), accounting for existing nets in the campaign will have little effect on the mean age of the net population and (ii) even at pre-campaign coverage levels above 40%, an approach that reduces LLIN distribution requirements by taking existing nets into account may have only a small chance of being cost-saving overall, depending largely on the feasibility of identifying nets in the field. Based on existing literature the epidemiological implications of such a strategy is likely to vary by transmission setting, and the risks of leaving older nets in the field when accounting for existing nets must be considered. Where pre-campaign coverage

  5. Planning long lasting insecticide treated net campaigns: should households’ existing nets be taken into account?

    Science.gov (United States)

    2013-01-01

    Background Mass distribution of long-lasting insecticide treated bed nets (LLINs) has led to large increases in LLIN coverage in many African countries. As LLIN ownership levels increase, planners of future mass distributions face the challenge of deciding whether to ignore the nets already owned by households or to take these into account and attempt to target individuals or households without nets. Taking existing nets into account would reduce commodity costs but require more sophisticated, and potentially more costly, distribution procedures. The decision may also have implications for the average age of nets in use and therefore on the maintenance of universal LLIN coverage over time. Methods A stochastic simulation model based on the NetCALC algorithm was used to determine the scenarios under which it would be cost saving to take existing nets into account, and the potential effects of doing so on the age profile of LLINs owned. The model accounted for variability in timing of distributions, concomitant use of continuous distribution systems, population growth, sampling error in pre-campaign coverage surveys, variable net ‘decay’ parameters and other factors including the feasibility and accuracy of identifying existing nets in the field. Results Results indicate that (i) where pre-campaign coverage is around 40% (of households owning at least 1 LLIN), accounting for existing nets in the campaign will have little effect on the mean age of the net population and (ii) even at pre-campaign coverage levels above 40%, an approach that reduces LLIN distribution requirements by taking existing nets into account may have only a small chance of being cost-saving overall, depending largely on the feasibility of identifying nets in the field. Based on existing literature the epidemiological implications of such a strategy is likely to vary by transmission setting, and the risks of leaving older nets in the field when accounting for existing nets must be considered

  6. MitProNet: A knowledgebase and analysis platform of proteome, interactome and diseases for mammalian mitochondria.

    Directory of Open Access Journals (Sweden)

    Jiabin Wang

    Full Text Available Mitochondrion plays a central role in diverse biological processes in most eukaryotes, and its dysfunctions are critically involved in a large number of diseases and the aging process. A systematic identification of mitochondrial proteomes and characterization of functional linkages among mitochondrial proteins are fundamental in understanding the mechanisms underlying biological functions and human diseases associated with mitochondria. Here we present a database MitProNet which provides a comprehensive knowledgebase for mitochondrial proteome, interactome and human diseases. First an inventory of mammalian mitochondrial proteins was compiled by widely collecting proteomic datasets, and the proteins were classified by machine learning to achieve a high-confidence list of mitochondrial proteins. The current version of MitProNet covers 1124 high-confidence proteins, and the remainders were further classified as middle- or low-confidence. An organelle-specific network of functional linkages among mitochondrial proteins was then generated by integrating genomic features encoded by a wide range of datasets including genomic context, gene expression profiles, protein-protein interactions, functional similarity and metabolic pathways. The functional-linkage network should be a valuable resource for the study of biological functions of mitochondrial proteins and human mitochondrial diseases. Furthermore, we utilized the network to predict candidate genes for mitochondrial diseases using prioritization algorithms. All proteins, functional linkages and disease candidate genes in MitProNet were annotated according to the information collected from their original sources including GO, GEO, OMIM, KEGG, MIPS, HPRD and so on. MitProNet features a user-friendly graphic visualization interface to present functional analysis of linkage networks. As an up-to-date database and analysis platform, MitProNet should be particularly helpful in comprehensive studies of

  7. ef1097 and ypkK encode enterococcin V583 and corynicin JK, members of a new family of antimicrobial proteins (bacteriocins) with modular structure from Gram-positive bacteria.

    Science.gov (United States)

    Swe, Pearl M; Heng, Nicholas C K; Ting, Yi-Tian; Baird, Hayley J; Carne, Alan; Tauch, Andreas; Tagg, John R; Jack, Ralph W

    2007-10-01

    Unlike the colicins, microcins and related peptide antibiotics, little is known about antibiotic proteins (M(r)>10,000) from Gram-positive bacteria, since only few examples have been described to date. In this study we used heterologous expression of recombinant proteins to access the 17 kDa antibiotic protein SA-M57 from Streptococcus pyogenes, along with two proteins of unknown function identified in publicly available databases: EF1097 from Enterococcus faecalis and YpkK from Corynebacterium jeikeium. Here we show that all three are antibiotic proteins with different spectra of antimicrobial activity that kill sensitive bacteria at nanomolar concentrations. In silico structure predictions indicate that although the three proteins share little sequence similarity, they may be composed of conserved secondary structural elements: a relatively unstructured, acidic N-terminal portion and a basic C-terminal portion characterized by two helical elements separated by a loop structure and stabilized by an essential disulphide. Expression of individual segments as well as protein chimaeras revealed that, at least in the case of YpkK, the C-terminal portion is responsible for the killing action of the protein, whereas the role of the N-terminal portion remains unclear. Both scnM57 and ef1097 appear to be widely distributed in Strep. pyogenes and Ent. faecalis (respectively), whereas ypkK is found only rarely amongst clinical isolates of C. jeikeium. Finally, we determined that the proteins kill sensitive bacteria without lysis, a feature that distinguishes them from known murolytic proteins.

  8. Positioning consumption

    DEFF Research Database (Denmark)

    Halkier, Bente; Keller, Margit

    2014-01-01

    positionings emerges based on empirical examples of research in parent–children consumption. Positionings are flexible discursive fixations of the relationship between the performances of the practitioner, other practitioners, media discourse and consumption activities. The basic positioning types...

  9. RadNet Air Quality (Deployable) Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — RadNet Deployable Monitoring is designed to collect radiological and meteorological information and data asset needed to establish the impact of radiation levels on...

  10. A Lightweight TwiddleNet Portal

    National Research Council Canada - National Science Library

    Rimikis, Antonios M

    2008-01-01

    TwiddleNet is a distributed architecture of personal servers that harnesses the power of the mobile devices, enabling real time information and file sharing of multiple data types from commercial-off-the-shelf platforms...

