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Sample records for hog pathway components

  1. Reconstruction of the High-Osmolarity Glycerol (HOG) Signaling Pathway from the Halophilic Fungus Wallemia ichthyophaga in Saccharomyces cerevisiae.

    Science.gov (United States)

    Konte, Tilen; Terpitz, Ulrich; Plemenitaš, Ana

    2016-01-01

    The basidiomycetous fungus Wallemia ichthyophaga grows between 1.7 and 5.1 M NaCl and is the most halophilic eukaryote described to date. Like other fungi, W. ichthyophaga detects changes in environmental salinity mainly by the evolutionarily conserved high-osmolarity glycerol (HOG) signaling pathway. In Saccharomyces cerevisiae, the HOG pathway has been extensively studied in connection to osmotic regulation, with a valuable knock-out strain collection established. In the present study, we reconstructed the architecture of the HOG pathway of W. ichthyophaga in suitable S. cerevisiae knock-out strains, through heterologous expression of the W. ichthyophaga HOG pathway proteins. Compared to S. cerevisiae, where the Pbs2 (ScPbs2) kinase of the HOG pathway is activated via the SHO1 and SLN1 branches, the interactions between the W. ichthyophaga Pbs2 (WiPbs2) kinase and the W. ichthyophaga SHO1 branch orthologs are not conserved: as well as evidence of poor interactions between the WiSho1 Src-homology 3 (SH3) domain and the WiPbs2 proline-rich motif, the absence of a considerable part of the osmosensing apparatus in the genome of W. ichthyophaga suggests that the SHO1 branch components are not involved in HOG signaling in this halophilic fungus. In contrast, the conserved activation of WiPbs2 by the S. cerevisiae ScSsk2/ScSsk22 kinase and the sensitivity of W. ichthyophaga cells to fludioxonil, emphasize the significance of two-component (SLN1-like) signaling via Group III histidine kinase. Combined with protein modeling data, our study reveals conserved and non-conserved protein interactions in the HOG signaling pathway of W. ichthyophaga and therefore significantly improves the knowledge of hyperosmotic signal processing in this halophilic fungus.

  2. Overexpression of OLE1 enhances stress tolerance and constitutively activates the MAPK HOG pathway in Saccharomyces cerevisiae.

    Science.gov (United States)

    Nasution, Olviyani; Lee, Young Mi; Kim, Eunjung; Lee, Yeji; Kim, Wankee; Choi, Wonja

    2017-03-01

    OLE1 of Saccharomyces cerevisiae encodes the sole and essential Δ-9 desaturase catalyzing the conversion of saturated to unsaturated fatty acids. Upon ectopic overexpression of OLE1 in S. cerevisiae, significant increases in the membrane oleic acid content were observed. OLE1-overexpressing strains displayed enhanced tolerance to various stresses, better proton efflux, lower membrane permeability, and lessened internal hydrogen peroxide content. The OLE1-mediated enhanced stress tolerance was considerably diminished upon deletion of HOG1, which encodes the mitogen-activated protein kinase (MAPK) Hog1 of the high osmolarity glycerol (HOG) pathway. Furthermore, OLE1 overexpression constitutively activated Hog1, which remained in the cytoplasm. Hog1 activation was accomplished through the MAPK kinase kinase (MAPKKK) Ssk2, but not Ste11 and Ssk22, the other MAPKKKs of the HOG pathway. Despite its cytoplasmic location, activated Hog1 was able to activate the expression of its canonical targets, including CTT1, HSP12, and STL1, and further, the cAMP and stress response elements present in the promoter. OLE1 overexpression neither caused nor relieved endoplasmic reticulum stress. Individually or in combination, the physiological and molecular changes caused by OLE1 overexpression may contribute to enhanced tolerance to various types of stress. Biotechnol. Bioeng. 2017;114: 620-631. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. The HOG pathway controls osmotic regulation of transcription via the stress response element (STRE) of the Saccharomyces cerevisiae CTT1 gene.

    Science.gov (United States)

    Schüller, C; Brewster, J L; Alexander, M R; Gustin, M C; Ruis, H

    1994-09-15

    The HOG signal pathway of the yeast Saccharomyces cerevisiae is defined by the PBS2 and HOG1 genes encoding members of the MAP kinase kinase and of the MAP kinase family, respectively. Mutations in this pathway (deletions of PBS2 or HOG1, or point mutations in HOG1) almost completely abolish the induction of transcription by osmotic stress that is mediated by stress response elements (STREs). We have demonstrated previously that STREs also mediate induction of transcription by heat shock, nitrogen starvation and oxidative stress. This study shows that they are also activated by low external pH, sorbate, benzoate or ethanol stress. Induction by these other stress signals appears to be HOG pathway independent. HOG1-dependent osmotic induction of transcription of the CTT1 gene encoding the cytosolic catalase T occurs in the presence of a protein synthesis inhibitor and can be detected rapidly after an increase of tyrosine phosphorylation of Hog1p triggered by high osmolarity. Consistent with a role of STREs in the induction of stress resistance, a number of other stress protein genes (e.g. HSP104) are regulated like CTT1. Furthermore, catalase T was shown to be important for viability under severe osmotic stress, and heat shock was demonstrated to provide cross-protection against osmotic stress.

  4. CaZF, a plant transcription factor functions through and parallel to HOG and calcineurin pathways in Saccharomyces cerevisiae to provide osmotolerance.

    Directory of Open Access Journals (Sweden)

    Deepti Jain

    Full Text Available Salt-sensitive yeast mutants were deployed to characterize a gene encoding a C2H2 zinc finger protein (CaZF that is differentially expressed in a drought-tolerant variety of chickpea (Cicer arietinum and provides salinity-tolerance in transgenic tobacco. In Saccharomyces cerevisiae most of the cellular responses to hyper-osmotic stress is regulated by two interconnected pathways involving high osmolarity glycerol mitogen-activated protein kinase (Hog1p and Calcineurin (CAN, a Ca(2+/calmodulin-regulated protein phosphatase 2B. In this study, we report that heterologous expression of CaZF provides osmotolerance in S. cerevisiae through Hog1p and Calcineurin dependent as well as independent pathways. CaZF partially suppresses salt-hypersensitive phenotypes of hog1, can and hog1can mutants and in conjunction, stimulates HOG and CAN pathway genes with subsequent accumulation of glycerol in absence of Hog1p and CAN. CaZF directly binds to stress response element (STRE to activate STRE-containing promoter in yeast. Transactivation and salt tolerance assays of CaZF deletion mutants showed that other than the transactivation domain a C-terminal domain composed of acidic and basic amino acids is also required for its function. Altogether, results from this study suggests that CaZF is a potential plant salt-tolerance determinant and also provide evidence that in budding yeast expression of HOG and CAN pathway genes can be stimulated in absence of their regulatory enzymes to provide osmotolerance.

  5. Macelignan inhibits bee pathogenic fungi Ascophaera apis growth through HOG1 pathway

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    Y.K. Shin

    2016-01-01

    Full Text Available Ascosphaera apis is a bee pathogen that causes bee larvae infection disease, to which treatment is not yet well investigated. The aim of this study was to investigate antifungal susceptibility in vitro against A. apis and to identify a new antifungal agent for this pathogen through minimal inhibitory concentration (MIC assay and western blot analysis. Macelignan had 1.56 and 3.125 μg/mL MIC against A. apis after 24 and 48 h, respectively, exhibiting the strongest growth inhibition against A. apis among the tested compounds (corosolic acid, dehydrocostus lactone, loganic acid, tracheloside, fangchinoline and emodin-8-O-β-D-glucopyranoside. Furthermore, macelignan showed a narrow-ranged spectrum against various fungal strains without any mammalian cell cytotoxicity. In spite of miconazole having powerful broad-ranged anti-fungal activity including A. apis, it demonstrated strong cytotoxicity. Therefore, even if macelignan alone was effective as an antifungal agent to treat A. apis, combined treatment with miconazole was more useful to overcome toxicity, drug resistance occurrence and cost effectiveness. Finally, HOG1 was revealed as a target molecule of macelignan in the anti-A. apis activity by inhibiting phosphorylation using S. cerevisiae as a model system. Based on our results, macelignan, a food-grade antimicrobial compound, would be an effective antifungal agent against A. apis infection in bees.

  6. 9 CFR 311.3 - Hog cholera.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Hog cholera. 311.3 Section 311.3... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.3 Hog cholera. (a) The carcasses of all hogs affected with hog cholera shall be condemned. (b) Inconclusive but suspicious symptoms...

  7. Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway

    Science.gov (United States)

    Jung, Kwang-Woo; Strain, Anna K; Nielsen, Kirsten; Jung, Kwang-Hwan; Bahn, Yong-Sun

    2012-01-01

    Maintenance of cation homeostasis is essential for survival of all living organisms in their biological niches. It is also important for the survival of human pathogenic fungi in the host, where cation concentrations and pH will vary depending on different anatomical sites. However, the exact role of diverse cation transporters and ion channels in virulence of fungal pathogens remains elusive. In this study we functionally characterized ENA1 and NHA1, encoding a putative Na+/ATPase and Na+/H+ antiporter, respectively, in Cryptococcus neoformans, a basidiomycete fungal pathogen which causes fatal meningoencephalitis. Expression of NHA1 and ENA1 is induced in response to salt and osmotic shock mainly in a Hog1-dependent manner. Phenotypic analysis of the ena1, nha1, and ena1 nha1 mutants revealed that Ena1 controls cellular levels of toxic cations, such as Na+ and Li+ whereas both Ena1 and Nha1 are important for controlling less toxic K+ ions. Under alkaline conditions, Ena1 was highly induced and required for growth in the presence of low levels of Na+ or K+ salt and Nha1 played a role in survival under K+ stress. In contrast, Nha1, but not Ena1, was essential for survival at acidic conditions (pH 4.5) under high K+ stress. In addition, Ena1 and Nha1 were required for maintenance of plasma membrane potential and stability, which appeared to modulate antifungal drug susceptibility. Perturbation of ENA1 and NHA1 enhanced capsule production and melanin synthesis. However, Nha1 was dispensable for virulence of C. neoformans although Ena1 was essential. In conclusion, Ena1 and Nha1 play redundant and discrete roles in cation homeostasis, pH regulation, membrane potential, and virulence in C. neoformans, suggesting that these transporters could be novel antifungal drug targets for treatment of cryptococcosis. PMID:22343280

  8. Anaerobic digestion of hog wastes

    Energy Technology Data Exchange (ETDEWEB)

    Taiganides, E P; Baumann, E R; Johnson, H P; Hazen, T E

    1963-01-01

    A short history, a list of advantages and limitations, and a short introduction to the principles of the process of anaerobic digestion are given. Six five gallon bottle digesters were daily fed hog manure, maintained at 35/sup 0/C, and constantly agitated. Satisfactory operation was assured at 3.2 g VS/l/day with a detention time of 10 days, yielding 490-643 ml gas/g VS/day with a CH/sub 4/ content of 59% (2.1 x 10/sup 7/ joules/m/sup 3/). A figure and discussion portray the interrelationships of loading rate, solids concentration and detention time. They estimate that a marginal profit might be obtained by the operation of a heated digester handling the wastes of 10,000 hogs.

  9. Hogged wood fuel price analysis in the U.S. Pacific Northwest

    International Nuclear Information System (INIS)

    Biederman, R.T.; Blazek, C.F.; Fox, P.J.

    1991-01-01

    The purpose of this paper is to discuss the results of a comprehensive analysis of wood residues used for meeting energy requirements in the Pacific Northwest region of the United States. These wood residues are generated primarily from cutting, sawing, planning, sanding, and debarking activities in the lumber and plywood industries. While high-quality wood residues are commonly used as raw material in the manufacture of pulp and board commodities, a very large amount of wood residues are ultimately used for plant fuel purposes. The characteristics of this market for hogged wood fuel are examined in depth, with particular emphasis given to the factors which affect the supply, demand and price of hogged wood. Hogged wood has played an enormous role in the Pacific Northwest for over sixty years, a result of the massive regional timber harvest. Utilization of this renewable energy resource continues to be a large component in regional energy supply. Despite having a large number of highly integrated mills that both use and produce wood residues, the Pacific Northwest region experiences a lively trade in hogged wood. The IGT study discussed herein examines the determinants of the regional market price for hogged wood. A number of useful leading indicators are identified, and a statistical forecasting model is prepared to help predict future hogged wood prices. This model provides insight into the factors that are, and are not, important determinants of hogged wood price. The issue of fuel substitution is addressed in relation to the potential of hogged wood to displace some amount of primary energy sources such as natural gas and electricity. Also examined in the study are techniques to estimate the actual quantity of hogged wood available, and the quantity demanded by the marketplace. Conclusions presented in the study have important ramifications for understanding the price behavior and utilization of hogged wood fuel. 4 refs., 12 figs

  10. A Unique Fungal Two-Component System Regulates Stress Responses, Drug Sensitivity, Sexual Development, and Virulence of Cryptococcus neoformans

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    Bahn, Yong-Sun; Kojima, Kaihei; Cox, Gary M.

    2006-01-01

    The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and differentiation. The basidiomycetous human fungal pathogen Cryptococcus neoformans uniquely uses the stress-activated Pbs2-Hog1 MAPK system to govern a plethora of cellular events, including stress responses, drug sensitivity, sexual reproduction, and virulence. Here, we characterized a fungal “two-component” system that controls these fundamental cellular functions via the Pbs2-Hog1 MAPK cascade. A typical response regulator, Ssk1, modulated all Hog1-dependent phenotypes by controlling Hog1 phosphorylation, indicating that Ssk1 is the major upstream signaling component of the Pbs2-Hog1 pathway. A second response regulator, Skn7, governs sensitivity to Na+ ions and the antifungal agent fludioxonil, negatively controls melanin production, and functions independently of Hog1 regulation. To control these response regulators, C. neoformans uses multiple sensor kinases, including two-component–like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. Our findings highlight unique adaptations of this global two-component MAPK signaling cascade in a ubiquitous human fungal pathogen. PMID:16672377

  11. Stimulation of p38 (HOG1) kinase pathway by ionizing radiation results in downstream modulation of ATF/CREB transcription factor activity in NIH-3T3 cells

    International Nuclear Information System (INIS)

    Stevenson, Mary Ann; Yao Jin

    1997-01-01

    Purpose/Objective:p38 kinase, a member of the MAP kinase family, is activated in response to stresses such as high osmolarity and UV irradiation as well exposure to cytokines such as IL1β and TNFα. The kinase is part of a signal transduction pathway that leads from receptor activation through a three kinase cascade resulting in the activation of p38. p38 activation then leads to the phosphorylation of target proteins that include transcription factors such as nuclear factor of interleukin 6 and members of the activating transcription factor (ATF) family, and in addition, the stress protein, HSP27, via activation of MAPKAP2 kinase. In the present report, we have investigated the potential role of p38 in the response of NIH-3T3 cells to ionizing radiation. Materials and Methods:NIH-3T3 cells were grown to confluence in DMEM+10%CS and then serum deprived for 24 hours in DMEM+0.1%CS. Radiation exposures were delivered using a Philips RT250 (250Kvp X-ray tube). Activated forms of p38 kinase and ATF/CREB transcription factors were identified using immunoblotting techniques employing activation specific antibodies raised against the phosphorylated forms of the kinases/transcription factors. Kinase activity was directly measured using immunokinase assays. DNA binding of transcription factors to their respective consensus sequences was assayed by EMSA. Results:We found that p38 becomes rapidly phosphorylated and activated by exposure to ionizing radiation. Significantly, p38 is activated to a similar degree and with a similar time course by serum derpviation and entry of cells into a non-proliferating G 0 state, suggesting a causal role for p38 in quiescence. Phosphorylation of p38 directly correlated with phosphorylation and activation of ATF/CREB family members as well as DNA binding by these activated factors. Conclusion:Activation of p38 kinase and downstream transcription factors may play an important role in the response of cells to ionizing radiation. We are

  12. Evolutionary conservation of plant gibberellin signalling pathway components

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    Reski Ralf

    2007-11-01

    Full Text Available Abstract Background: Gibberellins (GA are plant hormones that can regulate germination, elongation growth, and sex determination. They ubiquitously occur in seed plants. The discovery of gibberellin receptors, together with advances in understanding the function of key components of GA signalling in Arabidopsis and rice, reveal a fairly short GA signal transduction route. The pathway essentially consists of GID1 gibberellin receptors that interact with F-box proteins, which in turn regulate degradation of downstream DELLA proteins, suppressors of GA-controlled responses. Results: Arabidopsis sequences of the gibberellin signalling compounds were used to screen databases from a variety of plants, including protists, for homologues, providing indications for the degree of conservation of the pathway. The pathway as such appears completely absent in protists, the moss Physcomitrella patens shares only a limited homology with the Arabidopsis proteins, thus lacking essential characteristics of the classical GA signalling pathway, while the lycophyte Selaginella moellendorffii contains a possible ortholog for each component. The occurrence of classical GA responses can as yet not be linked with the presence of homologues of the signalling pathway. Alignments and display in neighbour joining trees of the GA signalling components confirm the close relationship of gymnosperms, monocotyledonous and dicotyledonous plants, as suggested from previous studies. Conclusion: Homologues of the GA-signalling pathway were mainly found in vascular plants. The GA signalling system may have its evolutionary molecular onset in Physcomitrella patens, where GAs at higher concentrations affect gravitropism and elongation growth.

  13. Amino acids as regulators and components of nonproteinogenic pathways

    NARCIS (Netherlands)

    Meijer, Alfred J.

    2003-01-01

    Amino acids are not only important precursors for the synthesis of proteins and other N-containing compounds, but also participate in the regulation of major metabolic pathways. Glutamate and aspartate, for example, are components of the malate/aspartate shuttle and their concentrations control the

  14. Characterisation of ethylene pathway components in non-climacteric capsicum.

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    Aizat, Wan M; Able, Jason A; Stangoulis, James C R; Able, Amanda J

    2013-11-28

    Climacteric fruit exhibit high ethylene and respiration levels during ripening but these levels are limited in non-climacteric fruit. Even though capsicum is in the same family as the well-characterised climacteric tomato (Solanaceae), it is non-climacteric and does not ripen normally in response to ethylene or if harvested when mature green. However, ripening progresses normally in capsicum fruit when they are harvested during or after what is called the 'Breaker stage'. Whether ethylene, and components of the ethylene pathway such as 1-aminocyclopropane 1-carboxylate (ACC) oxidase (ACO), ACC synthase (ACS) and the ethylene receptor (ETR), contribute to non-climacteric ripening in capsicum has not been studied in detail. To elucidate the behaviour of ethylene pathway components in capsicum during ripening, further analysis is therefore needed. The effects of ethylene or inhibitors of ethylene perception, such as 1-methylcyclopropene, on capsicum fruit ripening and the ethylene pathway components may also shed some light on the role of ethylene in non-climacteric ripening. The expression of several isoforms of ACO, ACS and ETR were limited during capsicum ripening except one ACO isoform (CaACO4). ACS activity and ACC content were also low in capsicum despite the increase in ACO activity during the onset of ripening. Ethylene did not stimulate capsicum ripening but 1-methylcyclopropene treatment delayed the ripening of Breaker-harvested fruit. Some of the ACO, ACS and ETR isoforms were also differentially expressed upon treatment with ethylene or 1-methylcyclopropene. ACS activity may be the rate limiting step in the ethylene pathway of capsicum which restricts ACC content. The differential expression of several ethylene pathway components during ripening and upon ethylene or 1-methylclopropene treatment suggests that the ethylene pathway may be regulated differently in non-climacteric capsicum compared to the climacteric tomato. Ethylene independent pathways may

  15. Agrobacterium tumefaciens-Mediated Transformation of Pseudocercospora fijiensis to Determine the Role of PfHog1 in Osmotic Stress Regulation and Virulence Modulation.

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    Onyilo, Francis; Tusiime, Geoffrey; Chen, Li-Hung; Falk, Bryce; Stergiopoulos, Ioannis; Tripathi, Jaindra N; Tushemereirwe, Wilberforce; Kubiriba, Jerome; Changa, Charles; Tripathi, Leena

    2017-01-01

    Black Sigatoka disease, caused by Pseudocercospora fijiensis is a serious constraint to banana production worldwide. The disease continues to spread in new ecological niches and there is an urgent need to develop strategies for its control. The high osmolarity glycerol (HOG) pathway in Saccharomyces cerevisiae is well known to respond to changes in external osmolarity. HOG pathway activation leads to phosphorylation, activation and nuclear transduction of the HOG1 mitogen-activated protein kinases (MAPKs). The activated HOG1 triggers several responses to osmotic stress, including up or down regulation of different genes, regulation of protein translation, adjustments to cell cycle progression and synthesis of osmolyte glycerol. This study investigated the role of the MAPK-encoding PfHog1 gene on osmotic stress adaptation and virulence of P. fijie nsis. RNA interference-mediated gene silencing of PfHog1 significantly suppressed growth of P. fijiensis on potato dextrose agar media supplemented with 1 M NaCl, indicating that PfHog1 regulates osmotic stress. In addition, virulence of the PfHog1 -silenced mutants of P. fijiensis on banana was significantly reduced, as observed from the low rates of necrosis and disease development on the infected leaves. Staining with lacto phenol cotton blue further confirmed the impaired mycelial growth of the PfHog1 in the infected leaf tissues, which was further confirmed with quantification of the fungal biomass using absolute- quantitative PCR. Collectively, these findings demonstrate that PfHog1 plays a critical role in osmotic stress regulation and virulence of P. fijiensis on its host banana. Thus, PfHog1 could be an interesting target for the control of black Sigatoka disease in banana.

  16. Agrobacterium tumefaciens-Mediated Transformation of Pseudocercospora fijiensis to Determine the Role of PfHog1 in Osmotic Stress Regulation and Virulence Modulation

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    Francis Onyilo

    2017-05-01

    Full Text Available Black Sigatoka disease, caused by Pseudocercospora fijiensis is a serious constraint to banana production worldwide. The disease continues to spread in new ecological niches and there is an urgent need to develop strategies for its control. The high osmolarity glycerol (HOG pathway in Saccharomyces cerevisiae is well known to respond to changes in external osmolarity. HOG pathway activation leads to phosphorylation, activation and nuclear transduction of the HOG1 mitogen-activated protein kinases (MAPKs. The activated HOG1 triggers several responses to osmotic stress, including up or down regulation of different genes, regulation of protein translation, adjustments to cell cycle progression and synthesis of osmolyte glycerol. This study investigated the role of the MAPK-encoding PfHog1 gene on osmotic stress adaptation and virulence of P. fijiensis. RNA interference-mediated gene silencing of PfHog1 significantly suppressed growth of P. fijiensis on potato dextrose agar media supplemented with 1 M NaCl, indicating that PfHog1 regulates osmotic stress. In addition, virulence of the PfHog1-silenced mutants of P. fijiensis on banana was significantly reduced, as observed from the low rates of necrosis and disease development on the infected leaves. Staining with lacto phenol cotton blue further confirmed the impaired mycelial growth of the PfHog1 in the infected leaf tissues, which was further confirmed with quantification of the fungal biomass using absolute- quantitative PCR. Collectively, these findings demonstrate that PfHog1 plays a critical role in osmotic stress regulation and virulence of P. fijiensis on its host banana. Thus, PfHog1 could be an interesting target for the control of black Sigatoka disease in banana.

  17. Neural circuit components of the Drosophila OFF motion vision pathway.

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    Meier, Matthias; Serbe, Etienne; Maisak, Matthew S; Haag, Jürgen; Dickson, Barry J; Borst, Alexander

    2014-02-17

    Detecting the direction of visual motion is an essential task of the early visual system. The Reichardt detector has been proven to be a faithful description of the underlying computation in insects. A series of recent studies addressed the neural implementation of the Reichardt detector in Drosophila revealing the overall layout in parallel ON and OFF channels, its input neurons from the lamina (L1→ON, and L2→OFF), and the respective output neurons to the lobula plate (ON→T4, and OFF→T5). While anatomical studies showed that T4 cells receive input from L1 via Mi1 and Tm3 cells, the neurons connecting L2 to T5 cells have not been identified so far. It is, however, known that L2 contacts, among others, two neurons, called Tm2 and L4, which show a pronounced directionality in their wiring. We characterized the visual response properties of both Tm2 and L4 neurons via Ca(2+) imaging. We found that Tm2 and L4 cells respond with an increase in activity to moving OFF edges in a direction-unselective manner. To investigate their participation in motion vision, we blocked their output while recording from downstream tangential cells in the lobula plate. Silencing of Tm2 and L4 completely abolishes the response to moving OFF edges. Our results demonstrate that both cell types are essential components of the Drosophila OFF motion vision pathway, prior to the computation of directionality in the dendrites of T5 cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Identification and Characterization of Components of the Mitotic Spindle Checkpoint Pathway in Fission Yeast

    National Research Council Canada - National Science Library

    Kadura, Shelia

    2001-01-01

    .... The fission yeast, Schizosaccharomyces pombe, is a useful system for discovering and characterizing components of this regulatory pathway because genetic approaches can be coupled with excellent cytology...

  19. Contract Hog Production: A Case Study of Financial Arrangements

    OpenAIRE

    Ross, Brent; Barry, Peter

    2005-01-01

    A case study is presented about the financing arrangements, contract terms, and business relationships of a set of contract hog producers whose loans from community banks have been guaranteed by the Illinois Farm Development Authority. The results reflect the maturity and stability of contract hog production, although agribusiness and farmer integrators largely fill different market niches and contract with different types of producers.

  20. Pedestrian detection in infrared image using HOG and Autoencoder

    Science.gov (United States)

    Chen, Tianbiao; Zhang, Hao; Shi, Wenjie; Zhang, Yu

    2017-11-01

    In order to guarantee the safety of driving at night, vehicle-mounted night vision system was used to detect pedestrian in front of cars and send alarm to prevent the potential dangerous. To decrease the false positive rate (FPR) and increase the true positive rate (TPR), a pedestrian detection method based on HOG and Autoencoder (HOG+Autoencoder) was presented. Firstly, the HOG features of input images were computed and encoded by Autoencoder. Then the encoded features were classified by Softmax. In the process of training, Autoencoder was trained unsupervised. Softmax was trained with supervision. Autoencoder and Softmax were stacked into a model and fine-tuned by labeled images. Experiment was conducted to compare the detection performance between HOG and HOG+Autoencoder, using images collected by vehicle-mounted infrared camera. There were 80000 images for training set and 20000 for the testing set, with a rate of 1:3 between positive and negative images. The result shows that when TPR is 95%, FPR of HOG+Autoencoder is 0.4%, while the FPR of HOG is 5% with the same TPR.

  1. Hydroquinone, a benzene metabolite, induces Hog1-dependent stress response signaling and causes aneuploidy in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Shiga, Takeki; Suzuki, Hiroyuki; Yamamoto, Hiroaki; Yamamoto, Kazuo; Yamamoto, Ayumi

    2010-01-01

    Previously, we have shown that phenyl hydroquinone, a hepatic metabolite of the Ames test-negative carcinogen o-phenylphenol, efficiently induced aneuploidy in Saccharomyces cerevisiae by arresting the cell cycle at the G2/M transition as a result of the activation of the Hog1 (p38 MAPK homolog)-Swe1 (Wee1 homolog) pathway. In this experiment, we examined the aneuploidy forming effects of hydroquinone, a benzene metabolite, since both phenyl hydroquinone and hydroquinone are Ames-test negative carcinogens and share similar molecular structures. As was seen in phenyl hydroquinone, hydroquinone induced aneuploidy in yeast by delaying the cell cycle at the G2/M transition. Deficiencies in SWE1 and HOG1 abolished the hydroquinone-induced delay at the G2/M transition and aneuploidy formation. Furthermore, Hog1 was phosphorylated by hydroquinone, which may stabilize Swe1. These data indicate that the hydroquinone-induced G2/M transition checkpoint, which is activated by the Hog1-Swe1 pathway, plays a role in the formation of aneuploidy. (author)

  2. HOG MAP kinase regulation of alternariol biosynthesis in Alternaria alternata is important for substrate colonization.

    Science.gov (United States)

    Graf, Eva; Schmidt-Heydt, Markus; Geisen, Rolf

    2012-07-16

    Strains of the genus Alternaria are ubiquitously present and frequently found on fruits, vegetables and cereals. One of the most commonly found species from this genus is A. alternata which is able to produce the mycotoxin alternariol among others. To date only limited knowledge is available about the regulation of the biosynthesis of alternariol, especially under conditions relevant to food. Tomatoes are a typical substrate of A. alternata and have a high water activity. On the other hand cereals with moderate water activity are also frequently colonized by A. alternata. In the current analysis it was demonstrated that even minor changes in the osmotic status of the substrate affect the alternariol biosynthesis of strains from vegetables resulting in nearly complete inhibition. High osmolarity in the environment is usually transmitted to the transcriptional level of downstream regulated genes by the HOG signal cascade (high osmolarity glycerol cascade) which is a MAP kinase transduction pathway. The phosphorylation status of the A. alternata HOG (AaHOG) was determined. Various concentrations of NaCl induce the phosphorylation of AaHOG in a concentration, time and strain dependent manner. A strain with a genetically inactivated aahog gene was no longer able to produce alternariol indicating that the activity of the aahog gene is required for alternariol biosynthesis. Further experiments revealed that the biosynthesis of alternariol is important for the fungus to colonize tomato tissue. The tight water activity dependent regulation of alternariol biosynthesis ensures alternariol biosynthesis at conditions which indicate an optimal colonization substrate for the fungus. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Economic Dynamics of the German Hog-Price Cycle

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    Ernst Berg

    2015-06-01

    Full Text Available We investigated the economic dynamics of the German hog-price cycle with an innovative ‘diagnostic’ modeling approach. Hog-price cycles are conventionally modeled stochastically—most recently as randomly-shifting sinusoidal oscillations. Alternatively, we applied Nonlinear Time Series analysis to empirically reconstruct a deterministic, low-dimensional, and nonlinear attractor from observed hog prices. We next formulated a structural (explanatory model of the pork industry to synthesize the empirical hog-price attractor. Model simulations demonstrate that low price-elasticity of demand contributes to aperiodic price cycling – a well know result – and further reveal two other important driving factors: investment irreversibility (caused by high specificity of technology, and liquidity-driven investment behavior of German farmers.

  4. Actin is an essential component of plant gravitropic signaling pathways

    Science.gov (United States)

    Braun, Markus; Hauslage, Jens; Limbach, Christoph

    2003-08-01

    A role of the actin cytoskeleton in the different phases of gravitropism in higher plant organs seems obvious, but experimental evidence is still inconclusive and contradictory. In gravitropically tip-growing rhizoids and protonemata, however, it is well documented that actin is an essential component of the tip-growth machinery and is involved either in the cellular mechanisms that lead to gravity sensing and in the processes of the graviresponses that result in the reorientation of the growth direction. All these processes depend on a complexly organized and highly dynamic organization of actin filaments whose diverse functions are coordinated by numerous associated proteins. Actin filaments and myosins mediate the transport of secretory vehicles to the growing tip and precisely control the delivery of cell wall material. In addition, both cell types use a very efficient actomyosin-based system to control and correct the position of their statoliths and to direct sedimenting statoliths to confined graviperception sites at the plasma membrane. The studies presented in this paper provide evidence for the essential role of actin in plant gravity sensing and the gravitropic responses. A unique actin-organizing center exists in the tip of characean rhizoids and protonemata which is associated with and dynamically regulated by a specific set of actin-dynamizing proteins. It is concluded that this highly dynamic apical actin array is an essential prerequisite for gravity sensing and gravity-oriented tip growth.

  5. Thermography hogging the limelight at Big Sky

    Energy Technology Data Exchange (ETDEWEB)

    Plastow, C. [Fluke Electronics Canada, Mississauga, ON (Canada)

    2010-02-15

    The high levels of humidity and ammonia found at hog farms can lead to premature corrosion of electrical systems and create potential hazards, such as electrical fires. Big Sky Farms in Saskatchewan has performed on-site inspections at its 44 farms and 16 feed mills using handheld thermography technology from Fluke Electronics. Ti thermal imaging units save time and simplify inspections. The units could be used for everything, from checking out the bearings at the feed mills to electrical circuits and relays. The Ti25 is affordable and has the right features for a preventative maintenance program. Operators of Big Sky Farms use the Ti25 to inspect all circuit breakers of 600 volts or lower as well as transformers where corrosion often causes connections to break off. The units are used to look at bearings, do scanning and thermal imaging on motors. To date, the Ti25 has detected and highlighted 5 or 6 problems on transformers alone that could have been major issues. At one site, the Ti25 indicated that all 30 circuit breakers had loose connections and were overeating. Big Sky Farms fixed the problem right away before a disaster happened. In addition to reducing inspection times, the Ti25 can record all measurements and keep a record of all the readings for downloading. 2 figs.

  6. Evolution of JAK-STAT pathway components: mechanisms and role in immune system development.

    Directory of Open Access Journals (Sweden)

    Clifford Liongue

    Full Text Available BACKGROUND: Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK-Signal transducer and activator of transcription (STAT pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP, Protein inhibitors against Stats (PIAS, and Suppressor of cytokine signaling (SOCS proteins across a diverse range of organisms. RESULTS: Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components. CONCLUSION: Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity.

  7. Differential gene expression and Hog1 interaction with osmoresponsive genes in the extremely halotolerant black yeast Hortaea werneckii

    Directory of Open Access Journals (Sweden)

    Plemenitaš Ana

    2007-08-01

    Full Text Available Abstract Background Fluctuations in external salinity force eukaryotic cells to respond by changes in the gene expression of proteins acting in protective biochemical processes, thus counteracting the changing osmotic pressure. The high-osmolarity glycerol (HOG signaling pathway is essential for the efficient up-regulation of the osmoresponsive genes. In this study, the differential gene expression of the extremely halotolerant black yeast Hortaea werneckii was explored. Furthermore, the interaction of mitogen-activated protein kinase HwHog1 and RNA polymerase II with the chromatin in cells adapted to an extremely hypersaline environment was analyzed. Results A cDNA subtraction library was constructed for H. werneckii, adapted to moderate salinity or an extremely hypersaline environment of 4.5 M NaCl. An uncommon osmoresponsive set of 95 differentially expressed genes was identified. The majority of these had not previously been connected with the adaptation of salt-sensitive S. cerevisiae to hypersaline conditions. The transcriptional response in hypersaline-adapted and hypersaline-stressed cells showed that only a subset of the identified genes responded to acute salt-stress, whereas all were differentially expressed in adapted cells. Interaction with HwHog1 was shown for 36 of the 95 differentially expressed genes. The majority of the identified osmoresponsive and HwHog1-dependent genes in H. werneckii have not been previously reported as Hog1-dependent genes in the salt-sensitive S. cerevisiae. The study further demonstrated the co-occupancy of HwHog1 and RNA polymerase II on the chromatin of 17 up-regulated and 2 down-regulated genes in 4.5 M NaCl-adapted H. werneckii cells. Conclusion Extremely halotolerant H. werneckii represents a suitable and highly relevant organism to study cellular responses to environmental salinity. In comparison with the salt-sensitive S. cerevisiae, this yeast shows a different set of genes being expressed at

  8. Human Impairment from Living near Confined Animal (Hog) Feeding Operations

    International Nuclear Information System (INIS)

    Kilburn, K.H.; Kilburn, K.H.

    2012-01-01

    Problem. To determine whether neighbors around manure lagoons and massive hog confinement buildings who complained of offensive odors and symptoms had impaired brain and lung functions. Method. We compared near hog manure neighbors of lagoons to people living beyond 3 kilometers in Ohio and to unexposed people controls in a nearby state for neuro physiological, cognitive, recall and memory functions, and pulmonary performance. Results. The 25 exposed subjects averaged 4.3 neuro behavioral abnormalities, significantly different from 2.5 for local controls and 2.3 for Tennessee controls. Exposed subjects mean forced vital capacity and expiratory volume in 1 sec were reduced significantly compared to local and regional controls. Conclusions. Near neighbors of hog enclosures and manure lagoon gases had impaired neuro behavioral functions and pulmonary functions and these effects extended to nearby people thought to be controls. Hydrogen sulfide must be abated because people living near lagoons cannot avoid rotten egg gas.

  9. Respon Imun Anak Babi Pasca Vaksinasi Hog Cholera

    Directory of Open Access Journals (Sweden)

    I Made Jayanata

    2016-10-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui pengaruh antibodi maternal terhadap titer antibodi anak babi yang di vaksin hog cholera umur 7 hari. Penelitian menggunakan tujuh sampel babi dari induk yang divaksin secara teratur yang diberikan perlakuan vaksinasi pada umur 7 hari. Pengambilan sampel serum dilakukan pravaksinasi (7 hari, dan satu minggu serta dua minggu pasca vaksinasi. Untuk menentukan titer antibodi virus Hog cholera pada sampel anak babi dilakukan uji ELISA. Data yang diperoleh kemudian dianalisis mengunakan paired sampel T test antara titer antibodi hog cholera. Hasil paired sample T test menunjukkan terjadinya penurunan titer antibodi maternal yang nyata (p<0,05 pada pra vaksinasi ( umur 7 hari dengan satu minggu pasca vaksinasi dan sangat nyata (p<0,01 dengan hari dua minggu pasca vaksinasi. Dari hasil penelitian ini dapat disimpulkan bahwa antibodi maternal yang tinggi akan mengakibatkan penurunan pada titer antibodi pasca vaksinasi. Perlu dilakukan penelitian lebih lanjut untuk mengetahui waktu vaksinasi yang efektif

  10. 9 CFR 309.5 - Swine; disposal because of hog cholera.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Swine; disposal because of hog cholera... INSPECTION AND CERTIFICATION ANTE-MORTEM INSPECTION § 309.5 Swine; disposal because of hog cholera. (a) All swine found by an inspector to be affected with hog cholera shall be identified as U.S. Condemned and...

  11. Modelling the Asymmetric Volatility in Hog Prices in Taiwan : The Impact of Joining the WTO

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); B-W. Huang (Bing-Wen); M-G. Chen (Meng-Gu)

    2010-01-01

    textabstractPrices in the hog industry in Taiwan are determined according to an auction system. There are significant differences in hog prices before, during and after joining the World Trade Organization (WTO). The paper models growth rates and volatility in daily hog prices in Taiwan from 23

  12. Cold exposure affects carbohydrates and lipid metabolism, and induces Hog1p phosphorylation in Dekkera bruxellensis strain CBS 2499.

    Science.gov (United States)

    Galafassi, Silvia; Toscano, Marco; Vigentini, Ileana; Zambelli, Paolo; Simonetti, Paolo; Foschino, Roberto; Compagno, Concetta

    2015-05-01

    Dekkera bruxellensis is a yeast known to affect the quality of wine and beer. This species, due to its high ethanol and acid tolerance, has been reported also to compete with Saccharomyces cerevisiae in distilleries producing fuel ethanol. In order to understand how this species responds when exposed to low temperatures, some mechanisms like synthesis and accumulation of intracellular metabolites, changes in lipid composition and activation of the HOG-MAPK pathway were investigated in the genome sequenced strain CBS 2499. We show that cold stress caused intracellular accumulation of glycogen, but did not induce accumulation of trehalose and glycerol. The cellular fatty acid composition changed after the temperature downshift, and a significant increase of palmitoleic acid was observed. RT-PCR analysis revealed that OLE1 encoding for Δ9-fatty acid desaturase was up-regulated, whereas TPS1 and INO1 didn't show changes in their expression. In D. bruxellensis Hog1p was activated by phosphorylation, as described in S. cerevisiae, highlighting a conserved role of the HOG-MAP kinase signaling pathway in cold stress response.

  13. Improving HOG with image segmentation: application to human detection

    NARCIS (Netherlands)

    Salas, Y.S.; Bermudez, D.V.; Peña, A.M.L.; Gomez, D.G.; Gevers, T.

    2012-01-01

    In this paper we improve the histogram of oriented gradients (HOG), a core descriptor of state-of-the-art object detection, by the use of higher-level information coming from image segmentation. The idea is to re-weight the descriptor while computing it without increasing its size. The benefits of

  14. MaHog1, a Hog1-type mitogen-activated protein kinase gene, contributes to stress tolerance and virulence of the entomopathogenic fungus Metarhizium acridum.

    Science.gov (United States)

    Jin, Kai; Ming, Yue; Xia, Yu Xian

    2012-12-01

    Fungal biocontrol agents have great potential in integrated pest management. However, poor efficacy and sensitivity to various adverse factors have hampered their wide application. In eukaryotic cells, Hog1 kinase plays a critical role in stress responses. In this study, MaHog1 (GenBank accession no. EFY85878), encoding a member of the Hog1/Sty1/p38 mitogen-activated protein kinase family in Metarhizium (Me.) acridum, was identified. Targeted gene disruption was used to analyse the role of MaHog1 in virulence and tolerance of adverse factors. Mutants with MaHog1 depletion showed increased sensitivity to high osmotic stress, high temperature and oxidative stress, and exhibited remarkable resistance to cell wall-disturbing agents. These results suggest that Hog1 kinase has a conserved function in regulating multistress responses among fungi, and that MaHog1 might influence cell wall biogenesis in Me. acridum. Bioassays conducted with topical inoculation and intrahaemocoel injection revealed that MaHog1 is required for both penetration and postpenetration development of Me. acridum. MaHog1 disruption resulted in a significant reduction in virulence, likely due to the combination of a decrease in conidial germination, a reduction in appressorium formation and a decline in growth rate in insect haemolymph, which might be caused by impairing fungal tolerance of various stresses during infection.

  15. Assessing landowners' attitudes toward wild hogs and support for control options.

    Science.gov (United States)

    Caplenor, Carlotta A; Poudyal, Neelam C; Muller, Lisa I; Yoest, Chuck

    2017-10-01

    Wild hogs (Sus scrofa) are an invasive species with destructive habits, particularly rooting and wallowing, which can directly impact agricultural crops, pasture land, and water quality. Considering wild hogs are widely dispersed across the landscape, they are extremely difficult to control. Disagreements can arise among different stakeholders over whether and how their populations should be managed. The purpose of this article was to examine Tennessee, United States landowners' attitudes toward wild hogs, to compare acceptability of control methods, and to evaluate factors significantly influencing public support for regulations to control wild hogs. Logistic regression was employed to analyze data collected from a statewide survey of rural landowners in the fall of 2015. Landowners had overwhelmingly negative attitudes towards wild hogs, and were concerned about their impact on the natural environment and rural economy. Although landowners showed support for controlling wild hogs, levels of acceptability for management options varied. Respondents favored active management and supported education and incentive-based control programs to control wild hogs. Cognitive concepts such as social and personal norms and awareness of consequences, as well as demographic characteristics, significantly predicted landowners' support for state regulations to control wild hogs in Tennessee. Findings increase our understanding of the human dimensions of wild hog management and that of other similarly invasive animals, and may guide resource managers in designing effective and socially acceptable management strategies to control wild hog populations in Tennessee and elsewhere. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Rent Sharing in Multi-Site Hog Production

    OpenAIRE

    Brian P. Cozzarin; Randall E. Westgren

    2000-01-01

    A firm-level model of three-site hog production is used compare a franchise organizational structure to a three-firm alliance. The results of the simulations imply that the franchise system is better equipped to mitigate underproduction in the nursery and finishing units, the nursery and finishing units lose relatively more profit than they otherwise would in an alliance. The pig-space guatantee does little to offset the financial risk for the nursery and finishing units when underproduction ...

  17. Production Contracts and the Spot Market Price of Hogs

    OpenAIRE

    Key, Nigel D.

    2010-01-01

    The increasing use of production contracts in the hog sector has reduced the number of spot market transactions, raised concerns about price manipulation and helped to spur legislation requiring price reporting by packers. Using data from the 2002 and 2007 Censuses of Agriculture, this study looks for evidence of market manipulation by examining whether the local prevalence of contracting affects the average price received by independent producers. The empirical approach uses a fixed-effects ...

  18. COUNTRY OF ORIGIN LABELING: IMPLICATIONS FOR THE MANITOBA HOG INDUSTRY

    OpenAIRE

    Grier, Kevin; Martin, Larry J.; Mayer, Holly

    2002-01-01

    This project was undertaken at the request of the Manitoba Pork Council in order to assess the impact of the Country Of Origin Labeling (COL) provisions of the US Farm Bill. The Council needs to know the consequences (economic and otherwise) of COL upon Manitoba hog farmers. The Farm Security and Rural Investment Act of 2002 (the Farm Bill) contains a provision that requires the United States Department of Agriculture (USDA) to issue country of origin labeling guidelines for voluntary use by ...

  19. Directing folding pathways for multi-component DNA origami nanostructures with complex topology

    International Nuclear Information System (INIS)

    Marras, A E; Zhou, L; Su, H-J; Castro, C E; Kolliopoulos, V

    2016-01-01

    Molecular self-assembly has become a well-established technique to design complex nanostructures and hierarchical mesoscale assemblies. The typical approach is to design binding complementarity into nucleotide or amino acid sequences to achieve the desired final geometry. However, with an increasing interest in dynamic nanodevices, the need to design structures with motion has necessitated the development of multi-component structures. While this has been achieved through hierarchical assembly of similar structural units, here we focus on the assembly of topologically complex structures, specifically with concentric components, where post-folding assembly is not feasible. We exploit the ability to direct folding pathways to program the sequence of assembly and present a novel approach of designing the strand topology of intermediate folding states to program the topology of the final structure, in this case a DNA origami slider structure that functions much like a piston-cylinder assembly in an engine. The ability to program the sequence and control orientation and topology of multi-component DNA origami nanostructures provides a foundation for a new class of structures with internal and external moving parts and complex scaffold topology. Furthermore, this work provides critical insight to guide the design of intermediate states along a DNA origami folding pathway and to further understand the details of DNA origami self-assembly to more broadly control folding states and landscapes. (paper)

  20. Directing folding pathways for multi-component DNA origami nanostructures with complex topology

    Science.gov (United States)

    Marras, A. E.; Zhou, L.; Kolliopoulos, V.; Su, H.-J.; Castro, C. E.