  11. Homology Groups of a Pipeline Petri Net

    Directory of Open Access Journals (Sweden)

    A. A. Husainov

    2013-01-01

    Full Text Available Petri net is said to be elementary if every place can contain no more than one token. In this paper, it is studied topological properties of the elementary Petri net for a pipeline consisting of n functional devices. If the work of the functional devices is considered continuous, we can come to some topological space of “intermediate” states. In the paper, it is calculated the homology groups of this topological space. By induction on n, using the Addition Sequence for homology groups of semicubical sets, it is proved that in dimension 0 and 1 the integer homology groups of these nets are equal to the group of integers, and in the remaining dimensions are zero. Directed homology groups are studied. A connection of these groups with deadlocks and newsletters is found. This helps to prove that all directed homology groups of the pipeline elementary Petri nets are zeroth.

  12. Casein protein results in higher prandial and exercise induced whole body protein anabolism than whey protein in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Engelen, Mariëlle P K J; Rutten, Erica P A; De Castro, Carmen L N; Wouters, Emiel F M; Schols, Annemie M W J; Deutz, Nicolaas E P

    2012-09-01

    Exercise is known to improve physical functioning and health status in Chronic Obstructive Pulmonary Disease (COPD). Recently, disturbances in protein turnover and amino acid kinetics have been observed after exercise in COPD. The objective was to investigate which dairy protein is able to positively influence the protein metabolic response to exercise in COPD. 8 COPD patients and 8 healthy subjects performed a cycle test on two days while ingesting casein or whey protein. Whole body protein breakdown (WbPB), synthesis (WbPS), splanchnic amino acid extraction (SPE), and NetWbPS (=WbPS-WbPB) were measured using stable isotope methodology during 20 min of exercise (at 50% peak work load of COPD group). The controls performed a second exercise test at the same relative workload. Exercise was followed by 1 h of recovery. In the healthy group, WbPS, SPE, and NetPS were higher during casein than during whey feeding (Panabolism than whey protein which was maintained during and following exercise in COPD. Optimizing protein intake might be of importance for muscle maintenance during daily physical activities in COPD. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Net accumulation of the Greenland ice sheet

    DEFF Research Database (Denmark)

    Kiilsholm, Sissi; Christensen, Jens Hesselbjerg; Dethloff, Klaus

    2003-01-01

    improvement compared to the driving OAGCM. Estimates of the regional net balance are also better represented by the RCM. In the future climate the net balance for the Greenland Ice Sheet is reduced in all the simulation, but discrepancies between the amounts when based on ECHAM4/OPYC3 and HIRHAM are found....... In both scenarios, the estimated melt rates are larger in HIRHAM than in the driving model....

  14. CDMA and TDMA based neural nets.

    Science.gov (United States)

    Herrero, J C

    2001-06-01

    CDMA and TDMA telecommunication techniques were established long time ago, but they have acquired a renewed presence due to the rapidly increasing mobile phones demand. In this paper, we are going to see they are suitable for neural nets, if we leave the concept "connection" between processing units and we adopt the concept "messages" exchanged between them. This may open the door to neural nets with a higher number of processing units and flexible configuration.

  15. Mastering AngularJD for .NET developers

    CERN Document Server

    Majid, Mohammad Wadood

    2015-01-01

    This book is envisioned for traditional developers and programmers who want to develop client-side applications using the AngularJS framework and ASP.NET Web API 2 with Visual Studio. .NET developers who have already built web applications or web services and who have a fundamental knowledge of HTML, JavaScript, and CSS and want to explore single-page applications will also find this guide useful. Basic knowledge of AngularJS would be helpful.

  16. .NET 4.5 parallel extensions

    CERN Document Server

    Freeman, Bryan

    2013-01-01

    This book contains practical recipes on everything you will need to create task-based parallel programs using C#, .NET 4.5, and Visual Studio. The book is packed with illustrated code examples to create scalable programs.This book is intended to help experienced C# developers write applications that leverage the power of modern multicore processors. It provides the necessary knowledge for an experienced C# developer to work with .NET parallelism APIs. Previous experience of writing multithreaded applications is not necessary.

  17. A Lightweight TwiddleNet Portal

    Science.gov (United States)

    2008-03-01

    designed to exploit the multiple networking modalities available in the current generation of smartphones . TwiddleNet enables well-organized and well...of Sonopia and will have a comprehensive review of the service in the coming weeks [12]. Twango, which was acquired by Nokia in July 2007, is an...EXPERIMENTATION As already mentioned the main purpose of this thesis is the development of a TwiddleNet portal running on a smartphone or a PDA, which can allow

  18. CCS - and its relationship to net theory

    DEFF Research Database (Denmark)

    Nielsen, Mogens

    1987-01-01

    In this paper we give a short introduction to Milner's Calculus for Communicating Systems - a paradigm for concurrent computation. We put special emphasis on the basic concepts and tools from the underlying "algebraic approach", and their relationship to the approach to concurrency within net...... theory. Furthermore, we provide an operational version of the language CCS with "true concurrency" in the sense of net theory, and a discussion of the possible use of such a marriage of the two theories of concurrency....

  19. Visual Studio 2013 and .NET 4.5 expert cookbook

    CERN Document Server

    Sur, Abhishek

    2014-01-01

    If you are a Visual Studio 2013 or .NET developer who would like to sharpen your existing skill set and adapt to new .NET technologies, this is the book for you. A basic understanding of .NET and C# is required.

  20. HANPP Collection: Global Patterns in Net Primary Productivity (NPP)

    Data.gov (United States)

    National Aeronautics and Space Administration — The Global Patterns in Net Primary Productivity (NPP) portion of the Human Appropriation of Net Primary Productivity (HANPP) Collection maps the net amount of solar...

  1. Obg-like ATPase 1 regulates global protein serine/threonine phosphorylation in cancer cells by suppressing the GSK3β-inhibitor 2-PP1 positive feedback loop.