    2016-05-01

    Molecular self-assembly has become a well-established technique to design complex nanostructures and hierarchical mesoscale assemblies. The typical approach is to design binding complementarity into nucleotide or amino acid sequences to achieve the desired final geometry. However, with an increasing interest in dynamic nanodevices, the need to design structures with motion has necessitated the development of multi-component structures. While this has been achieved through hierarchical assembly of similar structural units, here we focus on the assembly of topologically complex structures, specifically with concentric components, where post-folding assembly is not feasible. We exploit the ability to direct folding pathways to program the sequence of assembly and present a novel approach of designing the strand topology of intermediate folding states to program the topology of the final structure, in this case a DNA origami slider structure that functions much like a piston-cylinder assembly in an engine. The ability to program the sequence and control orientation and topology of multi-component DNA origami nanostructures provides a foundation for a new class of structures with internal and external moving parts and complex scaffold topology. Furthermore, this work provides critical insight to guide the design of intermediate states along a DNA origami folding pathway and to further understand the details of DNA origami self-assembly to more broadly control folding states and landscapes.

  1. Selective killing of cancer cells by leaf extract of Ashwagandha: components, activity and pathway analyses.

    Science.gov (United States)

    Widodo, Nashi; Takagi, Yasuomi; Shrestha, Bhupal G; Ishii, Tetsuro; Kaul, Sunil C; Wadhwa, Renu

    2008-04-08

    Ashwagandha, also called as "Queen of Ayurveda" and "Indian ginseng", is a commonly used plant in Indian traditional medicine, Ayurveda. Its roots have been used as herb remedy to treat a variety of ailments and to promote general wellness. However, scientific evidence to its effects is limited to only a small number of studies. We had previously identified anti-cancer activity in the leaf extract (i-Extract) of Ashwagandha and demonstrated withanone as a cancer inhibitory factor (i-Factor). In the present study, we fractionated the i-Extract to its components by silica gel column chromatography and subjected them to cell based activity analyses. We found that the cancer inhibitory leaf extract (i-Extract) has, at least, seven components that could cause cancer cell killing; i-Factor showed the highest selectivity for cancer cells and i-Factor rich Ashwagandha leaf powder was non-toxic and anti-tumorigenic in mice assays. We undertook a gene silencing and pathway analysis approach and found that i-Extract and its components kill cancer cells by at least five different pathways, viz. p53 signaling, GM-CFS signaling, death receptor signaling, apoptosis signaling and G2-M DNA damage regulation pathway. p53 signaling was most common. Visual analysis of p53 and mortalin staining pattern further revealed that i-Extract, fraction F1, fraction F4 and i-Factor caused an abrogation of mortalin-p53 interactions and reactivation of p53 function while the fractions F2, F3, F5 work through other mechanisms.

  2. Altered Expression of Wnt Signaling Pathway Components in Osteogenesis of Mesenchymal Stem Cells in Osteoarthritis Patients.

    Science.gov (United States)

    Tornero-Esteban, Pilar; Peralta-Sastre, Ascensión; Herranz, Eva; Rodríguez-Rodríguez, Luis; Mucientes, Arkaitz; Abásolo, Lydia; Marco, Fernando; Fernández-Gutiérrez, Benjamín; Lamas, José Ramón

    2015-01-01

    Osteoarthritis (OA) is characterized by altered homeostasis of joint cartilage and bone, whose functional properties rely on chondrocytes and osteoblasts, belonging to mesenchymal stem cells (MSCs). WNT signaling acts as a hub integrating and crosstalking with other signaling pathways leading to the regulation of MSC functions. The aim of this study was to evaluate the existence of a differential signaling between Healthy and OA-MSCs during osteogenesis. MSCs of seven OA patients and six healthy controls were isolated, characterised and expanded. During in vitro osteogenesis, cells were recovered at days 1, 10 and 21. RNA and protein content was obtained. Expression of WNT pathway genes was evaluated using RT-qPCR. Functional studies were also performed to study the MSC osteogenic commitment and functional and post-traslational status of β-catenin and several receptor tyrosine kinases. Several genes were downregulated in OA-MSCs during osteogenesis in vitro. These included soluble Wnts, inhibitors, receptors, co-receptors, several kinases and transcription factors. Basal levels of β-catenin were higher in OA-MSCs, but calcium deposition and expression of osteogenic genes was similar between Healthy and OA-MSCs. Interestingly an increased phosphorylation of p44/42 MAPK (ERK1/2) signaling node was present in OA-MSCs. Our results point to the existence in OA-MSCs of alterations in expression of Wnt pathway components during in vitro osteogenesis that are partially compensated by post-translational mechanisms modulating the function of other pathways. We also point the relevance of other signaling pathways in OA pathophysiology suggesting their role in the maintenance of joint homeostasis through modulation of MSC osteogenic potential.

  3. Tapasin-related protein TAPBPR is an additional component of the MHC class I presentation pathway

    DEFF Research Database (Denmark)

    Boyle, Louise H; Hermann, Clemens; Boname, Jessica M

    2013-01-01

    Tapasin is an integral component of the peptide-loading complex (PLC) important for efficient peptide loading onto MHC class I molecules. We investigated the function of the tapasin-related protein, TAPBPR. Like tapasin, TAPBPR is widely expressed, IFN-γ-inducible, and binds to MHC class I coupled...... with β2-microglobulin in the endoplasmic reticulum. In contrast to tapasin, TAPBPR does not bind ERp57 or calreticulin and is not an integral component of the PLC. β2-microglobulin is essential for the association between TAPBPR and MHC class I. However, the association between TAPBPR and MHC class I...... occurs in the absence of a functional PLC, suggesting peptide is not required. Expression of TAPBPR decreases the rate of MHC class I maturation through the secretory pathway and prolongs the association of MHC class I on the PLC. The TAPBPR:MHC class I complex trafficks through the Golgi apparatus...

  4. Interaction Dynamics Determine Signaling and Output Pathway Responses

    Directory of Open Access Journals (Sweden)

    Klement Stojanovski

    2017-04-01

    Full Text Available The understanding of interaction dynamics in signaling pathways can shed light on pathway architecture and provide insights into targets for intervention. Here, we explored the relevance of kinetic rate constants of a key upstream osmosensor in the yeast high-osmolarity glycerol-mitogen-activated protein kinase (HOG-MAPK pathway to signaling output responses. We created mutant pairs of the Sln1-Ypd1 complex interface that caused major compensating changes in the association (kon and dissociation (koff rate constants (kinetic perturbations but only moderate changes in the overall complex affinity (Kd. Yeast cells carrying a Sln1-Ypd1 mutant pair with moderate increases in kon and koff displayed a lower threshold of HOG pathway activation than wild-type cells. Mutants with higher kon and koff rates gave rise to higher basal signaling and gene expression but impaired osmoadaptation. Thus, the kon and koff rates of the components in the Sln1 osmosensor determine proper signaling dynamics and osmoadaptation.

  5. A second component of the SltA-dependent cation tolerance pathway in Aspergillus nidulans.

    Science.gov (United States)

    Mellado, Laura; Calcagno-Pizarelli, Ana Maria; Lockington, Robin A; Cortese, Marc S; Kelly, Joan M; Arst, Herbert N; Espeso, Eduardo A

    2015-09-01

    The transcriptional response to alkali metal cation stress is mediated by the zinc finger transcription factor SltA in Aspergillus nidulans and probably in other fungi of the pezizomycotina subphylum. A second component of this pathway has been identified and characterized. SltB is a 1272 amino acid protein with at least two putative functional domains, a pseudo-kinase and a serine-endoprotease, involved in signaling to the transcription factor SltA. Absence of SltB activity results in nearly identical phenotypes to those observed for a null sltA mutant. Hypersensitivity to a variety of monovalent and divalent cations, and to medium alkalinization are among the phenotypes exhibited by a null sltB mutant. Calcium homeostasis is an exception and this cation improves growth of sltΔ mutants. Moreover, loss of kinase HalA in conjunction with loss-of-function sltA or sltB mutations leads to pronounced calcium auxotrophy. sltA sltB double null mutants display a cation stress sensitive phenotype indistinguishable from that of single slt mutants showing the close functional relationship between these two proteins. This functional relationship is reinforced by the fact that numerous mutations in both slt loci can be isolated as suppressors of poor colonial growth resulting from certain null vps (vacuolar protein sorting) mutations. In addition to allowing identification of sltB, our sltB missense mutations enabled prediction of functional regions in the SltB protein. Although the relationship between the Slt and Vps pathways remains enigmatic, absence of SltB, like that of SltA, leads to vacuolar hypertrophy. Importantly, the phenotypes of selected sltA and sltB mutations demonstrate that suppression of null vps mutations is not dependent on the inability to tolerate cation stress. Thus a specific role for both SltA and SltB in the VPS pathway seems likely. Finally, it is noteworthy that SltA and SltB have a similar, limited phylogenetic distribution, being restricted to

  6. 9 CFR 311.30 - Livestock suffocated and hogs scalded alive.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Livestock suffocated and hogs scalded alive. 311.30 Section 311.30 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT... PARTS § 311.30 Livestock suffocated and hogs scalded alive. All livestock which have been suffocated in...

  7. A method for real-time implementation of HOG feature extraction

    Science.gov (United States)

    Luo, Hai-bo; Yu, Xin-rong; Liu, Hong-mei; Ding, Qing-hai

    2011-08-01

    Histogram of oriented gradient (HOG) is an efficient feature extraction scheme, and HOG descriptors are feature descriptors which is widely used in computer vision and image processing for the purpose of biometrics, target tracking, automatic target detection(ATD) and automatic target recognition(ATR) etc. However, computation of HOG feature extraction is unsuitable for hardware implementation since it includes complicated operations. In this paper, the optimal design method and theory frame for real-time HOG feature extraction based on FPGA were proposed. The main principle is as follows: firstly, the parallel gradient computing unit circuit based on parallel pipeline structure was designed. Secondly, the calculation of arctangent and square root operation was simplified. Finally, a histogram generator based on parallel pipeline structure was designed to calculate the histogram of each sub-region. Experimental results showed that the HOG extraction can be implemented in a pixel period by these computing units.

  8. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    Science.gov (United States)

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  9. A molecular systems approach to modelling human skin pigmentation: identifying underlying pathways and critical components.

    Science.gov (United States)

    Raghunath, Arathi; Sambarey, Awanti; Sharma, Neha; Mahadevan, Usha; Chandra, Nagasuma

    2015-04-29

    Ultraviolet radiations (UV) serve as an environmental stress for human skin, and result in melanogenesis, with the pigment melanin having protective effects against UV induced damage. This involves a dynamic and complex regulation of various biological processes that results in the expression of melanin in the outer most layers of the epidermis, where it can exert its protective effect. A comprehensive understanding of the underlying cross talk among different signalling molecules and cell types is only possible through a systems perspective. Increasing incidences of both melanoma and non-melanoma skin cancers necessitate the need to better comprehend UV mediated effects on skin pigmentation at a systems level, so as to ultimately evolve knowledge-based strategies for efficient protection and prevention of skin diseases. A network model for UV-mediated skin pigmentation in the epidermis was constructed and subjected to shortest path analysis. Virtual knock-outs were carried out to identify essential signalling components. We describe a network model for UV-mediated skin pigmentation in the epidermis. The model consists of 265 components (nodes) and 429 directed interactions among them, capturing the manner in which one component influences the other and channels information. Through shortest path analysis, we identify novel signalling pathways relevant to pigmentation. Virtual knock-outs or perturbations of specific nodes in the network have led to the identification of alternate modes of signalling as well as enabled determining essential nodes in the process. The model presented provides a comprehensive picture of UV mediated signalling manifesting in human skin pigmentation. A systems perspective helps provide a holistic purview of interconnections and complexity in the processes leading to pigmentation. The model described here is extensive yet amenable to expansion as new data is gathered. Through this study, we provide a list of important proteins essential

  10. Evidence of a New Role for the High-Osmolarity Glycerol Mitogen-Activated Protein Kinase Pathway in Yeast: Regulating Adaptation to Citric Acid Stress†

    OpenAIRE

    Lawrence, Clare L.; Botting, Catherine H.; Antrobus, Robin; Coote, Peter J.

    2004-01-01

    Screening the Saccharomyces cerevisiae disruptome, profiling transcripts, and determining changes in protein expression have identified an important new role for the high-osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathway in the regulation of adaptation to citric acid stress. Deletion of HOG1, SSK1, PBS2, PTC2, PTP2, and PTP3 resulted in sensitivity to citric acid. Furthermore, citric acid resulted in the dual phosphorylation, and thus activation, of Hog1p. Despite mino...

  11. Depletion of key protein components of the RISC pathway impairs pre-ribosomal RNA processing.

    Science.gov (United States)

    Liang, Xue-Hai; Crooke, Stanley T

    2011-06-01

    Little is known about whether components of the RNA-induced silencing complex (RISC) mediate the biogenesis of RNAs other than miRNA. Here, we show that depletion of key proteins of the RISC pathway by antisense oligonucleotides significantly impairs pre-rRNA processing in human cells. In cells depleted of Drosha or Dicer, different precursors to 5.8S rRNA strongly accumulated, without affecting normal endonucleolytic cleavages. Moderate yet distinct processing defects were also observed in Ago2-depleted cells. Physical links between pre-rRNA and these proteins were identified by co-immunoprecipitation analyses. Interestingly, simultaneous depletion of Dicer and Drosha led to a different processing defect, causing slower production of 28S rRNA and its precursor. Both Dicer and Ago2 were detected in the nuclear fraction, and reduction of Dicer altered the structure of the nucleolus, where pre-rRNA processing occurs. Together, these results suggest that Drosha and Dicer are implicated in rRNA biogenesis.

  12. Interaction of PLP with GFP-MAL2 in the human oligodendroglial cell line HOG.

    Directory of Open Access Journals (Sweden)

    Raquel Bello-Morales

    Full Text Available The velocity of the nerve impulse conduction of vertebrates relies on the myelin sheath, an electrically insulating layer that surrounds axons in both the central and peripheral nervous systems, enabling saltatory conduction of the action potential. Oligodendrocytes are the myelin-producing glial cells in the central nervous system. A deeper understanding of the molecular basis of myelination and, specifically, of the transport of myelin proteins, will contribute to the search of the aetiology of many dysmyelinating and demyelinating diseases, including multiple sclerosis. Recent investigations suggest that proteolipid protein (PLP, the major myelin protein, could reach myelin sheath by an indirect transport pathway, that is, a transcytotic route via the plasma membrane of the cell body. If PLP transport relies on a transcytotic process, it is reasonable to consider that this myelin protein could be associated with MAL2, a raft protein essential for transcytosis. In this study, carried out with the human oligodendrocytic cell line HOG, we show that PLP colocalized with green fluorescent protein (GFP-MAL2 after internalization from the plasma membrane. In addition, both immunoprecipitation and immunofluorescence assays, indicated the existence of an interaction between GFP-MAL2 and PLP. Finally, ultrastructural studies demonstrated colocalization of GFP-MAL2 and PLP in vesicles and tubulovesicular structures. Taken together, these results prove for the first time the interaction of PLP and MAL2 in oligodendrocytic cells, supporting the transcytotic model of PLP transport previously suggested.

  13. Hog Producers' Risk Management Attitudes and Desire for Additional Risk Management Education

    OpenAIRE

    Patrick, George F.; Peiter, Amy J.; Knight, Thomas O.; Coble, Keith H.; Baquet, Alan E.

    2007-01-01

    Hog producers in Indiana and Nebraska were surveyed about sources of risk, effectiveness of risk management strategies, and prior participation in and desire for additional risk management education. Ownership of hogs by the producer, size of the operation, and age did have significant effects on ratings of both sources of risk and effectiveness of risk management strategies. Probit analysis found age, prior attendance, knowledge and prior use of the tool, level of integration, and concern ab...

  14. Study of the Ubiquitous Hog Farm System Using Wireless Sensor Networks for Environmental Monitoring and Facilities Control

    Directory of Open Access Journals (Sweden)

    Jeonghwan Hwang

    2010-12-01

    Full Text Available Many hog farmers are now suffering from high pig mortality rates due to various wasting diseases and increased breeding costs, etc. It is therefore necessary for hog farms to implement systematic and scientific pig production technology to increase productivity and produce high quality pork in order to solve these problems. In this study, we describe such a technology by suggesting a ubiquitous hog farm system which applies WSN (Wireless Sensor Network technology to the pig industry. We suggest that a WSN and CCTV (Closed-circuit television should be installed on hog farms to collect environmental and image information which shall then help producers not only in monitoring the hog farm via the Web from outside the farm, but also facilitate the control of hog farm facilities in remote locations. In addition, facilities can be automatically controlled based on breeding environment parameters which are already set up and a SMS notice service to notify of deviations shall provide users with convenience. Hog farmers may increase production and improve pork quality through this ubiquitous hog farm system and prepare a database with information collected from environmental factors and the hog farm control devices, which is expected to provide information needed to design and implement suitable control strategies for hog farm operation.

  15. A Hybrid Vehicle Detection Method Based on Viola-Jones and HOG + SVM from UAV Images.

    Science.gov (United States)

    Xu, Yongzheng; Yu, Guizhen; Wang, Yunpeng; Wu, Xinkai; Ma, Yalong

    2016-08-19

    A new hybrid vehicle detection scheme which integrates the Viola-Jones (V-J) and linear SVM classifier with HOG feature (HOG + SVM) methods is proposed for vehicle detection from low-altitude unmanned aerial vehicle (UAV) images. As both V-J and HOG + SVM are sensitive to on-road vehicles' in-plane rotation, the proposed scheme first adopts a roadway orientation adjustment method, which rotates each UAV image to align the roads with the horizontal direction so the original V-J or HOG + SVM method can be directly applied to achieve fast detection and high accuracy. To address the issue of descending detection speed for V-J and HOG + SVM, the proposed scheme further develops an adaptive switching strategy which sophistically integrates V-J and HOG + SVM methods based on their different descending trends of detection speed to improve detection efficiency. A comprehensive evaluation shows that the switching strategy, combined with the road orientation adjustment method, can significantly improve the efficiency and effectiveness of the vehicle detection from UAV images. The results also show that the proposed vehicle detection method is competitive compared with other existing vehicle detection methods. Furthermore, since the proposed vehicle detection method can be performed on videos captured from moving UAV platforms without the need of image registration or additional road database, it has great potentials of field applications. Future research will be focusing on expanding the current method for detecting other transportation modes such as buses, trucks, motors, bicycles, and pedestrians.

  16. A Hybrid Vehicle Detection Method Based on Viola-Jones and HOG + SVM from UAV Images

    Science.gov (United States)

    Xu, Yongzheng; Yu, Guizhen; Wang, Yunpeng; Wu, Xinkai; Ma, Yalong

    2016-01-01

    A new hybrid vehicle detection scheme which integrates the Viola-Jones (V-J) and linear SVM classifier with HOG feature (HOG + SVM) methods is proposed for vehicle detection from low-altitude unmanned aerial vehicle (UAV) images. As both V-J and HOG + SVM are sensitive to on-road vehicles’ in-plane rotation, the proposed scheme first adopts a roadway orientation adjustment method, which rotates each UAV image to align the roads with the horizontal direction so the original V-J or HOG + SVM method can be directly applied to achieve fast detection and high accuracy. To address the issue of descending detection speed for V-J and HOG + SVM, the proposed scheme further develops an adaptive switching strategy which sophistically integrates V-J and HOG + SVM methods based on their different descending trends of detection speed to improve detection efficiency. A comprehensive evaluation shows that the switching strategy, combined with the road orientation adjustment method, can significantly improve the efficiency and effectiveness of the vehicle detection from UAV images. The results also show that the proposed vehicle detection method is competitive compared with other existing vehicle detection methods. Furthermore, since the proposed vehicle detection method can be performed on videos captured from moving UAV platforms without the need of image registration or additional road database, it has great potentials of field applications. Future research will be focusing on expanding the current method for detecting other transportation modes such as buses, trucks, motors, bicycles, and pedestrians. PMID:27548179

  17. Arabic sign language recognition based on HOG descriptor

    Science.gov (United States)

    Ben Jmaa, Ahmed; Mahdi, Walid; Ben Jemaa, Yousra; Ben Hamadou, Abdelmajid

    2017-02-01

    We present in this paper a new approach for Arabic sign language (ArSL) alphabet recognition using hand gesture analysis. This analysis consists in extracting a histogram of oriented gradient (HOG) features from a hand image and then using them to generate an SVM Models. Which will be used to recognize the ArSL alphabet in real-time from hand gesture using a Microsoft Kinect camera. Our approach involves three steps: (i) Hand detection and localization using a Microsoft Kinect camera, (ii) hand segmentation and (iii) feature extraction using Arabic alphabet recognition. One each input image first obtained by using a depth sensor, we apply our method based on hand anatomy to segment hand and eliminate all the errors pixels. This approach is invariant to scale, to rotation and to translation of the hand. Some experimental results show the effectiveness of our new approach. Experiment revealed that the proposed ArSL system is able to recognize the ArSL with an accuracy of 90.12%.

  18. DMPD: Cellular reprogramming by gram-positive bacterial components: a review. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16885502 Cellular reprogramming by gram-positive bacterial components: a review. Bu...(.csml) Show Cellular reprogramming by gram-positive bacterial components: a review. PubmedID 16885502 Title... Cellular reprogramming by gram-positive bacterial components: a review. Authors

  19. Assessing hog lagoon waste contamination in the Cape Fear Watershed using Bacteroidetes 16S rRNA gene pyrosequencing.

    Science.gov (United States)

    Arfken, Ann M; Song, Bongkeun; Mallin, Michael A

    2015-09-01

    Hog lagoons can be major sources of waste and nutrient contamination to watersheds adjacent to pig farms. Fecal source tracking methods targeting Bacteroidetes 16S rRNA genes in pig fecal matter may underestimate or fail to detect hog lagoon contamination in riverine environments. In order to detect hog lagoon wastewater contamination in the Cape Fear Watershed, where a large number of hog farms are present, we conducted pyrosequencing analyses of Bacteroidetes 16S rRNA genes in hog lagoon waste and identified new hog lagoon-specific marker sequences. Additional pyrosequencing analyses of Bacteroidetes 16S rRNA genes were conducted with surface water samples collected at 4 sites during 5 months in the Cape Fear Watershed. Using an operational taxonomic unit (OTU) identity cutoff value of 97 %, these newly identified hog lagoon markers were found in 3 of the river samples, while only 1 sample contained the pig fecal marker. In the sample containing the pig fecal marker, there was a relatively high percentage (14.1 %) of the hog lagoon markers and a low pig fecal marker relative abundance of 0.4 % in the Bacteroidetes 16S rRNA gene sequences. This suggests that hog lagoon contamination must be somewhat significant in order for pig fecal markers to be detected, and low levels of hog lagoon contamination cannot be detected targeting only pig-specific fecal markers. Thus, new hog lagoon markers have a better detection capacity for lagoon waste contamination, and in conjunction with a pig fecal marker, provide a more comprehensive and accurate detection of hog lagoon waste contamination in susceptible watersheds.

  20. Overexpressing key component genes of the secretion pathway for enhanced secretion of an Aspergillus niger glucose oxidase in Trichoderma reesei.

    Science.gov (United States)

    Wu, Yilan; Sun, Xianhua; Xue, Xianli; Luo, Huiying; Yao, Bin; Xie, Xiangming; Su, Xiaoyun

    2017-11-01

    Vast interest exists in developing T. reesei for production of heterologous proteins. Although rich genomic and transcriptomic information has been uncovered for the T. reesei secretion pathway, little is known about whether engineering its key components could enhance expression of a heterologous gene. In this study, snc1, a v-SNARE gene, was first selected for overexpression in T. reesei. In engineered T. reesei with additional copies of snc1, the Aspergillus niger glucose oxidase (AnGOD) was produced to a significantly higher level (2.2-fold of the parental strain). hac1 and bip1, two more component genes in the secretion pathway, were further tested for overexpression and found to be also beneficial for AnGOD secretion. The overexpression of one component gene more or less affected the expression of the other two genes, suggesting a complex regulating mechanism. Our study demonstrates the potential of engineering the secretion pathway for enhancing heterologous gene production in T. reesei. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Descending motor pathways and the spinal motor system. Limbic and non-limbic components

    NARCIS (Netherlands)

    G. Holstege (Gert)

    1990-01-01

    textabstractFor a thorough understanding of the descending pathways of the motor system originating in the forebrain, knowledge about the anatomy and function of the structures in the more caudally located parts of the central nervous system is indispensable. In this paper an overview will be

  2. Descending motor pathways and the spinal motor system. Limbic and non-limbic components

    NARCIS (Netherlands)

    Holstege, G.

    1991-01-01

    For a thorough understanding of the descending pathways of the motor system originating in the forebrain, knowledge about the anatomy and function of the structures in the more caudally located parts of the central nervous system is indispensable. In this paper an overview will be presented of these

  3. Components of a Fanconi-like pathway control Pso2-independent DNA interstrand crosslink repair in yeast.

    Directory of Open Access Journals (Sweden)

    Thomas A Ward

    Full Text Available Fanconi anemia (FA is a devastating genetic disease, associated with genomic instability and defects in DNA interstrand cross-link (ICL repair. The FA repair pathway is not thought to be conserved in budding yeast, and although the yeast Mph1 helicase is a putative homolog of human FANCM, yeast cells disrupted for MPH1 are not sensitive to ICLs. Here, we reveal a key role for Mph1 in ICL repair when the Pso2 exonuclease is inactivated. We find that the yeast FANCM ortholog Mph1 physically and functionally interacts with Mgm101, a protein previously implicated in mitochondrial DNA repair, and the MutSα mismatch repair factor (Msh2-Msh6. Co-disruption of MPH1, MGM101, MSH6, or MSH2 with PSO2 produces a lesion-specific increase in ICL sensitivity, the elevation of ICL-induced chromosomal rearrangements, and persistence of ICL-associated DNA double-strand breaks. We find that Mph1-Mgm101-MutSα directs the ICL-induced recruitment of Exo1 to chromatin, and we propose that Exo1 is an alternative 5'-3' exonuclease utilised for ICL repair in the absence of Pso2. Moreover, ICL-induced Rad51 chromatin loading is delayed when both Pso2 and components of the Mph1-Mgm101-MutSα and Exo1 pathway are inactivated, demonstrating that the homologous recombination stages of ICL repair are inhibited. Finally, the FANCJ- and FANCP-related factors Chl1 and Slx4, respectively, are also components of the genetic pathway controlled by Mph1-Mgm101-MutSα. Together this suggests that a prototypical FA-related ICL repair pathway operates in budding yeast, which acts redundantly with the pathway controlled by Pso2, and is required for the targeting of Exo1 to chromatin to execute ICL repair.

  4. The human keratinocyte two-dimensional gel protein database (update 1995): mapping components of signal transduction pathways

    DEFF Research Database (Denmark)

    Celis, J E; Rasmussen, H H; Gromov, P

    1995-01-01

    identified (protein name, organelle components, etc.) using a procedure or a combination of procedures that include (i) comigration with known human proteins, (ii) 2-D gel immunoblotting using specific antibodies, (iii) microsequencing of Coomassie Brilliant Blue stained proteins, (iv) mass spectrometry, (v......)vaccinia virus expression of full length cDNAs, and (vi) in vitro transcription/translation of full-length cDNAs. This year, special emphasis has been given to the identification of signal transduction components by using 2-D gel immunoblotting of crude keratinocyte lysates in combination with enhanced......--through a systematic study of ekeratinocytes--qualitative and quantitative information on proteins and their genes that may allow us to identify abnormal patterns of gene expression and to pinpoint signaling pathways and components affected in various skin diseases, cancer included. Udgivelsesdato: 1995-Dec...

  5. Spook and Spookier code for stage-specific components of the ecdysone biosynthetic pathway in Diptera

    DEFF Research Database (Denmark)

    Ono, Hajime; Rewitz, Kim; Shinoda, Tetsu

    2006-01-01

    is eliminated in larvae carrying mutations in molting defective (mld), a gene encoding a nuclear zinc finger protein that is required for production of ecdysone during Drosophila larval development. Intriguingly, mld is not present in the Bombyx mori genome, and we have identified only one spook homolog in both...... Bombyx and Manduca that is expressed in both embryos and larva. These studies suggest an evolutionary split between Diptera and Lepidoptera in how the ecdysone biosynthetic pathway is regulated during development....

  6. A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway.

    Science.gov (United States)

    Salašová, Alena; Yokota, Chika; Potěšil, David; Zdráhal, Zbyněk; Bryja, Vítězslav; Arenas, Ernest

    2017-07-11

    Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients. Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development. Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. Our study shows for the first time that LRRK2 activates the WNT

  7. The connections of Wnt pathway components with cell cycle and centrosome: side effects or a hidden logic?

    Science.gov (United States)

    Bryja, Vítězslav; Červenka, Igor; Čajánek, Lukáš

    2017-12-01

    Wnt signaling cascade has developed together with multicellularity to orchestrate the development and homeostasis of complex structures. Wnt pathway components - such as β-catenin, Dishevelled (DVL), Lrp6, and Axin-- are often dedicated proteins that emerged in evolution together with the Wnt signaling cascade and are believed to function primarily in the Wnt cascade. It is interesting to see that in recent literature many of these proteins are connected with cellular functions that are more ancient and not limited to multicellular organisms - such as cell cycle regulation, centrosome biology, or cell division. In this review, we summarize the recent literature describing this crosstalk. Specifically, we attempt to find the answers to the following questions: Is the response to Wnt ligands regulated by the cell cycle? Is the centrosome and/or cilium required to activate the Wnt pathway? How do Wnt pathway components regulate the centrosomal cycle and cilia formation and function? We critically review the evidence that describes how these connections are regulated and how they help to integrate cell-to-cell communication with the cell and the centrosomal cycle in order to achieve a fine-tuned, physiological response.

  8. Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application

    Directory of Open Access Journals (Sweden)

    Romilly E. Hodges

    2015-01-01

    Full Text Available Research into human biotransformation and elimination systems continues to evolve. Various clinical and in vivo studies have been undertaken to evaluate the effects of foods and food-derived components on the activity of detoxification pathways, including phase I cytochrome P450 enzymes, phase II conjugation enzymes, Nrf2 signaling, and metallothionein. This review summarizes the research in this area to date, highlighting the potential for foods and nutrients to support and/or modulate detoxification functions. Clinical applications to alter detoxification pathway activity and improve patient outcomes are considered, drawing on the growing understanding of the relationship between detoxification functions and different disease states, genetic polymorphisms, and drug-nutrient interactions. Some caution is recommended, however, due to the limitations of current research as well as indications that many nutrients exert biphasic, dose-dependent effects and that genetic polymorphisms may alter outcomes. A whole-foods approach may, therefore, be prudent.

  9. [Analysis on "component-target-pathway" of Paeonia lactiflora in treating cardiac diseases based on data mining].

    Science.gov (United States)

    Liu, Yang; Zhang, Fang-Bo; Tang, Shi-Huan; Wang, Ping; Li, Sen; Su, Jin; Zhou, Rong-Rong; Zhang, Jia-Qi; Sun, Hui-Feng

    2018-04-01

    Based on the literature review and modern application of Paeonia lactiflora in heart diseases, this article would predict the target of drug and disease by intergrative pharmacology platform of traditional Chinese medicine (TCMIP, http://www.tcmip.cn), and then explore the molecular mechanism of P. lactiflora in treatment of heart disease, providing theoretical basis and method for further studies on P. lactiflora. According to the ancient books, P. lactiflora with functions of "removing the vascular obstruction, removing the lumps, relieving pain, diuretic, nutrient qi" and other effects, have been used for many times to treat heart disease. Some prescriptions are also favored by the modern physicians nowadays. With the development of science, the chemical components that play a role in heart disease and the interrelation between these components and the body become the research hotspot. In order to further reveal the pharmacological substance base and molecular mechanism of P. lactiflora for the treatment of such diseases, TCM-IP was used to obtain multiple molecular targets and signaling pathways in treatment of heart disease. ATP1A1, a common target of drug and disease, was related to energy, and HDAC2 mainly regulated cardiomyocyte hypertrophy gene and cardiomyocyte expression. Other main drug targets such as GCK, CHUK and PRKAA2 indirectly regulated heart disease through many pathways; multiple disease-associated signaling pathways interfered with various heart diseases including coronary heart disease, myocardial ischemia and myocardial hypertrophy through influencing energy metabolism, enzyme activity and gene expression. In conclusion, P. lactiflora plays a role in protecting heart function by regulating the gene expression of cardiomyocytes directly. Meanwhile, it can indirectly intervene in other pathways of heart function, and thus participate in the treatment of heart disease. In this paper, the molecular mechanism of P. lactiflora for treatment of

  10. Working Memory Components and Problem-Solving Accuracy: Are There Multiple Pathways?

    Science.gov (United States)

    Swanson, H. Lee; Fung, Wenson

    2016-01-01

    This study determined the working memory (WM) components (executive, phonological short-term memory [STM], and visual-spatial sketchpad) that best predicted mathematical word problem-solving accuracy in elementary schoolchildren (N = 392). The battery of tests administered to assess mediators between WM and problem-solving included measures of…

  11. Simultaneous genome-wide inference of physical, genetic, regulatory, and functional pathway components.

    Directory of Open Access Journals (Sweden)

    Christopher Y Park

    2010-11-01

    Full Text Available Biomolecular pathways are built from diverse types of pairwise interactions, ranging from physical protein-protein interactions and modifications to indirect regulatory relationships. One goal of systems biology is to bridge three aspects of this complexity: the growing body of high-throughput data assaying these interactions; the specific interactions in which individual genes participate; and the genome-wide patterns of interactions in a system of interest. Here, we describe methodology for simultaneously predicting specific types of biomolecular interactions using high-throughput genomic data. This results in a comprehensive compendium of whole-genome networks for yeast, derived from ∼3,500 experimental conditions and describing 30 interaction types, which range from general (e.g. physical or regulatory to specific (e.g. phosphorylation or transcriptional regulation. We used these networks to investigate molecular pathways in carbon metabolism and cellular transport, proposing a novel connection between glycogen breakdown and glucose utilization supported by recent publications. Additionally, 14 specific predicted interactions in DNA topological change and protein biosynthesis were experimentally validated. We analyzed the systems-level network features within all interactomes, verifying the presence of small-world properties and enrichment for recurring network motifs. This compendium of physical, synthetic, regulatory, and functional interaction networks has been made publicly available through an interactive web interface for investigators to utilize in future research at http://function.princeton.edu/bioweaver/.

  12. A New Method of Histogram Computation for Efficient Implementation of the HOG Algorithm

    Directory of Open Access Journals (Sweden)

    Mariana-Eugenia Ilas

    2018-03-01

    Full Text Available In this paper we introduce a new histogram computation method to be used within the histogram of oriented gradients (HOG algorithm. The new method replaces the arctangent with the slope computation and the classical magnitude allocation based on interpolation with a simpler algorithm. The new method allows a more efficient implementation of HOG in general, and particularly in field-programmable gate arrays (FPGAs, by considerably reducing the area (thus increasing the level of parallelism, while maintaining very close classification accuracy compared to the original algorithm. Thus, the new method is attractive for many applications, including car detection and classification.

  13. Transcriptional stimulation of rate-limiting components of the autophagic pathway improves plant fitness

    Czech Academy of Sciences Publication Activity Database

    Minina, E. A.; Moschou, P. N.; Vetukuri, R. R.; Sanchez-Vera, V.; Cardoso, C.; Liu, Q.; Elander, P. H.; Dalman, K.; Beganovic, M.; Lindberg Yilmaz, J.; Marmon, S.; Shabala, S.; Suarez, M.; Ljung, K.; Novák, Ondřej; Shabala, S.; Stymne, S.; Hofius, D.; Bozhkov, P. V.

    2018-01-01

    Roč. 69, č. 6 (2018), s. 1415-1432 ISSN 0022-0957 Institutional support: RVO:61389030 Keywords : Aging * ATG genes * Autophagy * Autophagy-related ubiquitin-like conjugation systems * Biomass * Oil content * Ratelimiting components of autophagic flux * Seed yield * Stress resistance * Transcriptional regulation Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 5.830, year: 2016

  14. Pathways and mechanisms linking dietary components to cardiometabolic disease: thinking beyond calories.

    Science.gov (United States)

    Stanhope, K L; Goran, M I; Bosy-Westphal, A; King, J C; Schmidt, L A; Schwarz, J-M; Stice, E; Sylvetsky, A C; Turnbaugh, P J; Bray, G A; Gardner, C D; Havel, P J; Malik, V; Mason, A E; Ravussin, E; Rosenbaum, M; Welsh, J A; Allister-Price, C; Sigala, D M; Greenwood, M R C; Astrup, A; Krauss, R M

    2018-05-14

    Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference 'Diet and Cardiometabolic Health - Beyond Calories', and this paper summarizes the presentations and follow-up discussions. Regarding the health effects of dietary fat, sugar and non-nutritive sweeteners, it is concluded that food-specific saturated fatty acids and sugar-sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential 'beyond calories' mechanisms may lead to new strategies for attenuating the obesity crisis. © 2018 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

  15. Role of Host Type IA Phosphoinositide 3-Kinase Pathway Components in Invasin-Mediated Internalization of Yersinia enterocolitica.

    Science.gov (United States)

    Dowd, Georgina C; Bhalla, Manmeet; Kean, Bernard; Thomas, Rowan; Ireton, Keith

    2016-06-01

    Many bacterial pathogens subvert mammalian type IA phosphoinositide 3-kinase (PI3K) in order to induce their internalization into host cells. How PI3K promotes internalization is not well understood. Also unclear is whether type IA PI3K affects different pathogens through similar or distinct mechanisms. Here, we performed an RNA interference (RNAi)-based screen to identify components of the type IA PI3K pathway involved in invasin-mediated entry of Yersinia enterocolitica, an enteropathogen that causes enteritis and lymphadenitis. The 69 genes targeted encode known upstream regulators or downstream effectors of PI3K. A similar RNAi screen was previously performed with the food-borne bacterium Listeria monocytogenes The results of the screen with Y. enterocolitica indicate that at least nine members of the PI3K pathway are needed for invasin-mediated entry. Several of these proteins, including centaurin-α1, Dock180, focal adhesion kinase (FAK), Grp1, LL5α, LL5β, and PLD2 (phospholipase D2), were recruited to sites of entry. In addition, centaurin-α1, FAK, PLD2, and mTOR were required for remodeling of the actin cytoskeleton during entry. Six of the human proteins affecting invasin-dependent internalization also promote InlB-mediated entry of L. monocytogenes Our results identify several host proteins that mediate invasin-induced effects on the actin cytoskeleton and indicate that a subset of PI3K pathway components promote internalization of both Y. enterocolitica and L. monocytogenes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  16. Human gait recognition by pyramid of HOG feature on silhouette images

    Science.gov (United States)

    Yang, Guang; Yin, Yafeng; Park, Jeanrok; Man, Hong

    2013-03-01

    As a uncommon biometric modality, human gait recognition has a great advantage of identify people at a distance without high resolution images. It has attracted much attention in recent years, especially in the fields of computer vision and remote sensing. In this paper, we propose a human gait recognition framework that consists of a reliable background subtraction method followed by the pyramid of Histogram of Gradient (pHOG) feature extraction on the silhouette image, and a Hidden Markov Model (HMM) based classifier. Through background subtraction, the silhouette of human gait in each frame is extracted and normalized from the raw video sequence. After removing the shadow and noise in each region of interest (ROI), pHOG feature is computed on the silhouettes images. Then the pHOG features of each gait class will be used to train a corresponding HMM. In the test stage, pHOG feature will be extracted from each test sequence and used to calculate the posterior probability toward each trained HMM model. Experimental results on the CASIA Gait Dataset B1 demonstrate that with our proposed method can achieve very competitive recognition rate.

  17. Five-dimensional Monopole Equation with Hedge-Hog Ansatz and Abel's Differential Equation

    OpenAIRE

    Kihara, Hironobu

    2008-01-01

    We review the generalized monopole in the five-dimensional Euclidean space. A numerical solution with the Hedge-Hog ansatz is studied. The Bogomol'nyi equation becomes a second order autonomous non-linear differential equation. The equation can be translated into the Abel's differential equation of the second kind and is an algebraic differential equation.

  18. Do Transaction Costs and Risk Preferences Influence Marketing Arrangements in the Illinois Hog Industry?

    NARCIS (Netherlands)

    Franken, J.R.V.; Pennings, J.M.E.; Garcia, P.

    2008-01-01

    Studies of hog industry structure often invoke risk reduction and transaction costs explanations for empirical observations but fail to directly examine the core concepts of risk behavior and transaction costs theories. Using a more unified conceptual framework and unique survey and accounting data,

  19. 78 FR 45057 - Safety Zone; Alpena Area HOG Rally Fireworks, Alpena, Michigan

    Science.gov (United States)

    2013-07-26

    ...-AA00 Safety Zone; Alpena Area HOG Rally Fireworks, Alpena, Michigan AGENCY: Coast Guard, DHS. ACTION... rally in Alpena, Michigan with a fireworks display. Fireworks will be launched near the end of Mason Street, South of State Avenue, approximately 50 yards west of Thunder Bay in Alpena, Michigan. The...

  20. Price Density Forecasts in the U.S. Hog Market: Composite Procedures

    NARCIS (Netherlands)

    Trujillo Barrera, A.A.; Garcia, P.; Mallory, M.

    2013-01-01

    Abstract We develop and evaluate quarterly out-of-sample individual and composite density forecasts for U.S. hog prices using data from 1975.I to 2010.IV. Individual forecasts are generated from time series models and the implied distribution of USDA outlook forecasts. Composite density forecasts

  1. [Life cycle of Gongylonema mucronatum Seurat, 1916, parasite of the African hedge-hog (author's transl)].

    Science.gov (United States)

    Quentin, J C; Seguignes, M

    1979-01-01

    The Gongylonematid Nematode parasite of the Tunisian hedge-hog has been identified as Gongylonema mucronatum Seurat, 1916. The infective larva has been obtained from Locusta migratoria as intermediate host. The larval characters of this Gongylonema link it to the species G. pulchrum.

  2. Project recovers free wasted energy from an OSB dryer while eliminating a hog boiler

    Energy Technology Data Exchange (ETDEWEB)

    Normandin, A.; Levesque, S.; Laflamme, Y.; Charron, R. [Mesar-Environair Inc., Quebec, PQ (Canada)

    2008-09-15

    This article described how a mill producing oriented strand board (OSB) in Quebec optimized its energy balance with the installation of a flue gas heat recovery (FGHR) system developed by Mesar-Environair Inc. Many OSB mills produce enough wood waste heat to supply their hog boilers with valuable, yet inexpensive, fuel. The objective of this project was to recover waste heat and to find an application in the milling process to re-valorize it. The plant was using 3 hog boilers to heat thermal oil for their process, but only the newest hog boiler was in compliance for particulate emissions levels. The solution involved the use of a direct contact heat exchanger to meet the mill's requirements. The process consisted of pumping the log pond water in a counter-current direction to the humid OSB dryer flue gas. The energy was transferred from the gas to the water via vapor condensation. The customized equipment recovered most of the wasted heat and transferred it to the plant's log ponds. Cool process water from the log ponds was then recirculated through the condenser to trap the wasted energy. The efficiency of the main hog boiler and the chip dry was about 80 per cent. The FGHR process was designed to recover 85 per cent of the wasted energy that was directed to the atmosphere. The heat recovery unit can typically generate temperatures of 70 to 80 degrees C. In addition to fewer emissions of carbon dioxide and nitrogen oxides going out the stack, the FGHR system offers the advantages of heating the process water without additional fuel, and shutting down an old hog boiler. 1 tabs., 3 figs.

  3. Phytophthora effector targets a novel component of small RNA pathway in plants to promote infection.

    Science.gov (United States)

    Qiao, Yongli; Shi, Jinxia; Zhai, Yi; Hou, Yingnan; Ma, Wenbo

    2015-05-05

    A broad range of parasites rely on the functions of effector proteins to subvert host immune response and facilitate disease development. The notorious Phytophthora pathogens evolved effectors with RNA silencing suppression activity to promote infection in plant hosts. Here we report that the Phytophthora Suppressor of RNA Silencing 1 (PSR1) can bind to an evolutionarily conserved nuclear protein containing the aspartate-glutamate-alanine-histidine-box RNA helicase domain in plants. This protein, designated PSR1-Interacting Protein 1 (PINP1), regulates the accumulation of both microRNAs and endogenous small interfering RNAs in Arabidopsis. A null mutation of PINP1 causes embryonic lethality, and silencing of PINP1 leads to developmental defects and hypersusceptibility to Phytophthora infection. These phenotypes are reminiscent of transgenic plants expressing PSR1, supporting PINP1 as a direct virulence target of PSR1. We further demonstrate that the localization of the Dicer-like 1 protein complex is impaired in the nucleus of PINP1-silenced or PSR1-expressing cells, indicating that PINP1 may facilitate small RNA processing by affecting the assembly of dicing complexes. A similar function of PINP1 homologous genes in development and immunity was also observed in Nicotiana benthamiana. These findings highlight PINP1 as a previously unidentified component of RNA silencing that regulates distinct classes of small RNAs in plants. Importantly, Phytophthora has evolved effectors to target PINP1 in order to promote infection.