    Science.gov (United States)

    Xu, Dong; Song, Renduo; Wang, Guohui; Jeyabal, Prince V S; Weiskoff, Amanda M; Ding, Kefeng; Shi, Zheng-Zheng

    2016-01-19

    OLA1 is an Obg family P-loop NTPase that possesses both GTP- and ATP-hydrolyzing activities. Here we report that OLA1 is a GSK3β interacting protein, and through its ATPase activity, inhibits the GSK3β-mediated activation of protein serine/threonine phosphatase 1 (PP1). It is hypothesized that GSK3β phosphorylates inhibitor 2 (I-2) of PP1 at Thr-72 and activates the PP1 · I-2 complex, which in turn dephosphorylates and stimulates GSK3β, thus forming a positive feedback loop. We revealed that the positive feedback loop is normally suppressed by OLA1, and becomes over-activated under OLA1 deficiency, resulting in increased cellular PP1 activity and dephosphorylation of multiple Ser/Thr phosphoproteins, and more strikingly, decreased global protein threonine phosphorylation. Furthermore, using xenograft models of colon cancer (H116) and ovarian cancer (SKOV3), we established a correlation among downregulation of OLA1, over-activation of the positive feedback loop as indicated by under-phosphorylation of I-2, and more aggressive tumor growth. This study provides the first evidence for the existence of a GSK3β-I-2-PP1 positive feedback loop in human cancer cells, and identifies OLA1 as an endogenous suppressor of this signaling motif.

  2. ASP.NET web API build RESTful web applications and services on the .NET framework

    CERN Document Server

    Kanjilal, Joydip

    2013-01-01

    This book is a step-by-step, practical tutorial with a simple approach to help you build RESTful web applications and services on the .NET framework quickly and efficiently.This book is for ASP.NET web developers who want to explore REST-based services with C# 5. This book contains many real-world code examples with explanations whenever necessary. Some experience with C# and ASP.NET 4 is expected.

  3. Net carbon flux in organic and conventional olive production systems

    Science.gov (United States)

    Saeid Mohamad, Ramez; Verrastro, Vincenzo; Bitar, Lina Al; Roma, Rocco; Moretti, Michele; Chami, Ziad Al

    2014-05-01

    Agricultural systems are considered as one of the most relevant sources of atmospheric carbon. However, agriculture has the potentiality to mitigate carbon dioxide mainly through soil carbon sequestration. Some agricultural practices, particularly fertilization and soil management, can play a dual role in the agricultural systems regarding the carbon cycle contributing to the emissions and to the sequestration process in the soil. Good soil and input managements affect positively Soil Organic Carbon (SOC) changes and consequently the carbon cycle. The present study aimed at comparing the carbon footprint of organic and conventional olive systems and to link it to the efficiency of both systems on carbon sequestration by calculating the net carbon flux. Data were collected at farm level through a specific and detailed questionnaire based on one hectare as a functional unit and a system boundary limited to olive production. Using LCA databases particularly ecoinvent one, IPCC GWP 100a impact assessment method was used to calculate carbon emissions from agricultural practices of both systems. Soil organic carbon has been measured, at 0-30 cm depth, based on soil analyses done at the IAMB laboratory and based on reference value of SOC, the annual change of SOC has been calculated. Substracting sequestrated carbon in the soil from the emitted on resulted in net carbon flux calculation. Results showed higher environmental impact of the organic system on Global Warming Potential (1.07 t CO2 eq. yr-1) comparing to 0.76 t CO2 eq. yr-1 in the conventional system due to the higher GHG emissions caused by manure fertilizers compared to the use of synthetic foliar fertilizers in the conventional system. However, manure was the main reason behind the higher SOC content and sequestration in the organic system. As a resultant, the organic system showed higher net carbon flux (-1.7 t C ha-1 yr-1 than -0.52 t C ha-1 yr-1 in the conventional system reflecting higher efficiency as a

  4. Freeze-out conditions from net-proton and net-charge fluctuations at RHIC

    Energy Technology Data Exchange (ETDEWEB)

    Alba, Paolo; Alberico, Wanda [Department of Physics, Torino University and INFN, Sezione di Torino, via P. Giuria 1, 10125 Torino (Italy); Bellwied, Rene [Department of Physics, University of Houston, Houston, TX 77204 (United States); Bluhm, Marcus [Department of Physics, Torino University and INFN, Sezione di Torino, via P. Giuria 1, 10125 Torino (Italy); Department of Physics, North Carolina State University, Raleigh, NC 27695 (United States); Mantovani Sarti, Valentina [Department of Physics, Torino University and INFN, Sezione di Torino, via P. Giuria 1, 10125 Torino (Italy); Nahrgang, Marlene [Department of Physics, Duke University, Durham, NC 27708-0305 (United States); Frankfurt Institute for Advanced Studies (FIAS), Ruth-Moufang-Str. 1, 60438 Frankfurt am Main (Germany); Ratti, Claudia [Department of Physics, Torino University and INFN, Sezione di Torino, via P. Giuria 1, 10125 Torino (Italy)

    2014-11-10

    We calculate ratios of higher-order susceptibilities quantifying fluctuations in the number of net-protons and in the net-electric charge using the Hadron Resonance Gas (HRG) model. We take into account the effect of resonance decays, the kinematic acceptance cuts in rapidity, pseudo-rapidity and transverse momentum used in the experimental analysis, as well as a randomization of the isospin of nucleons in the hadronic phase. By comparing these results to the latest experimental data from the STAR Collaboration, we determine the freeze-out conditions from net-electric charge and net-proton distributions and discuss their consistency.

  5. pH-Sensitive Coiled-Coil Peptide-Cross-Linked Hyaluronic Acid Nanogels: Synthesis and Targeted Intracellular Protein Delivery to CD44 Positive Cancer Cells.

    Science.gov (United States)

    Ding, Lingling; Jiang, Yu; Zhang, Jian; Klok, Harm-Anton; Zhong, Zhiyuan

    2018-02-12

    The clinical translation of protein drugs that act intracellularly is limited by the absence of safe and efficient intracellular protein delivery vehicles. Here, pH-sensitive coiled-coil peptide-cross-linked hyaluronic acid nanogels (HA-cNGs) were designed and investigated for targeted intracellular protein delivery to CD44 overexpressing MCF-7 breast cancer cells. HA-cNGs were obtained with a small size of 176 nm from an equivalent mixture of hyaluronic acid conjugates with GY(EIAALEK) 3 GC (E3) and GY(KIAALKE) 3 GC (K3) peptides, respectively, at pH 7.4 by nanoprecipitation. Circular dichroism (CD) proved the formation of coiled-coil structures between E3 and K3 peptides at pH 7.4 while fast uncoiling at pH 5.0. HA-cNGs showed facile loading of cytochrome C (CC) and greatly accelerated CC release under mild acidic conditions (18.4%, 76.8%, and 91.4% protein release in 24 h at pH 7.4, 6.0, and 5.0, respectively). Confocal microscopy and flow cytometry displayed efficient internalization of CC-loaded HA-cNGs and effective endosomal escape of CC in MCF-7 cancer cells. Remarkably, HA-cNGs loaded with saporin, a ribosome inactivating protein, exhibited significantly enhanced apoptotic activity to MCF-7 cells with a low IC 50 of 12.2 nM. These coiled-coil peptide-cross-linked hyaluronic acid nanogels have appeared as a simple and multifunctional platform for efficient intracellular protein delivery.