  4. An essential nuclear protein in trypanosomes is a component of mRNA transcription/export pathway.

    Directory of Open Access Journals (Sweden)

    Mariana Serpeloni

    Full Text Available In eukaryotic cells, different RNA species are exported from the nucleus via specialized pathways. The mRNA export machinery is highly integrated with mRNA processing, and includes a different set of nuclear transport adaptors as well as other mRNA binding proteins, RNA helicases, and NPC-associated proteins. The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, a widespread and neglected human disease which is endemic to Latin America. Gene expression in Trypanosoma has unique characteristics, such as constitutive polycistronic transcription of protein-encoding genes and mRNA processing by trans-splicing. In general, post-transcriptional events are the major points for regulation of gene expression in these parasites. However, the export pathway of mRNA from the nucleus is poorly understood. The present study investigated the function of TcSub2, which is a highly conserved protein ortholog to Sub2/ UAP56, a component of the Transcription/Export (TREX multiprotein complex connecting transcription with mRNA export in yeast/human. Similar to its orthologs, TcSub2 is a nuclear protein, localized in dispersed foci all over the nuclei -except the fibrillar center of nucleolus- and at the interface between dense and non-dense chromatin areas, proposing the association of TcSub2 with transcription/processing sites. These findings were analyzed further by BrUTP incorporation assays and confirmed that TcSub2 is physically associated with active RNA polymerase II (RNA pol II, but not RNA polymerase I (RNA pol I or Spliced Leader (SL transcription, demonstrating participation particularly in nuclear mRNA metabolism in T. cruzi. The double knockout of the TcSub2 gene is lethal in T. cruzi, suggesting it has an essential function. Alternatively, RNA interference assays were performed in Trypanosoma brucei. It allowed demonstrating that besides being an essential protein, its knockdown causes mRNA accumulation in the nucleus and

  5. Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment

    Directory of Open Access Journals (Sweden)

    Sonntag William E

    2011-10-01

    Full Text Available Abstract Background Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline. Methods Three independent cohorts of adult (12-13 months and aged (26-28 months F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG. Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6 and Iba1. Results We report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance. Conclusions These data demonstrate a

  6. Population characteristics and viability of the introduced hog deer (Axis porcinus Zimmermann, 1780 in Phu Khieo Wildlife Sanctuary, Thailand

    Directory of Open Access Journals (Sweden)

    Worawidh Wajjwalku

    2012-07-01

    Full Text Available The purposes of this study were to study population characteristics of hog deer released into the wild, namely: density,age structure, sex ratio, recruitment rate, threats to hog deer, carrying capacity and inter-specific relationships, as well as toassess the population viability over time. In this study, direct observation was used to study the hog deer population characteristics,and population density was estimated from the pellet-group count method. Vortex program was used to analyze thepopulation viability. Results showed that the population density of hog deer at Thung Ka Mung (TKM in Phu Khieo WildlifeSanctuary (PKWS was 2.03-2.04 individuals/hectare (SD = 1.25. The population structure showed that the average herd sizewas 9.57 individuals. Hog deer in TKM preferred to stay with a group (91.5%, rather than being solitary (8.5%. The sex ratiofor males to females was 54.64:100, and for females to fawns was 100:26.18. The annual recruitment rate was 16.98 %. Theirpredators were Asian wild dogs, Burmese pythons, Asiatic jackals, leopard cats and clouded leopards. The mortality rate ofthe existing hog deer in TKM during the study period was 18.1%. The habitat sharing by camera traps revealed 4 ungulatespecies. They were sambar deer, barking deer, wild boar, and elephant, and their relative abundance were 28.41%, 7.38%,4.70%, and 2.01% respectively. Fifty-year simulation modeling using population viability analysis indicated the sustainabilityof this population. Hog deer population in the simulations did not exhibit sensitivity to an increase or decrease in carryingcapacity. Habitat management should be carried out continuously in TKM area, which is the main habitat for hog deer inPKWS.

  7. Identification of lysophosphatidylcholine, γ-stearoyl (LPCD) as an endogenous Na+, K+-ATPase inhibitor in volume-expanded hog plasma

    International Nuclear Information System (INIS)

    Tamura, M.; Inagami, T.

    1986-01-01

    We have shown that the Na + , K + -ATPase inhibitory activities in the plasma of volume-expanded hog consist of multiple components. One group of the major inhibitory activities induced by intravascular saline infusion was identified as unsaturated free fatty acids. The present study was undertaken to determine the identity of the remaining Na + , K + -ATPase inhibitory activity in the plasma of volume-expanded hogs. Three peaks with ouabain displacing activity (ODA) were separated by HPLC on a reversed phase octadecyl column. The slowest eluting material which showed good solubility in water and recognizable optical absorbance at 214 nm was purified further by three additional steps of reverse phase HPLC. FAB mass spectrometry and 1 H NMR spectroscopy identified this substance as lysophosphatidylcholine, γ-stearoyl. Both purified and synthetic LPCS showed dose-dependent inhibition of Na + , K + -ATPase and displacement of [ 3 H] ouabain from the ATPase. Lysophosphatidylcholines containing either palmitoyl or myristoyl groups also exhibited the Na + , K + -ATPase inhibitory activity and the ODA. The ODA in the LPCS containing fraction increased during the saline infusion. These results indicate that LPCS is an endogenous Na + , K + -ATPase inhibitor which is induced by the expansion of plasma volume

  8. Simulation of the Impact of SRT on Anaerobic Digestability of Ultrasonicated Hog Manure

    Directory of Open Access Journals (Sweden)

    Elsayed Elbeshbishy

    2010-05-01

    Full Text Available Ultrasonication at a specific energy of 500 kJ/kgTS was applied to hog manure in a continuous mode completely mixed anaerobic digestion. A process model in BioWin was developed, calibrated and tested at different solids retention times (SRTs to evaluate the process economics. The results showed that there was a 36% increase in volatile suspended solids (VSS removal efficiency, a 20% increase in methane production rate, a 13.5% increase in destruction of bound proteins, and a reduction from 988 to 566 ppm in H2S concentration in the digester headspace. Furthermore, a calibrated model of the process using BioWin to assess the impact of SRTs on the economics of anaerobic digestion for unsonicated and sonicated hog manure revealed that ultrasonication resulted in a net benefit of $42–46/ton dry solids at SRTs of 15–30 days.

  9. Simulation of the impact of SRT on anaerobic digestability of ultrasonicated hog manure

    Energy Technology Data Exchange (ETDEWEB)

    Elbeshbishy, E.; Hafez, H.; Nakhla, G. [Department of Civil and Environmental Engineering, University of Western Ontario, London, Ontario N6A 5B9 (Canada); Nakevski, A.; Ray, M. [Department of Chemical and Biochemical Engineering, University of Western Ontario, London, Ontario N6A 5B9 (Canada)

    2010-07-01

    Ultrasonication at a specific energy of 500 kJ/kgTS was applied to hog manure in a continuous mode completely mixed anaerobic digestion. A process model in BioWin was developed, calibrated and tested at different solids retention times (SRTs) to evaluate the process economics. The results showed that there was a 36% increase in volatile suspended solids (VSS) removal efficiency, a 20% increase in methane production rate, a 13.5% increase in destruction of bound proteins, and a reduction from 988 to 566 ppm in H{sub 2}S concentration in the digester headspace. Furthermore, a calibrated model of the process using BioWin to assess the impact of SRTs on the economics of anaerobic digestion for unsonicated and sonicated hog manure revealed that ultrasonication resulted in a net benefit of $42-46/ton dry solids at SRTs of 15-30 days. (author)

  10. Expression of factors and key components associated with the PI3K signaling pathway in colon cancer.

    Science.gov (United States)

    Chen, Hua; Gao, Junyi; Du, Zhenhua; Zhang, Xuequn; Yang, Fei; Gao, Wei

    2018-04-01

    The pathophysiology of colorectal cancer (CRC) has not been fully elucidated. The dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway frequently contributes to the tumorigenesis and progression of human cancer. The aim of the present study was to explore the expression and clinical significance of a number of associated factors and key components of the PI3K signaling pathway, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (p110α), phosphorylated protein kinase B (p-Akt) Ser473, p-mammalian target of rapamycin (mTOR) Ser2448, cyclin D1, cyclin dependent kinase (CDK)4, RELA proto-oncogene, nuclear factor-κβ subunit (p65), Ras and extracellular signal-regulated kinase (ERK)1/2 in human CRC. The expression of target proteins was detected using immunohistochemistry (IHC) in 65 CRC cases and 15 colonic adenoma cases. The association between the expression of target proteins and clinical pathological parameters was analyzed using a χ 2 test. IHC results revealed that the expression of all target proteins was significantly increased in CRC tissues compared with in colonic adenoma tissues (P0.05). Cyclin D1, CDK4 and Ras were revealed to be expressed significantly higher in poorly differentiated CRC compared with moderately differentiated CRC (Pcancer tissues with lymph node metastasis compared with cancer tissues without lymph node metastasis (P<0.05). These results suggest that the target proteins may all participate in the tumorigenesis of CRC. Furthermore, cyclin D1, CDK4, Ras, p65 and ERK1/2 may be important in the progression of CRC. The results of the present study may provide novel predictive factors and therapeutic targets for CRC.

  11. The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation.

    Science.gov (United States)

    Martins, Telma S; Pereira, Clara; Canadell, David; Vilaça, Rita; Teixeira, Vítor; Moradas-Ferreira, Pedro; de Nadal, Eulàlia; Posas, Francesc; Costa, Vítor

    2018-01-01

    Iron acquisition systems have to be tightly regulated to assure a continuous supply of iron, since it is essential for survival, but simultaneously to prevent iron overload that is toxic to the cells. In budding yeast, the low‑iron sensing transcription factor Aft1p is a master regulator of the iron regulon. Our previous work revealed that bioactive sphingolipids modulate iron homeostasis as yeast cells lacking the sphingomyelinase Isc1p exhibit an upregulation of the iron regulon. In this study, we show that Isc1p impacts on iron accumulation and localization. Notably, Aft1p is activated in isc1Δ cells due to a decrease in its phosphorylation and an increase in its nuclear levels. Consistently, the expression of a phosphomimetic version of Aft1p-S210/S224 that favours its nuclear export abolished iron accumulation in isc1Δ cells. Notably, the Hog1p kinase, homologue of mammalian p38, interacts with and directly phosphorylates Aft1p at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in isc1Δ cells, which likely contributes to Aft1p dephosphorylation and consequently to Aft1p activation and iron overload in isc1Δ cells. These results suggest that alterations in sphingolipid composition in isc1Δ cells may impact on iron homeostasis by disturbing the regulation of Aft1p by Hog1p. To our knowledge, Hog1p is the first kinase reported to directly regulate Aft1p, impacting on iron homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Activation of the Saccharomyces cerevisiae filamentation/invasion pathway by osmotic stress in high-osmolarity glycogen pathway mutants

    Science.gov (United States)

    Davenport, K. D.; Williams, K. E.; Ullmann, B. D.; Gustin, M. C.; McIntire, L. V. (Principal Investigator)

    1999-01-01

    Mitogen-activated protein kinase (MAPK) cascades are frequently used signal transduction mechanisms in eukaryotes. Of the five MAPK cascades in Saccharomyces cerevisiae, the high-osmolarity glycerol response (HOG) pathway functions to sense and respond to hypertonic stress. We utilized a partial loss-of-function mutant in the HOG pathway, pbs2-3, in a high-copy suppressor screen to identify proteins that modulate growth on high-osmolarity media. Three high-copy suppressors of pbs2-3 osmosensitivity were identified: MSG5, CAK1, and TRX1. Msg5p is a dual-specificity phosphatase that was previously demonstrated to dephosphorylate MAPKs in yeast. Deletions of the putative MAPK targets of Msg5p revealed that kss1delta could suppress the osmosensitivity of pbs2-3. Kss1p is phosphorylated in response to hyperosmotic shock in a pbs2-3 strain, but not in a wild-type strain nor in a pbs2-3 strain overexpressing MSG5. Both TEC1 and FRE::lacZ expressions are activated in strains lacking a functional HOG pathway during osmotic stress in a filamentation/invasion-pathway-dependent manner. Additionally, the cellular projections formed by a pbs2-3 mutant on high osmolarity are absent in strains lacking KSS1 or STE7. These data suggest that the loss of filamentation/invasion pathway repression contributes to the HOG mutant phenotype.

  13. Ship detection based on rotation-invariant HOG descriptors for airborne infrared images

    Science.gov (United States)

    Xu, Guojing; Wang, Jinyan; Qi, Shengxiang

    2018-03-01

    Infrared thermal imagery is widely used in various kinds of aircraft because of its all-time application. Meanwhile, detecting ships from infrared images attract lots of research interests in recent years. In the case of downward-looking infrared imagery, in order to overcome the uncertainty of target imaging attitude due to the unknown position relationship between the aircraft and the target, we propose a new infrared ship detection method which integrates rotation invariant gradient direction histogram (Circle Histogram of Oriented Gradient, C-HOG) descriptors and the support vector machine (SVM) classifier. In details, the proposed method uses HOG descriptors to express the local feature of infrared images to adapt to changes in illumination and to overcome sea clutter effects. Different from traditional computation of HOG descriptor, we subdivide the image into annular spatial bins instead of rectangle sub-regions, and then Radial Gradient Transform (RGT) on the gradient is applied to achieve rotation invariant histogram information. Considering the engineering application of airborne and real-time requirements, we use SVM for training ship target and non-target background infrared sample images to discriminate real ships from false targets. Experimental results show that the proposed method has good performance in both the robustness and run-time for infrared ship target detection with different rotation angles.

  14. Using infrared HOG-based pedestrian detection for outdoor autonomous searching UAV with embedded system

    Science.gov (United States)

    Shao, Yanhua; Mei, Yanying; Chu, Hongyu; Chang, Zhiyuan; He, Yuxuan; Zhan, Huayi

    2018-04-01

    Pedestrian detection (PD) is an important application domain in computer vision and pattern recognition. Unmanned Aerial Vehicles (UAVs) have become a major field of research in recent years. In this paper, an algorithm for a robust pedestrian detection method based on the combination of the infrared HOG (IR-HOG) feature and SVM is proposed for highly complex outdoor scenarios on the basis of airborne IR image sequences from UAV. The basic flow of our application operation is as follows. Firstly, the thermal infrared imager (TAU2-336), which was installed on our Outdoor Autonomous Searching (OAS) UAV, is used for taking pictures of the designated outdoor area. Secondly, image sequences collecting and processing were accomplished by using high-performance embedded system with Samsung ODROID-XU4 and Ubuntu as the core and operating system respectively, and IR-HOG features were extracted. Finally, the SVM is used to train the pedestrian classifier. Experiment show that, our method shows promising results under complex conditions including strong noise corruption, partial occlusion etc.

  15. An evolutionarily stable strategy and the critical point of hog futures trading entities based on replicator dynamic theory: 2006-2015 data for China's 22 provinces.

    Science.gov (United States)

    Pang, Jinbo; Deng, Lingfei; Wang, Gangyi

    2017-01-01

    Although frequent fluctuations in domestic hog prices seriously affect the stability and robustness of the hog supply chain, hog futures (an effective hedging instrument) have not been listed in China. To better understand hog futures market hedging, it is important to study the steady state of intersubjective bidding. This paper uses evolutionary game theory to construct a game model between hedgers and speculators in the hog futures market, and replicator dynamic equations are then used to obtain the steady state between the two trading entities. The results show that the steady state is one in which hedgers adopt a "buy" strategy and speculators adopt a "do not speculate" strategy, but this type of extreme steady state is not easily realized. Thus, to explore the rational proportion of hedgers and speculators in the evolutionary stabilization strategy, bidding processes were simulated using weekly average hog prices from 2006 to 2015, such that the conditions under which hedgers and speculators achieve a steady state could be analyzed. This task was performed to achieve the stability critical point, and we show that only when the value of λ is satisfied and the conditions of hog futures price changes and futures price are satisfied can hedgers and speculators achieve a rational proportion and a stable hog futures market. This market can thus provide a valuable reference for the development of the Chinese hog futures market and the formulation and guidance of relevant departmental policies.

  16. The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection

    DEFF Research Database (Denmark)

    Ali, Youssif M; Lynch, Nicholas J; Haleem, Kashif S

    2012-01-01

    The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation...... to pneumococcal infection and fail to opsonize Streptococcus pneumoniae in the none-immune host. This defect in complement opsonisation severely compromises pathogen clearance in the lectin pathway deficient host. Using sera from mice and humans with defined complement deficiencies, we demonstrate that mouse...... of C4. This study corroborates the essential function of MASP-2 in the lectin pathway and highlights the importance of MBL-independent lectin pathway activation in the host defense against pneumococci....

  17. Detection and segmentation of virus plaque using HOG and SVM: toward automatic plaque assay.

    Science.gov (United States)

    Mao, Yihao; Liu, Hong; Ye, Rong; Shi, Yonghong; Song, Zhijian

    2014-01-01

    Plaque assaying, measurement of the number, diameter, and area of plaques in a Petri dish image, is a standard procedure gauging the concentration of phage in biology. This paper presented a novel and effective method for implementing automatic plaque assaying. The method was mainly comprised of the following steps: In the training stage, after pre-processing the images for noise suppression, an initial training set was readied by sampling positive (with a plaque at the center) and negative (plaque-free) patches from the training images, and extracting the HOG features from each patch. The linear SVM classifier was trained in a self-learnt supervised learning strategy to avoid possible missing detection. Specifically, the training set which contained positive and negative patches sampled manually from training images was used to train the preliminary classifier which exhaustively searched the training images to predict the label for the unlabeled patches. The mislabeled patches were evaluated by experts and relabeled. And all the newly labeled patches and their corresponding HOG features were added to the initial training set to train the final classifier. In the testing stage, a sliding-window technique was first applied to the unseen image for obtaining HOG features, which were inputted into the classifier to predict whether the patch was positive. Second, a locally adaptive Otsu method was performed on the positive patches to segment the plaques. Finally, after removing the outliers, the parameters of the plaques were measured in the segmented plaques. The experimental results demonstrated that the accuracy of the proposed method was similar to the one measured manually by experts, but it took less than 30 seconds.

  18. FRUIT FLIES (DIPTERA: TEPHRITIDAE AND THEIR PARASITOIDS ASSOCIATED WITH DIFFERENT HOG PLUM GENOTYPES IN TERESINA, PIAUÍ

    Directory of Open Access Journals (Sweden)

    LEONARDO DA SILVA SOUSA

    2017-10-01

    Full Text Available ABSTRACT The aim of this work was to identify and quantify the infestation of fruit fly species and their parasitoids, associated with 20 hog plum genotypes (Spondias mombin L. in a commercial orchard in Teresina, Piauí, Brazil. The survey was conducted by fruit sampling and monitoring through traps stocked with bait food, in the period from January to December 2012. Overall, 6560 fruits were collected (79.58 kg, resulting in 23059 pupae, of which 10080 fruit flies of the genus Anastrepha and 4984 braconid parasitoids emerged. Anastrepha obliqua species was the predominant with 99.92%. F16P13 and F11P10 genotypes had the highest infestation indexes and F15P11 and F04P01 genotypes, the lowest. The main parasitoids collected were Opius bellus (77.65%, Doryctobracon areolatus (19.88% and Utetes anastrephae (2.47%. The average parasitism rate among genotypes was of 30.46%. In traps, a total of 1434 fruit flies were collected, whose species were: A. obliqua (97.6%, A. serpentina (1.4%, A. fraterculus (0.4%, A. striata (0.4%, A. dissimilis (0.1%, A. pseudoparallela (0.1%. Anastrepha obliqua species was predominant in the area, based on faunistic analysis. The infestation index in the orchard was relevant for five months (January-May, coinciding with the period of availability of hog plum fruits, reaching the highest peak in March (2.86 FAT. There was a significant negative correlation between number of fruit flies in the orchard and the average air temperature, and a significant positive correlation with rainfall and relative humidity. However, the main factor that influenced the observed infestation index in the hog plum orchard was fruit availability.

  19. Simulation of the Impact of SRT on Anaerobic Digestability of Ultrasonicated Hog Manure

    OpenAIRE

    Elbeshbishy; Nakevski; Hafez; Ray; Nakhla

    2010-01-01

    Ultrasonication at a specific energy of 500 kJ/kgTS was applied to hog manure in a continuous mode completely mixed anaerobic digestion. A process model in BioWin was developed, calibrated and tested at different solids retention times (SRTs) to evaluate the process economics. The results showed that there was a 36% increase in volatile suspended solids (VSS) removal efficiency, a 20% increase in methane production rate, a 13.5% increase in destruction of bound proteins, and a reduction from ...

  20. Transcription factor Brn-3α mRNA in cancers, relationship with AR, ER receptors and AKT/m-TOR pathway components

    Science.gov (United States)

    Spirina, L. V.; Gorbunov, A. K.; Chigevskaya, S. Y.; Usynin, Y. A.; Kondakova, I. V.; Slonimskaya, E. M.; Usynin, E. A.; Choinzonov, E. L.; Zaitseva, O. S.

    2017-09-01

    Transcription factors POU4F1 (neurogenic factor Brn-3α) play a pivotal role in cancers development. The aim of the study was to reveal the Brn-3α expression, AR, ER expression in cancers development, association with AKT/mTOR pathway activation. 30 patients with locally advanced prostate cancer, 20 patients with papillary thyroid cancer, T2-3N0-1M0 stages and 40 patients with renal cell cancer T2-3N0M0-1 were involved into the study. The expressions of Brn-3α, AR, ERα, components of AKT/m-TOR signaling pathway genes were performed by real-time PCR. The dependence of Brn-3α expression on mRNA levels of steroid hormone receptors and components of AKT/m-TOR signaling pathway in studied cancers were shown. High levels of mRNA of nuclear factor, steroid hormone receptors were found followed by the activation of this signaling pathway in prostate cancer tissue. The reduction of transcription factor Brn-3α was accompanied with tumor invasive growth with increasing rates of AR, ER and 4E-BP1 mRNA. Thyroid cancer development happened in a case of a Brn-3α and steroid hormone receptors decrease. The activation of AKT/m-TOR signaling pathway was established in the metastatic renal cancers, accompanied with the increase of ER mRNA. But there was no correlation between the steroid receptor and Brn-3α. One-direction changes of Brn-3α were observed in the development of prostate and thyroid cancer due to its effect on the steroid hormone receptors and the activation of AKT/m-TOR signaling pathway components. The influence of this factor on the development of the kidney cancer was mediated through m-TOR activity modifications, the key enzyme of oncogenesis.

  1. Finisher hog production in the Southeastern United States: Ancillary measurements derived from the National Air Emissions Monitoring Study (NAEMS)

    Science.gov (United States)

    Robarge, W. P.; Lee, S.; Walker, J. T.

    2010-12-01

    Measurements of emissions of gases and fine particulate matter from swine animal feeding operations (AFOs) in the southeastern US have typically been confined to relatively short periods (days to several weeks) and have generally focused on waste lagoons. Access to swine animal housing units and other ancillary information has been limited. The National Air Emissions Monitoring Study (NAEMS) provided a unique opportunity to characterize emissions from swine housing units for an extended period of time (~ 2 years), and allowed access to ancillary measurements regarding nutrient flows (feed amounts and composition), manure dynamics, animal inventories, water usage and farm management. Presented here is a summary of the observations made for a NAEMS finisher site (NC3B) selected as being representative of swine production in the southeastern US. Finisher hogs are raised in rotations (~ 140 days) with a target market weight of 123 kg/hog. Among the population during a rotation (700-800 hogs/barn) the actual growth rate varies with a series of “grade-outs” of market-weight hogs starting ~ 110 days from initial load-in. Derivation of the standing live-weight in the barns during a rotation therefore requires use of a growth model and summation over several different “populations” of hogs within a single barn. Up to 5 different feed formulations are fed during a rotation with %N content ranging from (3.4 to 2.2% N; total feed consumed 181,000 kg/barn). Across 4 complete rotations, N consumed was ~50 g N per hog/day. Of this amount, we estimate ~ 60% is excreted as fecal matter and urine. The TAN (NH3 + NH4+) content of the shallow pits is consistently higher (1880 ±390 mg TAN/L) than that found in the anaerobic lagoon (800 ±70 mg TAN/L), except immediately after recharge following pit-pull (pH of the two liquids was similar). The presence of a recalcitrant layer of sludge in the shallow pits (liquid height = 20 cm; sludge depth = 5-10 cm; TAN = 2500 mg N/L; total

  2. Low-temperature anaerobic treatment of hog manure and transformation of biogas into green energy

    Energy Technology Data Exchange (ETDEWEB)

    Van-Anh Truong, L.; Royer, R.

    2004-08-01

    A new environmental solution for hog manure management has been developed by Bio-Terre Systems Inc. in collaboration with Agriculture and Agri-Food Canada. The technical approach combines low-temperature anaerobic digestion, concentration of solids and production of biogas, a renewable energy source. Both small and large agricultural producers can benefit from this approach which helps transform organic matter into value-added by-products. They can fertilize their land with the liquid fraction, supply energy for their buildings with the biogas produced, and export surplus nutrients with the solid fraction. The technology also solves odour problems and destroys pathogenic microorganisms. No pretreatment is needed for this technology which makes use of robust anaerobic microorganisms that are low temperature tolerant. It is a stable process that provides continuous production of biogas with high energy potential. The automated system does not require much monitoring or maintenance. The environmental advantages include the production of biogas rich in methane, which can be used for electrical energy on the farm or sent to the electric power grids; production of high-value, odorless liquid fertilizer; a 50 per cent reduction of the amount of phosphorous in the liquid fraction; and, a 90 per cent reduction in greenhouse gas emissions from hog manure. The profitability of capital investment is assured by both the energy-savings and the agricultural benefits. 1 tab., 1 fig.

  3. Mammalian folylpoly-γ-glutamate synthetase. 1. Purification and general properties of the hog liver enzyme

    International Nuclear Information System (INIS)

    Cichowicz, D.J.; Shane, B.

    1987-01-01

    Folylpolyglutamate synthetase was purified 30,000-150,000-fold from hog liver. Purification required the use of protease inhibitors, and the protein was purified to homogeneity in two forms. Both forms of the enzyme were monomers of M/sub r/ 62,000 and had similar specific activities. The specific activity of the homogeneous protein was over 2000-fold higher than reported for partially purified folylpolyglutamate synthetases from other mammalian sources. Enzyme activity was absolutely dependent on the presence of a reducing agent and a monovalent cation, of which K + was most effective. The purified enzyme catalyzed a MgATP-dependent addition of glutamate to tetrahydrofolate with the concomitant stoichiometric formation of MgADP and phosphate. Under conditions that resembled the expected substrate and enzyme concentrations in hog liver, tetrahydrofolate was metabolized to long glutamate chain length derivatives with the hexaglutamate, the major in vivo folate derivative, predominating. Enzyme activity was maximal at about pH 9.5. The high-pH optimum was primarily due to an increase in the K/sub m/ value for the L-glutamate substrate at lower pH values, and the reaction proceeded effectively at physiological pH provided high levels of glutamate were supplied

  4. A novel technique for hydrogen production from hog-manure in supercritical partial oxidation (SCWPO)

    Energy Technology Data Exchange (ETDEWEB)

    Youssef, Emhemmed A.; Charpentier, Paul [Western Ontario Univ., London, ON (Canada). Dept. of Chemical and Biochemical Engineering; Nakhla, George [Western Ontario Univ., London, ON (Canada). Dept. of Chemical and Biochemical Engineering; Western Ontario Univ., London, ON (Canada). Dept. of Civil and Environmental Engineering; Elbeshbishy, Elsayed; Hafez, Hisham [Western Ontario Univ., London, ON (Canada). Dept. of Civil and Environmental Engineering

    2010-07-01

    In this study, the catalytic hydrogen production from hog manure using supercritical water partial oxidation was investigated in a batch reactor at a temperature of 500 C, and pressure of 28 MPa using several metallic catalysts. Hog manure was characterized by a total and soluble chemical oxygen demand (TCOD, SCOD) of 57000 and 28000 mg/L, total and volatile suspended solids (TSS, VSS) of 25000, 19000, and ammonia of 2400 mg/L, respectively. The order of H{sub 2} production was the following: Pd/AC > Ru/Al{sub 2}O{sub 3} > Ru/AC > AC > NaOH. The order of COD reduction efficiency was as follows: NaOH > Ru/AC > AC > Ru/Al{sub 2}O{sub 3} > Pd/AC. The behaviour of the volatile fatty acids (VFA's), ethanol, methanol, ammonia, H{sub 2}S, and Sulfate was investigated experimentally and discussed. A 35 % reduction in the H{sub 2} and CH{sub 4} yields was observed in the sequential gasification partial oxidation (oxidant at an 80 % of theoretical requirement) experiments compared to the gasification experiments (catalyst only). Moreover, this reduction in gas yields was coincided with a 45 % reduction in the liquid effluent chemical oxygen demand (COD), 60 % reduction of the ammonia concentration in the liquid effluent, and 20 % reduction in the H{sub 2}S concentration in the effluent gas. (orig.)

  5. Automatic Samples Selection Using Histogram of Oriented Gradients (HOG Feature Distance

    Directory of Open Access Journals (Sweden)

    Inzar Salfikar

    2018-01-01

    Full Text Available Finding victims at a disaster site is the primary goal of Search-and-Rescue (SAR operations. Many technologies created from research for searching disaster victims through aerial imaging. but, most of them are difficult to detect victims at tsunami disaster sites with victims and backgrounds which are look similar. This research collects post-tsunami aerial imaging data from the internet to builds dataset and model for detecting tsunami disaster victims. Datasets are built based on distance differences from features every sample using Histogram-of-Oriented-Gradient (HOG method. We use the longest distance to collect samples from photo to generate victim and non-victim samples. We claim steps to collect samples by measuring HOG feature distance from all samples. the longest distance between samples will take as a candidate to build the dataset, then classify victim (positives and non-victim (negatives samples manually. The dataset of tsunami disaster victims was re-analyzed using cross-validation Leave-One-Out (LOO with Support-Vector-Machine (SVM method. The experimental results show the performance of two test photos with 61.70% precision, 77.60% accuracy, 74.36% recall and f-measure 67.44% to distinguish victim (positives and non-victim (negatives.

  6. Active Components with Inhibitory Activities on IFN-γ/STAT1 and IL-6/STAT3 Signaling Pathways from Caulis Trachelospermi

    Directory of Open Access Journals (Sweden)

    Xiao-Ting Liu

    2014-08-01

    Full Text Available Initial investigation for new active herbal extract with inhibiting activity on JAK/STAT signaling pathway revealed that the extract of Caulis Trachelospermi, which was separated by 80% alcohol extraction and subsequent HP-20 macroporous resin column chromatography, was founded to strongly inhibit IFN-γ-induced STAT1-responsive luciferase activity (IFN-γ/STAT1 with IC50 value of 2.43 μg/mL as well as inhibiting IL-6-induced STAT3-responsive luciferase activity (IL-6/STAT3 with IC50 value of 1.38 μg/mL. Subsequent study on its active components led to the isolation and identification of two new dibenzylbutyrolactone lignans named 4-demethyltraxillaside (1 and nortrachelogenin 4-O-β-d-glucopyranoside (2, together with six known compounds. The lignan compounds 1–4 together with other lignan compounds isolated in previous study were tested the activities on IFN-γ/STAT1 and IL-6/STAT3 pathways. The following result showed that the main components trachelogenin and arctigenin had corresponding activities on IFN-γ/STAT1 pathway with IC50 values of 3.14 μM and 9.46 μM as well as trachelogenin, arctigenin and matairesinol strongly inhibiting IL-6/STAT3 pathway with IC50 values of 3.63 μM, 6.47 μM and 2.92 μM, respectively.

  7. Scoping calculation for components of the cow-milk dose pathway for evaluating the dose contribution from iodine-131

    International Nuclear Information System (INIS)

    Ikenberry, T.A.; Napier, B.A.

    1992-12-01

    A series of scoping calculations have been undertaken to evaluate The absolute and relative contribution of different exposure pathways to doses that may have been received by individuals living in the vicinity of the Hanford site. This scoping calculation (Calculation 001) examined the contributions of the various exposure pathways associated with environmental transport and accumulation of iodine-131 in the pasture-cow-milk pathway. Addressed in this calculation were the contributions to thyroid dose of infants and adult from (1) the ingestion by dairy cattle of various feedstuffs (pasturage, silage, alfalfa hay, and grass hay) in four different feeding regimes; (2) ingestion of soil by dairy cattle; (3) ingestion of stared feed on which airborne iodine-131 had been deposited; and (4) inhalation of airborne iodine-131 by dairy cows

  8. Post-translational regulation of miRNA pathway components, AGO1 and HYL1, in plants

    DEFF Research Database (Denmark)

    Cho, Seok Keun; Ryu, Moon Young; Shah, Pratik

    2016-01-01

    , the complexity of the proteome increases, and this then influences most biological processes. Although small RNAs are crucial regulatory elements for gene expression in most eukaryotes, PTMs of small RNA microprocessor and RNA silencing components have not been extensively investigated in plants. To date...... findings on the PTMs of microprocessor and RNA silencing components in plants....

  9. Osmostress induces autophosphorylation of Hog1 via a C-terminal regulatory region that is conserved in p38α.

    Directory of Open Access Journals (Sweden)

    Inbal Maayan

    Full Text Available Many protein kinases require phosphorylation at their activation loop for induction of catalysis. Mitogen-activated protein kinases (MAPKs are activated by a unique mode of phosphorylation, on neighboring Tyrosine and Threonine residues. Whereas many kinases obtain their activation via autophosphorylation, MAPKs are usually phosphorylated by specific, dedicated, MAPK kinases (MAP2Ks. Here we show however, that the yeast MAPK Hog1, known to be activated by the MAP2K Pbs2, is activated in pbs2Δ cells via an autophosphorylation activity that is induced by osmotic pressure. We mapped a novel domain at the Hog1 C-terminal region that inhibits this activity. Removal of this domain provides a Hog1 protein that is partially independent of MAP2K, namely, partially rescues osmostress sensitivity of pbs2Δ cells. We further mapped a short domain (7 amino acid residues long that is critical for induction of autophosphorylation. Its removal abolishes autophosphorylation, but maintains Pbs2-mediated phosphorylation. This 7 amino acids stretch is conserved in the human p38α. Similar to the case of Hog1, it's removal from p38α abolishes p38α's autophosphorylation capability, but maintains, although reduces, its activation by MKK6. This study joins a few recent reports to suggest that, like many protein kinases, MAPKs are also regulated via induced autoactivation.

  10. Osmostress induces autophosphorylation of Hog1 via a C-terminal regulatory region that is conserved in p38α.

    Science.gov (United States)

    Maayan, Inbal; Beenstock, Jonah; Marbach, Irit; Tabachnick, Shira; Livnah, Oded; Engelberg, David

    2012-01-01

    Many protein kinases require phosphorylation at their activation loop for induction of catalysis. Mitogen-activated protein kinases (MAPKs) are activated by a unique mode of phosphorylation, on neighboring Tyrosine and Threonine residues. Whereas many kinases obtain their activation via autophosphorylation, MAPKs are usually phosphorylated by specific, dedicated, MAPK kinases (MAP2Ks). Here we show however, that the yeast MAPK Hog1, known to be activated by the MAP2K Pbs2, is activated in pbs2Δ cells via an autophosphorylation activity that is induced by osmotic pressure. We mapped a novel domain at the Hog1 C-terminal region that inhibits this activity. Removal of this domain provides a Hog1 protein that is partially independent of MAP2K, namely, partially rescues osmostress sensitivity of pbs2Δ cells. We further mapped a short domain (7 amino acid residues long) that is critical for induction of autophosphorylation. Its removal abolishes autophosphorylation, but maintains Pbs2-mediated phosphorylation. This 7 amino acids stretch is conserved in the human p38α. Similar to the case of Hog1, it's removal from p38α abolishes p38α's autophosphorylation capability, but maintains, although reduces, its activation by MKK6. This study joins a few recent reports to suggest that, like many protein kinases, MAPKs are also regulated via induced autoactivation.

  11. SAR Target Recognition via Supervised Discriminative Dictionary Learning and Sparse Representation of the SAR-HOG Feature

    Directory of Open Access Journals (Sweden)

    Shengli Song

    2016-08-01

    Full Text Available Automatic target recognition (ATR in synthetic aperture radar (SAR images plays an important role in both national defense and civil applications. Although many methods have been proposed, SAR ATR is still very challenging due to the complex application environment. Feature extraction and classification are key points in SAR ATR. In this paper, we first design a novel feature, which is a histogram of oriented gradients (HOG-like feature for SAR ATR (called SAR-HOG. Then, we propose a supervised discriminative dictionary learning (SDDL method to learn a discriminative dictionary for SAR ATR and propose a strategy to simplify the optimization problem. Finally, we propose a SAR ATR classifier based on SDDL and sparse representation (called SDDLSR, in which both the reconstruction error and the classification error are considered. Extensive experiments are performed on the MSTAR database under standard operating conditions and extended operating conditions. The experimental results show that SAR-HOG can reliably capture the structures of targets in SAR images, and SDDL can further capture subtle differences among the different classes. By virtue of the SAR-HOG feature and SDDLSR, the proposed method achieves the state-of-the-art performance on MSTAR database. Especially for the extended operating conditions (EOC scenario “Training 17 ∘ —Testing 45 ∘ ”, the proposed method improves remarkably with respect to the previous works.

  12. Validation of enzyme immunoassay applied to the serological diagnosis of hog brucellosis

    International Nuclear Information System (INIS)

    Ramondino, Romina; Marticorena, Damian

    1997-01-01

    The application of an enzyme immunization test in the serological diagnostic of a disease demands its validation as a previous stage. A test validation requires to know: cut off, diagnostic and relative specificity and sensitivity and harmonization grade between the new test and the classical test in use. The purpose of this work is the following: a) To determine the cut off and to calculate the specificity of two immunization tests, indirect (I-ELISA) and competitive (C-ELISA) by the analysis of serum coming from Canada (country free of this disease); b) To calculate the values of relative sensitivity of the tests with serum coming from infected populations and diagnostic sensitivity with samples of serum from hogs with positive isolation to Brucella suis

  13. HedgeHOGS: A Rapid Nuclear Hedge Sizing and Analysis Tool

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, Adam F. [United States Military Academy, West Point, NY (United States); Steinfeldt, Bradley Alexander [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Lafleur, Jarret Marshall [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Hawley, Marilyn F. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Shannon, Lisa M. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2017-07-01

    The U.S. nuclear stockpile hedge is an inventory of non-deployed nuclear warheads and a force structure capable of deploying those warheads. Current guidance is to retain this hedge to mitigate the risk associated with the technical failure of any single warhead type or adverse geopolitical developments that could require augmentation of the force. The necessary size of the hedge depends on the composition of the nuclear stockpile and assumed constraints. Knowing the theoretical minimum hedge given certain constraints is useful when considering future weapons policy. HedgeHOGS, an Excel-based tool, was developed to enable rapid calculation of the minimum hedge size associated with varying active stockpile composition and hedging strategies.

  14. Transcriptional Responses of Escherichia coli to a Small-Molecule Inhibitor of LolCDE, an Essential Component of the Lipoprotein Transport Pathway

    Science.gov (United States)

    Lorenz, Christian; Dougherty, Thomas J.

    2016-01-01

    ABSTRACT In Gram-negative bacteria, a dedicated machinery consisting of LolABCDE components targets lipoproteins to the outer membrane. We used a previously identified small-molecule inhibitor of the LolCDE complex of Escherichia coli to assess the global transcriptional consequences of interference with lipoprotein transport. Exposure of E. coli to the LolCDE inhibitor at concentrations leading to minimal and significant growth inhibition, followed by transcriptome sequencing, identified a small group of genes whose transcript levels were decreased and a larger group whose mRNA levels increased 10- to 100-fold compared to those of untreated cells. The majority of the genes whose mRNA concentrations were reduced were part of the flagellar assembly pathway, which contains an essential lipoprotein component. Most of the genes whose transcript levels were elevated encode proteins involved in selected cell stress pathways. Many of these genes are involved with envelope stress responses induced by the mislocalization of outer membrane lipoproteins. Although several of the genes whose RNAs were induced have previously been shown to be associated with the general perturbation of the cell envelope by antibiotics, a small subset was affected only by LolCDE inhibition. Findings from this work suggest that the efficiency of the Lol system function may be coupled to a specific monitoring system, which could be exploited in the development of reporter constructs suitable for use for screening for additional inhibitors of lipoprotein trafficking. IMPORTANCE Inhibition of the lipoprotein transport pathway leads to E. coli death and subsequent lysis. Early significant changes in the levels of RNA for a subset of genes identified to be associated with some periplasmic and envelope stress responses were observed. Together these findings suggest that disruption of this key pathway can have a severe impact on balanced outer membrane synthesis sufficient to affect viability. PMID

  15. Transcriptional Responses of Escherichia coli to a Small-Molecule Inhibitor of LolCDE, an Essential Component of the Lipoprotein Transport Pathway.

    Science.gov (United States)

    Lorenz, Christian; Dougherty, Thomas J; Lory, Stephen

    2016-12-01

    In Gram-negative bacteria, a dedicated machinery consisting of LolABCDE components targets lipoproteins to the outer membrane. We used a previously identified small-molecule inhibitor of the LolCDE complex of Escherichia coli to assess the global transcriptional consequences of interference with lipoprotein transport. Exposure of E. coli to the LolCDE inhibitor at concentrations leading to minimal and significant growth inhibition, followed by transcriptome sequencing, identified a small group of genes whose transcript levels were decreased and a larger group whose mRNA levels increased 10- to 100-fold compared to those of untreated cells. The majority of the genes whose mRNA concentrations were reduced were part of the flagellar assembly pathway, which contains an essential lipoprotein component. Most of the genes whose transcript levels were elevated encode proteins involved in selected cell stress pathways. Many of these genes are involved with envelope stress responses induced by the mislocalization of outer membrane lipoproteins. Although several of the genes whose RNAs were induced have previously been shown to be associated with the general perturbation of the cell envelope by antibiotics, a small subset was affected only by LolCDE inhibition. Findings from this work suggest that the efficiency of the Lol system function may be coupled to a specific monitoring system, which could be exploited in the development of reporter constructs suitable for use for screening for additional inhibitors of lipoprotein trafficking. Inhibition of the lipoprotein transport pathway leads to E. coli death and subsequent lysis. Early significant changes in the levels of RNA for a subset of genes identified to be associated with some periplasmic and envelope stress responses were observed. Together these findings suggest that disruption of this key pathway can have a severe impact on balanced outer membrane synthesis sufficient to affect viability. Copyright © 2016 Lorenz et al.

  16. Metabolic pathways leading to detoxification of triptolide, a major active component of the herbal medicine Tripterygium wilfordii.

    Science.gov (United States)

    Du, Fuying; Liu, Zhaohua; Li, Xinxiu; Xing, Jie

    2014-08-01

    Triptolide (TP) shows promising anti-inflammatory and antitumor activity but with severe toxicity. TP is a natural reactive electrophile containing three epoxide groups, which are usually linked to hepatotoxicity via their ability to covalently bind to cellular macromolecules. In this study, metabolic pathways leading to detoxification of TP were evaluated in glutathione (GSH)-depleted (treated with L-buthionine-S,R-sulfoxinine, BSO) and aminobenzotriazole (ABT; a non-specific inhibitor for P450s)-treated mice. The toxicity of TP in mice was evaluated in terms of mortality and levels of serum alanine transaminase (ALT). In incubates with NADPH- and GSH-supplemented liver microsomes, seven GSH conjugates derived from TP were detected. In mice, these hydrolytically unstable GSH conjugates underwent γ-glutamyltranspeptidase/dipeptidases-mediated hydrolysis leading to two major cysteinylglycine conjugates, which underwent further hydrolysis by dipeptidases to form two cysteine conjugates of TP. In ABT-treated mice, the hydroxylated metabolites of TP were found at a lower level than normal mice, and their subsequent conjugated metabolites were not found. The level of cysteinylglycine and cysteine conjugates derived from NADPH-independent metabolism increased in mice treated with both TP and BSO (or ABT), which could be the stress response to toxicity of TP. Compared with normal mice, mortality and ALT levels were significantly higher in TP-treated mice, indicating the toxicity of TP. Pretreatment of ABT increased the toxicity caused by TP, whereas the mortality decreased in GSH-depleted mice. Metabolism by cytochrome P450 enzymes to less reactive metabolites implied a high potential for detoxification of TP. The GSH conjugation pathway also contributed to TP's detoxification in mice. Copyright © 2013 John Wiley & Sons, Ltd.

  17. The MAPKK FgMkk1 of Fusarium graminearum regulates vegetative differentiation, multiple stress response, and virulence via the cell wall integrity and high-osmolarity glycerol signaling pathways.