  6. PlanNET: Homology-based predicted interactome for multiple planarian transcriptomes.

    Science.gov (United States)

    Castillo-Lara, S; Abril, J F

    2017-11-24

    Planarians are emerging as a model organism to study regeneration in animals. However, the little available data of protein-protein interactions hinders the advances in understanding the mechanisms underlying its regenerating capabilities. We have developed a protocol to predict protein-protein interactions using sequence homology data and a reference Human interactome. This methodology was applied on eleven Schmidtea mediterranea transcriptomic sequence datasets. Then, using Neo4j as our database manager, we developed PlanNET, a web application to explore the multiplicity of networks and the associated sequence annotations. By mapping RNA-seq expression experiments onto the predicted networks, and allowing a transcript-centric exploration of the planarian interactome, we provide researchers with a useful tool to analyse possible pathways and to design new experiments, as well as a reproducible methodology to predict, store, and explore protein interaction networks for non-model organisms. The web application PlanNET is available at https://compgen.bio.ub.edu/PlanNET. The source code used is available at https://compgen.bio.ub.edu/PlanNET/downloads. jabril@ub.edu. Supplementary data are available at Bioinformatics online.

  7. Modest net autotrophy in the oligotrophic ocean

    Science.gov (United States)

    Letscher, Robert T.; Moore, J. Keith

    2017-04-01

    The metabolic state of the oligotrophic subtropical ocean has long been debated. Net community production (NCP) represents the balance of autotrophic carbon fixation with heterotrophic respiration. Many in vitro NCP estimates based on oxygen incubation methods and the corresponding scaling relationships used to predict the ecosystem metabolic balance have suggested the ocean gyres to be net heterotrophic; however, all in situ NCP methods find net autotrophy. Reconciling net heterotrophy requires significant allochthonous inputs of organic carbon to the oligotrophic gyres to sustain a preponderance of respiration over in situ production. Here we use the first global ecosystem-ocean circulation model that contains representation of the three allochthonous carbon sources to the open ocean, to show that the five oligotrophic gyres exhibit modest net autotrophy throughout the seasonal cycle. Annually integrated rates of NCP vary in the range 1.5-2.2 mol O2 m-2 yr-1 across the five gyre systems; however, seasonal NCP rates are as low as 1 ± 0.5 mmol O2 m-2 d-1 for the North Atlantic. Volumetric NCP rates are heterotrophic below the 10% light level; however, they become net autotrophic when integrated over the euphotic zone. Observational uncertainties when measuring these modest autotrophic NCP rates as well as the metabolic diversity encountered across space and time complicate the scaling up of in vitro measurements to the ecosystem scale and may partially explain the previous reports of net heterotrophy. The oligotrophic ocean is autotrophic at present; however, it could shift toward seasonal heterotrophy in the future as rising temperatures stimulate respiration.

  8. Migration and risk: net migration in marginal ecosystems and hazardous areas

    Science.gov (United States)

    de Sherbinin, Alex; Levy, Marc; Adamo, Susana; MacManus, Kytt; Yetman, Greg; Mara, Valentina; Razafindrazay, Liana; Goodrich, Benjamin; Srebotnjak, Tanja; Aichele, Cody; Pistolesi, Linda

    2012-12-01

    The potential for altered ecosystems and extreme weather events in the context of climate change has raised questions concerning the role that migration plays in either increasing or reducing risks to society. Using modeled data on net migration over three decades from 1970 to 2000, we identify sensitive ecosystems and regions at high risk of climate hazards that have seen high levels of net in-migration and out-migration over the time period. This paper provides a literature review on migration related to ecosystems, briefly describes the methodology used to develop the estimates of net migration, then uses those data to describe the patterns of net migration for various ecosystems and high risk regions. The study finds that negative net migration generally occurs over large areas, reflecting its largely rural character, whereas areas of positive net migration are typically smaller, reflecting its largely urban character. The countries with largest population such as China and India tend to drive global results for all the ecosystems found in those countries. Results suggest that from 1970 to 2000, migrants in developing countries have tended to move out of marginal dryland and mountain ecosystems and out of drought-prone areas, and have moved towards coastal ecosystems and areas that are prone to floods and cyclones. For North America results are reversed for dryland and mountain ecosystems, which saw large net influxes of population in the period of record. Uncertainties and potential sources of error in these estimates are addressed.

  9. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, MFD; Duk, JM; Burger, MPM; de Bruijn, HWA; Stolz, E; Herbrink, P

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  10. Paraoxonase-1 activity is positively related to phospholipid transfer protein activity in type 2 diabetes mellitus: Role of large HDL particles

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Gruppen, Eke G.; Dallinga-Thie, Geesje M.

    2016-01-01

    High density lipoprotein (HDL)-associated paraoxonase-1 (PON-1) exerts anti-oxidative properties, whereas phospholipid transfer protein (PLTP) is able to convert mature HDL into larger and smaller HDL particles. Here we tested associations of PON-1 with PLTP in type 2 diabetes mellitus (T2DM), a

  11. Paraoxonase-1 activity is positively related to phospholipid transfer protein activity in type 2 diabetes mellitus : Role of large HDL particles

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Gruppen, Eke G.; Dallinga-Thie, Geesje M.

    Objectives: High density lipoprotein (HDL)-associated paraoxonase-1 (PON-1) exerts anti -oxidative properties, whereas phospholipid transfer protein (PLTP) is able to convert mature HDL into larger and smaller HDL particles. Here we tested associations of PON-1 with PLTP in type 2 diabetes mellitus

  12. An aptly positioned azido group in the spacer of a protein cross-linker for facile mapping of lysines in close proximity

    NARCIS (Netherlands)

    Kasper, P.T.; Back, J.W.; Vitale, M.R.; Hartog, A.F.; Roseboom, W.; de Koning, L.J.; van Maarseveen, J.H.; Muijsers, A.O.; de Koster, C.G.; de Jong, L.

    2007-01-01

    Cross-links between amino acid residues in close proximity can provide distance constraints for the validation of models of the 3D structure proteins. The mapping of cross-links by the identification of linked peptides in proteolytic digests is facilitated by cleavable cross-linkers that enable

  13. SOCIAL NET: A CASE STUDY OF THE UNIVERSITY NET OF POPULAR COOPERATIVES TECHNOLOGICAL INCUBATORS (PCTIS NET FROM THE INTERACTION AMONG THE INCUBATORS

    Directory of Open Access Journals (Sweden)

    Marília Matos Pereira Lopes

    2014-07-01

    Full Text Available The objective of this assignment was to identify if the University Net of Popular Cooperatives Technological Incubators (PCTIs Net is a social net. The research was an exploratory nature study with descriptive character, the technical procedure of the present research was the case study. The questionnaire was applied in 82% of the incubators belonging to the PCTIs Net, and interviews. The information acquired through the questionnaire was gathered and tabulated to compose the characterization of the net incubators and the social analyzer. With the Pajek program was created the social analyzer and the centralizing box. Was performed to compare the results with previous work Rennó et al. (2010 proposed that the same goal using a different approach. Ending the analysis guided by the characteristics of a social net, it was observed that the PCTIs Net is a social net, however it was emphasized that the existing communication is a point where the net needs to be fortified.

  14. The net charge at interfaces between insulators

    Science.gov (United States)

    Bristowe, N. C.; Littlewood, P. B.; Artacho, Emilio

    2011-03-01

    The issue of the net charge at insulating oxide interfaces is briefly reviewed with the ambition of dispelling myths of such charges being affected by covalency and related charge density effects. For electrostatic analysis purposes, the net charge at such interfaces is defined by the counting of discrete electrons and core ion charges, and by the definition of the reference polarization of the separate, unperturbed bulk materials. The arguments are illustrated for the case of a thin film of LaAlO3 over SrTiO3 in the absence of free carriers, for which the net charge is exactly 0.5e per interface formula unit, if the polarization response in both materials is referred to zero bulk values. Further consequences of the argument are extracted for structural and chemical alterations of such interfaces, in which internal rearrangements are distinguished from extrinsic alterations (changes of stoichiometry, redox processes), only the latter affecting the interfacial net charge. The arguments are reviewed alongside the proposal of Stengel and Vanderbilt (2009 Phys. Rev. B 80 241103) of using formal polarization values instead of net interfacial charges, based on the interface theorem of Vanderbilt and King-Smith (1993 Phys. Rev. B 48 4442-55). Implications for non-centrosymmetric materials are discussed, as well as for interfaces for which the charge mismatch is an integer number of polarization quanta.

  15. Automating Ontological Annotation with WordNet

    Energy Technology Data Exchange (ETDEWEB)

    Sanfilippo, Antonio P.; Tratz, Stephen C.; Gregory, Michelle L.; Chappell, Alan R.; Whitney, Paul D.; Posse, Christian; Paulson, Patrick R.; Baddeley, Bob L.; Hohimer, Ryan E.; White, Amanda M.

    2006-01-22

    Semantic Web applications require robust and accurate annotation tools that are capable of automating the assignment of ontological classes to words in naturally occurring text (ontological annotation). Most current ontologies do not include rich lexical databases and are therefore not easily integrated with word sense disambiguation algorithms that are needed to automate ontological annotation. WordNet provides a potentially ideal solution to this problem as it offers a highly structured lexical conceptual representation that has been extensively used to develop word sense disambiguation algorithms. However, WordNet has not been designed as an ontology, and while it can be easily turned into one, the result of doing this would present users with serious practical limitations due to the great number of concepts (synonym sets) it contains. Moreover, mapping WordNet to an existing ontology may be difficult and requires substantial labor. We propose to overcome these limitations by developing an analytical platform that (1) provides a WordNet-based ontology offering a manageable and yet comprehensive set of concept classes, (2) leverages the lexical richness of WordNet to give an extensive characterization of concept class in terms of lexical instances, and (3) integrates a class recognition algorithm that automates the assignment of concept classes to words in naturally occurring text. The ensuing framework makes available an ontological annotation platform that can be effectively integrated with intelligence analysis systems to facilitate evidence marshaling and sustain the creation and validation of inference models.

  16. Ontological Annotation with WordNet

    Energy Technology Data Exchange (ETDEWEB)

    Sanfilippo, Antonio P.; Tratz, Stephen C.; Gregory, Michelle L.; Chappell, Alan R.; Whitney, Paul D.; Posse, Christian; Paulson, Patrick R.; Baddeley, Bob; Hohimer, Ryan E.; White, Amanda M.

    2006-06-06

    Semantic Web applications require robust and accurate annotation tools that are capable of automating the assignment of ontological classes to words in naturally occurring text (ontological annotation). Most current ontologies do not include rich lexical databases and are therefore not easily integrated with word sense disambiguation algorithms that are needed to automate ontological annotation. WordNet provides a potentially ideal solution to this problem as it offers a highly structured lexical conceptual representation that has been extensively used to develop word sense disambiguation algorithms. However, WordNet has not been designed as an ontology, and while it can be easily turned into one, the result of doing this would present users with serious practical limitations due to the great number of concepts (synonym sets) it contains. Moreover, mapping WordNet to an existing ontology may be difficult and requires substantial labor. We propose to overcome these limitations by developing an analytical platform that (1) provides a WordNet-based ontology offering a manageable and yet comprehensive set of concept classes, (2) leverages the lexical richness of WordNet to give an extensive characterization of concept class in terms of lexical instances, and (3) integrates a class recognition algorithm that automates the assignment of concept classes to words in naturally occurring text. The ensuing framework makes available an ontological annotation platform that can be effectively integrated with intelligence analysis systems to facilitate evidence marshaling and sustain the creation and validation of inference models.