    Science.gov (United States)

    Yun, Yingzi; Liu, Zunyong; Zhang, Jingze; Shim, Won-Bo; Chen, Yun; Ma, Zhonghua

    2014-07-01

    Mitogen-activated protein (MAP) kinases play crucial roles in regulating fungal development, growth and pathogenicity, and in responses to the environment. In this study, we characterized a MAP kinase kinase FgMkk1 in Fusarium graminearum, the causal agent of wheat head blight. Phenotypic analyses of the FgMKK1 mutant (ΔFgMKK1) showed that FgMkk1 is involved in the regulation of hyphal growth, pigmentation, conidiation, deoxynivalenol biosynthesis and virulence of F. graminearum. ΔFgMKK1 also showed increased sensitivity to cell wall-damaging agents, and to osmotic and oxidative stresses, but exhibited decreased sensitivity to the fungicides iprodione and fludioxonil. In addition, the mutant revealed increased sensitivity to a biocontrol agent, Trichoderma atroviride. Western blot assays revealed that FgMkk1 positively regulates phosphorylation of the MAP kinases Mgv1 and FgOs-2, the key component in the cell wall integrity (CWI) and high-osmolarity glycerol (HOG) signalling pathway respectively. Yeast two-hybrid assay indicated that Mgv1 interacts with a transcription factor FgRlm1. The FgRLM1 mutant (ΔFgRLM1) showed increased sensitivity to cell wall-damaging agents and exhibited decreased virulence. Taken together, our data indicated that FgMkk1 is an upstream component of Mgv1, and regulates vegetative differentiation, multiple stress response and virulence via the CWI and HOG signalling pathways. FgRlm1 may be a downstream component of Mgv1 in the CWI pathway in F. graminearum. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  18. Amino acids and insulin act additively to regulate components of the ubiquitin-proteasome pathway in C2C12 myotubes

    Directory of Open Access Journals (Sweden)

    Lomax Michael A

    2007-03-01

    Full Text Available Abstract Background The ubiquitin-proteasome system is the predominant pathway for myofibrillar proteolysis but a previous study in C2C12 myotubes only observed alterations in lysosome-dependent proteolysis in response to complete starvation of amino acids or leucine from the media. Here, we determined the interaction between insulin and amino acids in the regulation of myotube proteolysis Results Incubation of C2C12 myotubes with 0.2 × physiological amino acids concentration (0.2 × PC AA, relative to 1.0 × PC AA, significantly increased total proteolysis and the expression of 14-kDa E2 ubiquitin conjugating enzyme (p Conclusion In a C2C12 myotube model of myofibrillar protein turnover, amino acid limitation increases proteolysis in a ubiquitin-proteasome-dependent manner. Increasing amino acids or leucine alone, act additively with insulin to down regulate proteolysis and expression of components of ubiquitin-proteasome pathway. The effects of amino acids on proteolysis but not insulin and leucine, are blocked by inhibition of the mTOR signalling pathway.

  19. Evidence for the Induction of Key Components of the NOTCH Signaling Pathway via Deltamethrin and Azamethiphos Treatment in the Sea Louse Caligus rogercresseyi

    Directory of Open Access Journals (Sweden)

    Sebastian Boltaña

    2016-05-01

    Full Text Available The extensive use of organophosphates and pyrethroids in the aquaculture industry has negatively impacted parasite sensitivity to the delousing effects of these antiparasitics, especially among sea lice species. The NOTCH signaling pathway is a positive regulator of ABC transporter subfamily C expression and plays a key role in the generation and modulation of pesticide resistance. However, little is known about the molecular mechanisms behind pesticide resistance, partly due to the lack of genomic and molecular information on the processes involved in the resistance mechanism of sea lice. Next-generation sequencing technologies provide an opportunity for rapid and cost-effective generation of genome-scale data. The present study, through RNA-seq analysis, determined that the sea louse Caligus rogercresseyi (C. rogercresseyi specifically responds to the delousing drugs azamethiphos and deltamethrin at the transcriptomic level by differentially activating mRNA of the NOTCH signaling pathway and of ABC genes. These results suggest that frequent antiparasitic application may increase the activity of inhibitory mRNA components, thereby promoting inhibitory NOTCH output and conditions for increased resistance to delousing drugs. Moreover, data analysis underscored that key functions of NOTCH/ABC components were regulated during distinct phases of the drug response, thus indicating resistance modifications in C. rogercresseyi resulting from the frequent use of organophosphates and pyrethroids.

  20. Independent component and pathway-based analysis of miRNA-regulated gene expression in a model of type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Hagedorn Peter H

    2011-02-01

    Full Text Available Abstract Background Several approaches have been developed for miRNA target prediction, including methods that incorporate expression profiling. However the methods are still in need of improvements due to a high false discovery rate. So far, none of the methods have used independent component analysis (ICA. Here, we developed a novel target prediction method based on ICA that incorporates both seed matching and expression profiling of miRNA and mRNA expressions. The method was applied on a cellular model of type 1 diabetes. Results Microrray profiling identified eight miRNAs (miR-124/128/192/194/204/375/672/708 with differential expression. Applying ICA on the mRNA profiling data revealed five significant independent components (ICs correlating to the experimental conditions. The five ICs also captured the miRNA expressions by explaining >97% of their variance. By using ICA, seven of the eight miRNAs showed significant enrichment of sequence predicted targets, compared to only four miRNAs when using simple negative correlation. The ICs were enriched for miRNA targets that function in diabetes-relevant pathways e.g. type 1 and type 2 diabetes and maturity onset diabetes of the young (MODY. Conclusions In this study, ICA was applied as an attempt to separate the various factors that influence the mRNA expression in order to identify miRNA targets. The results suggest that ICA is better at identifying miRNA targets than negative correlation. Additionally, combining ICA and pathway analysis constitutes a means for prioritizing between the predicted miRNA targets. Applying the method on a model of type 1 diabetes resulted in identification of eight miRNAs that appear to affect pathways of relevance to disease mechanisms in diabetes.

  1. Microbial Disruption of Autophagy Alters Expression of the RISC Component AGO2, a Critical Regulator of the miRNA Silencing Pathway.

    Science.gov (United States)

    Sibony, Michal; Abdullah, Majd; Greenfield, Laura; Raju, Deepa; Wu, Ted; Rodrigues, David M; Galindo-Mata, Esther; Mascarenhas, Heidi; Philpott, Dana J; Silverberg, Mark S; Jones, Nicola L

    2015-12-01

    Autophagy is implicated in Crohn's disease (CD) pathogenesis. Recent evidence suggests autophagy regulates the microRNA (miRNA)-induced silencing complex (miRISC). Therefore, autophagy may play a novel role in CD by regulating expression of miRISC, thereby altering miRNA silencing. As microbes associated with CD can alter autophagy, we hypothesized that microbial disruption of autophagy affects the critical miRISC component AGO2. AGO2 expression was assessed in epithelial and immune cells, and intestinal organoids with disrupted autophagy. Microarray technology was used to determine the expression of downstream miRNAs in cells with defective autophagy. Increased AGO2 was detected in autophagy-deficient ATG5-/- and ATG16-/- mouse embryonic fibroblast cells (MEFs) in comparison with wild-type MEFs. Chemical agents and VacA toxin, which disrupt autophagy, increased AGO2 expression in MEFs, epithelial cells lines, and human monocytes, respectively. Increased AGO2 was also detected in ATG7-/- intestinal organoids, in comparison with wild-type organoids. Five miRNAs were differentially expressed in autophagy-deficient MEFs. Pathway enrichment analysis of the differentially expressed miRNAs implicated signaling pathways previously associated with CD. Taken together, our results suggest that autophagy is involved in the regulation of the critical miRISC component AGO2 in epithelial and immune cells and primary intestinal epithelial cells. We propose a mechanism by which autophagy alters miRNA expression, which likely impacts the regulation of CD-associated pathways. Furthermore, as enteric microbial products can manipulate autophagy and AGO2, our findings suggest a novel mechanism by which enteric microbes could influence miRNA to promote disease.

  2. HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers.

    Science.gov (United States)

    Pai, Sara I; Jack Lee, J; Carey, Thomas E; Westra, William H; Ferrone, Soldano; Moore, Charles; Mosunjac, Marina B; Shin, Dong M; Ferris, Robert L

    2018-02-01

    Human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies and are often excluded from cancer immunotherapy regimens. To evaluate the immune competence of this cancer patient population, we evaluated HLA class I antigen presenting machinery (APM) component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(-) head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(-) controls diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers in the United States were identified. HLA class I APM component, PD-1, and PD-L1 expression were analyzed by immunohistochemical staining with monoclonal antibodies (mAbs). Clinical data was abstracted from the medical records. There was no significant difference between the cases and controls in LMP2, TAP1, HLA-A and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p = .004, p = .026, and p = .006, respectively) but not in the HIV(-) controls. In addition, HLA-A expression was significantly associated with PD-L1 expression in the HIV(+) HNC cases only (p = .029). HIV-infected individuals diagnosed with HNC do not have any detectable defects in HLA class I APM component expression and in PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit from the recently FDA-approved immune checkpoint blockade therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. PSM/SH2-B distributes selected mitogenic receptor signals to distinct components in the PI3-kinase and MAP kinase signaling pathways.

    Science.gov (United States)

    Deng, Youping; Xu, Hu; Riedel, Heimo

    2007-02-15

    The Pro-rich, PH, and SH2 domain containing mitogenic signaling adapter PSM/SH2-B has been implicated as a cellular partner of various mitogenic receptor tyrosine kinases and related signaling mechanisms. Here, we report in a direct comparison of three peptide hormones, that PSM participates in the assembly of distinct mitogenic signaling complexes in response to insulin or IGF-I when compared to PDGF in cultured normal fibroblasts. The complex formed in response to insulin or IGF-I involves the respective peptide hormone receptor and presumably the established components leading to MAP kinase activation. However, our data suggest an alternative link from the PDGF receptor via PSM directly to MEK1/2 and consequently also to p44/42 activation, possibly through a scaffold protein. At least two PSM domains participate, the SH2 domain anticipated to link PSM to the respective receptor and the Pro-rich region in an association with an unidentified downstream component resulting in direct MEK1/2 and p44/42 regulation. The PDGF receptor signaling complex formed in response to PDGF involves PI 3-kinase in addition to the same components and interactions as described for insulin or IGF-I. PSM associates with PI 3-kinase via p85 and in addition the PSM PH domain participates in the regulation of PI 3-kinase activity, presumably through membrane interaction. In contrast, the PSM Pro-rich region appears to participate only in the MAP kinase signal. Both pathways contribute to the mitogenic response as shown by cell proliferation, survival, and focus formation. PSM regulates p38 MAP kinase activity in a pathway unrelated to the mitogenic response.

  4. Protein arginine methyltransferase 5 is an essential component of the hypoxia-inducible factor 1 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Ji-Hong; Choi, Yong-Joon; Cho, Chung-Hyun [Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799 (Korea, Republic of); Park, Jong-Wan, E-mail: parkjw@snu.ac.kr [Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799 (Korea, Republic of)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer HIF-1{alpha} is expressed PRMT5-dependently in hypoxic cancer cells. Black-Right-Pointing-Pointer The HIF-1 regulation of hypoxia-induced genes is attenuated in PRMT5-knocked-down cells. Black-Right-Pointing-Pointer The de novo synthesis of HIF-1{alpha} depends on PRMT5. Black-Right-Pointing-Pointer PRMT5 is involved in the HIF-1{alpha} translation initiated by 5 Prime UTR of HIF-1{alpha} mRNA. -- Abstract: Protein arginine methyltransferase 5 (PRMT5) is an enzyme that transfers one or two methyl groups to the arginine residues of histones or non-histone proteins, and that plays critical roles in cellular processes as diverse as receptor signaling and gene expression. Furthermore, PRMT5 is highly expressed in tumors, where it may be associated with tumor growth. Although much research has been conducted on PRMT5, little is known regarding its role in adaption to hypoxia. As hypoxia-inducible factor 1 (HIF-1) is a key player in hypoxic response, we examined the possible involvement of PRMT5 in the HIF-1 signaling pathway. Of the siRNAs targeting PRMT1-8, only PRMT5 siRNA attenuated the hypoxic induction of HIF-1{alpha} in A549 cells, and this result was reproducible in all three cancer cell lines examined. PRMT5 knock-down also repressed the promoter activities and the transcript levels of HIF-1-governed genes. Mechanistically, de novo synthesis of HIF-1{alpha} protein was reduced in PRMT5-knocked-down A549 cells, and this was rescued by PRMT5 restoration. In contrast, HIF-1{alpha} transcription, RNA processing, and protein stability were unaffected by PRMT5 knock-down. Furthermore, PRMT5 was found to be essential for the HIF-1{alpha} translation initiated by the 5 Prime UTR of HIF-1{alpha} mRNA. Given our results and previous reports, we believe that PRMT5 probably promotes tumor growth by stimulating cell proliferation and by participating in the construction of a tumor-favorable microenvironment via HIF-1 activation.

  5. Protein arginine methyltransferase 5 is an essential component of the hypoxia-inducible factor 1 signaling pathway

    International Nuclear Information System (INIS)

    Lim, Ji-Hong; Choi, Yong-Joon; Cho, Chung-Hyun; Park, Jong-Wan

    2012-01-01

    Highlights: ► HIF-1α is expressed PRMT5-dependently in hypoxic cancer cells. ► The HIF-1 regulation of hypoxia-induced genes is attenuated in PRMT5-knocked-down cells. ► The de novo synthesis of HIF-1α depends on PRMT5. ► PRMT5 is involved in the HIF-1α translation initiated by 5′ UTR of HIF-1α mRNA. -- Abstract: Protein arginine methyltransferase 5 (PRMT5) is an enzyme that transfers one or two methyl groups to the arginine residues of histones or non-histone proteins, and that plays critical roles in cellular processes as diverse as receptor signaling and gene expression. Furthermore, PRMT5 is highly expressed in tumors, where it may be associated with tumor growth. Although much research has been conducted on PRMT5, little is known regarding its role in adaption to hypoxia. As hypoxia-inducible factor 1 (HIF-1) is a key player in hypoxic response, we examined the possible involvement of PRMT5 in the HIF-1 signaling pathway. Of the siRNAs targeting PRMT1–8, only PRMT5 siRNA attenuated the hypoxic induction of HIF-1α in A549 cells, and this result was reproducible in all three cancer cell lines examined. PRMT5 knock-down also repressed the promoter activities and the transcript levels of HIF-1-governed genes. Mechanistically, de novo synthesis of HIF-1α protein was reduced in PRMT5-knocked-down A549 cells, and this was rescued by PRMT5 restoration. In contrast, HIF-1α transcription, RNA processing, and protein stability were unaffected by PRMT5 knock-down. Furthermore, PRMT5 was found to be essential for the HIF-1α translation initiated by the 5′ UTR of HIF-1α mRNA. Given our results and previous reports, we believe that PRMT5 probably promotes tumor growth by stimulating cell proliferation and by participating in the construction of a tumor-favorable microenvironment via HIF-1 activation.

  6. Induction of biogenic magnetization and redox control by a component of the target of rapamycin complex 1 signaling pathway.

    Directory of Open Access Journals (Sweden)

    Keiji Nishida

    Full Text Available Most organisms are simply diamagnetic, while magnetotactic bacteria and migratory animals are among organisms that exploit magnetism. Biogenic magnetization not only is of fundamental interest, but also has industrial potential. However, the key factor(s that enable biogenic magnetization in coordination with other cellular functions and metabolism remain unknown. To address the requirements for induction and the application of synthetic bio-magnetism, we explored the creation of magnetism in a simple model organism. Cell magnetization was first observed by attraction towards a magnet when normally diamagnetic yeast Saccharomyces cerevisiae were grown with ferric citrate. The magnetization was further enhanced by genetic modification of iron homeostasis and introduction of ferritin. The acquired magnetizable properties enabled the cells to be attracted to a magnet, and be trapped by a magnetic column. Superconducting quantum interference device (SQUID magnetometry confirmed and quantitatively characterized the acquired paramagnetism. Electron microscopy and energy-dispersive X-ray spectroscopy showed electron-dense iron-containing aggregates within the magnetized cells. Magnetization-based screening of gene knockouts identified Tco89p, a component of TORC1 (Target of rapamycin complex 1, as important for magnetization; loss of TCO89 and treatment with rapamycin reduced magnetization in a TCO89-dependent manner. The TCO89 expression level positively correlated with magnetization, enabling inducible magnetization. Several carbon metabolism genes were also shown to affect magnetization. Redox mediators indicated that TCO89 alters the intracellular redox to an oxidized state in a dose-dependent manner. Taken together, we demonstrated that synthetic induction of magnetization is possible and that the key factors are local redox control through carbon metabolism and iron supply.

  7. Location of the carbohydrates present in the HK-ATPase vesicles isolated from hog gastric mucosa

    International Nuclear Information System (INIS)

    Hall, K.; Perez, G.; Anderson, D.; Gutierrez, C.; Munson, K.; Hersey, S.J.; Kaplan, J.H.; Sachs, G.

    1990-01-01

    The glycosylation of H+K(+)-ATPase vesicles isolated from hog gastric mucosa was investigated by various methods. Following protein separation on sodium dodecyl sulfate reducing gels and transfer to poly(vinyl difluoride) membranes, binding of concanavalin A was confined to the 94-kDa band which corresponds to the catalytic subunit. In contrast, wheat germ agglutinin binding occurred in a region below the 94-kDa subunit, corresponding to the 60-85-kDa region, and also to protein just above the catalytic subunit. Treatment with glycopeptidase F removed most of the concanavalin A staining and also the wheat germ agglutinin staining found below the 94-kDa region, but spared the higher molecular weight wheat germ agglutinin reactive material. During the deglycosylation experiments a protein of 35-kDa was produced. Sequencing analysis of V8 protease generated peptide fragments of the 35-kDa protein show at least 30% homology with the Na+K(+)-ATPase beta-subunits. Labeling of the carbohydrates by galactosyltransferase and [3H]uridine diphosphate-galactose showed that the sites of labeling were extracellular and were confined to the wheat germ agglutinin staining regions. Two molecular weight regions, below the 94-kDa region, of 60 and 85 kDa were identified. Electron microscopy using postembedding staining techniques showed that both concanavalin A and wheat germ agglutinin staining occurred on the extracellular face of the gastric vesicles

  8. Coupled Wave Energy and Erosion Dynamics along a Salt Marsh Boundary, Hog Island Bay, Virginia, USA

    Directory of Open Access Journals (Sweden)

    Anthony M. Priestas

    2015-09-01

    Full Text Available The relationship between lateral erosion of salt marshes and wind waves is studied in Hog Island Bay, Virginia USA, with high-resolution field measurements and aerial photographs. Marsh retreat is compared to wave climate calculated in the bay using the spectral wave-model Simulating Waves Nearshore (SWAN. We confirm the existence of a linear relationship between long-term salt marsh erosion and wave energy, and show that wave power can serve as a good proxy for average salt-marsh erosion rates. At each site, erosion rates are consistent across several temporal scales, ranging from months to decades, and are strongly related to wave power. On the contrary, erosion rates vary in space and weakly depend on the spatial distribution of wave energy. We ascribe this variability to spatial variations in geotechnical, biological, and morphological marsh attributes. Our detailed field measurements indicate that at a small spatial scale (tens of meters, a positive feedback between salt marsh geometry and wave action causes erosion rates to increase with boundary sinuosity. However, at the scale of the entire marsh boundary (hundreds of meters, this relationship is reversed: those sites that are more rapidly eroding have a marsh boundary which is significantly smoother than the marsh boundary of sheltered and slowly eroding marshes.

  9. Visual Localization by Place Recognition Based on Multifeature (D-λLBP++HOG

    Directory of Open Access Journals (Sweden)

    Yongliang Qiao

    2017-01-01

    Full Text Available Visual localization is widely used in the autonomous navigation system and Advanced Driver Assistance Systems (ADAS. This paper presents a visual localization method based on multifeature fusion and disparity information using stereo images. We integrate disparity information into complete center-symmetric local binary patterns (CSLBP to obtain a robust global image description (D-CSLBP. In order to represent the scene in depth, multifeature fusion of D-CSLBP and HOG features provides valuable information and permits decreasing the effect of some typical problems in place recognition such as perceptual aliasing. It improves visual recognition performance by taking advantage of depth, texture, and shape information. In addition, for real-time visual localization, local sensitive hashing method (LSH was used to compress the high-dimensional multifeature into binary vectors. It can thus speed up the process of image matching. To show its effectiveness, the proposed method is tested and evaluated using real datasets acquired in outdoor environments. Given the obtained results, our approach allows more effective visual localization compared with the state-of-the-art method FAB-MAP.

  10. Nonsyndromic cleft lip with or without cleft palate: Increased burden of rare variants within Gremlin-1, a component of the bone morphogenetic protein 4 pathway.

    Science.gov (United States)

    Al Chawa, Taofik; Ludwig, Kerstin U; Fier, Heide; Pötzsch, Bernd; Reich, Rudolf H; Schmidt, Gül; Braumann, Bert; Daratsianos, Nikolaos; Böhmer, Anne C; Schuencke, Hannah; Alblas, Margrieta; Fricker, Nadine; Hoffmann, Per; Knapp, Michael; Lange, Christoph; Nöthen, Markus M; Mangold, Elisabeth

    2014-06-01

    The genes Gremlin-1 (GREM1) and Noggin (NOG) are components of the bone morphogenetic protein 4 pathway, which has been implicated in craniofacial development. Both genes map to recently identified susceptibility loci (chromosomal region 15q13, 17q22) for nonsyndromic cleft lip with or without cleft palate (nsCL/P). The aim of the present study was to determine whether rare variants in either gene are implicated in nsCL/P etiology. The complete coding regions, untranslated regions, and splice sites of GREM1 and NOG were sequenced in 96 nsCL/P patients and 96 controls of Central European ethnicity. Three burden and four nonburden tests were performed. Statistically significant results were followed up in a second case-control sample (n = 96, respectively). For rare variants observed in cases, segregation analyses were performed. In NOG, four rare sequence variants (minor allele frequency elements. © 2014 Wiley Periodicals, Inc.

  11. Unique nonstructural proteins of Pneumonia Virus of Mice (PVM) promote degradation of interferon (IFN) pathway components and IFN-stimulated gene proteins.

    Science.gov (United States)

    Dhar, Jayeeta; Barik, Sailen

    2016-12-01

    Pneumonia Virus of Mice (PVM) is the only virus that shares the Pneumovirus genus of the Paramyxoviridae family with Respiratory Syncytial Virus (RSV). A deadly mouse pathogen, PVM has the potential to serve as a robust animal model of RSV infection, since human RSV does not fully replicate the human pathology in mice. Like RSV, PVM also encodes two nonstructural proteins that have been implicated to suppress the IFN pathway, but surprisingly, they exhibit no sequence similarity with their RSV equivalents. The molecular mechanism of PVM NS function, therefore, remains unknown. Here, we show that recombinant PVM NS proteins degrade the mouse counterparts of the IFN pathway components. Proteasomal degradation appears to be mediated by ubiquitination promoted by PVM NS proteins. Interestingly, NS proteins of PVM lowered the levels of several ISG (IFN-stimulated gene) proteins as well. These results provide a molecular foundation for the mechanisms by which PVM efficiently subverts the IFN response of the murine cell. They also reveal that in spite of their high sequence dissimilarity, the two pneumoviral NS proteins are functionally and mechanistically similar.

  12. Identification of potential genetic components involved in the deviant quorum-sensing signaling pathways of Burkholderia glumae through a functional genomics approach

    Directory of Open Access Journals (Sweden)

    Ruoxi eChen

    2015-03-01

    Full Text Available Burkholderia glumae is the chief causal agent for bacterial panicle blight of rice. The acyl-homoserine lactone (AHL-mediated quorum-sensing (QS system dependent on a pair of luxI and luxR homologs, tofI and tofR, is the primary cell-to-cell signaling mechanism determining the virulence of this bacterium. Production of toxoflavin, a major virulence factor of B. glumae, is known to be dependent on the tofI/tofR QS system. In our previous study, however, it was observed that B. glumae mutants defective in tofI or tofR produced toxoflavin if they grew on the surface of a solid medium, suggesting that alternative signaling pathways independent of tofI or tofR are activated in that growth condition for the production of toxoflavin. In this study, potential genetic components involved in the tofI- and tofR-independent signaling pathways for toxoflavin production were sought through screening random mini-Tn5 mutants of B. glumae to better understand the intercellular signaling pathways of this pathogen. Fifteen and three genes were initially identified as the potential genetic elements of the tofI- and tofR-independent pathways, respectively. Especially, the ORF (bglu_2g06320 divergently transcribed from toxJ, which encodes an orphan LuxR protein and controls toxoflavin biosynthesis, was newly identified in this study as a gene required for the tofR-independent toxoflavin production and named as toxK. Among those genes, flhD, dgcB, and wyzB were further studied to validate their functions in the tofI-independent toxoflavin production, and similar studies were also conducted with qsmR and toxK for their functions in the tofR-independent toxoflavin production. This work provides a foundation for future comprehensive studies of the intercellular signaling systems of B. glumae and other related pathogenic bacteria.

  13. Performance of the constructed wetland systems in pollutants removal from hog wastewater

    Directory of Open Access Journals (Sweden)

    Wallison da Silva Freitas

    2010-08-01

    Full Text Available The main objective of this work was to evaluate the efficiency of a constructed wetland systems (CWS for pollutants removal, in mono crop and multi crop with three different species of plants, originated from hog wastewater treatment (HW. Therefore, 5 CWS of 24.0 m x 1.1 m x 0.7 m were constructed, sealed with a membrane of polyvinyl chloride (PVC and filled with 0.4 m of small gravel. In CWS1, CWS2 and CWS3 grown to cattail (Typha latifolia L., Alternanthera philoxeroides (Mart. Griseb. and Tifton 85 grass (Cynodon dactylon Pers., respectively. In the bed of CWS4 was planted at 1st third Alternanthera, cattail, in the 2nd third and tifton-85 grass and in the 3rd third of. The CWS5 was not planted and it was used as control. After passing through a filter filled with crushed bagasse of sugar cane, the HW was applied to the CWS in a flow of 0.8 m3 d-1, which corresponded to a hydraulic detention time of 4.8 days. According to the results it was shown that the five CWS(s had statistically nearly the same removal of pollutants, and the average removal efficiency of TSS, COD, BOD and Zn, were 91, 89, 86 and 94%, respectively. Also high removals were obtained concerning the ST, N-total, NH4+ and P-total, with average values of 62, 59, 52 and 50%, respectively. The plants in all planted CWS worked in a similar way maintaining the system efficiency and the non cultivated CWS presented analogous capacity of pollutants removal when compared to the cultivated CWS(s.

  14. Myosin dephosphorylation during rapid relaxation of hog carotid artery smooth muscle.

    Science.gov (United States)

    Driska, S P; Stein, P G; Porter, R

    1989-02-01

    Changes in myosin light chain phosphorylation were measured during histamine-induced rhythmic contractions of hog carotid artery smooth muscle strips. Histamine made the muscle strips contract spontaneously every 1-5 min, and this allowed measurement of the time course of phosphorylation in relation to force development under conditions where diffusion of the agonist through tissue would not complicate the interpretation of the data. In the absence of histamine, phosphorylation was low [0.12 +/- 0.04 mol P/mol of the 20,000-Da light chain (LC 20)]. Phosphorylation was slightly (but not significantly) higher in the presence of 10 microM histamine in the relaxed state between contractions (0.20 +/- 0.03 mol P/mol LC 20). In muscle strips frozen during force development, when force had reached half of its peak value, phosphorylation was 0.38 +/- 0.06 mol P/mol LC 20. The highest levels of phosphorylation (0.49 +/- 0.04 mol P/mol LC 20) were found in strips frozen at the peak of the rhythmic contractions. Strips frozen when force had declined to half of the peak force showed low levels of phosphorylation (0.17 +/- 0.07 mol P/mol LC 20), indicating that the myosin light chain phosphatase activity was quite high. Mathematical modeling of the kinase and phosphatase reactions suggested that the apparent first-order phosphatase rate constant was at least 0.08 s-1 under these conditions. To obtain a better estimate of this rate constant, a second series of phosphorylation measurements were made early in the relaxation phase of the rhythmic contractions. The highest phosphatase rate constant obtained from these measurements was 0.23 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Ultra structure of the denervated vocal muscle mechanically in hogs (sus scrofa domestica

    Directory of Open Access Journals (Sweden)

    Leão, Henrique Zaquia

    2010-03-01

    Full Text Available Introduction: The literature is not clear in the ultra-structural manifestations of the vocal wrinkles after neural wound. Objective: To verify the alterations that occur in a vocal fold mechanically denervated. Method: In this prospective study, it were utilized 15 hogs of commercial race (Sus scrofa domesticates, with age of 4 to 12 weeks. The animals were distributed in three groups, chosen at random. Everybody was submitted to the denervation of the right vocal fold, with surgical removal of a segment with three centimeters of the recurring right laryngeal nerve. After 45, 90 and 180 days of the operations, it was proceeded the biopsy of the vocal muscles, it was prosecuted the samples for transmission electron microscopy and, for the ultra-structural study, utilized the transmission electron microscopy Philips, model EM208S. Results: The biopsied groups with 45 and 90 days after operation of mechanical denervation, presented disorganization miofibrilar, only vestigial lines Z in many samples, as well like altered mithochondrions presenting limited sizes, and matrix mithocondrial rarefied with rare mithocondrial cristae present. The biopsied group with 180 days after operation of denervation, presented regular sarcomeres, mithocondrions with sizes and regular number with correct positioning between the sarcomerical units. Conclusion: The finds in the ultra-structure of the vocal muscles suggest to re enervation of the muscle being that the muscular mithochondrions were the most sensible structures to the denervated condition, successions by the cytoarchiteture of the miofibrilas; the finds in the ultra-structure of the vocal muscles suggests to reinervation of the muscle in the period of approximately six months.

  16. B. abortus RNA is the component involved in the down-modulation of MHC-I expression on human monocytes via TLR8 and the EGFR pathway

    Science.gov (United States)

    Milillo, M. Ayelén; Velásquez, Lis N.; Trotta, Aldana; Delpino, M. Victoria; Balboa, Luciana; Vermeulen, Mónica; Espindola, Sonia L.; Rodriguez-Rodrigues, Nahuel; Fernández, Gabriela C.; Oliveira, Sergio Costa; Giambartolomei, Guillermo H.

    2017-01-01

    Despite eliciting a potent CD8+ T cell response, Brucella abortus is able to persist and establish a chronic infection inside its host. We have previously reported that the infection of human monocytes/macrophages with B. abortus inhibits the IFN-γ-induced MHC-I cell surface expression down-modulating cytotoxic CD8+ T cell responses. MHC-I down-modulation depends on bacterial viability and results from the capacity of B. abortus to retain the MHC-I molecules within the Golgi apparatus. Furthermore, we recently demonstrated that epidermal growth factor receptor (EGFR) pathway is involved in this phenomenon and that this is an early event during infection. However, the components and mechanisms whereby B. abortus is able to down-modulate MHC-I remained to be elucidated. In this study we demonstrated that the down-modulation of MHC-I expression is not mediated by well-known Brucella virulence factors but instead by B. abortus RNA, a PAMP associated to viability (vita-PAMP). Surprisingly, completely degraded RNA was also able to inhibit MHC-I expression to the same extent as intact RNA. Accordingly, B. abortus RNA and its degradation products were able to mimic the MHC-I intracellular retention within the Golgi apparatus observed upon infection. We further demonstrated that TLR8, a single-stranded RNA and RNA degradation products sensor, was involved in MHC-I inhibition. On the other hand, neutralization of the EGFR reversed the MHC-I inhibition, suggesting a connection between the TLR8 and EGFR pathways. Finally, B. abortus RNA-treated macrophages display diminished capacity of antigen presentation to CD8+ T cells. Overall, our results indicate that the vita-PAMP RNA as well as its degradation products constitute novel virulence factors whereby B. abortus, by a TLR8-dependent mechanism and through the EGFR pathway, inhibits the IFN-γ-induced MHC-I surface expression on human monocytes/macrophages. Thus, bacteria can hide within infected cells and avoid the

  17. B. abortus RNA is the component involved in the down-modulation of MHC-I expression on human monocytes via TLR8 and the EGFR pathway.

    Directory of Open Access Journals (Sweden)

    M Ayelén Milillo

    2017-08-01

    Full Text Available Despite eliciting a potent CD8+ T cell response, Brucella abortus is able to persist and establish a chronic infection inside its host. We have previously reported that the infection of human monocytes/macrophages with B. abortus inhibits the IFN-γ-induced MHC-I cell surface expression down-modulating cytotoxic CD8+ T cell responses. MHC-I down-modulation depends on bacterial viability and results from the capacity of B. abortus to retain the MHC-I molecules within the Golgi apparatus. Furthermore, we recently demonstrated that epidermal growth factor receptor (EGFR pathway is involved in this phenomenon and that this is an early event during infection. However, the components and mechanisms whereby B. abortus is able to down-modulate MHC-I remained to be elucidated. In this study we demonstrated that the down-modulation of MHC-I expression is not mediated by well-known Brucella virulence factors but instead by B. abortus RNA, a PAMP associated to viability (vita-PAMP. Surprisingly, completely degraded RNA was also able to inhibit MHC-I expression to the same extent as intact RNA. Accordingly, B. abortus RNA and its degradation products were able to mimic the MHC-I intracellular retention within the Golgi apparatus observed upon infection. We further demonstrated that TLR8, a single-stranded RNA and RNA degradation products sensor, was involved in MHC-I inhibition. On the other hand, neutralization of the EGFR reversed the MHC-I inhibition, suggesting a connection between the TLR8 and EGFR pathways. Finally, B. abortus RNA-treated macrophages display diminished capacity of antigen presentation to CD8+ T cells. Overall, our results indicate that the vita-PAMP RNA as well as its degradation products constitute novel virulence factors whereby B. abortus, by a TLR8-dependent mechanism and through the EGFR pathway, inhibits the IFN-γ-induced MHC-I surface expression on human monocytes/macrophages. Thus, bacteria can hide within infected cells and

  18. Feeding habits of Molina's hog-nosed skunk, Conepatus chinga (Carnivora: Mephitidae) in the extreme south of Brazil

    OpenAIRE

    Peters, Felipe Bortolotto; Roth, Paulo Ricardo de Oliveira; Christoff, Alexandre Uarth

    2011-01-01

    Feeding habits of the Molina's hog-nosed skunk, Conepatus chinga (Molina, 1782) in the extreme south of Brazil. We analyzed 60 stomachs of road-kills of C. chinga in the extreme south of Brazil. The contents revealed 808 prey parts, including invertebrates (frequency of occurrence - FO = 96.7% and relative abundance - RA = 94.7%), vertebrates (FO = 18.3% and RA = 2.8%) and plants (FO = 31.7% and RA = 2.3%). We identified 18 kinds of food, including the invertebrate order Coleoptera which show...

  19. Aberrations of the p53 pathway components p53, MDM2 and CDKN2A appear independent in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Ino, Y; Gerdes, A M

    1999-01-01

    The two gene products of the CDKN2A gene, p16 and p19ARF, have recently been linked to each of two major tumour suppressor pathways in human carcinogenesis, the RB1 pathway and the p53 pathway. p16 inhibits the phosphorylation of the retinoblastoma gene product by cyclin D-dependent kinases...

  20. The PP2A Regulatory Subunit Tap46, a Component of the TOR Signaling Pathway, Modulates Growth and Metabolism in Plants[W

    Science.gov (United States)

    Ahn, Chang Sook; Han, Jeong-A; Lee, Ho-Seok; Lee, Semi; Pai, Hyun-Sook

    2011-01-01

    Tap42/α4, a regulatory subunit of protein phosphatase 2A, is a downstream effector of the target of rapamycin (TOR) protein kinase, which regulates cell growth in coordination with nutrient and environmental conditions in yeast and mammals. In this study, we characterized the functions and phosphatase regulation of plant Tap46. Depletion of Tap46 resulted in growth arrest and acute plant death with morphological markers of programmed cell death. Tap46 interacted with PP2A and PP2A-like phosphatases PP4 and PP6. Tap46 silencing modulated cellular PP2A activities in a time-dependent fashion similar to TOR silencing. Immunoprecipitated full-length and deletion forms of Arabidopsis thaliana TOR phosphorylated recombinant Tap46 protein in vitro, supporting a functional link between Tap46 and TOR. Tap46 depletion reproduced the signature phenotypes of TOR inactivation, such as dramatic repression of global translation and activation of autophagy and nitrogen mobilization, indicating that Tap46 may act as a positive effector of TOR signaling in controlling those processes. Additionally, Tap46 silencing in tobacco (Nicotiana tabacum) BY-2 cells caused chromatin bridge formation at anaphase, indicating its role in sister chromatid segregation. These findings suggest that Tap46, in conjunction with associated phosphatases, plays an essential role in plant growth and development as a component of the TOR signaling pathway. PMID:21216945

  1. Sistem Verifikasi Tanda Tangan Off-Line Berdasar Ciri Histogram Of Oriented Gradient (HOG Dan Histogram Of Curvature (HoC

    Directory of Open Access Journals (Sweden)

    Agus Wahyu Widodo

    2015-08-01

    Full Text Available Abstrak Tanda tangan dengan sifat uniknya merupakan salah satu dari sekian banyak atribut personal yang diterima secara luas untuk verifikasi indentitas seseorang, alat pembuktian kepemilikan berbagai transaksi atau dokumen di dalam masyarakat. Keberhasilan penggunaan ciri gradien dan curvature dalam bidang-bidang penelitian pengenalan pola dan bahwa tanda tangan dapat dikatakan merupakan hasil tulisan tangan yang tersusun atas beragam garis dan lengkungan (curve yang memiliki arah atau orientasi merupakan alasan bahwa kedua ciri tersebut digunakan sebagai metoda verifikasi tanda tangan offline di penelitian ini. Berbagai implementasi dari pre-processing, ekstraksi dan representasi ciri, dan pembelajaran SVM serta usaha perbaikan yang telah dilakukan dalam penelitian ini menunjukkan hasil bahwa ciri HOG dan HoC mampu dimanfaatkan dalam proses verifikasi tanda tangan secara offline.  Pada basis data GPDS960Signature, HOG dan HoC yang dihitung pada ukuran sel 30 x 30 piksel memberikan dengan nilai %FRR terbaik 26,90 dan %FAR 37,56.  Sedangkan pada basis data FUM-PHSDB, HOG dn HoC yang dihitung pada ukuran 60 x 60 piksel memberikan nilai %FRR terbaik 4 dan %FAR 57. Kata kunci: verifikasi tanda tangan, curvature, orientation, gradient, histogram of curvature (HoC, histogram of oriented gradient (HOG Abstract Signature with unique properties is one of the many personal attributes that are widely accepted to verify a person's identity, proof of ownership transactions instrument or document in the community. The successful use of gradient and curvature feature in the research fields of pattern recognition is the reason that both of these features are used as an offline signature verification method in this study. Various implementations of preprocessing, feature extraction and representation, and SVM learning has been done in the study showed results that HOG and HoC feature can be utilized in the process of offline signature verification.  HOG and

  2. Lysophosphatidylcholines containing polyunsaturated fatty acids were found as Na+,K+-ATPase inhibitors in acutely volume-expanded hog

    International Nuclear Information System (INIS)

    Tamura, M.; Harris, T.M.; Higashimori, K.; Sweetman, B.J.; Blair, I.A.; Inagami, T.

    1987-01-01

    Na + ,K + -ATPase inhibitors activities against the specific binding of ouabain to Na + ,K + -ATPase and 86 Rb uptake into hog erythrocytes have been purified from the plasma of acutely saline-infused hog. The purifications were performed by a combination of Amberlite XAD-2 adsorption chromatography and four steps of high-performance liquid chromatography with four different types of columns. Fast atom bombardment (FAB) mass and proton NMR spectrometric studies identified the purified substances as γ-arachidoyl- [LPCA(γ), 34%], β-arachidoyl- [LPCA(β), 4%], γ-linoleoyl- (LPCL, 33%), and γ-oleoyl- (LPCO, 25%) lysophosphatidylcholine, expressed in molar ratio in the plasma. Small amounts of γ-docosapentaenoyl-, γ-eicosatrienoyl-, and γpalmitoyllysophosphatidylcholine were also detected by both FAB mass and 1 H NMR spectrometric studies. The inhibition of Na + ,K + -ATPase activity due to these compounds was always more sensitive than that of both ouabain-binding and 86 Rb uptake activities. The ouabain-displacing activity in plasma due to these compounds increased with time during saline infusion. The maximal plasma level was approximately 10 times higher than that in the preinfusion plasma sample. Although these results suggest that γ-acyl-LPC's with long-chain polyunsaturated fatty acids are not simple competitive inhibitors to Na + ,K + -ATPase, these compounds could be implicated in the pathogenesis of the circulation abnormality through the modulation of membrane enzyme

  3. HIV-1 Promotes the Degradation of Components of the Type 1 IFN JAK/STAT Pathway and Blocks Anti-viral ISG Induction.

    Science.gov (United States)

    Gargan, Siobhan; Ahmed, Suaad; Mahony, Rebecca; Bannan, Ciaran; Napoletano, Silvia; O'Farrelly, Cliona; Borrow, Persephone; Bergin, Colm; Stevenson, Nigel J

    2018-04-01

    Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to provide a cure. During infection Type 1 IFNs normally play an essential role in viral clearance, but in vivo IFN-α only has a modest impact on HIV-1 infection, suggesting its possible targeting by HIV. Here, we report that the HIV protein, Vif, inhibits effective IFN-α signalling via degradation of essential JAK/STAT pathway components. We found that STAT1 and STAT3 are specifically reduced in HEK293T cells expressing Vif and that full length, infectious HIV-1 IIIB strain promotes their degradation in a Vif-dependent manner. HIV-1 IIIB infection of myeloid ThP-1 cells also reduced the IFN-α-mediated induction of the anti-viral gene, ISG15, but not MxA, revealing a functional consequence of this HIV-1-mediated immune evasion strategy. Interestingly, while total STAT levels were not reduced upon in vitro IIIB infection of primary human PBMCs, IFN-α-mediated phosphorylation of STAT1 and STAT3 and ISG induction were starkly reduced, with removal of Vif (IIIBΔVif), partially restoring pSTATs, ISG15 and MxB induction. Similarly, pSTAT1 and pSTAT3 expression and IFN-α-induced ISG15 were reduced in PBMCs from HIV-infected patients, compared to healthy controls. Furthermore, IFN-α pre-treatment of a CEM T lymphoblast cells significantly inhibited HIV infection/replication (measured by cellular p24), only in the absence of Vif (IIIBΔVif), but was unable to suppress full length IIIB infection. When analysing the mechanism by which Vif might target the JAK/STAT pathway, we found Vif interacts with both STAT1 and STAT3, (but not STAT2), and its expression promotes ubiquitination and MG132-sensitive, proteosomal degradation of both proteins. Vif's Elongin-Cullin-SOCS-box binding motif enables the formation of an active E3 ligase complex, which we found to be required for Vif's degradation of STAT1 and STAT3. In fact, the E3 ligase scaffold proteins, Cul5 and Rbx2, were also found to be

  4. Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study.

    Science.gov (United States)

    Hubbard, Gary P; Wolffram, Siegfried; de Vos, Ric; Bovy, Arnaud; Gibbins, Jonathan M; Lovegrove, Julie A

    2006-09-01

    Epidemiological data suggest that those who consume a diet rich in quercetin-containing foods may have a reduced risk of CVD. Furthermore, in vitro and ex vivo studies have observed the inhibition of collagen-induced platelet activation by quercetin. The aim of the present study was to investigate the possible inhibitory effects of quercetin ingestion from a dietary source on collagen-stimulated platelet aggregation and signalling. A double-blind randomised cross-over pilot study was undertaken. Subjects ingested a soup containing either a high or a low amount of quercetin. Plasma quercetin concentrations and platelet aggregation and signalling were assessed after soup ingestion. The high-quercetin soup contained 69 mg total quercetin compared with the low-quercetin soup containing 5 mg total quercetin. Plasma quercetin concentrations were significantly higher after high-quercetin soup ingestion than after low-quercetin soup ingestion and peaked at 2.59 (sem 0.42) mumol/l. Collagen-stimulated (0.5 mug/ml) platelet aggregation was inhibited after ingestion of the high-quercetin soup in a time-dependent manner. Collagen-stimulated tyrosine phosphorylation of a key component of the collagen-signalling pathway via glycoprotein VI, Syk, was significantly inhibited by ingestion of the high-quercetin soup. The inhibition of Syk tyrosine phosphorylation was correlated with the area under the curve for the high-quercetin plasma profile. In conclusion, the ingestion of quercetin from a dietary source of onion soup could inhibit some aspects of collagen-stimulated platelet aggregation and signalling ex vivo. This further substantiates the epidemiological data suggesting that those who preferentially consume high amounts of quercetin-containing foods have a reduced risk of thrombosis and potential CVD risk.

  5. Downstream components of RhoA required for signal pathway of superoxide formation during phagocytosis of serum opsonized zymosans in macrophages.

    Science.gov (United States)

    Kim, Jun Sub; Kim, Jae Gyu; Jeon, Chan Young; Won, Ha Young; Moon, Mi Young; Seo, Ji Yeon; Kim, Jong Il; Kim, Jaebong; Lee, Jae Yong; Choi, Soo Young; Park, Jinseu; Yoon Park, Jung Han; Ha, Kwon Soo; Kim, Pyeung Hyeun; Park, Jae Bong

    2005-12-31

    Rac1 and Rac2 are essential for the control of oxidative burst catalyzed by NADPH oxidase. It was also documented that Rho is associated with the superoxide burst reaction during phagocytosis of serum- (SOZ) and IgG-opsonized zymosan particles (IOZ). In this study, we attempted to reveal the signal pathway components in the superoxide formation regulated by Rho GTPase. Tat-C3 blocked superoxide production, suggesting that RhoA is essentially involved in superoxide formation during phagocytosis of SOZ. Conversely SOZ activated both RhoA and Rac1/2. Inhibition of RhoA-activated kinase (ROCK), an important downstream effector of RhoA, by Y27632 and myosin light chain kinase (MLCK) by ML-7 abrogated superoxide production by SOZ. Extracellular signaling-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were activated during phagocytosis of SOZ, and Tat-C3 and SB203580 reduced ERK1/2 and p38 MAPK activation, suggesting that RhoA and p38 MAPK may be upstream regulators of ERK1/2. Inhibition of ERK1/2, p38 MAPK, phosphatidyl inositol 3-kinase did not block translocation of RhoA to membranes, suggesting that RhoA is upstream to these kinases. Inhibition of RhoA by Tat-C3 blocked phosphorylation of p47(PHOX). Taken together, RhoA, ROCK, p38MAPK, ERK1/2, and p47(PHOX) may be subsequently activated, leading to activation of NADPH oxidase to produce superoxide.

  6. Genetic Variation in Complement Component 2 of the Classical Complement Pathway is Associated with Increased Mortality and Infection: A Study of 627 Trauma Patients

    Science.gov (United States)

    Morris, John A.; Francois, Cedric; Olson, Paul K.; Cotton, Bryan A.; Summar, Marshall; Jenkins, Judith M.; Norris, Patrick R.; Moore, Jason H.; Williams, Anna E.; McNew, Brent S.; Canter, Jeffrey A.

    2009-01-01

    Trauma is a disease of inflammation. Complement Component 2 (C2) is a protease involved in activation of complement through the classical pathway and has been implicated in a variety of chronic inflammatory diseases. We hypothesized that genetic variation in C2 (E318D) identifies a high-risk subgroup of trauma patients reflecting increased mortality and infection (Ventilator associated pneumonia: VAP). Consequently, genetic variation in C2 may stratify patient risk and illuminate underlying mechanisms for therapeutic intervention. Methods DNA samples from 702 trauma patients were genotyped for C2 E318D and linked with covariates (age: mean 42.8 years, gender: 74% male, ethnicity: 80% Caucasian, mechanism: 84% blunt, ISS: mean 25.0, admission lactate: mean 3.13 mEq/L) and outcomes: mortality 9.9% and VAP: 18.5%. VAP was defined by quantitative bronchoalveolar lavage (>104). Multivariate regression determined the relationship of genotype and covariates to risk of death and VAP. However, patients with ISS ≥ 45 were excluded from the multivariate analysis, as magnitude of injury overwhelms genetics and covariates in determining outcome. Results 52 patients (8.3%) had the high-risk heterozygous genotype, associated with a significant increase in mortality and VAP. Conclusion In 702 trauma patients, 8.3% had a high-risk genetic variation in C2 associated with increased mortality (OR=2.65) and infection (OR=2.00). This variation: 1) Identifies a previously unknown high risk group for infection and mortality; 2) Can be determined on admission; 3) May provide opportunity for early therapeutic intervention; and 4) Requires validation in a distinct cohort of patients. PMID:19430225

  7. Estimation of the dynamics and rate of transmission of classical swine fever (hog cholera) in wild pigs.

    Science.gov (United States)

    Hone, J; Pech, R; Yip, P

    1992-04-01

    Infectious diseases establish in a population of wildlife hosts when the number of secondary infections is greater than or equal to one. To estimate whether establishment will occur requires extensive experience or a mathematical model of disease dynamics and estimates of the parameters of the disease model. The latter approach is explored here. Methods for estimating key model parameters, the transmission coefficient (beta) and the basic reproductive rate (RDRS), are described using classical swine fever (hog cholera) in wild pigs as an example. The tentative results indicate that an acute infection of classical swine fever will establish in a small population of wild pigs. Data required for estimation of disease transmission rates are reviewed and sources of bias and alternative methods discussed. A comprehensive evaluation of the biases and efficiencies of the methods is needed.

  8. Influence of different yeast cell wall preparations and their components on performance and immune and metabolic pathways in Clostridium perfringens-challenged broiler chicks

    Science.gov (United States)

    A study was conducted to evaluate the influence of purification of yeast cell wall (YCW) preparations on broiler performance, and immunogenic and metabolic pathways under microbial challenge. A total of 240 day-of-hatch chicks were distributed among two battery brooder units (48 pens; 5 birds/pen; ...

  9. Ubiquitin conjugation by the N-end rule pathway and mRNAs for its components increase in muscles of diabetic rats

    Science.gov (United States)

    Lecker, S. H.; Solomon, V.; Price, S. R.; Kwon, Y. T.; Mitch, W. E.; Goldberg, A. L.

    1999-01-01

    Insulin deficiency (e.g., in acute diabetes or fasting) is associated with enhanced protein breakdown in skeletal muscle leading to muscle wasting. Because recent studies have suggested that this increased proteolysis is due to activation of the ubiquitin-proteasome (Ub-proteasome) pathway, we investigated whether diabetes is associated with an increased rate of Ub conjugation to muscle protein. Muscle extracts from streptozotocin-induced insulin-deficient rats contained greater amounts of Ub-conjugated proteins than extracts from control animals and also 40-50% greater rates of conjugation of (125)I-Ub to endogenous muscle proteins. This enhanced Ub-conjugation occurred mainly through the N-end rule pathway that involves E2(14k) and E3alpha. A specific substrate of this pathway, alpha-lactalbumin, was ubiquitinated faster in the diabetic extracts, and a dominant negative form of E2(14k) inhibited this increase in ubiquitination rates. Both E2(14k) and E3alpha were shown to be rate-limiting for Ub conjugation because adding small amounts of either to extracts stimulated Ub conjugation. Furthermore, mRNA for E2(14k) and E3alpha (but not E1) were elevated 2-fold in muscles from diabetic rats, although no significant increase in E2(14k) and E3alpha content could be detected by immunoblot or activity assays. The simplest interpretation of these results is that small increases in both E2(14k) and E3alpha in muscles of insulin-deficient animals together accelerate Ub conjugation and protein degradation by the N-end rule pathway, the same pathway activated in cancer cachexia, sepsis, and hyperthyroidism.

  10. Independent component and pathway-based analysis of miRNA-regulated gene expression in a model of type 1 diabetes

    DEFF Research Database (Denmark)

    Bang-Berthelsen, Claus Heiner; Pedersen, Lykke; Fløyel, Tina

    2011-01-01

    enrichment of sequence predicted targets, compared to only four miRNAs when using simple negative correlation. The ICs were enriched for miRNA targets that function in diabetes-relevant pathways e.g. type 1 and type 2 diabetes and maturity onset diabetes of the young (MODY). CONCLUSIONS: In this study, ICA...... (ICA). Here, we developed a novel target prediction method based on ICA that incorporates both seed matching and expression profiling of miRNA and mRNA expressions. The method was applied on a cellular model of type 1 diabetes. RESULTS: Microrray profiling identified eight miRNAs (miR-124...... between the predicted miRNA targets. Applying the method on a model of type 1 diabetes resulted in identification of eight miRNAs that appear to affect pathways of relevance to disease mechanisms in diabetes....

  11. Ubiquitin conjugation by the N-end rule pathway and mRNAs for its components increase in muscles of diabetic rats

    OpenAIRE

    Lecker, Stewart H.; Solomon, Vered; Price, S. Russ; Kwon, Yong Tae; Mitch, William E.; Goldberg, Alfred L.

    1999-01-01

    Insulin deficiency (e.g., in acute diabetes or fasting) is associated with enhanced protein breakdown in skeletal muscle leading to muscle wasting. Because recent studies have suggested that this increased proteolysis is due to activation of the ubiquitin-proteasome (Ub-proteasome) pathway, we investigated whether diabetes is associated with an increased rate of Ub conjugation to muscle protein. Muscle extracts from streptozotocin-induced insulin-deficient rats contained greater amounts of Ub...

  12. FvBck1, a Component of Cell Wall Integrity MAP Kinase Pathway, is Required for Virulence and Oxidative Stress Response in Sugarcane Pokkah Boeng Pathogen

    Directory of Open Access Journals (Sweden)

    Chengkang eZhang

    2015-10-01

    Full Text Available Fusarium verticillioides (formerly F. moniliforme is suggested as one of the causal agents of Pokkah Boeng, a serious disease of sugarcane worldwide. Currently, detailed molecular and physiological mechanism of pathogenesis is unknown. In this study, we focused on cell wall integrity MAPK pathway as one of the potential signaling mechanisms associated with Pokkah Boeng pathogenesis. We identified FvBCK1 gene that encodes a MAP kinase kinase kinase homolog and determined that it is not only required for growth, micro- and macro-conidia production, and cell wall integrity but also for response to osmotic and oxidative stresses. The deletion of FvBCK1 caused a significant reduction in virulence and FB1 production, a carcinogenic mycotoxin produced by the fungus. Moreover, we found the expression levels of three genes, which are known to be involved in superoxide scavenging, were down regulated in the mutant. We hypothesized that the loss of superoxide scavenging capacity was one of the reasons for reduced virulence, but overexpression of catalase or peroxidase gene failed to restore the virulence defect in the deletion mutant. When we introduced Magnaporthe oryzae MCK1 into the FvBck1 deletion mutant, while certain phenotypes were restored, the complemented strain failed to gain full virulence. In summary, FvBck1 plays a diverse role in F. verticillioides, and detailed investigation of downstream signaling pathways will lead to a better understanding of how this MAPK pathway regulates Pokkah Boeng on sugarcane.

  13. An assay for serum vitamin-B12 and for intrinsic factor antibody type I by means of hog intrinsic factor

    International Nuclear Information System (INIS)

    Hudak, J.; Berger, Z.; Varga, L.

    1980-01-01

    A new radioassay method was elaborated for the determination of the plasma level of vitamin B 12 and of the intrinsic factor antibody type I. The assay applies vitamin-B 12 labelled with 58 Co, but replaces human intrinsic factor by hog intrinsic factor. 124 cases were investigated by both the original and this modified method, and the results were in very good agreement. (L.E.)

  14. Enzyme-catalyzed degradation of biodegradable polymers derived from trimethylene carbonate and glycolide by lipases from Candida antarctica and Hog pancreas.

    Science.gov (United States)

    Liu, Feng; Yang, Jian; Fan, Zhongyong; Li, Suming; Kasperczyk, Janusz; Dobrzynski, Piotr

    2012-01-01

    Enzyme-catalyzed degradation of poly(trimethylene carbonate) homo-polymer (PTMC) and poly(trimethylene carbonate-co-glycolide) co-polymer (PTGA) was investigated in the presence of lipases from Candida antarctica and Hog pancreas. Degradation was monitored by gravimetry, size-exclusion chromatography (SEC), nuclear magnetic resonance (NMR), tensiometry and environmental scanning electron microscopy (ESEM). PTMC can be rapidly degraded by Candida antarctica lipase with 98% mass loss after 9 days, while degradation by Hog pancreas lipase leads to 27% mass loss. Introduction of 16% glycolide units in PTMC chains strongly affects the enzymatic degradation. Hog pancreas lipase becomes more effective to PTGA co-polymer with a mass loss of 58% after 9 days, while Candida antarctica lipase seems not able to degrade PTGA. Bimodal molecular weight distributions are observed during enzymatic degradation of both PTMC and PTGA, which can be assigned to the fact that the surface is largely degraded while the internal part remains intact. The composition of the PTGA co-polymer remains constant, and ESEM shows that the polymers are homogeneously eroded during enzymatic degradation. Contact angle measurements confirm the enzymatic degradation mechanism, i.e., enzyme adsorption on the polymer surface followed by enzyme-catalyzed chain cleavage.

  15. Nitrous oxide emissions and soil mineral nitrogen status following application of hog slurry and inorganic fertilisers to acidic soils under forage grass

    International Nuclear Information System (INIS)

    Mkhabela, M.S.; Gordon, R.; Madani, A.; Burton, D.; Hart, W.

    2008-01-01

    This paper examined the influence of hog slurry and inorganic fertilizers on nitrous oxide (N 2 O) emissions and soil inorganic nitrogen (N) composition. Factors controlling N 2 O production were also identified. The study was comprised of 3 field experiments conducted during the summer months of 2005 on 2 acidic soils seeded with forage grass at a site in Nova Scotia. Treatments included hog slurry; ammonium sulphate; potassium nitrate; and an unamended control site. Emissions were measured using vented polyvinyl chloride static chambers. Gas fluxes and NO 2 measurements were analyzed using gas chromatography. Data were then subjected to analysis of variance (ANOVA). N 2 O flux and soil mineral N data from each sampling day were analyzed separately. Cumulative N 2 O losses were also calculated. Results demonstrated that the addition of hog slurry resulted in lower N 2 O emissions than the samples containing potassium nitrate fertilizer. The study also demonstrated that nitrate (NO 3 ) production drives NO 2 production in acidic soils. It was concluded that further research is needed to verify results obtained during the study. 29 refs., 3 tabs., 3 figs

  16. Enhanced Gender Recognition System Using an Improved Histogram of Oriented Gradient (HOG Feature from Quality Assessment of Visible Light and Thermal Images of the Human Body

    Directory of Open Access Journals (Sweden)

    Dat Tien Nguyen

    2016-07-01

    Full Text Available With higher demand from users, surveillance systems are currently being designed to provide more information about the observed scene, such as the appearance of objects, types of objects, and other information extracted from detected objects. Although the recognition of gender of an observed human can be easily performed using human perception, it remains a difficult task when using computer vision system images. In this paper, we propose a new human gender recognition method that can be applied to surveillance systems based on quality assessment of human areas in visible light and thermal camera images. Our research is novel in the following two ways: First, we utilize the combination of visible light and thermal images of the human body for a recognition task based on quality assessment. We propose a quality measurement method to assess the quality of image regions so as to remove the effects of background regions in the recognition system. Second, by combining the features extracted using the histogram of oriented gradient (HOG method and the measured qualities of image regions, we form a new image features, called the weighted HOG (wHOG, which is used for efficient gender recognition. Experimental results show that our method produces more accurate estimation results than the state-of-the-art recognition method that uses human body images.

  17. Enhanced Gender Recognition System Using an Improved Histogram of Oriented Gradient (HOG) Feature from Quality Assessment of Visible Light and Thermal Images of the Human Body.

    Science.gov (United States)

    Nguyen, Dat Tien; Park, Kang Ryoung

    2016-07-21

    With higher demand from users, surveillance systems are currently being designed to provide more information about the observed scene, such as the appearance of objects, types of objects, and other information extracted from detected objects. Although the recognition of gender of an observed human can be easily performed using human perception, it remains a difficult task when using computer vision system images. In this paper, we propose a new human gender recognition method that can be applied to surveillance systems based on quality assessment of human areas in visible light and thermal camera images. Our research is novel in the following two ways: First, we utilize the combination of visible light and thermal images of the human body for a recognition task based on quality assessment. We propose a quality measurement method to assess the quality of image regions so as to remove the effects of background regions in the recognition system. Second, by combining the features extracted using the histogram of oriented gradient (HOG) method and the measured qualities of image regions, we form a new image features, called the weighted HOG (wHOG), which is used for efficient gender recognition. Experimental results show that our method produces more accurate estimation results than the state-of-the-art recognition method that uses human body images.

  18. Limonin, a Component of Dictamni Radicis Cortex, Inhibits Eugenol-Induced Calcium and cAMP Levels and PKA/CREB Signaling Pathway in Non-Neuronal 3T3-L1 Cells

    Directory of Open Access Journals (Sweden)

    Yeo Cho Yoon

    2015-12-01

    Full Text Available Limonin, one of the major components in dictamni radicis cortex (DRC, has been shown to play various biological roles in cancer, inflammation, and obesity in many different cell types and tissues. Recently, the odorant-induced signal transduction pathway (OST has gained attention not only because of its function in the perception of smell but also because of its numerous physiological functions in non-neuronal cells. However, little is known about the effects of limonin and DRC on the OST pathway in non-neuronal cells. We investigated odorant-stimulated increases in Ca2+ and cAMP, major second messengers in the OST pathway, in non-neuronal 3T3-L1 cells pretreated with limonin and ethanol extracts of DRC. Limonin and the extracts significantly decreased eugenol-induced Ca2+ and cAMP levels and upregulated phosphorylation of CREB and PKA. Our results demonstrated that limonin and DRC extract inhibit the OST pathway in non-neuronal cells by modulating Ca2+ and cAMP levels and phosphorylation of CREB.

  19. C. elegans fmi-1/flamingo and Wnt pathway components interact genetically to control the anteroposterior neurite growth of the VD GABAergic neurons.

    Science.gov (United States)

    Huarcaya Najarro, Elvis; Ackley, Brian D

    2013-05-01

    Directed axonal growth is essential to establish neuronal networks. During the early development of the VD neurons, an anterior neurite that will become the VD axon extends along the anteroposterior (A/P) axis in the ventral nerve cord (VNC) in Caenorhabditis elegans. Little is known about the cellular and molecular mechanisms that are important for correct neurite growth in the VNC. In fmi-1/flamingo mutant animals, we observed that some postembryonically born VD neurons had a posterior neurite instead of a normal anterior neurite, which caused aberrant VD commissure patterning along the A/P axis. In addition, VD anterior neurites had underextension defects in the VNC in fmi-1 animals, whereas VD commissure growth along the dorsoventral (D/V) axis occurred normally in these animals, suggesting that fmi-1 is important for neurite growth along the A/P axis but not the D/V axis. We also uncovered unknown details of the early development of the VD neurons, indicating that the neurite defects arose during their early development. Interestingly, though fmi-1 is present at this time in the VNC, we did not observe FMI-1 in the VD neurons themselves, suggesting that fmi-1 might be working in a cell non-autonomous fashion. Furthermore, fmi-1 appears to be working in a novel pathway, independently from the planar cell polarity pathway and in parallel to lin-17/frizzled and dsh-1/dishevelled, to determine the direction of neurite growth. Our findings indicate that redundant developmental pathways regulate neurite growth in the VNC in C. elegans. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Effect of hog production wastewater in the development and quality of Eucalyptus urophylla substrate produced in urban solid waste

    Directory of Open Access Journals (Sweden)

    Raquel Oliveira Batista

    2013-08-01

    Full Text Available The objective of this study was to analyze the use of hog production wastewater in the production of seedlings of Eucalyptus urophylla, using a compound of municipal solid waste (SRSU as substrate, and evaluating the effect of different proportions of ARS and of seedling ages in their morphological and nutritional quality. The experiment was conducted in a greenhouse at the Experimental Hydraulics, Irrigation and Drainage, Department of Agricultural Engineering. The statistical design was randomized blocks with different numbers of repetitions, consisting of 10 treatments in a 5 x 2 factorial design (5 proportions of ARS supplemented with nitrogen fertilization and 2 seedling ages. The variables measured were shoot height (H, stem diameter (SD, shoot dry matter (SDM, root dry mass (RDM, total dry matter (TDM, ratio of seedling height / diameter of the girth (H / SD, ratio of dry weight of shoot / root dry mass (SDM / RDM, Dickson quality index (DQI and concentrations of nutrients in the plants leaf, stem and root. These characteristics were evaluated at 75 and 90 days after seeding (DAS. It was concluded that the proportion of 50% ARS improved the nutritional and morphological characteristics of eucalyptus. The seedlings achieved morphological characteristics suitable for planting in the field 90 days after sowing and showed appropriate levels for most nutrients at both ages.

  1. Feeding habits of Molina's hog-nosed skunk, Conepatus chinga (Carnivora: Mephitidae in the extreme south of Brazil

    Directory of Open Access Journals (Sweden)

    Felipe Bortolotto Peters

    2011-04-01

    Full Text Available Feeding habits of the Molina's hog-nosed skunk, Conepatus chinga (Molina, 1782 in the extreme south of Brazil. We analyzed 60 stomachs of road-kills of C. chinga in the extreme south of Brazil. The contents revealed 808 prey parts, including invertebrates (frequency of occurrence - FO = 96.7% and relative abundance - RA = 94.7%, vertebrates (FO = 18.3% and RA = 2.8% and plants (FO = 31.7% and RA = 2.3%. We identified 18 kinds of food, including the invertebrate order Coleoptera which showed the highest FO (86.7% and RA (75.2%. Other important orders were Orthoptera (FO = 35% and RA = 10.4% and Araneae (FO = 41.7% and RA = 4%. The combination of occurrence and abundance of the preys consumed allowed classifying C. chinga as an omnivorous with a predominance of insects, especially Coleoptera, consuming other invertebrates, vertebrates and plants in smaller numbers. Behavioral and morphological adaptations of C. chinga favor the predation of insects, which are preys that offer low physical resistance and are available in all terrestrial environments.

  2. Thermodynamic analysis and kinetic modelling of dioxin formation and emissions from power boilers firing salt-laden hog fuel.

    Science.gov (United States)

    Duo, Wenli; Leclerc, Denys

    2007-04-01

    Both organic chlorine (e.g. PVC) and inorganic chlorides (e.g. NaCl) can be significant chlorine sources for dioxin and furan (PCDD/F) formation in combustion processes. This paper presents a thermodynamic analysis of high temperature salt chemistry. Its influence on PCDD/F formation in power boilers burning salt-laden wood waste is examined through the relationships between Cl2, HCl, NaCl(g) and NaCl(c). These analyses show that while HCl is a product of combustion of PVC-laden municipal solid waste, NaCl can be converted to HCl in hog fuel boilers by reactions with SO2 or alumino-silicate materials. Cl2 is a strong chlorinating agent for PCDD/F formation. HCl can be oxidized to Cl2 by O2, and Cl2 can be reduced back to HCl by SO2. The presence of sulphur at low concentrations thus enhances PCDD/F formation by increasing HCl concentrations. At high concentrations, sulphur inhibits de novo formation of PCDD/Fs through Cl2 reduction by excess SO2. The effect of NH3, CO and NOx on PCDD/F formation is also discussed. A semi-empirical kinetic model is proposed. This model considers both precursor and de novo formation mechanisms. A simplified version is used as a stack emission model. The kinetic model indicates that stack dioxin emissions will increase linearly with decreasing electrostatic precipitator (ESP) efficiency and exponentially with increasing ESP temperature.

  3. Classification of molecular structure images by using ANN, RF, LBP, HOG, and size reduction methods for early stomach cancer detection

    Science.gov (United States)

    Aytaç Korkmaz, Sevcan; Binol, Hamidullah

    2018-03-01

    Patients who die from stomach cancer are still present. Early diagnosis is crucial in reducing the mortality rate of cancer patients. Therefore, computer aided methods have been developed for early detection in this article. Stomach cancer images were obtained from Fırat University Medical Faculty Pathology Department. The Local Binary Patterns (LBP) and Histogram of Oriented Gradients (HOG) features of these images are calculated. At the same time, Sammon mapping, Stochastic Neighbor Embedding (SNE), Isomap, Classical multidimensional scaling (MDS), Local Linear Embedding (LLE), Linear Discriminant Analysis (LDA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and Laplacian Eigenmaps methods are used for dimensional the reduction of the features. The high dimension of these features has been reduced to lower dimensions using dimensional reduction methods. Artificial neural networks (ANN) and Random Forest (RF) classifiers were used to classify stomach cancer images with these new lower feature sizes. New medical systems have developed to measure the effects of these dimensions by obtaining features in different dimensional with dimensional reduction methods. When all the methods developed are compared, it has been found that the best accuracy results are obtained with LBP_MDS_ANN and LBP_LLE_ANN methods.

  4. CD40-CD40 Ligand Pathway is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis.

    Science.gov (United States)

    Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall'Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

    2015-03-26

    Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40-CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40-CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40-CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40-CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis.

  5. CD40–CD40 Ligand Pathway Is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis

    Science.gov (United States)

    Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall’Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

    2015-01-01

    Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40–CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40–CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40–CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40–CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis. PMID:25822797

  6. Smad signaling pathway is a pivotal component of tissue inhibitor of metalloproteinases-3 regulation by transforming growth factor beta in human chondrocytes.

    Science.gov (United States)

    Qureshi, Hamid Yaqoob; Ricci, Gemma; Zafarullah, Muhammad

    2008-09-01

    Transforming growth factor beta (TGF-beta1) promotes cartilage matrix synthesis and induces tissue inhibitor of metalloproteinases-3 (TIMP-3), which inhibits matrix metalloproteinases, aggrecanases and TNF-alpha-converting enzyme implicated in articular cartilage degradation and joint inflammation. TGF-beta1 activates Akt, ERK and Smad2 pathways in chondrocytes. Here we investigated previously unexplored roles of specific Smads in TGF-beta1 induction of TIMP-3 gene by pharmacological and genetic knockdown approaches. TGF-beta1-induced Smad2 phosphorylation and TIMP-3 protein expression could be inhibited by the Smad2/3 phosphorylation inhibitors, PD169316 and SB203580 and by Smad2-specific siRNA. Specific inhibitor of Smad3 (SIS3) and Smad3 siRNA abolished TGF-beta induction of TIMP-3. Smad2/3 siRNAs also down regulated TIMP-3 promoter-driven luciferase activities, suggesting transcriptional regulation. SiRNA-driven co-Smad4 knockdown abrogated TIMP-3 augmentation by TGF-beta. TIMP-3 promoter deletion analysis revealed that -828 deletion retains the original promoter activity while -333 and -167 deletions display somewhat reduced activity suggesting that most of the TGF-beta-responsive, cis-acting elements are found in the -333 fragment. Chromatin Immunoprecipitation (ChIP) analysis confirmed binding of Smad2 and Smad4 with the -940 and -333 promoter sequences. These results suggest that receptor-activated Smad2 and Smad3 and co-Smad4 critically mediate TGF-beta-stimulated TIMP-3 expression in human chondrocytes and TIMP-3 gene is a target of Smad signaling pathway.

  7. [Participation of the piRNA pathway in recruiting a component of RNA polymerase I transcription initiation complex to germline cell nucleoli].

    Science.gov (United States)

    Fefelova, E A; Stolyarenko, A D; Yakushev, E Y; Gvozdev, V A; Klenov, M S

    2017-01-01

    Proteins of the Piwi family and short Piwi-interacting RNAs (piRNAs) ensure the protection of the genome from transposable elements. We have previously shown that nuclear Piwi protein tends to concentrate in the nucleoli of the cells of Drosophila melanogaster ovaries. It could be hypothesized that the function of Piwi in the nucleolus is associated with the repression of R1 and R2 retrotransposons inserted into the rDNA cluster. Here, we show that Piwi participates in recruiting Udd protein to nucleoli. Udd is a component of the conserved Selectivity Factor I-like (SL1-like) complex, which is required for transcription initiation by RNA polymerase I. We found that Udd localization depends on Piwi in germline cells, but not in somatic cells of the ovaries. In contrast, knockdowns of the SL1-like components (Udd or TAF1b) do not disrupt Piwi localization. We also observed that the absence of Udd or TAF1b in germline cells, as well as the impairment of Piwi nuclear localization lead to the accumulation of late stage egg chambers in the ovaries, which could be explained by reduced rRNA transcription. These results allow us to propose for the first time a role for Piwi in the nucleolus that is not directly associated with transposable element repression.

  8. Key Components of Different Plant Defense Pathways Are Dispensable for Powdery Mildew Resistance of the Arabidopsis mlo2 mlo6 mlo12 Triple Mutant.

    Science.gov (United States)

    Kuhn, Hannah; Lorek, Justine; Kwaaitaal, Mark; Consonni, Chiara; Becker, Katia; Micali, Cristina; Ver Loren van Themaat, Emiel; Bednarek, Paweł; Raaymakers, Tom M; Appiano, Michela; Bai, Yuling; Meldau, Dorothea; Baum, Stephani; Conrath, Uwe; Feussner, Ivo; Panstruga, Ralph

    2017-01-01

    Loss of function mutations of particular plant MILDEW RESISTANCE LOCUS O ( MLO ) genes confer durable and broad-spectrum penetration resistance against powdery mildew fungi. Here, we combined genetic, transcriptomic and metabolomic analyses to explore the defense mechanisms in the fully resistant Arabidopsis thaliana mlo2 mlo6 mlo12 triple mutant. We found that this genotype unexpectedly overcomes the requirement for indolic antimicrobials and defense-related secretion, which are critical for incomplete resistance of mlo2 single mutants. Comparative microarray-based transcriptome analysis of mlo2 mlo6 mlo12 mutants and wild type plants upon Golovinomyces orontii inoculation revealed an increased and accelerated accumulation of many defense-related transcripts. Despite the biotrophic nature of the interaction, this included the non-canonical activation of a jasmonic acid/ethylene-dependent transcriptional program. In contrast to a non-adapted powdery mildew pathogen, the adapted powdery mildew fungus is able to defeat the accumulation of defense-relevant indolic metabolites in a MLO protein-dependent manner. We suggest that a broad and fast activation of immune responses in mlo2 mlo6 mlo12 plants can compensate for the lack of single or few defense pathways. In addition, our results point to a role of Arabidopsis MLO2, MLO6, and MLO12 in enabling defense suppression during invasion by adapted powdery mildew fungi.

  9. Analysis of triglyceride synthesis unveils a green algal soluble diacylglycerol acyltransferase and provides clues to potential enzymatic components of the chloroplast pathway.

    Science.gov (United States)

    Bagnato, Carolina; Prados, María B; Franchini, Gisela R; Scaglia, Natalia; Miranda, Silvia E; Beligni, María V

    2017-03-09

    Microalgal triglyceride (TAG) synthesis has attracted considerable attention. Particular emphasis has been put towards characterizing the algal homologs of the canonical rate-limiting enzymes, diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT). Less work has been done to analyze homologs from a phylogenetic perspective. In this work, we used HMMER iterative profiling and phylogenetic and functional analyses to determine the number and sequence characteristics of algal DGAT and PDAT, as well as related sequences that constitute their corresponding superfamilies. We included most algae with available genomes, as well as representative eukaryotic and prokaryotic species. Amongst our main findings, we identified a novel clade of DGAT1-like proteins exclusive to red algae and glaucophyta and a previously uncharacterized subclade of DGAT2 proteins with an unusual number of transmembrane segments. Our analysis also revealed the existence of a novel DGAT exclusive to green algae with moderate similarity to plant soluble DGAT3. The DGAT3 clade shares a most recent ancestor with a group of uncharacterized proteins from cyanobacteria. Subcellular targeting prediction suggests that most green algal DGAT3 proteins are imported to the chloroplast, evidencing that the green algal chloroplast might have a soluble pathway for the de novo synthesis of TAGs. Heterologous expression of C. reinhardtii DGAT3 produces an increase in the accumulation of TAG, as evidenced by thin layer chromatography. Our analysis contributes to advance in the knowledge of complex superfamilies involved in lipid metabolism and provides clues to possible enzymatic players of chloroplast TAG synthesis.

  10. Variability of Atmospheric Radon-222 and Secondary Aerosol Components in Accordance with Air Mass Transport Pathways at Jeju Island, Korea, during 2011-2014

    International Nuclear Information System (INIS)

    Bu, Jun-Oh; Song, Jung-Min; Kim, Won-Hyung; Kang, Chang-Hee; Chambers, Scott D.; Williams, Alastair G.; Lee, Chulkyu

    2016-01-01

    Real-time monitoring of hourly atmospheric Radon-222 concentration and three daily monitoring of the secondary aerosol components of PM_1_0 were performed throughout 2011-2014 at Gosan station, Jeju Island, in order to characterize their background levels and temporal variation. The annual mean radon and PM_1_0 mass concentrations were 2326 ± 1198 mBq/m"3 and 37.1 ± 19.5 μg/m"3, respectively. Based on cluster analyses of air mass back trajectories, the frequencies of air masses originating from continental China, the Korean Peninsula, and North Pacific Ocean routes were 53, 28, and 19%, respectively. When the air masses were transported to Jeju Island from continental China, the concentrations of radon and secondary aerosol components (nss-SO_4"2"-, NO_3"-, NH_4"+) were relatively high: 2577 mBq/m"3 and 14.4 μg/m"3, respectively. In cases when the air masses have moved from the Korean Peninsula, the corresponding concentrations were 2247 mBq/m"3 and 11.4 μg/m"3, respectively. On the other hand, when the air masses came from the North Pacific Ocean, their radon and secondary aerosol concentrations decreased much further, 1372 mBq/m"3 and 10.5 μg/m"3, respectively. Consequently, the variability of atmospheric radon concentrations at Gosan station might be characterized by synoptic changes in air mass fetch as well as diurnal changes in atmospheric mixing depth.

  11. Variability of Atmospheric Radon-222 and Secondary Aerosol Components in Accordance with Air Mass Transport Pathways at Jeju Island, Korea, during 2011-2014

    Energy Technology Data Exchange (ETDEWEB)

    Bu, Jun-Oh; Song, Jung-Min; Kim, Won-Hyung; Kang, Chang-Hee [Jeju National University, Jeju (Korea, Republic of); Chambers, Scott D.; Williams, Alastair G. [Australian Nuclear Science and Technology Organisation, Kirrawee DC (Australia); Lee, Chulkyu [Korea Meteorological Administration, Seoul (Korea, Republic of)

    2016-06-15

    Real-time monitoring of hourly atmospheric Radon-222 concentration and three daily monitoring of the secondary aerosol components of PM{sub 10} were performed throughout 2011-2014 at Gosan station, Jeju Island, in order to characterize their background levels and temporal variation. The annual mean radon and PM{sub 10} mass concentrations were 2326 ± 1198 mBq/m{sup 3} and 37.1 ± 19.5 μg/m{sup 3}, respectively. Based on cluster analyses of air mass back trajectories, the frequencies of air masses originating from continental China, the Korean Peninsula, and North Pacific Ocean routes were 53, 28, and 19%, respectively. When the air masses were transported to Jeju Island from continental China, the concentrations of radon and secondary aerosol components (nss-SO{sub 4}{sup 2-}, NO{sub 3}{sup -}, NH{sub 4}{sup +}) were relatively high: 2577 mBq/m{sup 3} and 14.4 μg/m{sup 3}, respectively. In cases when the air masses have moved from the Korean Peninsula, the corresponding concentrations were 2247 mBq/m{sup 3} and 11.4 μg/m{sup 3}, respectively. On the other hand, when the air masses came from the North Pacific Ocean, their radon and secondary aerosol concentrations decreased much further, 1372 mBq/m{sup 3} and 10.5 μg/m{sup 3}, respectively. Consequently, the variability of atmospheric radon concentrations at Gosan station might be characterized by synoptic changes in air mass fetch as well as diurnal changes in atmospheric mixing depth.

  12. Argonne Liquid-Metal Advanced Burner Reactor : components and in-vessel system thermal-hydraulic research and testing experience - pathway forward.

    Energy Technology Data Exchange (ETDEWEB)

    Kasza, K.; Grandy, C.; Chang, Y.; Khalil, H.; Nuclear Engineering Division

    2007-06-30

    This white paper provides an overview and status report of the thermal-hydraulic nuclear research and development, both experimental and computational, conducted predominantly at Argonne National Laboratory. Argonne from the early 1970s through the early 1990s was the Department of Energy's (DOE's) lead lab for thermal-hydraulic development of Liquid Metal Reactors (LMRs). During the 1970s and into the mid-1980s, Argonne conducted thermal-hydraulic studies and experiments on individual reactor components supporting the Experimental Breeder Reactor-II (EBR-II), Fast Flux Test Facility (FFTF), and the Clinch River Breeder Reactor (CRBR). From the mid-1980s and into the early 1990s, Argonne conducted studies on phenomena related to forced- and natural-convection thermal buoyancy in complete in-vessel models of the General Electric (GE) Prototype Reactor Inherently Safe Module (PRISM) and Rockwell International (RI) Sodium Advanced Fast Reactor (SAFR). These two reactor initiatives involved Argonne working closely with U.S. industry and DOE. This paper describes the very important impact of thermal hydraulics dominated by thermal buoyancy forces on reactor global operation and on the behavior/performance of individual components during postulated off-normal accident events with low flow. Utilizing Argonne's LMR expertise and design knowledge is vital to the further development of safe, reliable, and high-performance LMRs. Argonne believes there remains an important need for continued research and development on thermal-hydraulic design in support of DOE's and the international community's renewed thrust for developing and demonstrating the Global Nuclear Energy Partnership (GNEP) reactor(s) and the associated Argonne Liquid Metal-Advanced Burner Reactor (LM-ABR). This white paper highlights that further understanding is needed regarding reactor design under coolant low-flow events. These safety-related events are associated with the transition

  13. BH3-mimetics- and cisplatin-induced cell death proceeds through different pathways depending on the availability of death-related cellular components.

    Directory of Open Access Journals (Sweden)

    Vicente Andreu-Fernández

    Full Text Available BACKGROUND: Owing to their important function in regulating cell death, pharmacological inhibition of Bcl-2 proteins by dubbed BH3-mimetics is a promising strategy for apoptosis induction or sensitization to chemotherapy. However, the role of Apaf-1, the main protein constituent of the apoptosome, in the process has yet not been analyzed. Furthermore as new chemotherapeutics develop, the possible chemotherapy-induced toxicity to rapidly dividing normal cells, especially sensitive differentiated cells, has to be considered. Such undesirable effects would probably be ameliorated by selectively and locally inhibiting apoptosis in defined sensitive cells. METHODOLOGY AND PRINCIPAL FINDINGS: Mouse embryonic fibroblasts (MEFS from Apaf-1 knock out mouse (MEFS KO Apaf-1 and Bax/Bak double KO (MEFS KO Bax/Bak, MEFS from wild-type mouse (MEFS wt and human cervix adenocarcinoma (HeLa cells were used to comparatively investigate the signaling cell death-induced pathways of BH3-mimetics, like ABT737 and GX15-070, with DNA damage-inducing agent cisplatin (cis-diammineplatinum(II dichloride, CDDP. The study was performed in the absence or presence of apoptosis inhibitors namely, caspase inhibitors or apoptosome inhibitors. BH3-mimetic ABT737 required of Apaf-1 to exert its apoptosis-inducing effect. In contrast, BH3-mimetic GX15-070 and DNA damage-inducing CDDP induced cell death in the absence of both Bax/Bak and Apaf-1. GX15-070 induced autophagy-based cell death in all the cell lines analyzed. MEFS wt cells were protected from the cytotoxic effects of ABT737 and CDDP by chemical inhibition of the apoptosome through QM31, but not by using general caspase inhibitors. CONCLUSIONS: BH3-mimetic ABT737 not only requires Bax/Bak to exert its apoptosis-inducing effect, but also Apaf-1, while GX15-070 and CDDP induce different modalities of cell death in the absence of Bax/Bak or Apaf-1. Inclusion of specific Apaf-1 inhibitors in topical and well

  14. The Hog Cycle of Law Professors: An Econometric Time Series Analysis of the Entry-Level Job Market in Legal Academia.

    Science.gov (United States)

    Engel, Christoph; Hamann, Hanjo

    2016-01-01

    The (German) market for law professors fulfils the conditions for a hog cycle: In the short run, supply cannot be extended or limited; future law professors must be hired soon after they first present themselves, or leave the market; demand is inelastic. Using a comprehensive German dataset, we show that the number of market entries today is negatively correlated with the number of market entries eight years ago. This suggests short-sighted behavior of young scholars at the time when they decide to prepare for the market. Using our statistical model, we make out-of-sample predictions for the German academic market in law until 2020.

  15. Rhodiola crenulata and Its Bioactive Components, Salidroside and Tyrosol, Reverse the Hypoxia-Induced Reduction of Plasma-Membrane-Associated Na,K-ATPase Expression via Inhibition of ROS-AMPK-PKCξ Pathway

    Directory of Open Access Journals (Sweden)

    Shih-Yu Lee

    2013-01-01

    Full Text Available Exposure to hypoxia leads to impaired pulmonary sodium transport, which is associated with Na,K-ATPase dysfunction in the alveolar epithelium. The present study is designed to examine the effect and mechanism of Rhodiola crenulata extract (RCE and its bioactive components on hypoxia-mediated Na,K-ATPase endocytosis. A549 cells were exposed to hypoxia in the presence or absence of RCE, salidroside, or tyrosol. The generation of intracellular ROS was measured by using the fluorescent probe DCFH-DA, and the endocytosis was determined by measuring the expression level of Na,K-ATPase in the PM fraction. Rats exposed to a hypobaric hypoxia chamber were used to investigate the efficacy and underlying mechanism of RCE in vivo. Our results showed that RCE and its bioactive compounds significantly prevented the hypoxia-mediated endocytosis of Na,K-ATPase via the inhibition of the ROS-AMPK-PKCζ pathway in A549 cells. Furthermore, RCE also showed a comparable preventive effect on the reduction of Na,K-ATPase endocytosis and inhibition of AMPK-PKCξ pathway in the rodent model. Our study is the first to offer substantial evidence to support the efficacy of Rhodiola products against hypoxia-associated Na,K-ATPase endocytosis and clarify the ethnopharmacological relevance of Rhodiola crenulata as a popular folk medicine for high-altitude illness.

  16. Communication between Thiamin Cofactors in the Escherichia coli Pyruvate Dehydrogenase Complex E1 Component Active Centers EVIDENCE FOR A DIRECT PATHWAY BETWEEN THE 4′-AMINOPYRIMIDINE N1′ ATOMS

    Energy Technology Data Exchange (ETDEWEB)

    Nemeria, Natalia S; Arjunan, Palaniappa; Chandrasekhar, Krishnamoorthy; Mossad, Madouna; Tittmann, Kai; Furey, William; Jordan, Frank [Pitt; (Goettingen); (VA); (Rutgers)

    2010-11-03

    Kinetic, spectroscopic, and structural analysis tested the hypothesis that a chain of residues connecting the 4{prime}-aminopyrimidine N1{prime} atoms of thiamin diphosphates (ThDPs) in the two active centers of the Escherichia coli pyruvate dehydrogenase complex E1 component provides a signal transduction pathway. Substitution of the three acidic residues (Glu{sup 571}, Glu{sup 235}, and Glu{sup 237}) and Arg{sup 606} resulted in impaired binding of the second ThDP, once the first active center was filled, suggesting a pathway for communication between the two ThDPs. (1) Steady-state kinetic and fluorescence quenching studies revealed that upon E571A, E235A, E237A, and R606A substitutions, ThDP binding in the second active center was affected. (2) Analysis of the kinetics of thiazolium C2 hydrogen/deuterium exchange of enzyme-bound ThDP suggests half-of-the-sites reactivity for the E1 component, with fast (activated site) and slow exchanging sites (dormant site). The E235A and E571A variants gave no evidence for the slow exchanging site, indicating that only one of two active sites is filled with ThDP. (3) Titration of the E235A and E237A variants with methyl acetylphosphonate monitored by circular dichroism suggested that only half of the active sites were filled with a covalent predecarboxylation intermediate analog. (4) Crystal structures of E235A and E571A in complex with ThDP revealed the structural basis for the spectroscopic and kinetic observations and showed that either substitution affects cofactor binding, despite the fact that Glu{sup 235} makes no direct contact with the cofactor. The role of the conserved Glu{sup 571} residue in both catalysis and cofactor orientation is revealed by the combined results for the first time.

  17. RNAi-mediated silencing of MAP kinase signalling genes (Fmk1, Hog1, and Pbs2) in Fusarium oxysporum reduces pathogenesis on tomato plants.

    Science.gov (United States)

    Pareek, Manish; Rajam, Manchikatla Venkat

    2017-09-01

    Fusarium oxysporum is a soil-borne plant fungal pathogen, and causes colossal losses in several crop plants including tomato. Effective control measures include the use of harmful fungicides and resistant cultivars, but these methods have shown limited success. Conventional methods to validate fungal pathogenic genes are labour intensive. Therefore, an alternative strategy is required to efficiently characterize unknown pathogenic genes. RNA interference (RNAi) has emerged as a potential tool to functionally characterize novel fungal pathogenic genes and also to control fungal diseases. Here, we report an efficient method to produce stable RNAi transformants of F. oxysporum using Agrobacterium-mediated transformation (AMT). We have transformed F. oxysporum spores using RNAi constructs of Fmk1, Hog1, and Pbs2 MAP kinase signalling genes. Fmk1 RNAi fungal transformants showed loss of surface hydrophobicity, reduced invasive growth on tomato fruits and hypo-virulence on tomato seedlings. Hog1 and Pbs2 RNAi transformants showed altered conidial size, and reduced invasive growth and pathogenesis. These results showed that AMT using RNAi constructs is an effective approach for dissecting the role of genes involved in pathogenesis in F. oxysporum and this could be extended for other fungal systems. The obtained knowledge can be easily translated for developing fungal resistant crops by RNAi. Copyright © 2017 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  18. Perception of Job-Related Risk, Training, and Use of Personal Protective Equipment (PPE among Latino Immigrant Hog CAFO Workers in Missouri: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Athena K. Ramos

    2016-11-01

    Full Text Available Hog production in the United States is a large industry that has seen dramatic changes over the last few decades. Concentrated animal feeding operations (CAFOs are growing in number throughout the country. This pilot study explores the perception of risk, receipt of work-related training, provision and usage of personal protective equipment (PPE, and prevention preferences of Latino immigrant hog CAFO workers in Missouri. Forty workers (M age = 36.08 years, SD = 10.04; 92.5% male; 70.0% Mexican were interviewed. Results indicate that most workers did not perceive their job as dangerous. Limited English proficient workers were significantly less likely to report receiving any work-related training. Although most workers had access to employer provided PPE, usage was inconsistent. As the demographic composition of the farmworker population in the Midwest becomes increasingly comprised of hired immigrant workers, it will be imperative to develop occupational safety and health educational and outreach efforts focused on the needs of these workers.