  17. Development of net cage acoustic alarm system

    Science.gov (United States)

    Hong, Shih-Wei; Wei, Ruey-Chang

    2004-05-01

    In recent years, the fishery production has been drastically decreased in Taiwan, mainly due to overfishing and coast pollution; therefore, fishermen and corporations are encouraged by government to invest in ocean net cage aquaculture. However, the high-price fishes in the net cage are often coveted, so incidences of fish stealing and net cage breaking were found occasionally, which cause great economical loss. Security guards or a visual monitoring system has limited effect, especially in the night when these intrusions occur. This study is based on acoustic measure to build a net cage alarm system, which includes the sonobuoy and monitor station on land. The sonobuoy is a passive sonar that collects the sounds near the net cage and transmits the suspected signal to the monitor station. The signals are analyzed by the control program on the personal computer in the monitor station, and the alarms at different stages could be activated by the sound levels and durations of the analyzed data. To insure long hours of surveillance, a solar panel is applied to charge the battery, and a photodetector is used to activate the system.

  18. The NeuroDevNet vision.

    Science.gov (United States)

    Goldowitz, Dan; McArthur, Dawn

    2011-03-01

    The NeuroDevNet Network of Centres of Excellence has created the first trans-Canada effort devoted to the study of brain development from basic to clinical to societal perspectives. NeuroDevNet's vision is to accelerate efforts to (i) understand normal brain development; (ii) enhance our ability to make diagnoses of when normal development goes awry; and (iii) develop interventions to improve or prevent neurodevelopmental disorders. An early diagnosis coupled with the right therapies, The NeuroDevNet Network of Centres of Excellence has created the first trans-Canada effort devoted to the study of brain development from basic to clinical to societal perspectives. NeuroDevNet's vision is to accelerate efforts to (i) understand normal brain development; (ii) enhance our ability to make diagnoses of when normal development goes awry; and (iii) develop interventions to improve or prevent neurodevelopmental disorders. An early diagnosis coupled with the right therapies, Demonstration Projects. Funds were also allocated for an Opportunities Initiative. There is a wide of expertise amongst NeuroDevNet members. Researchers are supported by the management centre, three Platforms (Imaging; Genetics/ Epigenetics; Animal Models) and three Cores (Neuroethics; Neuroinformatics; Knowledge Translation). We emphasize multidisciplinary training of young researchers to advance the understanding of brain disorders that affect children. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. The net charge at interfaces between insulators

    Energy Technology Data Exchange (ETDEWEB)

    Bristowe, N C; Littlewood, P B [Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, J J Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Artacho, Emilio, E-mail: ncb30@cam.ac.uk [Department of Earth Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EQ (United Kingdom)

    2011-03-02

    The issue of the net charge at insulating oxide interfaces is briefly reviewed with the ambition of dispelling myths of such charges being affected by covalency and related charge density effects. For electrostatic analysis purposes, the net charge at such interfaces is defined by the counting of discrete electrons and core ion charges, and by the definition of the reference polarization of the separate, unperturbed bulk materials. The arguments are illustrated for the case of a thin film of LaAlO{sub 3} over SrTiO{sub 3} in the absence of free carriers, for which the net charge is exactly 0.5e per interface formula unit, if the polarization response in both materials is referred to zero bulk values. Further consequences of the argument are extracted for structural and chemical alterations of such interfaces, in which internal rearrangements are distinguished from extrinsic alterations (changes of stoichiometry, redox processes), only the latter affecting the interfacial net charge. The arguments are reviewed alongside the proposal of Stengel and Vanderbilt (2009 Phys. Rev. B 80 241103) of using formal polarization values instead of net interfacial charges, based on the interface theorem of Vanderbilt and King-Smith (1993 Phys. Rev. B 48 4442-55). Implications for non-centrosymmetric materials are discussed, as well as for interfaces for which the charge mismatch is an integer number of polarization quanta. (viewpoint)

  20. POTION: an end-to-end pipeline for positive Darwinian selection detection in genome-scale data through phylogenetic comparison of protein-coding genes.

    Science.gov (United States)

    Hongo, Jorge A; de Castro, Giovanni M; Cintra, Leandro C; Zerlotini, Adhemar; Lobo, Francisco P

    2015-08-01

    Detection of genes evolving under positive Darwinian evolution in genome-scale data is nowadays a prevailing strategy in comparative genomics studies to identify genes potentially involved in adaptation processes. Despite the large number of studies aiming to detect and contextualize such gene sets, there is virtually no software available to perform this task in a general, automatic, large-scale and reliable manner. This certainly occurs due to the computational challenges involved in this task, such as the appropriate modeling of data under analysis, the computation time to perform several of the required steps when dealing with genome-scale data and the highly error-prone nature of the sequence and alignment data structures needed for genome-wide positive selection detection. We present POTION, an open source, modular and end-to-end software for genome-scale detection of positive Darwinian selection in groups of homologous coding sequences. Our software represents a key step towards genome-scale, automated detection of positive selection, from predicted coding sequences and their homology relationships to high-quality groups of positively selected genes. POTION reduces false positives through several sophisticated sequence and group filters based on numeric, phylogenetic, quality and conservation criteria to remove spurious data and through multiple hypothesis corrections, and considerably reduces computation time thanks to a parallelized design. Our software achieved a high classification performance when used to evaluate a curated dataset of Trypanosoma brucei paralogs previously surveyed for positive selection. When used to analyze predicted groups of homologous genes of 19 strains of Mycobacterium tuberculosis as a case study we demonstrated the filters implemented in POTION to remove sources of errors that commonly inflate errors in positive selection detection. A thorough literature review found no other software similar to POTION in terms of customization

  1. xiNET: Cross-link Network Maps With Residue Resolution*

    Science.gov (United States)

    Combe, Colin W.; Fischer, Lutz; Rappsilber, Juri

    2015-01-01

    xiNET is a visualization tool for exploring cross-linking/mass spectrometry results. The interactive maps of the cross-link network that it generates are a type of node-link diagram. In these maps xiNET displays: (1) residue resolution positional information including linkage sites and linked peptides; (2) all types of cross-linking reaction product; (3) ambiguous results; and, (4) additional sequence information such as domains. xiNET runs in a browser and exports vector graphics which can be edited in common drawing packages to create publication quality figures. Availability: xiNET is open source, released under the Apache version 2 license. Results can be viewed by uploading data to http://crosslinkviewer.org/ or by downloading the software from http://github.com/colin-combe/crosslink-viewer and running it locally. PMID:25648531

  2. xiNET: cross-link network maps with residue resolution.