  19. Perception of Job-Related Risk, Training, and Use of Personal Protective Equipment (PPE) among Latino Immigrant Hog CAFO Workers in Missouri: A Pilot Study.

    Science.gov (United States)

    Ramos, Athena K; Fuentes, Axel; Trinidad, Natalia

    2016-01-01

    Hog production in the United States is a large industry that has seen dramatic changes over the last few decades. Concentrated animal feeding operations (CAFOs) are growing in number throughout the country. This pilot study explores the perception of risk, receipt of work-related training, provision and usage of personal protective equipment (PPE), and prevention preferences of Latino immigrant hog CAFO workers in Missouri. Forty workers (M age = 36.08 years, SD = 10.04; 92.5% male; 70.0% Mexican) were interviewed. Results indicate that most workers did not perceive their job as dangerous. Limited English proficient workers were significantly less likely to report receiving any work-related training. Although most workers had access to employer provided PPE, usage was inconsistent. As the demographic composition of the farmworker population in the Midwest becomes increasingly comprised of hired immigrant workers, it will be imperative to develop occupational safety and health educational and outreach efforts focused on the needs of these workers.

  20. An Introductory Review of Parallel Independent Component Analysis (p-ICA and a Guide to Applying p-ICA to Genetic Data and Imaging Phenotypes to Identify Disease-Associated Biological Pathways and Systems in Common Complex Disorders

    Directory of Open Access Journals (Sweden)

    Godfrey D Pearlson

    2015-09-01

    Full Text Available Complex inherited phenotypes, including those for many common medical and psychiatric diseases, are most likely underpinned by multiple genes contributing to interlocking molecular biological processes, along with environmental factors (Owen et al., 2010. Despite this, genotyping strategies for complex, inherited, disease-related phenotypes mostly employ univariate analyses, e.g. genome wide association (GWA. Such procedures most often identify isolated risk-related SNPs or loci, not the underlying biological pathways necessary to help guide the development of novel treatment approaches. This article focuses on the multivariate analysis strategy of parallel (i.e. simultaneous combination of SNP and neuroimage information independent component analysis (p-ICA, which typically yields large clusters of functionally related SNPs statistically correlated with phenotype components, whose overall molecular biologic relevance is inferred subsequently using annotation software suites. Because this is a novel approach, whose details are relatively new to the field we summarize its underlying principles and address conceptual questions regarding interpretation of resulting data and provide practical illustrations of the method.

  1. Component Pin Recognition Using Algorithms Based on Machine Learning

    Science.gov (United States)

    Xiao, Yang; Hu, Hong; Liu, Ze; Xu, Jiangchang

    2018-04-01

    The purpose of machine vision for a plug-in machine is to improve the machine’s stability and accuracy, and recognition of the component pin is an important part of the vision. This paper focuses on component pin recognition using three different techniques. The first technique involves traditional image processing using the core algorithm for binary large object (BLOB) analysis. The second technique uses the histogram of oriented gradients (HOG), to experimentally compare the effect of the support vector machine (SVM) and the adaptive boosting machine (AdaBoost) learning meta-algorithm classifiers. The third technique is the use of an in-depth learning method known as convolution neural network (CNN), which involves identifying the pin by comparing a sample to its training. The main purpose of the research presented in this paper is to increase the knowledge of learning methods used in the plug-in machine industry in order to achieve better results.

  2. Persistence of livestock-associated antibiotic-resistant Staphylococcus aureus among industrial hog operation workers in North Carolina over 14 days.

    Science.gov (United States)

    Nadimpalli, Maya; Rinsky, Jessica L; Wing, Steve; Hall, Devon; Stewart, Jill; Larsen, Jesper; Nachman, Keeve E; Love, Dave C; Pierce, Elizabeth; Pisanic, Nora; Strelitz, Jean; Harduar-Morano, Laurel; Heaney, Christopher D

    2015-02-01

    This study aimed to evaluate the persistence of nasal carriage of Staphylococcus aureus, methicillin-resistant S. aureus and multidrug-resistant S. aureus over 14 days of follow-up among industrial hog operation workers in North Carolina. Workers anticipating at least 24 h away from work were enrolled June-August 2012. Participants self-collected a nasal swab and completed a study journal on the evening of day 1, and each morning and evening on days 2-7 and 14 of the study. S. aureus isolated from nasal swabs were assessed for antibiotic susceptibility, spa type and absence of the scn gene. Livestock association was defined by absence of scn. Twenty-two workers provided 327 samples. S. aureus carriage end points did not change with time away from work (mean 49 h; range >0-96 h). Ten workers were persistent and six were intermittent carriers of livestock-associated S. aureus. Six workers were persistent and three intermittent carriers of livestock-associated multidrug-resistant S. aureus. One worker persistently carried livestock-associated methicillin-resistant S. aureus. Six workers were non-carriers of livestock-associated S. aureus. Eighty-two per cent of livestock-associated S. aureus demonstrated resistance to tetracycline. A majority of livestock-associated S. aureus isolates (n=169) were CC398 (68%) while 31% were CC9. No CC398 and one CC9 isolate was detected among scn-positive isolates. Nasal carriage of livestock-associated S. aureus, multidrug-resistant S. aureus and methicillin-resistant S. aureus can persist among industrial hog operation workers over a 14-day period, which included up to 96 h away from work. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Persistence of livestock-associated antibiotic-resistant Staphylococcus aureus among industrial hog operation workers in North Carolina over 14 days

    Science.gov (United States)

    Nadimpalli, Maya; Rinsky, Jessica L; Wing, Steve; Hall, Devon; Stewart, Jill; Larsen, Jesper; Nachman, Keeve E; Love, Dave C; Pierce, Elizabeth; Pisanic, Nora; Strelitz, Jean; Harduar-Morano, Laurel; Heaney, Christopher D

    2015-01-01

    Objectives This study aimed to evaluate the persistence of nasal carriage of Staphylococcus aureus, methicillin-resistant S. aureus and multidrug-resistant S. aureus over 14 days of follow-up among industrial hog operation workers in North Carolina. Methods Workers anticipating at least 24 h away from work were enrolled June–August 2012. Participants self-collected a nasal swab and completed a study journal on the evening of day 1, and each morning and evening on days 2–7 and 14 of the study. S. aureus isolated from nasal swabs were assessed for antibiotic susceptibility, spa type and absence of the scn gene. Livestock association was defined by absence of scn. Results Twenty-two workers provided 327 samples. S. aureus carriage end points did not change with time away from work (mean 49 h; range >0–96 h). Ten workers were persistent and six were intermittent carriers of livestock-associated S. aureus. Six workers were persistent and three intermittent carriers of livestock-associated multidrug-resistant S. aureus. One worker persistently carried livestock-associated methicillin-resistant S. aureus. Six workers were non-carriers of livestock-associated S. aureus. Eighty-two per cent of livestock-associated S. aureus demonstrated resistance to tetracycline. A majority of livestock-associated S. aureus isolates (n=169) were CC398 (68%) while 31% were CC9. No CC398 and one CC9 isolate was detected among scn-positive isolates. Conclusions Nasal carriage of livestock-associated S. aureus, multidrug-resistant S. aureus and methicillin-resistant S. aureus can persist among industrial hog operation workers over a 14-day period, which included up to 96 h away from work. PMID:25200855

  4. Distribution of the Multidrug Resistance Gene cfr in Staphylococcus Isolates from Pigs, Workers, and the Environment of a Hog Market and a Slaughterhouse in Guangzhou, China.

    Science.gov (United States)

    Wang, Jing; Lin, Da-Chuan; Guo, Xiao-Mu; Wei, Hong-Kun; Liu, Xiao-Qin; Chen, Xiao-Jie; Guo, Jian-Ying; Zeng, Zhen-Ling; Liu, Jian-Hua

    2015-07-01

    Bacteria harboring cfr, a multidrug resistance gene, have high prevalence in livestock in China and might be transmitted to humans through direct contact or via contaminated food products. To better understand the epidemiology of cfr producers in the food chain, the prevalence and genetic analysis of Staphylococcus isolates recovered from pigs, workers, and meat-handling facilities (a slaughterhouse and a hog market in Guangzhou, China) were examined. Twenty (4.5%) cfr-positive Staphylococcus isolates (18 Staphylococcus simulans, 1 S. cohnii, and 1 S. aureus) were derived from pigs (16/312), the environment (2/52), and workers (2/80). SmaI pulsed-field gel electrophoresis of 26 staphylococcal strains (22 S. simulans and 4 S. cohnii), including previously reported cfr-carrying staphylococci of animal food origin, exhibited 19 major pulsed-field gel electrophoresis patterns (A-S). Clonal spread of cfr-carrying staphylococci among pigs, workers, and meat products was detected. The genetic contexts of cfr in plasmids (pHNKF3, pHNZT2, and pHNCR35) obtained from S. simulans of swine or human origin were similar to that of Staphylococcus species isolated from human clinics and animal-derived food. The cfr-carrying S. aureus strain isolated from floor swabs of the hog market was spa-type t889 and belonged to the ST9 clonal lineage. In summary, both clonal spread and horizontal transmission via mobile elements contributed to cfr dissemination among staphylococcal isolates obtained from different sources. To monitor potential outbreaks of cfr-positive bacteria, continued surveillance of this gene in animals at slaughter and in animal-derived food is warranted.

  5. Removal of carbon, nitrogen and phosphorus from the separated liquid phase of hog manure by the multi-zone BioCAST technology.

    Science.gov (United States)

    Yerushalmi, Laleh; Alimahmoodi, Mahmood; Afroze, Niema; Godbout, Stephane; Mulligan, Catherine N

    2013-06-15

    The removal of chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP) at concentrations of 960 ± 38 to 2400 ± 96 mg/L, 143 ± 9 to 235 ± 15 mg/L and 25 ± 2 to 57 ± 4 mg/L, respectively, from the separated liquid phase of hog manure by the multi-zone BioCAST technology is discussed. Despite the inhibitory effect of hog waste toward microbial activities, removal efficiencies up to 89.2% for COD, 69.2% for TN and 47.6% for TP were obtained during 185 d of continuous operation. The free ammonia inhibition was postulated to be responsible for the steady reduction of COD and TP removal with the increase of TN/TP ratio from 3.6 to 5.8. On the contrary, the increase of COD/TN ratio from 4.8 to 14.1 improved the removal of all contaminants. Nitrogen removal did not show any dependence on the COD/TP ratio, despite the steady increase of COD and TP removal with this ratio in the range of 19.3-50.6. The removal efficiencies of organic and inorganic contaminants increased progressively owing to the adaptation of microbial biomass, resulting from the presence of suspended biomass in the mixed liquor that circulated continuously between the three zones of aerobic, microaerophilic and anoxic, as well as the attached biomass immobilized inside the aerobic zone. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Lysophosphatidylcholines containing polyunsaturated fatty acids were found as Na/sup +/,K/sup +/-ATPase inhibitors in acutely volume-expanded hog

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, M.; Harris, T.M.; Higashimori, K.; Sweetman, B.J.; Blair, I.A.; Inagami, T.

    1987-05-19

    Na/sup +/,K/sup +/-ATPase inhibitors activities against the specific binding of ouabain to Na/sup +/,K/sup +/-ATPase and /sup 86/Rb uptake into hog erythrocytes have been purified from the plasma of acutely saline-infused hog. The purifications were performed by a combination of Amberlite XAD-2 adsorption chromatography and four steps of high-performance liquid chromatography with four different types of columns. Fast atom bombardment (FAB) mass and proton NMR spectrometric studies identified the purified substances as ..gamma..-arachidoyl- (LPCA(..gamma..), 34%), ..beta..-arachidoyl- (LPCA(..beta..), 4%), ..gamma..-linoleoyl- (LPCL, 33%), and ..gamma..-oleoyl- (LPCO, 25%) lysophosphatidylcholine, expressed in molar ratio in the plasma. Small amounts of ..gamma..-docosapentaenoyl-, ..gamma..-eicosatrienoyl-, and ..gamma..palmitoyllysophosphatidylcholine were also detected by both FAB mass and /sup 1/H NMR spectrometric studies. The inhibition of Na/sup +/,K/sup +/-ATPase activity due to these compounds was always more sensitive than that of both ouabain-binding and /sup 86/Rb uptake activities. The ouabain-displacing activity in plasma due to these compounds increased with time during saline infusion. The maximal plasma level was approximately 10 times higher than that in the preinfusion plasma sample. Although these results suggest that ..gamma..-acyl-LPC's with long-chain polyunsaturated fatty acids are not simple competitive inhibitors to Na/sup +/,K/sup +/-ATPase, these compounds could be implicated in the pathogenesis of the circulation abnormality through the modulation of membrane enzyme.

  7. Combination of active components of Xiexin decoction ameliorates renal fibrosis through the inhibition of NF-κB and TGF-β1/Smad pathways in db/db diabetic mice.

    Directory of Open Access Journals (Sweden)

    Jia-Sheng Wu

    Full Text Available Xiexin decoction, a herbal therapeutic agent commonly used in traditional Chinese medicine, is recognized for its beneficial effects on diabetic nephropathy exerted through the combined action of multiple components, including Rhizoma Coptidis alkaloids (A, Radix et Rhizoma Rhei polysaccharides (P, and Radix Scutellaria flavones (F. Our previous studies have shown that a combination of A, P, and F (APF exhibits renoprotective effects against diabetic nephropathy. This study was aimed at determining the effects of APF on renal fibrosis in diabetic nephropathy and elucidating the underlying molecular mechanisms. To evaluate the effects of APF, in vivo, db/db diabetic mice were orally administered a low or high dose of APF (300 or 600 mg/kg, respectively once a day for 8 weeks. We evaluated the blood and urine indices of metabolic and renal function, renal tissue histopathology, renal inflammation, and fibrosis. APF treatment significantly ameliorated glucose and lipid metabolism dysfunction, decreased urinary albumin excretion, normalized creatinine clearance, and reduced the morphological changes in renal tissue. Additionally, APF administration in db/db diabetic mice reduced the elevated levels of renal inflammation mediators such as intercellular adhesion molecule-1, monocyte chemotactic protein-1, tumor necrosis factor-α, interleukin-1β, and active nuclear factor κB (NF-κB. APF treatment also reduced type I and IV collagen, transforming growth factor-β1 (TGF-β1, and TGF-β1 type II receptor expression levels, and decreased the phosphorylation of Smad2/3 in the kidneys of db/db diabetic mice. These results suggest that APF reduces renal fibrosis in diabetic nephropathy through the NF-κB and TGF-β1/Smad signaling pathways. In vitro, APF treatment reduced cell proliferation and protein expression of α-smooth muscle actin, collagen I, TGF-β1 and NF-κB in mesangial cells cultured with high glucose concentrations. Our findings indicate

  8. Fructose Synthesis and Transport at the Uterine-Placental Interface of Pigs: Cell-Specific Localization of SLC2A5, SLC2A8, and Components of the Polyol Pathway.

    Science.gov (United States)

    Steinhauser, Chelsie B; Landers, McKinsey; Myatt, Louise; Burghardt, Robert C; Vallet, Jeffrey L; Bazer, Fuller W; Johnson, Greg A

    2016-11-01

    The fetal fluids and uterine flushings of pigs contain higher concentrations of fructose than glucose, but fructose is not detected in maternal blood. Fructose can be synthesized from glucose via enzymes of the polyol pathway, aldose reductase (AKR1B1) and sorbitol dehydrogenase (SORD), transported across cell membranes by solute carriers SLC2A5 and SLC2A8, and converted to fructose-1-phosphate by ketohexokinase (KHK). SLC2A8, SLC2A5, AKR1B1, SORD, and KHK mRNAs and proteins were analyzed using quantitative PCR and immunohistochemistry or in situ hybridization in endometria and placentae of cyclic and pregnant gilts, cyclic gilts injected with estrogen, and ovariectomized gilts injected with progesterone. Progesterone up-regulated SLC2A8 protein in uterine luminal (LE) and glandular epithelia during the peri-implantation period, and expression became exclusively placental, chorion and blood vessels, after Day 30. P4 up-regulated SLC2A5 mRNA in uterine LE and glandular epithelia after implantation, and the chorion expressed SLC2A5 between Days 30 and 85. AKR1B1 and SORD proteins localized to uterine LE during the peri-implantation period, but expression switched to chorion by Day 20 and was maintained through Day 85. Uterine expression of AKR1B1 mRNA was down-regulated by estrogen. KHK protein localized to trophectoderm/chorion throughout gestation. These results provide evidence that components for the conversion of glucose to fructose and for fructose transport are present at the uterine-placental interface of pigs. The shift in expression from LE to chorion during pregnancy suggests free-floating conceptuses are supported by fructose synthesized by the uterus, but after implantation, the chorion becomes self-sufficient for fructose synthesis and transport. © 2016 by the Society for the Study of Reproduction, Inc.

  9. Partial pressure (or fugacity) of carbon dioxide, salinity and other variables collected from time series observations using Bubble type equilibrator for autonomous carbon dioxide (CO2) measurement, Carbon dioxide (CO2) gas analyzer and other instruments from MOORING_HOG_REEF_64W_32N in the North Atlantic Ocean from 2010-12-05 to 2015-01-07 (NODC Accession 0117060)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0117060 includes chemical, meteorological, physical and time series data collected from MOORING_HOG_REEF_64W_32N in the North Atlantic Ocean from...

  10. Other components

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    This chapter includes descriptions of electronic and mechanical components which do not merit a chapter to themselves. Other hardware requires mention because of particularly high tolerance or intolerance of exposure to radiation. A more systematic analysis of radiation responses of structures which are definable by material was given in section 3.8. The components discussed here are field effect transistors, transducers, temperature sensors, magnetic components, superconductors, mechanical sensors, and miscellaneous electronic components

  11. Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi

    Directory of Open Access Journals (Sweden)

    Peter M. Dracatos

    2016-09-01

    Full Text Available Nicotiana alata defensins 1 and 2 (NaD1 and NaD2 are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. Some plant defensins interact with fungal cell wall O-glycosylated proteins. Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An O-mannosyltransferase (pmt knockout (KO mutants (An∆pmtA, An∆pmtB, and An∆pmtC. An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. lycopersici (Fol signalling knockout mutants from the cell wall integrity (CWI and high osmolarity glycerol (HOG mitogen-activated protein kinase (MAPK pathways. HOG pathway mutants were sensitive to both NaD1 and NaD2, while CWI pathway mutants only displayed sensitivity to NaD2.

  12. Occurrence of Staphylococcus aureus in swine and swine workplace environments on industrial and antibiotic-free hog operations in North Carolina, USA: A One Health pilot study.

    Science.gov (United States)

    Davis, Meghan F; Pisanic, Nora; Rhodes, Sarah M; Brown, Alexis; Keller, Haley; Nadimpalli, Maya; Christ, Andrea; Ludwig, Shanna; Ordak, Carly; Spicer, Kristoffer; Love, David C; Larsen, Jesper; Wright, Asher; Blacklin, Sarah; Flowers, Billy; Stewart, Jill; Sexton, Kenneth G; Rule, Ana M; Heaney, Christopher D

    2018-05-01

    Occupational exposure to swine has been associated with increased Staphylococcus aureus carriage, including antimicrobial-resistant strains, and increased risk of infections. To characterize animal and environmental routes of worker exposure, we optimized methods to identify S. aureus on operations that raise swine in confinement with antibiotics (industrial hog operation: IHO) versus on pasture without antibiotics (antibiotic-free hog operation: AFHO). We associated findings from tested swine and environmental samples with those from personal inhalable air samplers on worker surrogates at one IHO and three AFHOs in North Carolina using a new One Health approach. We determined swine S. aureus carriage status by collecting swab samples from multiple anatomical sites, and we determined environmental positivity for airborne bioaerosols with inhalable and impinger samplers and a single-stage impactor (ambient air) cross-sectionally. All samples were analyzed for S. aureus, and isolates were tested for antimicrobial susceptibility, absence of scn (livestock marker), and spa type. Seventeen of twenty (85%) swine sampled at the one IHO carried S. aureus at >1 anatomical sites compared to none of 30 (0%) swine sampled at the three AFHOs. All S. aureus isolates recovered from IHO swine and air samples were scn negative and spa type t337; almost all isolates (62/63) were multidrug resistant. S. aureus was recovered from eight of 14 (67%) ambient air and two (100%) worker surrogate personal air samples at the one IHO, whereas no S. aureus isolates were recovered from 19 ambient and six personal air samples at the three AFHOs. Personal worker surrogate inhalable sample findings were consistent with both swine and ambient air data, indicating the potential for workplace exposure. IHO swine and the one IHO environment could be a source of potential pathogen exposure to workers, as supported by the detection of multidrug-resistant S. aureus (MDRSA) with livestock-associated spa

  13. Investigating multiple dysregulated pathways in rheumatoid arthritis based on pathway interaction network.

    Science.gov (United States)

    Song, Xian-Dong; Song, Xian-Xu; Liu, Gui-Bo; Ren, Chun-Hui; Sun, Yuan-Bo; Liu, Ke-Xin; Liu, Bo; Liang, Shuang; Zhu, Zhu

    2018-03-01

    The traditional methods of identifying biomarkers in rheumatoid arthritis (RA) have focussed on the differentially expressed pathways or individual pathways, which however, neglect the interactions between pathways. To better understand the pathogenesis of RA, we aimed to identify dysregulated pathway sets using a pathway interaction network (PIN), which considered interactions among pathways. Firstly, RA-related gene expression profile data, protein-protein interactions (PPI) data and pathway data were taken up from the corresponding databases. Secondly, principal component analysis method was used to calculate the pathway activity of each of the pathway, and then a seed pathway was identified using data gleaned from the pathway activity. A PIN was then constructed based on the gene expression profile, pathway data, and PPI information. Finally, the dysregulated pathways were extracted from the PIN based on the seed pathway using the method of support vector machines and an area under the curve (AUC) index. The PIN comprised of a total of 854 pathways and 1064 pathway interactions. The greatest change in the activity score between RA and control samples was observed in the pathway of epigenetic regulation of gene expression, which was extracted and regarded as the seed pathway. Starting with this seed pathway, one maximum pathway set containing 10 dysregulated pathways was extracted from the PIN, having an AUC of 0.8249, and the result indicated that this pathway set could distinguish RA from the controls. These 10 dysregulated pathways might be potential biomarkers for RA diagnosis and treatment in the future.

  14. Evolution of the TOR Pathway.

    NARCIS (Netherlands)

    Dam, T.J.P. van; Zwartkruis, F.J.; Bos, J.L.; Snel, B.

    2011-01-01

    The TOR kinase is a major regulator of growth in eukaryotes. Many components of the TOR pathway are implicated in cancer and metabolic diseases in humans. Analysis of the evolution of TOR and its pathway may provide fundamental insight into the evolution of growth regulation in eukaryotes and

  15. Electronic components

    CERN Document Server

    Colwell, Morris A

    1976-01-01

    Electronic Components provides a basic grounding in the practical aspects of using and selecting electronics components. The book describes the basic requirements needed to start practical work on electronic equipment, resistors and potentiometers, capacitance, and inductors and transformers. The text discusses semiconductor devices such as diodes, thyristors and triacs, transistors and heat sinks, logic and linear integrated circuits (I.C.s) and electromechanical devices. Common abbreviations applied to components are provided. Constructors and electronics engineers will find the book useful

  16. Flood-inundation maps for Big Creek from the McGinnis Ferry Road bridge to the confluence of Hog Wallow Creek, Alpharetta and Roswell, Georgia

    Science.gov (United States)

    Musser, Jonathan W.

    2015-08-20

    Digital flood-inundation maps for a 12.4-mile reach of Big Creek that extends from 260 feet above the McGinnis Ferry Road bridge to the U.S. Geological Survey (USGS) streamgage at Big Creek below Hog Wallow Creek at Roswell, Georgia (02335757), were developed by the USGS in cooperation with the cities of Alpharetta and Roswell, Georgia. The inundation maps, which can be accessed through the USGS Flood Inundation Mapping Science Web site at http://water.usgs.gov/osw/flood_inundation/, depict estimates of the areal extent and depth of flooding corresponding to selected water levels (stages) at the USGS streamgage at Big Creek near Alpharetta, Georgia (02335700). Real-time stage information from this USGS streamgage may be obtained at http://waterdata.usgs.gov/ and can be used in conjunction with these maps to estimate near real-time areas of inundation. The National Weather Service (NWS) is incorporating results from this study into the Advanced Hydrologic Prediction Service (AHPS) flood-warning system http://water.weather.gov/ahps/). The NWS forecasts flood hydrographs for many streams where the USGS operates streamgages and provides flow data. The forecasted peak-stage information for the USGS streamgage at Big Creek near Alpharetta (02335700), available through the AHPS Web site, may be used in conjunction with the maps developed for this study to show predicted areas of flood inundation.

  17. Pathway-based analyses.

    Science.gov (United States)

    Kent, Jack W

    2016-02-03

    New technologies for acquisition of genomic data, while offering unprecedented opportunities for genetic discovery, also impose severe burdens of interpretation and penalties for multiple testing. The Pathway-based Analyses Group of the Genetic Analysis Workshop 19 (GAW19) sought reduction of multiple-testing burden through various approaches to aggregation of highdimensional data in pathways informed by prior biological knowledge. Experimental methods testedincluded the use of "synthetic pathways" (random sets of genes) to estimate power and false-positive error rate of methods applied to simulated data; data reduction via independent components analysis, single-nucleotide polymorphism (SNP)-SNP interaction, and use of gene sets to estimate genetic similarity; and general assessment of the efficacy of prior biological knowledge to reduce the dimensionality of complex genomic data. The work of this group explored several promising approaches to managing high-dimensional data, with the caveat that these methods are necessarily constrained by the quality of external bioinformatic annotation.

  18. Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high osmolarity glycerol pathways and regulates multiple stress responses and secondary metabolism in Fusarium graminearum.

    Science.gov (United States)

    Gu, Qin; Zhang, Chengqi; Yu, Fangwei; Yin, Yanni; Shim, Won-Bo; Ma, Zhonghua

    2015-08-01

    Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress resistance, longevity and nutrient sensing. However, the functions of Sch9 orthologs in filamentous fungi, particularly in pathogenic species, have not been characterized to date. Here, we investigated biological and genetic functions of FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (ΔFgSch9) was defective in aerial hyphal growth, hyphal branching and conidial germination. The mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents, and to rapamycin, while showing increased thermal tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that plays an important role in regulating mycotoxin biosynthesis and virulence of F. graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both ΔFgSch9 and FgHog1 null mutant (ΔFgHog1) exhibited increased sensitivity to osmotic and oxidative stresses. This defect was more severe in the FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a mediator of the TOR and high osmolarity glycerol pathways, and regulates vegetative differentiation, multiple stress responses and secondary metabolism in F. graminearum. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  19. Principal components

    NARCIS (Netherlands)

    Hallin, M.; Hörmann, S.; Piegorsch, W.; El Shaarawi, A.

    2012-01-01

    Principal Components are probably the best known and most widely used of all multivariate analysis techniques. The essential idea consists in performing a linear transformation of the observed k-dimensional variables in such a way that the new variables are vectors of k mutually orthogonal

  20. Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Wufeng Fan

    2017-01-01

    Full Text Available In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM based on pathway interaction network (PIN which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs, and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

  1. Bitter gourd (Momordica charantia) as a rich source of bioactive components to combat cancer naturally: Are we on the right track to fully unlock its potential as inhibitor of deregulated signaling pathways.

    Science.gov (United States)

    Farooqi, Ammad Ahmad; Khalid, Sumbul; Tahir, Fatima; Sabitaliyevich, Uteuliev Yerzhan; Yaylim, Ilhan; Attar, Rukset; Xu, Baojun

    2018-05-10

    Research over decades has progressively explored pharmacological actions of bitter gourd (Momordica charantia). Biologically and pharmacologically active molecules isolated from M. charantia have shown significant anti-cancer activity in cancer cell lines and xenografted mice. In this review spotlight was set on the bioactive compounds isolated from M. charantia that effectively inhibited cancer development and progression via regulation of protein network in cancer cells. We summarize most recent high-quality research work in cancer cell lines and xenografted mice related to tumor suppressive role-play of M. charantia and its bioactive compounds. Although M. charantia mediated health promoting, anti-diabetic, hepatoprotective, anti-inflammatory effects have been extensively investigated, there is insufficient information related to regulation of signaling networks by bioactive molecules obtained from M. charantia in different cancers. M. charantia has been shown to modulate AKT/mTOR/p70S6K signaling, p38MAPK-MAPKAPK-2/HSP-27 pathway, cell cycle regulatory proteins and apoptosis-associated proteins in different cancers. However, still there are visible knowledge gaps related to the drug targets in different cancers because we have not yet developed comprehensive understanding of the M. charantia mediated regulation of signal transduction pathways. To explore these questions, experimental platforms are needed that can prove to be helpful in getting a step closer to personalized medicine. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Molecular Pathways

    Science.gov (United States)

    Lok, Benjamin H.; Powell, Simon N.

    2012-01-01

    The Rad52 protein was largely ignored in humans and other mammals when the mouse knockout revealed a largely “no-effect” phenotype. However, using synthetic lethal approaches to investigate context dependent function, new studies have shown that Rad52 plays a key survival role in cells lacking the function of the BRCA1-BRCA2 pathway of homologous recombination. Biochemical studies also showed significant differences between yeast and human Rad52, in which yeast Rad52 can promote strand invasion of RPA-coated single-stranded DNA in the presence of Rad51, but human Rad52 cannot. This results in the paradox of how is human Rad52 providing Rad51 function: presumably there is something missing in the biochemical assays that exists in-vivo, but the nature of this missing factor is currently unknown. Recent studies have suggested that Rad52 provides back-up Rad51 function for all members of the BRCA1-BRCA2 pathway, suggesting that Rad52 may be a target for therapy in BRCA pathway deficient cancers. Screening for ways to inhibit Rad52 would potentially provide a complementary strategy for targeting BRCA-deficient cancers in addition to PARP inhibitors. PMID:23071261

  3. Benchmarking pathway interaction network for colorectal cancer to identify dysregulated pathways

    Directory of Open Access Journals (Sweden)

    Q. Wang

    Full Text Available Different pathways act synergistically to participate in many biological processes. Thus, the purpose of our study was to extract dysregulated pathways to investigate the pathogenesis of colorectal cancer (CRC based on the functional dependency among pathways. Protein-protein interaction (PPI information and pathway data were retrieved from STRING and Reactome databases, respectively. After genes were aligned to the pathways, each pathway activity was calculated using the principal component analysis (PCA method, and the seed pathway was discovered. Subsequently, we constructed the pathway interaction network (PIN, where each node represented a biological pathway based on gene expression profile, PPI data, as well as pathways. Dysregulated pathways were then selected from the PIN according to classification performance and seed pathway. A PIN including 11,960 interactions was constructed to identify dysregulated pathways. Interestingly, the interaction of mRNA splicing and mRNA splicing-major pathway had the highest score of 719.8167. Maximum change of the activity score between CRC and normal samples appeared in the pathway of DNA replication, which was selected as the seed pathway. Starting with this seed pathway, a pathway set containing 30 dysregulated pathways was obtained with an area under the curve score of 0.8598. The pathway of mRNA splicing, mRNA splicing-major pathway, and RNA polymerase I had the maximum genes of 107. Moreover, we found that these 30 pathways had crosstalks with each other. The results suggest that these dysregulated pathways might be used as biomarkers to diagnose CRC.

  4. Molecular pathways

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine Terra

    2014-01-01

    Pathologic organ fibrosis is a condition that can affect all major tissues and is typically ascribed to the excessive accumulation of extracellular matrix components, predominantly collagens. It typically leads to compromise of organ function and subsequent organ failure, and it is estimated...

  5. Hierarchically organized layout for visualization of biochemical pathways.

    Science.gov (United States)

    Tsay, Jyh-Jong; Wu, Bo-Liang; Jeng, Yu-Sen

    2010-01-01

    Many complex pathways are described as hierarchical structures in which a pathway is recursively partitioned into several sub-pathways, and organized hierarchically as a tree. The hierarchical structure provides a natural way to visualize the global structure of a complex pathway. However, none of the previous research on pathway visualization explores the hierarchical structures provided by many complex pathways. In this paper, we aim to develop algorithms that can take advantages of hierarchical structures, and give layouts that explore the global structures as well as local structures of pathways. We present a new hierarchically organized layout algorithm to produce layouts for hierarchically organized pathways. Our algorithm first decomposes a complex pathway into sub-pathway groups along the hierarchical organization, and then partition each sub-pathway group into basic components. It then applies conventional layout algorithms, such as hierarchical layout and force-directed layout, to compute the layout of each basic component. Finally, component layouts are joined to form a final layout of the pathway. Our main contribution is the development of algorithms for decomposing pathways and joining layouts. Experiment shows that our algorithm is able to give comprehensible visualization for pathways with hierarchies, cycles as well as complex structures. It clearly renders the global component structures as well as the local structure in each component. In addition, it runs very fast, and gives better visualization for many examples from previous related research. 2009 Elsevier B.V. All rights reserved.

  6. Motion Component Supported Boosted Classifier for CAR Detection in Aerial Imagery

    Science.gov (United States)

    Tuermer, S.; Leitloff, J.; Reinartz, P.; Stilla, U.

    2011-04-01

    Research of automatic vehicle detection in aerial images has been done with a lot of innovation and constantly rising success for years. However information was mostly taken from a single image only. Our aim is using the additional information which is offered by the temporal component, precisely the difference of the previous and the consecutive image. On closer viewing the moving objects are mainly vehicles and therefore we provide a method which is able to limit the search space of the detector to changed areas. The actual detector is generated of HoG features which are composed and linearly weighted by AdaBoost. Finally the method is tested on a motorway section including an exit and congested traffic near Munich, Germany.

  7. Concentrations of cadmium, Cobalt, Lead, Nickel, and Zinc in Blood and Fillets of Northern Hog Sucker (Hypentelium nigricans) from streams contaminated by lead-Zinc mining: Implications for monitoring

    Science.gov (United States)

    Schmitt, C.J.; Brumbaugh, W.G.; May, T.W.

    2009-01-01

    Lead (Pb) and other metals can accumulate in northern hog sucker (Hypentelium nigricans) and other suckers (Catostomidae), which are harvested in large numbers from Ozark streams by recreational fishers. Suckers are also important in the diets of piscivorous wildlife and fishes. Suckers from streams contaminated by historic Pb-zinc (Zn) mining in southeastern Missouri are presently identified in a consumption advisory because of Pb concentrations. We evaluated blood sampling as a potentially nonlethal alternative to fillet sampling for Pb and other metals in northern hog sucker. Scaled, skin-on, bone-in "fillet" and blood samples were obtained from northern hog suckers (n = 75) collected at nine sites representing a wide range of conditions relative to Pb-Zn mining in southeastern Missouri. All samples were analyzed for cadmium (Cd), cobalt (Co), Pb, nickel (Ni), and Zn. Fillets were also analyzed for calcium as an indicator of the amount of bone, skin, and mucus included in the samples. Pb, Cd, Co, and Ni concentrations were typically higher in blood than in fillets, but Zn concentrations were similar in both sample types. Concentrations of all metals except Zn were typically higher at sites located downstream from active and historic Pb-Zn mines and related facilities than at nonmining sites. Blood concentrations of Pb, Cd, and Co were highly correlated with corresponding fillet concentrations; log-log linear regressions between concentrations in the two sample types explained 94% of the variation for Pb, 73-83% of the variation for Co, and 61% of the variation for Cd. In contrast, relations for Ni and Zn explained Fillet Pb and calcium concentrations were correlated (r = 0.83), but only in the 12 fish from the most contaminated site; concentrations were not significantly correlated across all sites. Conversely, fillet Cd and calcium were correlated across the range of sites (r = 0.78), and the inclusion of calcium in the fillet-to-blood relation explained an

  8. Non-Smad signaling pathways.

    Science.gov (United States)

    Mu, Yabing; Gudey, Shyam Kumar; Landström, Maréne

    2012-01-01

    Transforming growth factor-beta (TGFβ) is a key regulator of cell fate during embryogenesis and has also emerged as a potent driver of the epithelial-mesenchymal transition during tumor progression. TGFβ signals are transduced by transmembrane type I and type II serine/threonine kinase receptors (TβRI and TβRII, respectively). The activated TβR complex phosphorylates Smad2 and Smad3, converting them into transcriptional regulators that complex with Smad4. TGFβ also uses non-Smad signaling pathways such as the p38 and Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways to convey its signals. Ubiquitin ligase tumor necrosis factor (TNF)-receptor-associated factor 6 (TRAF6) and TGFβ-associated kinase 1 (TAK1) have recently been shown to be crucial for the activation of the p38 and JNK MAPK pathways. Other TGFβ-induced non-Smad signaling pathways include the phosphoinositide 3-kinase-Akt-mTOR pathway, the small GTPases Rho, Rac, and Cdc42, and the Ras-Erk-MAPK pathway. Signals induced by TGFβ are tightly regulated and specified by post-translational modifications of the signaling components, since they dictate the subcellular localization, activity, and duration of the signal. In this review, we discuss recent findings in the field of TGFβ-induced responses by non-Smad signaling pathways.

  9. Ubiquitylation and the Fanconi Anemia Pathway

    Science.gov (United States)

    Garner, Elizabeth; Smogorzewska, Agata

    2012-01-01

    The Fanconi anemia (FA) pathway maintains genome stability through co-ordination of DNA repair of interstrand crosslinks (ICLs). Disruption of the FA pathway yields hypersensitivity to interstrand crosslinking agents, bone marrow failure and cancer predisposition. Early steps in DNA damage dependent activation of the pathway are governed by monoubiquitylation of FANCD2 and FANCI by the intrinsic FA E3 ubiquitin ligase, FANCL. Downstream FA pathway components and associated factors such as FAN1 and SLX4 exhibit ubiquitin-binding motifs that are important for their DNA repair function, underscoring the importance of ubiquitylation in FA pathway mediated repair. Importantly, ubiquitylation provides the foundations for cross-talk between repair pathways, which in concert with the FA pathway, resolve interstrand crosslink damage and maintain genomic stability. PMID:21605559

  10. A low temperature anaerobic digestion system reduces instability and produces optimal methane yield : case study of a Farrow to Finish farm marketing 10,000 hogs per year in Quebec

    Energy Technology Data Exchange (ETDEWEB)

    Villeneuve, E.; Boivin, S.; Hince, J.-F. [Bio-Terre Systems, Sherbrooke, PQ (Canada); Masse, D. [Agriculture and Agri-Food Canada, Ottawa, ON (Canada)

    2008-07-01

    This presentation described a joint collaboration between Agriculture and Agri-Food Canada (AAFC) and Bio-Terre Systems that resulted in the development of an innovative environmental solution for manure management. The solution which combines low-temperature anaerobic digestion, concentration of solids and production of green energy, responds to the growth of hog production in North America. A case study of a Farrow to Finish farm marketing 10,000 swine in St.-Hilaire, Quebec was presented with particular reference to background information on the farm, process stability and process performance. The Bio-Terre technology was discussed in detail including a discussion of the psychrophilic anaerobic digestion and microorganisms and sequencing batch reactor (SBR) process. The advantages and disadvantages of this process were presented. It was concluded that the process offers many benefits, including energy economy, improved health of animals, odorless spreading, better fertilizer, and reduction of land required. tabs., figs.

  11. Pathway Distiller - multisource biological pathway consolidation.

    Science.gov (United States)

    Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

    2012-01-01

    One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

  12. Targeting Wnt Pathways in Disease

    Science.gov (United States)

    Zimmerman, Zachary F.; Moon, Randall T.

    2012-01-01

    Wnt-mediated signal transduction pathways have long been recognized for their roles in regulating embryonic development, and have more recently been linked to cancer, neurologic diseases, inflammatory diseases, and disorders of endocrine function and bone metabolism in adults. Although therapies targeting Wnt signaling are attractive in theory, in practice it has been difficult to obtain specific therapeutics because many components of Wnt signaling pathways are also involved in other cellular processes, thereby reducing the specificity of candidate therapeutics. New technologies, and advances in understanding the mechanisms of Wnt signaling, have improved our understanding of the nuances of Wnt signaling and are leading to promising new strategies to target Wnt signaling pathways. PMID:23001988

  13. The lectin pathway of complement

    DEFF Research Database (Denmark)

    Ballegaard, Vibe Cecilie Diederich; Haugaard, Anna Karen; Garred, P

    2014-01-01

    The pattern recognition molecules of the lectin complement pathway are important components of the innate immune system with known functions in host-virus interactions. This paper summarizes current knowledge of how these intriguing molecules, including mannose-binding lectin (MBL), Ficolin-1, -2......-1, -2 and -3 and CL-11 could have similar functions in HIV infection as the ficolins have been shown to play a role in other viral infections, and CL-11 resembles MBL and the ficolins in structure and binding capacity.......The pattern recognition molecules of the lectin complement pathway are important components of the innate immune system with known functions in host-virus interactions. This paper summarizes current knowledge of how these intriguing molecules, including mannose-binding lectin (MBL), Ficolin-1, -2...

  14. Evolutionary Conservation of the Components in the TOR Signaling Pathways.

    Science.gov (United States)

    Tatebe, Hisashi; Shiozaki, Kazuhiro

    2017-11-01

    Target of rapamycin (TOR) is an evolutionarily conserved protein kinase that controls multiple cellular processes upon various intracellular and extracellular stimuli. Since its first discovery, extensive studies have been conducted both in yeast and animal species including humans. Those studies have revealed that TOR forms two structurally and physiologically distinct protein complexes; TOR complex 1 (TORC1) is ubiquitous among eukaryotes including animals, yeast, protozoa, and plants, while TOR complex 2 (TORC2) is conserved in diverse eukaryotic species other than plants. The studies have also identified two crucial regulators of mammalian TORC1 (mTORC1), Ras homolog enriched in brain (RHEB) and RAG GTPases. Of these, RAG regulates TORC1 in yeast as well and is conserved among eukaryotes with the green algae and land plants as apparent exceptions. RHEB is present in various eukaryotes but sporadically missing in multiple taxa. RHEB, in the budding yeast Saccharomyces cerevisiae , appears to be extremely divergent with concomitant loss of its function as a TORC1 regulator. In this review, we summarize the evolutionarily conserved functions of the key regulatory subunits of TORC1 and TORC2, namely RAPTOR, RICTOR, and SIN1. We also delve into the evolutionary conservation of RHEB and RAG and discuss the conserved roles of these GTPases in regulating TORC1.

  15. Viabilidade econômica da implantação de uma unidade de abate e processamento de suínos = Economic feasibility of installing a hog slaughter and processing facility

    Directory of Open Access Journals (Sweden)

    Leonardo Feron Bisognin

    2015-01-01

    Full Text Available Tradicionalmente as famílias da região Centro-Serra do estado do Rio Grande do Sul criam suínos (Sus scrofa domesticus como fonte de subsistência, porém nesta região estão inseridas apenas algumas pequenas agroindústrias de abate e processamento de carne suína. Uma destas agroindústrias possui certificação para comercialização apenas em território municipal, no entanto devido ao interesse na ampliação do negócio para o território estadual, é necessária a construção de uma nova planta industrial. Deste modo, com o objetivo de analisar a viabilidade econômica da implantação de uma nova unidade industrial nesta região, foi utilizado um questionário de campo e pesquisas de mercado, além de análises do orçamento de infraestrutura para o levantamento dos custos de implantação de uma nova unidade. Os dados obtidos foram lançados em um fluxo de caixa com prazo de dez anos na intenção de avaliar a viabilidade econômica. Foram utilizados os indicadores Taxa Interna de Retorno – TIR, Valor Presente Líquido – VPL, e o tempo de retorno do capital investido – Payback, como forma de analisar o investimento. A análise econômica resultou em uma TIR de 22%, VPL de R$ 271.099,67 para uma taxa de atratividade de 10 %, e Payback de três anos e onze meses. Com esses resultados positivos, do ponto de vista econômico, a implantação de uma nova unidade de abate e processamento de suínos para a referida região apresenta-se como um investimento altamente atrativo. = Despite families of the Centro-Serra of Rio Grande do Sul traditionally raises hogs as a source of living, there are some small slaughters and pork processing facilities in this region. One of these agro industries has certification for marketing in municipality. Due the interest in expanding the business all over the state, it is necessary to build a new industrial plant. In this context, the present study aims to analyze the economic feasibility of

  16. No evidence for induction of key components of the Notch signaling pathway (Notch-1, Jagged-1) by treatment with UV-B, 1,25(OH)(2)D(3), and/or epigenetic drugs (TSA, 5-Aza) in human keratinocytes in vitro.

    Science.gov (United States)

    Reichrath, Sandra; Reichrath, Jörg

    2012-01-01

    Notch signaling is of high importance for growth and survival of various cell types. We now analyzed the protein expression of two key components of the Notch signaling pathway (Notch-1, Jagged-1) in spontaneously immortalized (HaCaT) and in malignant (SCL-1) human keratinocytes, using western analysis. We found that Notch-1 and its corresponding ligand Jagged-1 are expressed in both cell lines, with no marked change following UV-B treatment. Moreover, treatment of both cell lines before or after UV-B irradiation with 1,25-dihydroxyvitamin D(3), the biologically active form of vitamin D, and/or epigenetic modulating drugs (TSA; 5-Aza) did not result in a marked modulation of the protein expression of Notch-1 or Jagged-1. Under the experimental conditions of this study, treatment with 1,25(OH)(2)D(3) protected human keratinocytes in part against the antiproliferative effects of UV-B-radiation. In conclusion, our findings do not point at a differential expression of these two key components of Notch signaling in non-malignant as compared to malignant human keratinocytes, indicating that alterations in their expression are not of importance for the photocarcinogenesis of human squamous cell carcinomas. Moreover, our findings do not support the hypothesis that modulation of Notch signaling may be involved in the photoprotective effect of 1,25-dihydroxyvitamin D(3), that we and others reported previously. Additionally, we demonstrate that epigenetic modulating drugs (TSA, 5-Aza) do not markedly modulate the expression Notch-1 or Jagged-1 in UV-B-treated human keratinocytes in vitro.

  17. Modularized Smad-regulated TGFβ signaling pathway.

    Science.gov (United States)

    Li, Yongfeng; Wang, Minli; Carra, Claudio; Cucinotta, Francis A

    2012-12-01

    The transforming Growth Factor β (TGFβ) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. TGFβ signaling can be induced by several factors including ionizing radiation. The pathway is regulated in a negative feedback loop through promoting the nuclear import of the regulatory Smads and a subsequent expression of inhibitory Smad7, that forms ubiquitin ligase with Smurf2, targeting active TGFβ receptors for degradation. In this work, we proposed a mathematical model to study the Smad-regulated TGFβ signaling pathway. By modularization, we are able to analyze mathematically each component subsystem and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, in the TGFβ signaling pathway is discussed and supported as well by numerical simulation, indicating the robustness of the model. Published by Elsevier Inc.

  18. Pentose pathway in human liver

    International Nuclear Information System (INIS)

    Magnusson, I.; Chandramouli, V.; Schumann, W.C.; Kumaran, K.; Wahren, J.; Landau, B.R.

    1988-01-01

    [1- 14 C]Ribose and [1- 14 C]glucose were given to normal subjects along with glucose loads (1 g per kg of body weight) after administration of diflunisal and acetaminophen, drugs that are excreted in urine as glucuronides. Distributions of 14 C were determined in the carbons of the excreted glucoronides and in the glucose from blood samples drawn from hepatic veins before and after glucagon administration. Eighty percent or more of the 14 C from [1- 14 C]ribose incorporated into the glucuronic acid moiety of the glucuronides was in carbons 1 and 3, with less than 8% in carbon 2. In glucuronic acid from glucuronide excreted when [2- 14 C]glucose was given, 3.5-8.1% of the 14 C was in carbon 1, 2.5-4.3% in carbon 3, and more than 70% in carbon 2. These distributions are in accord with the glucuronides sampling the glucose unit of the glucose 6-phosphate pool that is a component of the pentose pathway and is intermediate in glycogen formation. It is concluded that the glucuronic acid conjugates of the drugs can serve as a noninvasive means of sampling hepatic glucose 6-phosphate. In human liver, as in animal liver, the classical pentose pathway functions, not the L-type pathway, and only a small percentage of the glucose is metabolized via the pathway

  19. Survival pathways under stress

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Survival pathways under stress. Bacteria survive by changing gene expression. pattern. Three important pathways will be discussed: Stringent response. Quorum sensing. Proteins performing function to control oxidative damage.

  20. Pathways Intern Report

    Science.gov (United States)

    Huggett, Daniel James

    2017-01-01

    The National Aeronautics and Space Administration (NASA) provides a formal training program for prospective employees titled, Pathways Intern Employment. The Pathways program targets graduate and undergraduate students who strive to become an active contributor to NASA's goal of space exploration. The report herein provides an account of Daniel Huggett's Pathways experience for the Spring and Summer 2017 semesters.

  1. Neurophysiology and itch pathways.

    Science.gov (United States)

    Schmelz, Martin

    2015-01-01

    As we all can easily differentiate the sensations of itch and pain, the most straightforward neurophysiologic concept would consist of two specific pathways that independently encode itch and pain. Indeed, a neuronal pathway for histamine-induced itch in the peripheral and central nervous system has been described in animals and humans, and recently several non-histaminergic pathways for itch have been discovered in rodents that support a dichotomous concept differentiated into a pain and an itch pathway, with both pathways being composed of different "flavors." Numerous markers and mediators have been found that are linked to itch processing pathways. Thus, the delineation of neuronal pathways for itch from pain pathways seemingly proves that all sensory aspects of itch are based on an itch-specific neuronal pathway. However, such a concept is incomplete as itch can also be induced by the activation of the pain pathway in particular when the stimulus is applied in a highly localized spatial pattern. These opposite views reflect the old dispute between specificity and pattern theories of itch. Rather than only being of theoretic interest, this conceptual problem has key implication for the strategy to treat chronic itch as key therapeutic targets would be either itch-specific pathways or unspecific nociceptive pathways.

  2. Mitigating component performance variation

    Science.gov (United States)

    Gara, Alan G.; Sylvester, Steve S.; Eastep, Jonathan M.; Nagappan, Ramkumar; Cantalupo, Christopher M.

    2018-01-09

    Apparatus and methods may provide for characterizing a plurality of similar components of a distributed computing system based on a maximum safe operation level associated with each component and storing characterization data in a database and allocating non-uniform power to each similar component based at least in part on the characterization data in the database to substantially equalize performance of the components.

  3. The way Wnt works: Components and mechanism

    Science.gov (United States)

    SAITO-DIAZ, KENYI; CHEN, TONY W.; WANG, XIAOXI; THORNE, CURTIS A.; WALLACE, HEATHER A.; PAGE-MCCAW, ANDREA; LEE, ETHAN

    2013-01-01

    The canonical Wnt/β-catenin pathway is an ancient and evolutionarily conserved signaling pathway that is required for the proper development of all metazoans, from the basal demosponge Amphimedon queenslandica to humans. Misregulation of Wnt signaling is implicated in many human diseases, making this pathway an intense area of research in industry as well as academia. In this review, we explore our current understanding of the molecular steps involved in the transduction of a Wnt signal. We will focus on how the critical Wnt pathway component, β-catenin, is in a “futile cycle” of constant synthesis and degradation and how this cycle is disrupted upon pathway activation. We describe the role of the Wnt pathway in major human cancers and in the control of stem cell self-renewal in the developing organism and in adults. Finally, we describe well-accepted criteria that have been proposed as evidence for the involvement of a molecule in regulating the canonical Wnt pathway. PMID:23256519

  4. Immunotoxicity testing: Implementation of mechanistic understanding, key pathways of toxicological concern and components of these pathways.

    Science.gov (United States)

    At present, several animal-based assays are used to assess immunotoxic effects such as immunosuppression and sensitization. Growing societal and ethical concerns, European legislation and current research demands by industry are driving animal-based toxicity testing towards new a...

  5. Metabolic pathways for the whole community.

    Science.gov (United States)

    Hanson, Niels W; Konwar, Kishori M; Hawley, Alyse K; Altman, Tomer; Karp, Peter D; Hallam, Steven J

    2014-07-22

    A convergence of high-throughput sequencing and computational power is transforming biology into information science. Despite these technological advances, converting bits and bytes of sequence information into meaningful insights remains a challenging enterprise. Biological systems operate on multiple hierarchical levels from genomes to biomes. Holistic understanding of biological systems requires agile software tools that permit comparative analyses across multiple information levels (DNA, RNA, protein, and metabolites) to identify emergent properties, diagnose system states, or predict responses to environmental change. Here we adopt the MetaPathways annotation and analysis pipeline and Pathway Tools to construct environmental pathway/genome databases (ePGDBs) that describe microbial community metabolism using MetaCyc, a highly curated database of metabolic pathways and components covering all domains of life. We evaluate Pathway Tools' performance on three datasets with different complexity and coding potential, including simulated metagenomes, a symbiotic system, and the Hawaii Ocean Time-series. We define accuracy and sensitivity relationships between read length, coverage and pathway recovery and evaluate the impact of taxonomic pruning on ePGDB construction and interpretation. Resulting ePGDBs provide interactive metabolic maps, predict emergent metabolic pathways associated with biosynthesis and energy production and differentiate between genomic potential and phenotypic expression across defined environmental gradients. This multi-tiered analysis provides the user community with specific operating guidelines, performance metrics and prediction hazards for more reliable ePGDB construction and interpretation. Moreover, it demonstrates the power of Pathway Tools in predicting metabolic interactions in natural and engineered ecosystems.

  6. Reusable Component Services

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Reusable Component Services (RCS) is a super-catalog of components, services, solutions and technologies that facilitates search, discovery and collaboration in...

  7. The Hippo Pathway: Immunity and Cancer.

    Science.gov (United States)

    Taha, Zaid; J Janse van Rensburg, Helena; Yang, Xiaolong

    2018-03-28

    Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work.

  8. Software component quality evaluation

    Science.gov (United States)

    Clough, A. J.

    1991-01-01

    The paper describes a software inspection process that can be used to evaluate the quality of software components. Quality criteria, process application, independent testing of the process and proposed associated tool support are covered. Early results indicate that this technique is well suited for assessing software component quality in a standardized fashion. With automated machine assistance to facilitate both the evaluation and selection of software components, such a technique should promote effective reuse of software components.

  9. Transuranic element pathways to man

    International Nuclear Information System (INIS)

    Bennett, B.G.

    1976-01-01

    Transfer to man of transuranic element contamination may occur by the inhalation or ingestion pathways. The measurements of globally dispersed fall-out radioactivity have provided pertinent data on the environmental behaviour of plutonium. Additional data may eventually become available for americium. From the measured and inferred concentrations of fall-out plutonium, the inhalation intake has been determined and the ICRP Task Group lung model used to estimate deposition in the lung and transfer to other body organs. The computed body burden reached a maximum of 4pCi in 1964 and is currently about 2.5pCi. A complete diet sampling has been conducted to determine ingestion intake. Plutonium concentration in food ranged from 0.01pCi/kg in shellfish to undetected (less than 0.0003pCi/kg) in milk. Annual intake in total diet is estimated to have been 1.6pCi in 1972. Low uptake by the gastrointestinal tract makes contribution to organ burdens from ingestion negligible. Long-term pathway considerations include plant uptake from the cumulative deposit in soil and resuspension. Downward movement in soil may limit the significance of these long-term pathway components. (author)

  10. Reactor component automatic grapple

    International Nuclear Information System (INIS)

    Greenaway, P.R.

    1982-01-01

    A grapple for handling nuclear reactor components in a medium such as liquid sodium which, upon proper seating and alignment of the grapple with the component as sensed by a mechanical logic integral to the grapple, automatically seizes the component. The mechanical logic system also precludes seizure in the absence of proper seating and alignment. (author)

  11. Repurposing learning object components

    NARCIS (Netherlands)

    Verbert, K.; Jovanovic, J.; Gasevic, D.; Duval, E.; Meersman, R.

    2005-01-01

    This paper presents an ontology-based framework for repurposing learning object components. Unlike the usual practice where learning object components are assembled manually, the proposed framework enables on-the-fly access and repurposing of learning object components. The framework supports two

  12. Aberrant Wnt signaling pathway in medial temporal lobe structures of Alzheimer's disease

    DEFF Research Database (Denmark)

    Riise, Jesper; Plath, Niels; Pakkenberg, Bente

    2015-01-01

    alterations of the intracellular Wnt pathway signaling components β-catenin, Gsk3β and Tcf7l1/Tcf3 and the phosphorylation state of β-catenin and Gsk3β in the hippocampus suggestive of a link between AD and aberrant canonical activity. Alterations in Gsk3β co-appeared with hippocampal kinase...... on isolated Wnt pathway components. Here, we provide the first comprehensive pathway-focused evaluation of the Wnt pathway in the entorhinal cortex and hippocampus of AD brains. Our data demonstrate altered Wnt pathway gene expression at all levels of the pathway in both medial temporal lobe regions...

  13. Pathways from Poverty.

    Science.gov (United States)

    Baldwin, Barbara, Ed.

    1995-01-01

    Articles in this theme issue are based on presentations at the Pathways from Poverty Workshop held in Albuquerque, New Mexico, on May 18-25, 1995. The event aimed to foster development of a network to address rural poverty issues in the Western Rural Development Center (WRDC) region. Articles report on outcomes from the Pathways from Poverty…

  14. Crystallization Pathways in Biomineralization

    Science.gov (United States)

    Weiner, Steve; Addadi, Lia

    2011-08-01

    A crystallization pathway describes the movement of ions from their source to the final product. Cells are intimately involved in biological crystallization pathways. In many pathways the cells utilize a unique strategy: They temporarily concentrate ions in intracellular membrane-bound vesicles in the form of a highly disordered solid phase. This phase is then transported to the final mineralization site, where it is destabilized and crystallizes. We present four case studies, each of which demonstrates specific aspects of biological crystallization pathways: seawater uptake by foraminifera, calcite spicule formation by sea urchin larvae, goethite formation in the teeth of limpets, and guanine crystal formation in fish skin and spider cuticles. Three representative crystallization pathways are described, and aspects of the different stages of crystallization are discussed. An in-depth understanding of these complex processes can lead to new ideas for synthetic crystallization processes of interest to materials science.

  15. Altered Leukocyte Sphingolipid Pathway in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Larissa P. Maia

    2017-11-01

    Full Text Available Sphingolipid metabolism pathway is essential in membrane homeostasis, and its dysfunction has been associated with favorable tumor microenvironment, disease progression, and chemotherapy resistance. Its major components have key functions on survival and proliferation, with opposing effects. We have profiled the components of the sphingolipid pathway on leukocytes of breast cancer (BC patients undergoing chemotherapy treatment and without, including the five sphingosine 1-phosphate (S1P receptors, the major functional genes, and cytokines, in order to better understand the S1P signaling in the immune cells of these patients. To the best of our knowledge, this is the first characterization of the sphingolipid pathway in whole blood of BC patients. Skewed gene profiles favoring high SPHK1 expression toward S1P production during BC development was observed, which was reversed by chemotherapy treatment, and reached similar levels to those found in healthy donors. Such levels were also correlated with high levels of TNF-α. Our data revealed an important role of the sphingolipid pathway in immune cells in BC with skewed signaling of S1P receptors, which favored cancer development even under chemotherapy, and may probably be a trigger of cancer resistance. Thus, these molecules must be considered as a target pathway for combined BC therapeutics.

  16. Supply chain components

    OpenAIRE

    Vieraşu, T.; Bălăşescu, M.

    2011-01-01

    In this article I will go through three main logistics components, which are represented by: transportation, inventory and facilities, and the three secondary logistical components: information, production location, price and how they determine performance of any supply chain. I will discuss then how these components are used in the design, planning and operation of a supply chain. I will also talk about some obstacles a supply chain manager may encounter.

  17. Supply chain components

    Directory of Open Access Journals (Sweden)

    Vieraşu, T.

    2011-01-01

    Full Text Available In this article I will go through three main logistics components, which are represented by: transportation, inventory and facilities, and the three secondary logistical components: information, production location, price and how they determine performance of any supply chain. I will discuss then how these components are used in the design, planning and operation of a supply chain. I will also talk about some obstacles a supply chain manager may encounter.

  18. Control component retainer

    International Nuclear Information System (INIS)

    Walton, L.A.; King, R.A.

    1983-01-01

    An apparatus is described for retaining an undriven control component assembly disposed in a fuel assembly in a nuclear reactor of the type having a core grid plate. The first part of the mechanism involves a housing for the control component and the second part is a brace with a number of arms that reach under the grid plate. The brace and the housing are coupled together to firmly hold the control components in place even under strong flows of th coolant

  19. Component design for LMFBR's

    International Nuclear Information System (INIS)

    Fillnow, R.H.; France, L.L.; Zerinvary, M.C.; Fox, R.O.

    1975-01-01

    Just as FFTF has prototype components to confirm their design, FFTF is serving as a prototype for the design of the commercial LMFBR's. Design and manufacture of critical components for the FFTF system have been accomplished primarily using vendors with little or no previous experience in supplying components for high temperature sodium systems. The exposure of these suppliers, and through them a multitude of subcontractors, to the requirements of this program has been a necessary and significant step in preparing American industry for the task of supplying the large mechanical components required for commercial LMFBR's

  20. Hot gas path component

    Science.gov (United States)

    Lacy, Benjamin Paul; Kottilingam, Srikanth Chandrudu; Porter, Christopher Donald; Schick, David Edward

    2017-09-12

    Various embodiments of the disclosure include a turbomachine component. and methods of forming such a component. Some embodiments include a turbomachine component including: a first portion including at least one of a stainless steel or an alloy steel; and a second portion joined with the first portion, the second portion including a nickel alloy including an arced cooling feature extending therethrough, the second portion having a thermal expansion coefficient substantially similar to a thermal expansion coefficient of the first portion, wherein the arced cooling feature is located within the second portion to direct a portion of a coolant to a leakage area of the turbomachine component.

  1. Migration pathways in soils

    International Nuclear Information System (INIS)

    Gronow, J.R.

    1986-01-01

    This study looked at diffusive migration through three types of deformation; the projectile pathways, hydraulic fractures of the sediments and faults, and was divided into three experimental areas: autoradiography, the determination of diffusion coefficients and electron microscopy of model projectile pathways in clay. For the autoradiography, unstressed samples were exposed to two separate isotopes, Pm-147 (a possible model for Am behaviour) and the poorly sorbed iodide-125. The results indicated that there was no enhanced migration through deformed kaolin samples nor through fractured Great Meteor East (GME) sediment, although some was evident through the projectile pathways in GME and possibly through the GME sheared samples. The scanning electron microscopy of projectile pathways in clay showed that emplacement of a projectile appeared to have no effect on the orientation of particles at distances greater than two projectile radii from the centre of a projectile pathway. It showed that the particles were not simply aligned with the direction of motion of the projectile but that, the closer to the surface of a particular pathway, the closer the particles lay to their original orientation. This finding was of interest from two points of view: i) the ease of migration of a pollutant along the pathway, and ii) possible mechanisms of hole closure. It was concluded that, provided that there is no advective migration, the transport of radionuclides through sediments containing these defects would not be significantly more rapid than in undeformed sediments. (author)

  2. Components of Adenovirus Genome Packaging

    Science.gov (United States)

    Ahi, Yadvinder S.; Mittal, Suresh K.

    2016-01-01

    Adenoviruses (AdVs) are icosahedral viruses with double-stranded DNA (dsDNA) genomes. Genome packaging in AdV is thought to be similar to that seen in dsDNA containing icosahedral bacteriophages and herpesviruses. Specific recognition of the AdV genome is mediated by a packaging domain located close to the left end of the viral genome and is mediated by the viral packaging machinery. Our understanding of the role of various components of the viral packaging machinery in AdV genome packaging has greatly advanced in recent years. Characterization of empty capsids assembled in the absence of one or more components involved in packaging, identification of the unique vertex, and demonstration of the role of IVa2, the putative packaging ATPase, in genome packaging have provided compelling evidence that AdVs follow a sequential assembly pathway. This review provides a detailed discussion on the functions of the various viral and cellular factors involved in AdV genome packaging. We conclude by briefly discussing the roles of the empty capsids, assembly intermediates, scaffolding proteins, portal vertex and DNA encapsidating enzymes in AdV assembly and packaging. PMID:27721809

  3. DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in infl

  4. Components of Sexual Identity

    Science.gov (United States)

    Shively, Michael G.; DeCecco, John P.

    1977-01-01

    This paper examines the four components of sexual identity: biological sex, gender identity, social sex-role, and sexual orientation. Theories about the development of each component and how they combine and conflict to form the individual's sexual identity are discussed. (Author)

  5. Towards Cognitive Component Analysis

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Ahrendt, Peter; Larsen, Jan

    2005-01-01

    Cognitive component analysis (COCA) is here defined as the process of unsupervised grouping of data such that the ensuing group structure is well-aligned with that resulting from human cognitive activity. We have earlier demonstrated that independent components analysis is relevant for representing...

  6. Intersection of autophagy with pathways of antigen presentation.

    Science.gov (United States)

    Patterson, Natalie L; Mintern, Justine D

    2012-12-01

    Traditionally, macroautophagy (autophagy) is viewed as a pathway of cell survival. Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of stress. Interestingly, autophagy can also directly intersect with, and impact, other major pathways of cellular function. Here, we will review the contribution of autophagy to pathways of antigen presentation. The autophagy machinery acts to modulate both MHCI and MHCII antigen presentation. As such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.

  7. Quadrupolar transfer pathways

    Science.gov (United States)

    Antonijevic, Sasa; Bodenhausen, Geoffrey

    2006-06-01

    A set of graphical conventions called quadrupolar transfer pathways is proposed to describe a wide range of experiments designed for the study of quadrupolar nuclei with spin quantum numbers I = 1, 3/2, 2, 5/2, etc. These pathways, which inter alea allow one to appreciate the distinction between quadrupolar and Zeeman echoes, represent a generalization of the well-known coherence transfer pathways. Quadrupolar transfer pathways not merely distinguish coherences with different orders -2 I ⩽ p ⩽ +2 I, but allow one to follow the fate of coherences associated with single transitions that have the same coherence orderp=mIr-mIs but can be distinguished by a satellite orderq=(mIr)2-(mIs)2.

  8. HDR-Pathways

    Data.gov (United States)

    Department of Veterans Affairs — Pathways is a SOAP/REST web service interface accessed via HTTPS that provides administrative data (Appointments, Exam Requests and Exams information) from VistA in...

  9. Updating the Wnt pathways

    Science.gov (United States)

    Yu, Jia; Virshup, David M.

    2014-01-01

    In the three decades since the discovery of the Wnt1 proto-oncogene in virus-induced mouse mammary tumours, our understanding of the signalling pathways that are regulated by the Wnt proteins has progressively expanded. Wnts are involved in an complex signalling network that governs multiple biological processes and cross-talk with multiple additional signalling cascades, including the Notch, FGF (fibroblast growth factor), SHH (Sonic hedgehog), EGF (epidermal growth factor) and Hippo pathways. The Wnt signalling pathway also illustrates the link between abnormal regulation of the developmental processes and disease manifestation. Here we provide an overview of Wnt-regulated signalling cascades and highlight recent advances. We focus on new findings regarding the dedicated Wnt production and secretion pathway with potential therapeutic targets that might be beneficial for patients with Wnt-related diseases. PMID:25208913

  10. The mevalonate pathway in C. Elegans

    Directory of Open Access Journals (Sweden)

    Rauthan Manish

    2011-12-01

    Full Text Available Abstract The mevalonate pathway in human is responsible for the synthesis of cholesterol and other important biomolecules such as coenzyme Q, dolichols and isoprenoids. These molecules are required in the cell for functions ranging from signaling to membrane integrity, protein prenylation and glycosylation, and energy homeostasis. The pathway consists of a main trunk followed by sub-branches that synthesize the different biomolecules. The majority of our knowledge about the mevalonate pathway is currently focused on the cholesterol synthesis branch, which is the target of the cholesterol-lowering statins; less is known about the function and regulation of the non-cholesterol-related branches. To study them, we need a biological system where it is possible to specifically modulate these metabolic branches individually or in groups. The nematode Caenorhabditis elegans (C. elegans is a promising model to study these non-cholesterol branches since its mevalonate pathway seems very well conserved with that in human except that it has no cholesterol synthesis branch. The simple genetic makeup and tractability of C. elegans makes it relatively easy to identify and manipulate key genetic components of the mevalonate pathway, and to evaluate the consequences of tampering with their activity. This general experimental approach should lead to new insights into the physiological roles of the non-cholesterol part of the mevalonate pathway. This review will focus on the current knowledge related to the mevalonate pathway in C. elegans and its possible applications as a model organism to study the non-cholesterol functions of this pathway.

  11. GCS component development cycle

    Science.gov (United States)

    Rodríguez, Jose A.; Macias, Rosa; Molgo, Jordi; Guerra, Dailos; Pi, Marti

    2012-09-01

    The GTC1 is an optical-infrared 10-meter segmented mirror telescope at the ORM observatory in Canary Islands (Spain). First light was at 13/07/2007 and since them it is in the operation phase. The GTC control system (GCS) is a distributed object & component oriented system based on RT-CORBA8 and it is responsible for the management and operation of the telescope, including its instrumentation. GCS has used the Rational Unified process (RUP9) in its development. RUP is an iterative software development process framework. After analysing (use cases) and designing (UML10) any of GCS subsystems, an initial component description of its interface is obtained and from that information a component specification is written. In order to improve the code productivity, GCS has adopted the code generation to transform this component specification into the skeleton of component classes based on a software framework, called Device Component Framework. Using the GCS development tools, based on javadoc and gcc, in only one step, the component is generated, compiled and deployed to be tested for the first time through our GUI inspector. The main advantages of this approach are the following: It reduces the learning curve of new developers and the development error rate, allows a systematic use of design patterns in the development and software reuse, speeds up the deliverables of the software product and massively increase the timescale, design consistency and design quality, and eliminates the future refactoring process required for the code.

  12. 2-component heating systems

    Energy Technology Data Exchange (ETDEWEB)

    Radtke, W

    1987-03-01

    The knowledge accumulated only recently of the damage to buildings and the hazards of formaldehyde, radon and hydrocarbons has been inducing louder calls for ventilation, which, on their part, account for the fact that increasing importance is being attached to the controlled ventilation of buildings. Two-component heating systems provide for fresh air and thermal comfort in one. While the first component uses fresh air blown directly and controllably into the rooms, the second component is similar to the Roman hypocaustic heating systems, meaning that heated outer air is circulating under the floor, thus providing for hot surfaces and thermal comfort. Details concerning the two-component heating system are presented along with systems diagrams, diagrams of the heating system and tables identifying the respective costs. Descriptions are given of the two systems components, the fast heat-up, the two-component made, the change of air, heat recovery and control systems. Comparative evaluations determine the differences between two-component heating systems and other heating systems. Conclusive remarks are dedicated to energy conservation and comparative evaluations of costs. (HWJ).

  13. Reconstructing biochemical pathways from time course data.

    Science.gov (United States)

    Srividhya, Jeyaraman; Crampin, Edmund J; McSharry, Patrick E; Schnell, Santiago

    2007-03-01

    Time series data on biochemical reactions reveal transient behavior, away from chemical equilibrium, and contain information on the dynamic interactions among reacting components. However, this information can be difficult to extract using conventional analysis techniques. We present a new method to infer biochemical pathway mechanisms from time course data using a global nonlinear modeling technique to identify the elementary reaction steps which constitute the pathway. The method involves the generation of a complete dictionary of polynomial basis functions based on the law of mass action. Using these basis functions, there are two approaches to model construction, namely the general to specific and the specific to general approach. We demonstrate that our new methodology reconstructs the chemical reaction steps and connectivity of the glycolytic pathway of Lactococcus lactis from time course experimental data.

  14. Replaceable LMFBR core components

    International Nuclear Information System (INIS)

    Evans, E.A.; Cunningham, G.W.

    1976-01-01

    Much progress has been made in understanding material and component performance in the high temperature, fast neutron environment of the LMFBR. Current data have provided strong assurance that the initial core component lifetime objectives of FFTF and CRBR can be met. At the same time, this knowledge translates directly into the need for improved core designs that utilize improved materials and advanced fuels required to meet objectives of low doubling times and extended core component lifetimes. An industrial base for the manufacture of quality core components has been developed in the US, and all procurements for the first two core equivalents for FFTF will be completed this year. However, the problem of fabricating recycled plutonium while dramatically reducing fabrication costs, minimizing personnel exposure, and protecting public health and safety must be addressed

  15. Explosive Components Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The 98,000 square foot Explosive Components Facility (ECF) is a state-of-the-art facility that provides a full-range of chemical, material, and performance analysis...

  16. Component fragility research program

    International Nuclear Information System (INIS)

    Tsai, N.C.; Mochizuki, G.L.; Holman, G.S.

    1989-11-01

    To demonstrate how ''high-level'' qualification test data can be used to estimate the ultimate seismic capacity of nuclear power plant equipment, we assessed in detail various electrical components tested by the Pacific Gas ampersand Electric Company for its Diablo Canyon plant. As part of our Phase I Component Fragility Research Program, we evaluated seismic fragility for five Diablo Canyon components: medium-voltage (4kV) switchgear; safeguard relay board; emergency light battery pack; potential transformer; and station battery and racks. This report discusses our Phase II fragility evaluation of a single Westinghouse Type W motor control center column, a fan cooler motor controller, and three local starters at the Diablo Canyon nuclear power plant. These components were seismically qualified by means of biaxial random motion tests on a shaker table, and the test response spectra formed the basis for the estimate of the seismic capacity of the components. The seismic capacity of each component is referenced to the zero period acceleration (ZPA) and, in our Phase II study only, to the average spectral acceleration (ASA) of the motion at its base. For the motor control center, the seismic capacity was compared to the capacity of a Westinghouse Five-Star MCC subjected to actual fragility tests by LLNL during the Phase I Component Fragility Research Program, and to generic capacities developed by the Brookhaven National Laboratory for motor control center. Except for the medium-voltage switchgear, all of the components considered in both our Phase I and Phase II evaluations were qualified in their standard commercial configurations or with only relatively minor modifications such as top bracing of cabinets. 8 refs., 67 figs., 7 tabs

  17. Refractory alloy component fabrication

    International Nuclear Information System (INIS)

    Young, W.R.

    1984-01-01

    Purpose of this report is to describe joining procedures, primarily welding techniques, which were developed to construct reliable refractory alloy components and systems for advanced space power systems. Two systems, the Nb-1Zr Brayton Cycle Heat Receiver and the T-111 Alloy Potassium Boiler Development Program, are used to illustrate typical systems and components. Particular emphasis is given to specific problems which were eliminated during the development efforts. Finally, some thoughts on application of more recent joining technology are presented. 78 figures

  18. Impact test of components

    International Nuclear Information System (INIS)

    Borsoi, L.; Buland, P.; Labbe, P.

    1987-01-01

    Stops with gaps are currently used to support components and piping: it is simple, low cost, efficient and permits free thermal expansion. In order to keep the nonlinear nature of stops, such design is often modeled by beam elements (for the component) and nonlinear springs (for the stops). This paper deals with the validity and the limits of these models through the comparison of computational and experimental results. The experimental results come from impact laboratory tests on a simplified mockup. (orig.)

  19. Deciphering chemotaxis pathways using cross species comparisons

    Directory of Open Access Journals (Sweden)

    Armitage Judith P

    2010-01-01

    Full Text Available Abstract Background Chemotaxis is the process by which motile bacteria sense their chemical environment and move towards more favourable conditions. Escherichia coli utilises a single sensory pathway, but little is known about signalling pathways in species with more complex systems. Results To investigate whether chemotaxis pathways in other bacteria follow the E. coli paradigm, we analysed 206 species encoding at least 1 homologue of each of the 5 core chemotaxis proteins (CheA, CheB, CheR, CheW and CheY. 61 species encode more than one of all of these 5 proteins, suggesting they have multiple chemotaxis pathways. Operon information is not available for most bacteria, so we developed a novel statistical approach to cluster che genes into putative operons. Using operon-based models, we reconstructed putative chemotaxis pathways for all 206 species. We show that cheA-cheW and cheR-cheB have strong preferences to occur in the same operon as two-gene blocks, which may reflect a functional requirement for co-transcription. However, other che genes, most notably cheY, are more dispersed on the genome. Comparison of our operons with shuffled equivalents demonstrates that specific patterns of genomic location may be a determining factor for the observed in vivo chemotaxis pathways. We then examined the chemotaxis pathways of Rhodobacter sphaeroides. Here, the PpfA protein is known to be critical for correct partitioning of proteins in the cytoplasmically-localised pathway. We found ppfA in che operons of many species, suggesting that partitioning of cytoplasmic Che protein clusters is common. We also examined the apparently non-typical chemotaxis components, CheA3, CheA4 and CheY6. We found that though variants of CheA proteins are rare, the CheY6 variant may be a common type of CheY, with a significantly disordered C-terminal region which may be functionally significant. Conclusions We find that many bacterial species potentially have multiple

  20. Probabilistic pathway construction.

    Science.gov (United States)

    Yousofshahi, Mona; Lee, Kyongbum; Hassoun, Soha

    2011-07-01

    Expression of novel synthesis pathways in host organisms amenable to genetic manipulations has emerged as an attractive metabolic engineering strategy to overproduce natural products, biofuels, biopolymers and other commercially useful metabolites. We present a pathway construction algorithm for identifying viable synthesis pathways compatible with balanced cell growth. Rather than exhaustive exploration, we investigate probabilistic selection of reactions to construct the pathways. Three different selection schemes are investigated for the selection of reactions: high metabolite connectivity, low connectivity and uniformly random. For all case studies, which involved a diverse set of target metabolites, the uniformly random selection scheme resulted in the highest average maximum yield. When compared to an exhaustive search enumerating all possible reaction routes, our probabilistic algorithm returned nearly identical distributions of yields, while requiring far less computing time (minutes vs. years). The pathways identified by our algorithm have previously been confirmed in the literature as viable, high-yield synthesis routes. Prospectively, our algorithm could facilitate the design of novel, non-native synthesis routes by efficiently exploring the diversity of biochemical transformations in nature. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Pathways to youth homelessness.

    Science.gov (United States)

    Martijn, Claudine; Sharpe, Louise

    2006-01-01

    Research documents high levels of psychopathology among homeless youth. Most research, however, has not distinguished between disorders that are present prior to homelessness and those that develop following homelessness. Hence whether psychological disorders are the cause or consequence of homelessness has not been established. The aim of this study is to investigate causal pathways to homelessness amongst currently homeless youth in Australia. The study uses a quasi-qualitative methodology to generate hypotheses for larger-scale research. High rates of psychological disorders were confirmed in the sample 35 homeless youth aged 14-25. The rates of psychological disorders at the point of homelessness were greater than in normative samples, but the rates of clinical disorder increased further once homeless. Further in-depth analyses were conducted to identify the temporal sequence for each individual with a view to establishing a set of causal pathways to homelessness and trajectories following homelessness that characterised the people in the sample. Five pathways to homelessness and five trajectories following homelessness were identified that accounted for the entire sample. Each pathway constituted a series of interactions between different factors similar to that described by Craig and Hodson (1998. Psychological Medicine, 28, 1379-1388) as "complex subsidiary pathways". The major findings were that (1) trauma is a common experience amongst homeless youth prior to homelessness and figured in the causal pathways to homelessness for over half of the sample; (2) once homeless, for the majority of youth there is an increase in the number of psychological diagnoses including drug and alcohol diagnoses; and (3) crime did not precede homelessness for all but one youth; however, following homelessness, involvement in criminal activity was common and became a distinguishing factor amongst youth. The implications of these findings for future research and service

  2. Multiscale principal component analysis

    International Nuclear Information System (INIS)

    Akinduko, A A; Gorban, A N

    2014-01-01

    Principal component analysis (PCA) is an important tool in exploring data. The conventional approach to PCA leads to a solution which favours the structures with large variances. This is sensitive to outliers and could obfuscate interesting underlying structures. One of the equivalent definitions of PCA is that it seeks the subspaces that maximize the sum of squared pairwise distances between data projections. This definition opens up more flexibility in the analysis of principal components which is useful in enhancing PCA. In this paper we introduce scales into PCA by maximizing only the sum of pairwise distances between projections for pairs of datapoints with distances within a chosen interval of values [l,u]. The resulting principal component decompositions in Multiscale PCA depend on point (l,u) on the plane and for each point we define projectors onto principal components. Cluster analysis of these projectors reveals the structures in the data at various scales. Each structure is described by the eigenvectors at the medoid point of the cluster which represent the structure. We also use the distortion of projections as a criterion for choosing an appropriate scale especially for data with outliers. This method was tested on both artificial distribution of data and real data. For data with multiscale structures, the method was able to reveal the different structures of the data and also to reduce the effect of outliers in the principal component analysis

  3. Optical CDMA components requirements

    Science.gov (United States)

    Chan, James K.

    1998-08-01

    Optical CDMA is a complementary multiple access technology to WDMA. Optical CDMA potentially provides a large number of virtual optical channels for IXC, LEC and CLEC or supports a large number of high-speed users in LAN. In a network, it provides asynchronous, multi-rate, multi-user communication with network scalability, re-configurability (bandwidth on demand), and network security (provided by inherent CDMA coding). However, optical CDMA technology is less mature in comparison to WDMA. The components requirements are also different from WDMA. We have demonstrated a video transport/switching system over a distance of 40 Km using discrete optical components in our laboratory. We are currently pursuing PIC implementation. In this paper, we will describe the optical CDMA concept/features, the demonstration system, and the requirements of some critical optical components such as broadband optical source, broadband optical amplifier, spectral spreading/de- spreading, and fixed/programmable mask.

  4. Solid state lighting component

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Thomas; Keller, Bernd; Tarsa, Eric; Ibbetson, James; Morgan, Frederick; Dowling, Kevin; Lys, Ihor

    2017-10-17

    An LED component according to the present invention comprising an array of LED chips mounted on a submount with the LED chips capable of emitting light in response to an electrical signal. The array can comprise LED chips emitting at two colors of light wherein the LED component emits light comprising the combination of the two colors of light. A single lens is included over the array of LED chips. The LED chip array can emit light of greater than 800 lumens with a drive current of less than 150 milli-Amps. The LED chip component can also operate at temperatures less than 3000 degrees K. In one embodiment, the LED array is in a substantially circular pattern on the submount.

  5. An integrated magnetics component

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an integrated magnetics component comprising a magnetically permeable core comprising a base member extending in a horizontal plane and first, second, third and fourth legs protruding substantially perpendicularly from the base member. First, second, third...... and fourth output inductor windings are wound around the first, second, third and fourth legs, respectively. A first input conductor of the integrated magnetics component has a first conductor axis and extends in-between the first, second, third and fourth legs to induce a first magnetic flux through a first...... flux path of the magnetically permeable core. A second input conductor of the integrated magnetics component has a second coil axis extending substantially perpendicularly to the first conductor axis to induce a second magnetic flux through a second flux path of the magnetically permeable core...

  6. Cognitive Component Analysis

    DEFF Research Database (Denmark)

    Feng, Ling

    2008-01-01

    This dissertation concerns the investigation of the consistency of statistical regularities in a signaling ecology and human cognition, while inferring appropriate actions for a speech-based perceptual task. It is based on unsupervised Independent Component Analysis providing a rich spectrum...... of audio contexts along with pattern recognition methods to map components to known contexts. It also involves looking for the right representations for auditory inputs, i.e. the data analytic processing pipelines invoked by human brains. The main ideas refer to Cognitive Component Analysis, defined...... as the process of unsupervised grouping of generic data such that the ensuing group structure is well-aligned with that resulting from human cognitive activity. Its hypothesis runs ecologically: features which are essentially independent in a context defined ensemble, can be efficiently coded as sparse...

  7. Electronic components and systems

    CERN Document Server

    Dennis, W H

    2013-01-01

    Electronic Components and Systems focuses on the principles and processes in the field of electronics and the integrated circuit. Covered in the book are basic aspects and physical fundamentals; different types of materials involved in the field; and passive and active electronic components such as capacitors, inductors, diodes, and transistors. Also covered in the book are topics such as the fabrication of semiconductors and integrated circuits; analog circuitry; digital logic technology; and microprocessors. The monograph is recommended for beginning electrical engineers who would like to kn

  8. Policies built upon pathways

    NARCIS (Netherlands)

    Musterd, S.; Kovács, Z.; Musterd, S.; Kovács, Z.

    2013-01-01

    After the general introductions, the first substantive part of this volume (Part II) provides concise research-based discussions of policies developed in recognition of the important role played by the pathways along which city-regions have travelled. Our research has shown that it is highly

  9. Synthetic Metabolic Pathways

    DEFF Research Database (Denmark)

    topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Synthetic Metabolic Pathways: Methods and Protocols aims to ensure successful results in the further study...

  10. Dexter energy transfer pathways.

    Science.gov (United States)

    Skourtis, Spiros S; Liu, Chaoren; Antoniou, Panayiotis; Virshup, Aaron M; Beratan, David N

    2016-07-19

    Energy transfer with an associated spin change of the donor and acceptor, Dexter energy transfer, is critically important in solar energy harvesting assemblies, damage protection schemes of photobiology, and organometallic opto-electronic materials. Dexter transfer between chemically linked donors and acceptors is bridge mediated, presenting an enticing analogy with bridge-mediated electron and hole transfer. However, Dexter coupling pathways must convey both an electron and a hole from donor to acceptor, and this adds considerable richness to the mediation process. We dissect the bridge-mediated Dexter coupling mechanisms and formulate a theory for triplet energy transfer coupling pathways. Virtual donor-acceptor charge-transfer exciton intermediates dominate at shorter distances or higher tunneling energy gaps, whereas virtual intermediates with an electron and a hole both on the bridge (virtual bridge excitons) dominate for longer distances or lower energy gaps. The effects of virtual bridge excitons were neglected in earlier treatments. The two-particle pathway framework developed here shows how Dexter energy-transfer rates depend on donor, bridge, and acceptor energetics, as well as on orbital symmetry and quantum interference among pathways.

  11. Validating Timed Component Contracts

    DEFF Research Database (Denmark)

    Le Guilly, Thibaut; Liu, Shaoying; Olsen, Petur

    2015-01-01

    This paper presents a technique for testing software components with contracts that specify functional behavior, synchronization, as well as timing behavior. The approach combines elements from unit testing with model-based testing techniques for timed automata. The technique is implemented...... in an online testing tool, and we demonstrate its use on a concrete use case....

  12. Euler principal component analysis

    NARCIS (Netherlands)

    Liwicki, Stephan; Tzimiropoulos, Georgios; Zafeiriou, Stefanos; Pantic, Maja

    Principal Component Analysis (PCA) is perhaps the most prominent learning tool for dimensionality reduction in pattern recognition and computer vision. However, the ℓ 2-norm employed by standard PCA is not robust to outliers. In this paper, we propose a kernel PCA method for fast and robust PCA,

  13. Hybrid wars’ information component

    Directory of Open Access Journals (Sweden)

    T. A. Nevskaya

    2015-01-01

    Full Text Available The war of the new generation - hybrid war, the information component which is directed not so much on the direct destruction of the enemy, how to achieve the goals without warfare. Fighting in the information field is no less important than immediate military action.

  14. ITER plasma facing components

    International Nuclear Information System (INIS)

    Kuroda, T.; Vieider, G.; Akiba, M.

    1991-01-01

    This document summarizes results of the Conceptual Design Activities (1988-1990) for the International Thermonuclear Experimental Reactor (ITER) project, namely those that pertain to the plasma facing components of the reactor vessel, of which the main components are the first wall and the divertor plates. After an introduction and an executive summary, the principal functions of the plasma-facing components are delineated, i.e., (i) define the low-impurity region within which the plasma is produced, (ii) absorb the electromagnetic radiation and charged-particle flux from the plasma, and (iii) protect the blanket/shield components from the plasma. A list of critical design issues for the divertor plates and the first wall is given, followed by discussions of the divertor plate design (including the issues of material selection, erosion lifetime, design concepts, thermal and mechanical analysis, operating limits and overall lifetime, tritium inventory, baking and conditioning, safety analysis, manufacture and testing, and advanced divertor concepts) and the first wall design (armor material and design, erosion lifetime, overall design concepts, thermal and mechanical analysis, lifetime and operating limits, tritium inventory, baking and conditioning, safety analysis, manufacture and testing, an alternative first wall design, and the limiters used instead of the divertor plates during start-up). Refs, figs and tabs

  15. Spain's nuclear components industry

    International Nuclear Information System (INIS)

    Kaibel, E.

    1985-01-01

    Spanish industrial participation in supply of components for nuclear power plants has grown steadily over the last fifteen years. The share of Spanish companies in work for the five second generation nuclear power plants increased to 50% of total capital investments. The necessity to maintain Spanish technology and production in the nuclear field is emphasized

  16. The market for components

    International Nuclear Information System (INIS)

    Simon, M.; Stoelzl, D.

    1986-01-01

    The offers of the German nuclear components industry are shown at the examples of some masterpieces of engineering and their delivery capacities. Then, the success achieved with exports up to now are referred to. The forecast includes the demand, the side conditions of the technical competition, and the pricing and financing situation. (UA) [de

  17. Bayesian Independent Component Analysis

    DEFF Research Database (Denmark)

    Winther, Ole; Petersen, Kaare Brandt

    2007-01-01

    In this paper we present an empirical Bayesian framework for independent component analysis. The framework provides estimates of the sources, the mixing matrix and the noise parameters, and is flexible with respect to choice of source prior and the number of sources and sensors. Inside the engine...

  18. Component-oriented programming

    NARCIS (Netherlands)

    Bosch, J; Szyperski, C; Weck, W; Buschmann, F; Buchmann, AP; Cilia, MA

    2003-01-01

    This report covers the eighth Workshop on Component-Oriented Programming (WCOP). WCOP has been affiliated with ECOOP since its inception in 1996. The report summarizes the contributions made by authors of accepted position papers as well as those made by all attendees of the workshop sessions.

  19. Developing a Model Component

    Science.gov (United States)

    Fields, Christina M.