    Science.gov (United States)

    Combe, Colin W; Fischer, Lutz; Rappsilber, Juri

    2015-04-01

    xiNET is a visualization tool for exploring cross-linking/mass spectrometry results. The interactive maps of the cross-link network that it generates are a type of node-link diagram. In these maps xiNET displays: (1) residue resolution positional information including linkage sites and linked peptides; (2) all types of cross-linking reaction product; (3) ambiguous results; and, (4) additional sequence information such as domains. xiNET runs in a browser and exports vector graphics which can be edited in common drawing packages to create publication quality figures. xiNET is open source, released under the Apache version 2 license. Results can be viewed by uploading data to http://crosslinkviewer.org/ or by downloading the software from http://github.com/colin-combe/crosslink-viewer and running it locally. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Visual Control System of a Spraying Robot for Hyphantria cunea Larva Nets

    Directory of Open Access Journals (Sweden)

    Ying Zhao

    2015-01-01

    Full Text Available In order to implement automatic spraying on Hyphantria cunea larva nets, a spraying robot system with monocular hand-eye coordination and smart targeting abilities was designed according to the target net features. The system realized spatial two-dimensional motions driven by step motors on linear guide rails. Images were processed in real-time to extract the net curtain targets defined using the border area, and the optimal spraying position was then determined. An identification algorithm based on the global net image to distinguish targets before and after spray was proposed. A simulation environment was designed to verify the correctness of this method. Results showed that the highest rate of over spray is 288.5%, and the spray miss rate is 0.

  4. An application of timed Petri nets to S/C operations analysis: The Aristoteles autonomy concept

    Science.gov (United States)

    Barro, E.; Rossi, F.

    1990-10-01

    Petri nets as a methodology for the study and analysis of systems behavior are discussed. They can be tailored to timed approaches, to highlight all the system possible timing critical and deadlock conditions. As a consequence, it is valuable to apply a Petri nets-based methodology in the space environment. Spacecraft operations analysis during system definition is one area of possible application. The application of Petri nets, as a basis for an investigation methodology in the Aristoteles spacecraft autonomy concept definition is described. Significant results are obtained allowing the production of a consistent, formally clean and self explaining system description, to be used as an aid to design and a tool for system evaluation. Such positive achievements support the exploitation of Petri nets-based methodologies in spacecraft operations to describe and analyze the overall space system behavior.

  5. Position Information

    Data.gov (United States)

    Social Security Administration — The Position Information Data Asset provides the ability to search for active SSA position descriptions using various search criteria. An individual may search by PD...

  6. Does lack of secondary structure imply intrinsic disorder in proteins? A sequence analysis.

    Science.gov (United States)

    Rani, Pooja; Baruah, Anupaul; Biswas, Parbati

    2014-10-01

    Intrinsically disordered proteins (IDPs)/protein regions (IDPRs) lack unique three-dimensional structure at the level of secondary and/or tertiary structure and are represented as an ensemble of interchanging conformations. To investigate the role of presence/absence of secondary structures in promoting intrinsic disorder in proteins, a comparative sequence analysis of IDPs, IDPRs and proteins with minimal secondary structures (less than 5%) is required. A sequence analysis reveals proteins with minimal secondary structure content have high mean net positive charge, low mean net hydrophobicity and low sequence complexity. Interestingly, analysis of the relative local electrostatic interactions reveal that an increase in the relative repulsive interactions between amino acids separated by three or four residues lead to either loss of secondary structure or intrinsic disorder. IDPRs show increase in both local negative-negative and positive-positive repulsive interactions. While IDPs show a marked increase in the local negative-negative interactions, proteins with minimal secondary structure depict an increase in the local positive-positive interactions. IDPs and IDPRs are enriched in D, E and Q residues, while proteins with minimal secondary structure are depleted of these residues. Proteins with minimal secondary structures have higher content of G and C, while IDPs and IDPRs are depleted of these residues. These results confirm that proteins with minimal secondary structure have a distinctly different propensity for charge, hydrophobicity, specific amino acids and local electrostatic interactions as compared to IDPs/IDPRs. Thus we conclude that lack of secondary structure may be a necessary but not a sufficient condition for intrinsic disorder in proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Association mapping utilizing diverse barley lines reveals net form net blotch seedling resistance/susceptibility loci

    Science.gov (United States)

    Pyrenophora teres f. teres is a necrotrophic fungal pathogen and the causal agent of the economically important foliar disease net form net blotch (NFNB) of barley. The deployment of effective and durable resistance against P. teres f. teres has been hindered by the complexity of quantitative resist...

  8. Positive Psychology

    Science.gov (United States)

    Peterson, Christopher

    2009-01-01

    Positive psychology is a deliberate correction to the focus of psychology on problems. Positive psychology does not deny the difficulties that people may experience but does suggest that sole attention to disorder leads to an incomplete view of the human condition. Positive psychologists concern themselves with four major topics: (1) positive…

  9. Towards Self-Managed Executable Petri Nets

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius; Zhang, Weishan; Ingstrup, Mads

    2008-01-01

    An issue in self-managed systems is that different abstractions and programming models are used on different architectural layers, leading to systems that are harder to build and understand. To alleviate this, we introduce a self-management approach which combines high-level Petri nets...... with the capability of distributed communication among nets. Organized in a three-layer goal management, change management, and component control architecture this allows for self-management in distributed systems. We validate the approach through the Flamenco/CPN middleware that allows for self-management of service......-oriented pervasive computing systems through the runtime interpretation of colored Petri nets. The current work focuses on the change management and component control layers....

  10. Professional ASP.NET MVC 2

    CERN Document Server

    Galloway, Jon; Haack, Phil

    2010-01-01

    Top-selling MVC book from a top team at Microsoft—now fully updated!. ASP.NET MVC 2.0 is now available and shipping with Visual Studio 2010 and .NET 4. A new update to Microsoft's Model-View-Controller technologies, MVC 2.0 enables developers to build dynamic, data-driven Web sites. This in-depth book shows you step-by-step how to use MVC 2.0. You'll learn both the theory behind MVC 2.0, as well as walk through practical tutorials, where you'll create a real-world application. Topics include transitioning from ASP.NET development, as well as an overview of related tools and technologies, inclu

  11. .net core application lifecycle on Openshift

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    # .net core application lifecycle on Openshift I will show an example of a lifecycle of an OpenShift application with an emphasis on the continuous integration and deployment. The application compatible with [.net Standard](https://docs.microsoft.com/en-us/dotnet/standard/net-standard) can be easily deployed on OpenShift using [Source2Image](https://docs.openshift.com/enterprise/3.0/architecture/core_concepts/builds_and_image_streams.html#source-build) functionality, which doesn't require developers to maintain docker images of the application. I will also present how to efficiently integrate this feature into GitLab pipelines with an automated deployment of the "review" environment, as one its parts.

  12. Application and Theory of Petri Nets

    DEFF Research Database (Denmark)

    This volume contains the proceedings of the 13th International Conference onApplication and Theory of Petri Nets, held in Sheffield, England, in June 1992. The aim of the Petri net conferences is to create a forum for discussing progress in the application and theory of Petri nets. Typically......, the conferences have 150-200 participants, one third of these coming from industry and the rest from universities and research institutions. The 1992 conference was organized by the School of Computing and Management Sciences at Sheffield City Polytechnic, England. The volume contains twoinvited papers, by G....... Balbo and W. Reisig, 18 submitted papers, and seven project papers. The submitted papers and project presentations were selectedby the programme committee and a panel of referees from a large number of submissions....

  13. Chapter 17: Estimating Net Savings: Common Practices

    Energy Technology Data Exchange (ETDEWEB)

    Violette, D. M.; Rathbun, P.

    2014-09-01

    This chapter focuses on the methods used to estimate net energy savings in evaluation, measurement, and verification (EM&V) studies for energy efficiency (EE) programs. The chapter provides a definition of net savings, which remains an unsettled topic both within the EE evaluation community and across the broader public policy evaluation community, particularly in the context of attribution of savings to particular program. The chapter differs from the measure-specific Uniform Methods Project (UMP) chapters in both its approach and work product. Unlike other UMP resources that provide recommended protocols for determining gross energy savings, this chapter describes and compares the current industry practices for determining net energy savings, but does not prescribe particular methods.

  14. Isolation of Mesenchymal Stem Cells (MSCs) from Green Fluorescent Protein Positive (GFP+) Transgenic Rodents: The Grass Is Not Always Green(er)

    OpenAIRE

    Harting, Matthew T.; Jimenez, Fernando; Cox, Charles S.

    2009-01-01

    Cellular therapy is under intense basic science and clinical investigation as a therapeutic intervention. One of the challenges lies in tracking these cells in vivo. While there are many ways to label and track cells—each with strengths and weaknesses—the green fluorescent protein (GFP) is a reporter gene commonly employed. We report a significant and consistent reduction in the expression of GFP with the culture of mesenchymal stem cells (MSCs) isolated from the bone marrow of GFP+ transgeni...

  15. The transition from No Net Loss to a Net Gain of biodiversity is far from trivial

    DEFF Research Database (Denmark)

    Bull, Joseph William; Brownlie, S.

    2017-01-01

    The objectives of No Net Loss and Net Gain have emerged as key principles in conservation policy. Both give rise to mechanisms by which certain unavoidable biodiversity losses associated with development are quantified, and compensated with comparable gains (e.g. habitat restoration). The former...... seeks a neutral outcome for biodiversity after losses and gains are accounted for, and the latter seeks an improved outcome. Policy-makers often assume that the transition from one to the other is straightforward and essentially a question of the amount of compensation provided. Consequently, companies...... increasingly favour Net Gain type commitments, and financial institutions make lending conditional on either objective, depending on the habitat involved. We contend, however, that achieving Net Gain is fundamentally different to achieving No Net Loss, and moving from one to the other is less trivial than...

  16. Ubiquitous positioning

    CERN Document Server

    Mannings, Robin

    2008-01-01

    This groundbreaking resource offers a practical, in-depth understanding of Ubiquitous Positioning - positioning systems that identify the location and position of people, vehicles and objects in time and space in the digitized networked economy. The future and growth of ubiquitous positioning will be fueled by the convergence of many other areas of technology, from mobile telematics, Internet technology, and location systems, to sensing systems, geographic information systems, and the semantic web. This first-of-its-kind volume explores ubiquitous positioning from a convergence perspective, of

  17. APIs de seguridad en .NET Framework

    OpenAIRE

    Domínguez Ruiz, Abel

    2014-01-01

    Este trabajo hace un estudio de algunas de las herramientas de seguridad disponibles en .Net Framework así como la forma de usarlas en un desarrollo web bajo la metodología de desarrollo de ASP.NET siguiendo el modelo Vista-Controlador y usando como entorno de desarrollo Visual Studio. Además de repasar las herramientas disponibles y la forma de uso se ha desarrollado también una aplicación de ejemplo: ItemCoteca-Web; en la que se demuestra cómo resolver el registro de usuarios, la autenticac...

  18. An ECNO semantics for Petri nets

    DEFF Research Database (Denmark)

    Kindler, Ekkart

    2012-01-01

    The Event Coordination Notation (ECNO) allows modelling the behaviour of software on top of structural software models - and to generate program code from these models fully automatically. ECNO distinguishes between the local behaviour of elements (objects) and the global behaviour, which denes t...... work. In this paper, we will show that the ECNO, in turn, can be used for modelling the behaviour of Petri nets in a simple and concise way. What is more, we will show that the ECNO semantics of Place/Transition Systems can easily be extended to so-called signal-event nets....

  19. Introducing NET 40 With Visual Studio 2010

    CERN Document Server

    Mackey, A

    2010-01-01

    Microsoft is introducing a large number of changes to the way that the .NET Framework operates. Familiar technologies are being altered, best practices replaced, and developer methodologies adjusted. Many developers find it hard to keep up with the pace of change across .NET's ever-widening array of technologies. You may know what's happening in C#, but how about the Azure cloud? How is that going to affect your work? What are the limitations of the new pLINQ syntax? What you need is a roadmap. A guide to help you see the innovations that matter and to give you a head start on the opportunitie

  20. Deep Belief Nets for Topic Modeling

    DEFF Research Database (Denmark)

    Maaløe, Lars; Arngren, Morten; Winther, Ole

    2015-01-01

    -formative. In this paper we describe large-scale content based collaborative filtering for digital publishing. To solve the digital publishing recommender problem we compare two approaches: latent Dirichlet allocation (LDA) and deep be-lief nets (DBN) that both find low-dimensional latent representations for documents....... Efficient retrieval can be carried out in the latent representation. We work both on public benchmarks and digital media content provided by Issuu, an on-line publishing platform. This article also comes with a newly developed deep belief nets toolbox for topic modeling tailored towards performance...