    2013-01-01

    The Spaceport Command and Control System (SCCS) Simulation Computer Software Configuration Item (CSCI) is responsible for providing simulations to support test and verification of SCCS hardware and software. The Universal Coolant Transporter System (UCTS) was a Space Shuttle Orbiter support piece of the Ground Servicing Equipment (GSE). The initial purpose of the UCTS was to provide two support services to the Space Shuttle Orbiter immediately after landing at the Shuttle Landing Facility. The UCTS is designed with the capability of servicing future space vehicles; including all Space Station Requirements necessary for the MPLM Modules. The Simulation uses GSE Models to stand in for the actual systems to support testing of SCCS systems during their development. As an intern at Kennedy Space Center (KSC), my assignment was to develop a model component for the UCTS. I was given a fluid component (dryer) to model in Simulink. I completed training for UNIX and Simulink. The dryer is a Catch All replaceable core type filter-dryer. The filter-dryer provides maximum protection for the thermostatic expansion valve and solenoid valve from dirt that may be in the system. The filter-dryer also protects the valves from freezing up. I researched fluid dynamics to understand the function of my component. The filter-dryer was modeled by determining affects it has on the pressure and velocity of the system. I used Bernoulli's Equation to calculate the pressure and velocity differential through the dryer. I created my filter-dryer model in Simulink and wrote the test script to test the component. I completed component testing and captured test data. The finalized model was sent for peer review for any improvements. I participated in Simulation meetings and was involved in the subsystem design process and team collaborations. I gained valuable work experience and insight into a career path as an engineer.

  20. PathwayAccess: CellDesigner plugins for pathway databases.

    Science.gov (United States)

    Van Hemert, John L; Dickerson, Julie A

    2010-09-15

    CellDesigner provides a user-friendly interface for graphical biochemical pathway description. Many pathway databases are not directly exportable to CellDesigner models. PathwayAccess is an extensible suite of CellDesigner plugins, which connect CellDesigner directly to pathway databases using respective Java application programming interfaces. The process is streamlined for creating new PathwayAccess plugins for specific pathway databases. Three PathwayAccess plugins, MetNetAccess, BioCycAccess and ReactomeAccess, directly connect CellDesigner to the pathway databases MetNetDB, BioCyc and Reactome. PathwayAccess plugins enable CellDesigner users to expose pathway data to analytical CellDesigner functions, curate their pathway databases and visually integrate pathway data from different databases using standard Systems Biology Markup Language and Systems Biology Graphical Notation. Implemented in Java, PathwayAccess plugins run with CellDesigner version 4.0.1 and were tested on Ubuntu Linux, Windows XP and 7, and MacOSX. Source code, binaries, documentation and video walkthroughs are freely available at http://vrac.iastate.edu/~jlv.

  1. Adaptable component frameworks

    DEFF Research Database (Denmark)

    Katajainen, Jyrki; Simonsen, Bo

    2009-01-01

    The CPH STL is a special edition of the STL, the containers and algorithms part of the C++ standard library. The specification of the generic components of the STL is given in the C++ standard. Any implementation of the STL, e.g. the one that ships with your standard-compliant C++ compiler, should...... for vector, which is undoubtedly the most used container of the C++ standard library. In particular, we specify the details of a vector implementation that is safe with respect to referential integrity and strong exception safety. Additionally, we report the experiences and lessons learnt from...... the development of component frameworks which we hope to be of benefit to persons engaged in the design and implementation of generic software libraries....

  2. Components of laboratory accreditation.

    Science.gov (United States)

    Royal, P D

    1995-12-01

    Accreditation or certification is a recognition given to an operation or product that has been evaluated against a standard; be it regulatory or voluntary. The purpose of accreditation is to provide the consumer with a level of confidence in the quality of operation (process) and the product of an organization. Environmental Protection Agency/OCM has proposed the development of an accreditation program under National Environmental Laboratory Accreditation Program for Good Laboratory Practice (GLP) laboratories as a supplement to the current program. This proposal was the result of the Inspector General Office reports that identified weaknesses in the current operation. Several accreditation programs can be evaluated and common components identified when proposing a structure for accrediting a GLP system. An understanding of these components is useful in building that structure. Internationally accepted accreditation programs provide a template for building a U.S. GLP accreditation program. This presentation will discuss the traditional structure of accreditation as presented in the Organization of Economic Cooperative Development/GLP program, ISO-9000 Accreditation and ISO/IEC Guide 25 Standard, and the Canadian Association for Environmental Analytical Laboratories, which has a biological component. Most accreditation programs are managed by a recognized third party, either privately or with government oversight. Common components often include a formal review of required credentials to evaluate organizational structure, a site visit to evaluate the facility, and a performance evaluation to assess technical competence. Laboratory performance is measured against written standards and scored. A formal report is then sent to the laboratory indicating accreditation status. Usually, there is a scheduled reevaluation built into the program. Fee structures vary considerably and will need to be examined closely when building a GLP program.

  3. Fabricating nuclear components

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    Activities of the Nuclear Engineering Division of Vickers Ltd., particularly fabrication of long slim tubular components for power reactors and the construction of irradiation loops and rigs, are outlined. The processes include hydraulic forming for fabrication of various types of tubes and outer cases of fuel transfer buckets, various specialised welding operations including some applications of the TIG process, and induction brazing of specialised assemblies. (U.K.)

  4. Components of the environment

    International Nuclear Information System (INIS)

    Klinda, J.; Lieskovska, Z.

    1998-01-01

    This report of the Ministry of the Environment of the Slovak Republic deals with the components of the environment. The results of monitoring of air (emission situation), ambient air quality, atmospheric precipitation, tropospheric ozone, water (surface water, groundwater resources, waste water and drinking water), geological factors (geothermal energy, fuel deposits, ore deposits, non-metallic ore deposits), soil (area statistics, soil contamination. soil reaction and active extractable aluminium, soil erosion), flora and fauna (national strategy of biodiversity protection) are presented

  5. Ionitriding of Weapon Components

    Science.gov (United States)

    1974-01-01

    and documented tho production sequences required for the case- hardening of AISI 4140 and Nitralloy 13514 steels. Determination of processina...depths were established experimentally for Nitralloy 135M and for AISI 4140 steels. These steels are commonly used for the manufacture of nitrlded...weapons components. A temperature of 050F, upper limit for lonitrlding, was selected for the Nitralloy 135M to keep treatment times short. Since AISI 4140

  6. Components of QCD

    International Nuclear Information System (INIS)

    Sivers, D.

    1979-10-01

    Some aspects of a simple strategy for testing the validity of QCD perturbation theory are examined. The importance of explicit evaluation of higher-order contributions is illustrated by considering Z 0 decays. The recent progress toward understanding exclusive processes in QCD is discussed and some simple examples are given of how to isolate and test the separate components of the perturbation expansion in a hypothetical series of jet experiments

  7. Optimized Kernel Entropy Components.

    Science.gov (United States)

    Izquierdo-Verdiguier, Emma; Laparra, Valero; Jenssen, Robert; Gomez-Chova, Luis; Camps-Valls, Gustau

    2017-06-01

    This brief addresses two main issues of the standard kernel entropy component analysis (KECA) algorithm: the optimization of the kernel decomposition and the optimization of the Gaussian kernel parameter. KECA roughly reduces to a sorting of the importance of kernel eigenvectors by entropy instead of variance, as in the kernel principal components analysis. In this brief, we propose an extension of the KECA method, named optimized KECA (OKECA), that directly extracts the optimal features retaining most of the data entropy by means of compacting the information in very few features (often in just one or two). The proposed method produces features which have higher expressive power. In particular, it is based on the independent component analysis framework, and introduces an extra rotation to the eigen decomposition, which is optimized via gradient-ascent search. This maximum entropy preservation suggests that OKECA features are more efficient than KECA features for density estimation. In addition, a critical issue in both the methods is the selection of the kernel parameter, since it critically affects the resulting performance. Here, we analyze the most common kernel length-scale selection criteria. The results of both the methods are illustrated in different synthetic and real problems. Results show that OKECA returns projections with more expressive power than KECA, the most successful rule for estimating the kernel parameter is based on maximum likelihood, and OKECA is more robust to the selection of the length-scale parameter in kernel density estimation.

  8. Pathway analysis of IMC

    DEFF Research Database (Denmark)

    Skrypnyuk, Nataliya; Nielson, Flemming; Pilegaard, Henrik

    2009-01-01

    We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced into the...... into the syntax of IMC in order to make our analysis feasible. Finally we describe the analysis itself together with several theoretical results that we have proved for it.......We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced...

  9. Aquatic pathway 2

    International Nuclear Information System (INIS)

    1977-01-01

    This third part of the investigation discusses the preliminary results of sub-investigations concerning problems of the release of radioactive substances into the environment via the water pathway. On the basis of papers on the emission into the draining ditch and the exchange processes there, investigations of a possible incorporation via different exposure pathways are reported. Special regard is paid to drinking water supply aquatic foodstuffs, the river sediment, the utilisation of the agricultural surfaces and the draining ditch including its pre-pollution. The dynamics of contamination processes is reported on with regard to the problem of accidents. The colloquium will give an outline of the progress made so far and admit participants' suggestions for further work on the sub-investigations. The following colloquia will report further findings, in particular effects on aquatic ecosystems. (orig.) [de

  10. Conservation of Planar Polarity Pathway Function Across the Animal Kingdom.

    Science.gov (United States)

    Hale, Rosalind; Strutt, David

    2015-01-01

    Planar polarity is a well-studied phenomenon resulting in the directional coordination of cells in the plane of a tissue. In invertebrates and vertebrates, planar polarity is established and maintained by the largely independent core and Fat/Dachsous/Four-jointed (Ft-Ds-Fj) pathways. Loss of function of these pathways can result in a wide range of developmental or cellular defects, including failure of gastrulation and problems with placement and function of cilia. This review discusses the conservation of these pathways across the animal kingdom. The lack of vital core pathway components in basal metazoans suggests that the core planar polarity pathway evolved shortly after, but not necessarily alongside, the emergence of multicellularity.

  11. Lessons learned from mice deficient in lectin complement pathway molecules

    DEFF Research Database (Denmark)

    Genster, Ninette; Takahashi, Minoru; Sekine, Hideharu

    2014-01-01

    in turn activate downstream complement components, ultimately leading to elimination of the pathogen. Mice deficient in the key molecules of lectin pathway of complement have been generated in order to build knowledge of the molecular mechanisms of the lectin pathway in health and disease. Despite......The lectin pathway of the complement system is initiated when the pattern-recognition molecules, mannose-binding lectin (MBL), ficolins or collectin-11, bind to invading pathogens or damaged host cells. This leads to activation of MBL/ficolin/collectin-11 associated serine proteases (MASPs), which...... differences in the genetic arrangements of murine and human orthologues of lectin pathway molecules, the knockout mice have proven to be valuable models to explore the effect of deficiency states in humans. In addition, new insight and unexpected findings on the diverse roles of lectin pathway molecules...

  12. Pathways to diversification

    OpenAIRE

    Al Hashemi, Hamed

    2016-01-01

    A fundamental research question in regional economic development, is why some regions are able to diversify into new products and industries, while others continue to face challenges in diversification? This doctorate research explores the different pathways to diversification. It follows the three-stage modular structure of DBA for Cranfield School of Management. This thesis consists of a systematic literature review, a single qualitative case study on UAE, and a research synthesis of publis...

  13. The Glymphatic Pathway.

    Science.gov (United States)

    Benveniste, Helene; Lee, Hedok; Volkow, Nora D

    2017-01-01

    The overall premise of this review is that cerebrospinal fluid (CSF) is transported within a dedicated peri-vascular network facilitating metabolic waste clearance from the central nervous system while we sleep. The anatomical profile of the network is complex and has been defined as a peri-arterial CSF influx pathway and peri-venous clearance routes, which are functionally coupled by interstitial bulk flow supported by astrocytic aquaporin 4 water channels. The role of the newly discovered system in the brain is equivalent to the lymphatic system present in other body organs and has been termed the "glymphatic pathway" or "(g)lymphatics" because of its dependence on glial cells. We will discuss and review the general anatomy and physiology of CSF from the perspective of the glymphatic pathway, a discovery which has greatly improved our understanding of key factors that control removal of metabolic waste products from the central nervous system in health and disease and identifies an additional purpose for sleep. A brief historical and factual description of CSF production and transport will precede the ensuing discussion of the glymphatic system along with a discussion of its clinical implications.

  14. What is a clinical pathway? Refinement of an operational definition to identify clinical pathway studies for a Cochrane systematic review

    OpenAIRE

    Lawal, Adegboyega K.; Rotter, Thomas; Kinsman, Leigh; Machotta, Andreas; Ronellenfitsch, Ulrich; Scott, Shannon D.; Goodridge, Donna; Plishka, Christopher; Groot, Gary

    2016-01-01

    textabstractClinical pathways (CPWs) are a common component in the quest to improve the quality of health. CPWs are used to reduce variation, improve quality of care, and maximize the outcomes for specific groups of patients. An ongoing challenge is the operationalization of a definition of CPW in healthcare. This may be attributable to both the differences in definition and a lack of conceptualization in the field of clinical pathways. This correspondence article describes a process of refin...

  15. Reinforced seal component

    International Nuclear Information System (INIS)

    Jeanson, G.M.; Odent, R.P.

    1980-01-01

    The invention concerns a seal component of the kind comprising a soft sheath and a flexible reinforcement housed throughout the entire length of the sheath. The invention enables O ring seals to be made capable of providing a radial seal, that is to say between two sides or flat collars of two cylindrical mechanical parts, or an axial seal, that is to say between two co-axial axisymmetrical areas. The seal so ensured is relative, but it remains adequately sufficient for many uses, for instance, to ensure the separation of two successive fixed blading compartments of axial compressors used in gas diffusion isotope concentration facilities [fr

  16. Electronic components and technology

    CERN Document Server

    Sangwine, Stephen

    2007-01-01

    Most introductory textbooks in electronics focus on the theory while leaving the practical aspects to be covered in laboratory courses. However, the sooner such matters are introduced, the better able students will be to include such important concerns as parasitic effects and reliability at the very earliest stages of design. This philosophy has kept Electronic Components and Technology thriving for two decades, and this completely updated third edition continues the approach with a more international outlook.Not only does this textbook introduce the properties, behavior, fabrication, and use

  17. Autonomous component carrier selection

    DEFF Research Database (Denmark)

    Garcia, Luis Guilherme Uzeda; Pedersen, Klaus; Mogensen, Preben

    2009-01-01

    management and efficient system operation. Due to the expected large number of user-deployed cells, centralized network planning becomes unpractical and new scalable alternatives must be sought. In this article, we propose a fully distributed and scalable solution to the interference management problem...... in local areas, basing our study case on LTE-Advanced. We present extensive network simulation results to demonstrate that a simple and robust interference management scheme, called autonomous component carrier selection allows each cell to select the most attractive frequency configuration; improving...... the experience of all users and not just the few best ones; while overall cell capacity is not compromised....

  18. Impedance of accelerator components

    International Nuclear Information System (INIS)

    Corlett, J.N.

    1996-05-01

    As demands for high luminosity and low emittance particle beams increase, an understanding of the electromagnetic interaction of these beams with their vacuum chamber environment becomes more important in order to maintain the quality of the beam. This interaction is described in terms of the wake field in time domain, and the beam impedance in frequency domain. These concepts are introduced, and related quantities such as the loss factor are presented. The broadband Q = 1 resonator impedance model is discussed. Perturbation and coaxial wire methods of measurement of real components are reviewed

  19. Partitioning of genomic variance using biological pathways

    DEFF Research Database (Denmark)

    Edwards, Stefan McKinnon; Janss, Luc; Madsen, Per

    and that these variants are enriched for genes that are connected in biological pathways or for likely functional effects on genes. These biological findings provide valuable insight for developing better genomic models. These are statistical models for predicting complex trait phenotypes on the basis of SNP......-data and trait phenotypes and can account for a much larger fraction of the heritable component. A disadvantage is that this “black-box” modelling approach conceals the biological mechanisms underlying the trait. We propose to open the “black-box” by building SNP-set genomic models that evaluate the collective...... action of multiple SNPs in genes, biological pathways or other external findings on the trait phenotype. As proof of concept we have tested the modelling framework on several traits in dairy cattle....

  20. Interactions between photodegradation components

    Directory of Open Access Journals (Sweden)

    Abdollahi Yadollah

    2012-09-01

    Full Text Available Abstract Background The interactions of p-cresol photocatalytic degradation components were studied by response surface methodology. The study was designed by central composite design using the irradiation time, pH, the amount of photocatalyst and the p-cresol concentration as variables. The design was performed to obtain photodegradation % as actual responses. The actual responses were fitted with linear, two factor interactions, cubic and quadratic model to select an appropriate model. The selected model was validated by analysis of variance which provided evidences such as high F-value (845.09, very low P-value (2 = 0.999, adjusted R-squared (Radj2 = 0.998, predicted R-squared (Rpred2 = 0.994 and the adequate precision (95.94. Results From the validated model demonstrated that the component had interaction with irradiation time under 180 min of the time while the interaction with pH was above pH 9. Moreover, photocatalyst and p-cresol had interaction at minimal amount of photocatalyst (p-cresol. Conclusion These variables are interdependent and should be simultaneously considered during the photodegradation process, which is one of the advantages of the response surface methodology over the traditional laboratory method.

  1. Prognostics for Microgrid Components

    Science.gov (United States)

    Saxena, Abhinav

    2012-01-01

    Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

  2. Aquatic pathway 1

    International Nuclear Information System (INIS)

    1976-01-01

    This first part of the study discusses problems of exposure due to the emission of radioactive substances into the environment via the water pathway. Discussion is started with a paper on the fundamentals of calculation and another paper on the results of preliminary radiological model calculations. The colloquium will assess the present state of knowledge, helps to find an agreement between divergent opinions and determine open questions and possible solutions. Ten main problems have been raised, most of which pertain to site conditions. They are trated as sub-investigations by individual participants or working groups. The findings will be discussed in further colloquia. (orig.) [de

  3. The Reactome pathway knowledgebase.

    Science.gov (United States)

    Croft, David; Mundo, Antonio Fabregat; Haw, Robin; Milacic, Marija; Weiser, Joel; Wu, Guanming; Caudy, Michael; Garapati, Phani; Gillespie, Marc; Kamdar, Maulik R; Jassal, Bijay; Jupe, Steven; Matthews, Lisa; May, Bruce; Palatnik, Stanislav; Rothfels, Karen; Shamovsky, Veronica; Song, Heeyeon; Williams, Mark; Birney, Ewan; Hermjakob, Henning; Stein, Lincoln; D'Eustachio, Peter

    2014-01-01

    Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions. The current version 46 describes 7088 human proteins (34% of the predicted human proteome), participating in 6744 reactions based on data extracted from 15 107 research publications with PubMed links. The Reactome Web site and analysis tool set have been completely redesigned to increase speed, flexibility and user friendliness. The data model has been extended to support annotation of disease processes due to infectious agents and to mutation.

  4. Cultural pathways through universal development.

    Science.gov (United States)

    Greenfield, Patricia M; Keller, Heidi; Fuligni, Andrew; Maynard, Ashley

    2003-01-01

    We focus our review on three universal tasks of human development: relationship formation, knowledge acquisition, and the balance between autonomy and relatedness at adolescence. We present evidence that each task can be addressed through two deeply different cultural pathways through development: the pathways of independence and interdependence. Whereas core theories in developmental psychology are universalistic in their intentions, they in fact presuppose the independent pathway of development. Because the independent pathway is therefore well-known in psychology, we focus a large part of our review on empirically documenting the alternative, interdependent pathway for each developmental task. We also present three theoretical approaches to culture and development: the ecocultural, the sociohistorical, and the cultural values approach. We argue that an understanding of cultural pathways through human development requires all three approaches. We review evidence linking values (cultural values approach), ecological conditions (ecocultural approach), and socialization practices (sociohistorical approach) to cultural pathways through universal developmental tasks.

  5. Food Components and Supplements

    DEFF Research Database (Denmark)

    Parlesak, Alexandr

    2012-01-01

    The major part of food consists of chemical compounds that can be used for energy production, biological synthesis, or maintenance of metabolic processes by the host. These components are defined as nutrients, and can be categorized into macronutrients (proteins, carbohydrates, triglycerides......, and alcohol), minerals, and micronutrients. The latter category comprises 13 vitamins and a hand full of trace elements. Many micronutrients are used as food supplements and are ingested at doses exceeding the amounts that can be consumed along with food by a factor of 10–100. Both macro- and micronutrients...... can interact with enzyme systems related to xenobiotic metabolism either by regulation of their expression or direct interference with their enzymatic activity. During food consumption, we consume a wide range of xenobiotics along with the consumable food, either as an original part of the food (e...

  6. Sprayed skin turbine component

    Science.gov (United States)

    Allen, David B

    2013-06-04

    Fabricating a turbine component (50) by casting a core structure (30), forming an array of pits (24) in an outer surface (32) of the core structure, depositing a transient liquid phase (TLP) material (40) on the outer surface of the core structure, the TLP containing a melting-point depressant, depositing a skin (42) on the outer surface of the core structure over the TLP material, and heating the assembly, thus forming both a diffusion bond and a mechanical interlock between the skin and the core structure. The heating diffuses the melting-point depressant away from the interface. Subsurface cooling channels (35) may be formed by forming grooves (34) in the outer surface of the core structure, filling the grooves with a fugitive filler (36), depositing and bonding the skin (42), then removing the fugitive material.

  7. Food Components and Supplements

    DEFF Research Database (Denmark)

    Parlesak, Alexandr

    2012-01-01

    acting as carcinogens) to health-protective effects (e.g., flavonoids ameliorating detrimental effects of mitochondrial oxidative stress). In particular, secondary plant metabolites along with vitamins, specific types of macronutrients and live bacteria (probiotics) as well as substances promoting.......g., secondary plant metabolites such as flavonoids), or as contaminants that enter the food chain at different stages or during the food production process. For these components, a wide spectrum of biological effects was observed that ranges from health-threatening impacts (e.g., polycyclic aromatic amines....... The supplements and contaminants can compete directly with drug oxidation, induce or suppress the expression of xenobiotic-metabolizing enzymes, change the bioavailability of drugs, and, in the case of live bacteria, bring in their own xenobiotic metabolism, including cytochrome P450 (CYP) activity. In numerous...

  8. Component failure data handbook

    International Nuclear Information System (INIS)

    Gentillon, C.D.

    1991-04-01

    This report presents generic component failure rates that are used in reliability and risk studies of commercial nuclear power plants. The rates are computed using plant-specific data from published probabilistic risk assessments supplemented by selected other sources. Each data source is described. For rates with four or more separate estimates among the sources, plots show the data that are combined. The method for combining data from different sources is presented. The resulting aggregated rates are listed with upper bounds that reflect the variability observed in each rate across the nuclear power plant industry. Thus, the rates are generic. Both per hour and per demand rates are included. They may be used for screening in risk assessments or for forming distributions to be updated with plant-specific data

  9. High thermal load component

    International Nuclear Information System (INIS)

    Fuse, Toshiaki; Tachikawa, Nobuo.

    1996-01-01

    A cooling tube made of a pure copper is connected to the inner portion of an armour (heat resistant member) made of an anisotropic carbon/carbon composite (CFC) material. The CFC material has a high heat conductivity in longitudinal direction of fibers and has low conductivity in perpendicular thereto. Fibers extending in the armour from a heat receiving surface just above the cooling tube are directly connected to the cooling tube. A portion of the fibers extending from a heat receiving surface other than portions not just above the cooling tube is directly bonded to the cooling tube. Remaining fibers are disposed so as to surround the cooling tube. The armour and the cooling tube are soldered using an active metal flux. With such procedures, high thermal load components for use in a thermonuclear reactor are formed, which are excellent in a heat removing characteristic and hardly causes defects such as crackings and peeling. (I.N.)

  10. Impedance and component heating

    CERN Document Server

    Métral, E; Mounet, N; Pieloni, T; Salvant, B

    2015-01-01

    The impedance is a complex function of frequency, which represents, for the plane under consideration (longitudinal, horizontal or vertical), the force integrated over the length of an element, from a “source” to a “test” wave, normalized by their charges. In general, the impedance in a given plane is a nonlinear function of the test and source transverse coordinates, but it is most of the time sufficient to consider only the first few linear terms. Impedances can influence the motion of trailing particles, in the longitudinal and in one or both transverse directions, leading to energy loss, beam instabilities, or producing undesirable secondary effects such as excessive heating of sensitive components at or near the chamber wall, called beam-induced RF heating. The LHC performance limitations linked to impedances encountered during the 2010-2012 run are reviewed and the currently expected situation during the HL-LHC era is discussed.

  11. Columbia River pathway report

    International Nuclear Information System (INIS)

    1991-07-01

    This report summarizes the river-pathway portion of the first phase of the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project is estimating radiation doses that could have been received by the public from the Department of Energy's Hanford Site, in southeastern Washington State. Phase 1 of the river-pathway dose reconstruction effort sought to determine whether dose estimates could be calculated for populations in the area from above the Hanford Site at Priest Rapids Dam to below the site at McNary Dam from January 1964 to December 1966. Of the potential sources of radionuclides from the river, fish consumption was the most important. Doses from drinking water were lower at Pasco than at Richland and lower at Kennewick than at Pasco. The median values of preliminary dose estimates calculated by HEDR are similar to independent, previously published estimates of average doses to Richland residents. Later phases of the HEDR Project will address dose estimates for periods other than 1964--1966 and for populations downstream of McNary Dam. 17 refs., 19 figs., 1 tab

  12. Mapping Nursing Pathways

    Directory of Open Access Journals (Sweden)

    Melanie Birks

    2015-09-01

    Full Text Available Articulated education pathways between the vocational education training sector and universities provide opportunities for students wishing to progress to higher qualifications. Enrolled nurses seeking to advance their career in nursing can choose to enter baccalaureate degree programs through such alternative entry routes. Awarding of credit for prior studies is dependent on accurate assessment of the existing qualification against that which is sought. This study employed a modified Delphi method to inform the development of an evidence-based, structured approach to mapping the pathway from the nationally consistent training package of the Diploma of Nursing to the diversity of baccalaureate nursing programs across Australia. The findings of this study reflect the practical nature of the role of the enrolled nurse, particularly the greater emphasis placed on direct care activities as opposed to those related to professional development and the generation and use of evidence. These findings provide a valuable summative overview of the relationship between the Diploma of Nursing and the expectations of the registered nurse role.

  13. The exploration of contrasting pathways in Triple Negative Breast Cancer (TNBC).

    Science.gov (United States)

    Narrandes, Shavira; Huang, Shujun; Murphy, Leigh; Xu, Wayne

    2018-01-04

    Triple Negative Breast Cancers (TNBCs) lack the appropriate targets for currently used breast cancer therapies, conferring an aggressive phenotype, more frequent relapse and poorer survival rates. The biological heterogeneity of TNBC complicates the clinical treatment further. We have explored and compared the biological pathways in TNBC and other subtypes of breast cancers, using an in silico approach and the hypothesis that two opposing effects (Yin and Yang) pathways in cancer cells determine the fate of cancer cells. Identifying breast subgroup specific components of these opposing pathways may aid in selecting potential therapeutic targets as well as further classifying the heterogeneous TNBC subtype. Gene expression and patient clinical data from The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used for this study. Gene Set Enrichment Analysis (GSEA) was used to identify the more active pathways in cancer (Yin) than in normal and the more active pathways in normal (Yang) than in cancer. The clustering analysis was performed to compare pathways of TNBC with other types of breast cancers. The association of pathway classified TNBC sub-groups to clinical outcomes was tested using Cox regression model. Among 4729 curated canonical pathways in GSEA database, 133 Yin pathways (FDR pathways (p-value pathway while PPARα is the top Yang pathway in TNBC. The TNBC and other types of breast cancers showed different pathways enrichment significance profiles. Using top Yin and Yang pathways as classifier, the TNBC can be further subtyped into six sub-groups each having different clinical outcomes. We first reported that the FOMX1 pathway is the most upregulated and the PPARα pathway is the most downregulated pathway in TNBC. These two pathways could be simultaneously targeted in further studies. Also the pathway classifier we performed in this study provided insight into the TNBC heterogeneity.

  14. Serpentinization reaction pathways: implications for modeling approach

    Energy Technology Data Exchange (ETDEWEB)

    Janecky, D.R.

    1986-01-01

    Experimental seawater-peridotite reaction pathways to form serpentinites at 300/sup 0/C, 500 bars, can be accurately modeled using the EQ3/6 codes in conjunction with thermodynamic and kinetic data from the literature and unpublished compilations. These models provide both confirmation of experimental interpretations and more detailed insight into hydrothermal reaction processes within the oceanic crust. The accuracy of these models depends on careful evaluation of the aqueous speciation model, use of mineral compositions that closely reproduce compositions in the experiments, and definition of realistic reactive components in terms of composition, thermodynamic data, and reaction rates.

  15. The photovoltaic pathway

    International Nuclear Information System (INIS)

    Jourde, P.; Guerin de Montgareuil, A.; Mattera, F.; Jaussaud, C.; Boulanger, P.; Veriat, G.; Firon, M.

    2004-01-01

    Photovoltaic conversion, the direct transformation of light into electricity, is, of the three pathways for solar energy, the one experiencing most rapid growth, and for which scientific and technological advances are most promising, as regards significant improvements in its economic balance. While the long-term trend, in Europe, is favorable, with annual growth set at 30%, the cost per photovoltaic kilowatt-hour remains some ten times higher than that achieved with natural gas or nuclear energy (after connection to the grid), this being a handicap, at first blush, for high power ratings. For remote locations, where its advantage is unquestionable, in spite of the added cost of storage between insolation periods (this more than compensating for savings in terms of connection costs), this pathway sets its future prospects on marked module cost reductions. Such reduction may only be achieved by way of technological breakthroughs, to which CEA, active as it has been, in this area, for some thirty years, intends making a contribution, as linchpin of French research and technology, and a key protagonist on the European scene. One of the avenues being pursued concerns fabrication of high-efficiency cells from mineral or organic thin films, with particularly strong expectations with respect to the all-polymer path, complementary of the silicon pathway. Concurrently, device reliability needs must be improved, this being another factor making for an improved overall balance. To achieve easier transfer to industry of laboratory outcomes, CEA is relying, in particular, on the new cell fabrication platform set up in Grenoble, this complementing its other R and D resources, including those installed at Cadarache, allowing testing of cells and entire photovoltaic systems in actual operating conditions. Another path for cost reductions being explored by CEA research workers consists in construction of systems integrated into the built environment: this affords new prospects

  16. Initial Ada components evaluation

    Science.gov (United States)

    Moebes, Travis

    1989-01-01

    The SAIC has the responsibility for independent test and validation of the SSE. They have been using a mathematical functions library package implemented in Ada to test the SSE IV and V process. The library package consists of elementary mathematical functions and is both machine and accuracy independent. The SSE Ada components evaluation includes code complexity metrics based on Halstead's software science metrics and McCabe's measure of cyclomatic complexity. Halstead's metrics are based on the number of operators and operands on a logical unit of code and are compiled from the number of distinct operators, distinct operands, and total number of occurrences of operators and operands. These metrics give an indication of the physical size of a program in terms of operators and operands and are used diagnostically to point to potential problems. McCabe's Cyclomatic Complexity Metrics (CCM) are compiled from flow charts transformed to equivalent directed graphs. The CCM is a measure of the total number of linearly independent paths through the code's control structure. These metrics were computed for the Ada mathematical functions library using Software Automated Verification and Validation (SAVVAS), the SSE IV and V tool. A table with selected results was shown, indicating that most of these routines are of good quality. Thresholds for the Halstead measures indicate poor quality if the length metric exceeds 260 or difficulty is greater than 190. The McCabe CCM indicated a high quality of software products.

  17. Radiation damage in components

    International Nuclear Information System (INIS)

    Takano, Tomehachi

    1977-01-01

    The performance change of typical capacitors and resistors in electronic components by Co-60 γ-irradiation from the 1320 Ci source was examined in the range of 10 5 to 10 8 R. Specifically, the characteristic change during irradiation and the recovery after irradiation were continuously observed. The capacity change is +2.4% at maximum in ceramic and metallized paper capacitors, and -2.4% at maximum in mylar and paper capacitors. It is also +-0.4% at maximum in mica and polystyrene capacitors. Some of these capacitors showed the recovery of the capacity change, but the others did not. Dielectric loss varied by 15% at larger dose in some capacitors, and the recovery was not observed. While, the insulation resistance of the resistors of 10 15 Ω or more lowered to 10 13 Ω or less after 10 to 30 sec. irradiation, but recovered soon nearly to the initial values after irradiation was interrupted. The resistance change of carbon film resistors is about 0.2 to 2%, and recovered to the initial values in 100 hours after irradiation. The resistance change of composition resistors is large over the range of -13 to +35%, besides, no sign of recovery was seen. In carbon film resistors, the surface insulated type indicated far better results which are assumed to be caused by the selection of element materials and the forming of coating materials. (Wakatsuki, Y.)

  18. Summer 2014 Pathways Report

    Science.gov (United States)

    Hand, Zachary

    2014-01-01

    Over the summer I had the exciting opportunity to work for NASA at the Kennedy Space Center as a Mission Assurance Engineering intern. When I was offered a position in mission assurance for the Safety and Mission Assurance directorate's Launch Services Division, I didn't really know what I would be doing, but I knew it would be an excellent opportunity to learn and grow professionally. In this report I will provide some background information on the Launch Services Division, as well as detail my duties and accomplishments during my time as an intern. Additionally, I will relate the significance of my work experience to my current academic work and future career goals. This report contains background information on Mission Assurance Engineering, a description of my duties and accomplishments over the summer of 2014, and relates the significance of my work experience to my school work and future career goals. It is a required document for the Pathways program.

  19. Exposures from aquatic pathways

    International Nuclear Information System (INIS)

    Berkovski, V.; Voitsekhovitch, O.; Nasvit, O.; Zhelezniak, M.; Sansone, U.

    1996-01-01

    Methods for estimation aquatic pathways contribution to the total population exposure are discussed. Aquatic pathways are the major factor for radionuclides spreading from the Chernobyl Exclusion zone. An annual outflow of 90 Sr and 137 Cs comprised 10-20 TBq and 2-4 TBq respectively and the population exposed by this effluence constitutes almost 30 million people. The dynamic of doses from 90 Sr and ' C s, which Dnieper water have to delivered, is calculated. The special software has been developed to simulate the process of dose formation in the of diverse Dnieper regions. Regional peculiarities of municipal tap, fishing and irrigation are considered. Seventy-year prediction of dose structure and function of dose forming is performed. The exposure is estimated for 12 regions of the Dnieper basin and the Crimea. The maximal individual annual committed effective doses due to the use of water by ordinary members of the population in Kiev region from 90 Sr and 137 Cs in 1986 are 1.7*10 -5 Sv and 2.7*10 -5 Sv respectively. A commercial fisherman on Kiev reservoir in 1986 received 4.7*10 -4 Sv and 5*10 -3 Sv from 90 Sr and 137 Cs, respectively. The contributions to the collective cumulative (over 70 years) committed effective dose (CCCED 70 ) of irrigation, municipal tap water and fish consumption for members of the population respectively are 18%, 43%, 39% in Kiev region, 8%, 25%, 67% in Poltava region, and 50%, 50%, 0% (consumption of Dnieper fish is absent) in the Crimea. The predicted contribution of the Strontium-90 to CCCED 70 resulting from the use of water is 80%. The CCCED 70 to the population of the Dnieper regions (32.5 million people) is 3000 person-Sv due to the use the Dnieper water

  20. Multi-step non-covalent pathways to supramolecular systems

    NARCIS (Netherlands)

    Hermans, T.M.

    2010-01-01

    The spontaneous organization of building blocks into ordered structures governed by non-covalent interactions, or self-assembly, is a commonly encountered pathway in nature to obtain functional materials. These materials often consist of many different components ordered into intricate structures.

  1. Component-based development process and component lifecycle

    NARCIS (Netherlands)

    Crnkovic, I.; Chaudron, M.R.V.; Larsson, S.

    2006-01-01

    The process of component- and component-based system development differs in many significant ways from the "classical" development process of software systems. The main difference is in the separation of the development process of components from the development process of systems. This fact has a

  2. GOATS - Orbitology Component

    Science.gov (United States)

    Haber, Benjamin M.; Green, Joseph J.

    2010-01-01

    The GOATS Orbitology Component software was developed to specifically address the concerns presented by orbit analysis tools that are often written as stand-alone applications. These applications do not easily interface with standard JPL first-principles analysis tools, and have a steep learning curve due to their complicated nature. This toolset is written as a series of MATLAB functions, allowing seamless integration into existing JPL optical systems engineering modeling and analysis modules. The functions are completely open, and allow for advanced users to delve into and modify the underlying physics being modeled. Additionally, this software module fills an analysis gap, allowing for quick, high-level mission analysis trades without the need for detailed and complicated orbit analysis using commercial stand-alone tools. This software consists of a series of MATLAB functions to provide for geometric orbit-related analysis. This includes propagation of orbits to varying levels of generalization. In the simplest case, geosynchronous orbits can be modeled by specifying a subset of three orbit elements. The next case is a circular orbit, which can be specified by a subset of four orbit elements. The most general case is an arbitrary elliptical orbit specified by all six orbit elements. These orbits are all solved geometrically, under the basic problem of an object in circular (or elliptical) orbit around a rotating spheroid. The orbit functions output time series ground tracks, which serve as the basis for more detailed orbit analysis. This software module also includes functions to track the positions of the Sun, Moon, and arbitrary celestial bodies specified by right ascension and declination. Also included are functions to calculate line-of-sight geometries to ground-based targets, angular rotations and decompositions, and other line-of-site calculations. The toolset allows for the rapid execution of orbit trade studies at the level of detail required for the

  3. Precise generation of systems biology models from KEGG pathways.

    Science.gov (United States)

    Wrzodek, Clemens; Büchel, Finja; Ruff, Manuel; Dräger, Andreas; Zell, Andreas

    2013-02-21

    The KEGG PATHWAY database provides a plethora of pathways for a diversity of organisms. All pathway components are directly linked to other KEGG databases, such as KEGG COMPOUND or KEGG REACTION. Therefore, the pathways can be extended with an enormous amount of information and provide a foundation for initial structural modeling approaches. As a drawback, KGML-formatted KEGG pathways are primarily designed for visualization purposes and often omit important details for the sake of a clear arrangement of its entries. Thus, a direct conversion into systems biology models would produce incomplete and erroneous models. Here, we present a precise method for processing and converting KEGG pathways into initial metabolic and signaling models encoded in the standardized community pathway formats SBML (Levels 2 and 3) and BioPAX (Levels 2 and 3). This method involves correcting invalid or incomplete KGML content, creating complete and valid stoichiometric reactions, translating relations to signaling models and augmenting the pathway content with various information, such as cross-references to Entrez Gene, OMIM, UniProt ChEBI, and many more.Finally, we compare several existing conversion tools for KEGG pathways and show that the conversion from KEGG to BioPAX does not involve a loss of information, whilst lossless translations to SBML can only be performed using SBML Level 3, including its recently proposed qualitative models and groups extension packages. Building correct BioPAX and SBML signaling models from the KEGG database is a unique characteristic of the proposed method. Further, there is no other approach that is able to appropriately construct metabolic models from KEGG pathways, including correct reactions with stoichiometry. The resulting initial models, which contain valid and comprehensive SBML or BioPAX code and a multitude of cross-references, lay the foundation to facilitate further modeling steps.

  4. Pathways to Healing: Person-centered Responses to Complementary Services

    Science.gov (United States)

    Bertrand, Sharon W.; Fermon, Barbara; Coleman, Julie Foley

    2014-01-01

    Objectives: This research study assessed perceived changes in quality-of-life measures related to participation in complementary services consisting of a variety of nontraditional therapies and/or programs at Pathways: A Health Crisis Resource Center in Minneapolis, Minnesota. Design: Survey data were used to assess perceived changes participants ascribed to their experience with complementary services at Pathways. Quantitative data analysis was conducted using participant demographics together with participant ratings of items from the “Self-Assessment of Change” (SAC) measure developed at the University of Arizona, Tucson. Qualitative data analysis was conducted on written responses to an additional survey question: “To what extent has your participation at Pathways influenced your healing process?” Setting/Location: Pathways offers a variety of services, including one-to-one sessions using nontraditional healing therapies, support groups, educational classes, and practice groups such as yoga and meditation for those facing serious health challenges. These services are offered free of charge through community financial support using volunteer practitioners. Participants: People (126) diagnosed with serious health challenges who used Pathways services from 2007 through 2009. Interventions: Participation in self-selected Pathways services. Measures: Responses to items on the SAC measure plus written responses to the question, “To what extent has your participation at Pathways influenced your healing process?” Results: Quantitative findings: Participants reported experiencing significant changes across all components of the SAC measure. Qualitative findings: Responses to the open-ended survey question identified perspectives on the culture of Pathways and a shift in participants' perceptions of well-being based on their experience of Pathways services. Conclusions: Participation in services provided by the Pathways organization improved perceptions of

  5. Wnt pathway in Dupuytren disease: connecting profibrotic signals.

    Science.gov (United States)

    van Beuge, Marike M; Ten Dam, Evert-Jan P M; Werker, Paul M N; Bank, Ruud A

    2015-12-01

    A role of Wnt signaling in Dupuytren disease, a fibroproliferative disease of the hand and fingers, has not been fully elucidated. We examined a large set of Wnt pathway components and signaling targets and found significant dysregulation of 41 Wnt-related genes in tissue from the Dupuytren nodules compared with patient-matched control tissue. A large proportion of genes coding for Wnt proteins themselves was downregulated. However, both canonical Wnt targets and components of the noncanonical signaling pathway were upregulated. Immunohistochemical analysis revealed that protein expression of Wnt1-inducible secreted protein 1 (WISP1), a known Wnt target, was increased in nodules compared with control tissue, but knockdown of WISP1 using small interfering RNA (siRNA) in the Dupuytren myofibroblasts did not confirm a functional role. The protein expression of noncanonical pathway components Wnt5A and VANGL2 as well as noncanonical coreceptors Ror2 and Ryk was increased in nodules. On the contrary, the strongest downregulated genes in this study were 4 antagonists of Wnt signaling (DKK1, FRZB, SFRP1, and WIF1). Downregulation of these genes in the Dupuytren tissue was mimicked in vitro by treating normal fibroblasts with transforming growth factor β1 (TGF-β1), suggesting cross talk between different profibrotic pathways. Furthermore, siRNA-mediated knockdown of these antagonists in normal fibroblasts led to increased nuclear translocation of Wnt target β-catenin in response to TGF-β1 treatment. In conclusion, we have shown extensive dysregulation of Wnt signaling in affected tissue from Dupuytren disease patients. Components of both the canonical and the noncanonical pathways are upregulated, whereas endogenous antagonists are downregulated, possibly via interaction with other profibrotic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. The NEDD8 modification pathway in plants

    Directory of Open Access Journals (Sweden)

    Claus eSchwechheimer

    2014-03-01

    Full Text Available NEDD8, in plants and yeasts also known as RELATED TO UBIQUITIN (RUB, is an evolutionarily conserved 76 amino acid protein highly related to ubiquitin. Like ubiquitin, NEDD8 can be conjugated to and deconjugated from target proteins, but unlike ubiquitin, NEDD8 has not been reported to form chains similar to the different polymeric ubiquitin chains that have a role in a diverse set of cellular processes. NEDD8-modification is best known as a posttranslational modification of the cullin subunits of cullin-RING E3 ubiquitin ligases. In this context, structural analyses have revealed that neddylation induces a conformation change of the cullin that brings the ubiquitylation substrates into proximity of the interacting E2 conjugating enzyme. In turn, NEDD8 deconjugation destabilizes the cullin RING ligase complex allowing for the exchange of substrate recognition subunits via the exchange factor CAND1. In plants, components of the neddylation and deneddylation pathway were identified based on mutants with defects in auxin and light responses and the characterization of these mutants has been instrumental for the elucidation of the neddylation pathway. More recently, there has been evidence from animal and plant systems that NEDD8 conjugation may also regulate the behavior or fate of non-cullin substrates in a number of ways. Here, the current knowledge on NEDD8 processing, conjugation and deconjugation is presented, where applicable, in the context of specific signaling pathways from plants.

  7. What is a clinical pathway? Refinement of an operational definition to identify clinical pathway studies for a Cochrane systematic review

    NARCIS (Netherlands)

    A.K. Lawal (Adegboyega K.); T. Rotter (Thomas); L. Kinsman (Leigh); A. Machotta (Andreas); U. Ronellenfitsch (Ulrich); S.D. Scott (Shannon D.); D. Goodridge (Donna); C. Plishka (Christopher); G. Groot (Gary)

    2016-01-01

    textabstractClinical pathways (CPWs) are a common component in the quest to improve the quality of health. CPWs are used to reduce variation, improve quality of care, and maximize the outcomes for specific groups of patients. An ongoing challenge is the operationalization of a definition of CPW in

  8. Towards Prognostics for Electronics Components

    Data.gov (United States)

    National Aeronautics and Space Administration — Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is...

  9. Independent component analysis: recent advances

    OpenAIRE

    Hyv?rinen, Aapo

    2013-01-01

    Independent component analysis is a probabilistic method for learning a linear transform of a random vector. The goal is to find components that are maximally independent and non-Gaussian (non-normal). Its fundamental difference to classical multi-variate statistical methods is in the assumption of non-Gaussianity, which enables the identification of original, underlying components, in contrast to classical methods. The basic theory of independent component analysis was mainly developed in th...

  10. Statistics of Shared Components in Complex Component Systems

    Science.gov (United States)

    Mazzolini, Andrea; Gherardi, Marco; Caselle, Michele; Cosentino Lagomarsino, Marco; Osella, Matteo

    2018-04-01

    Many complex systems are modular. Such systems can be represented as "component systems," i.e., sets of elementary components, such as LEGO bricks in LEGO sets. The bricks found in a LEGO set reflect a target architecture, which can be built following a set-specific list of instructions. In other component systems, instead, the underlying functional design and constraints are not obvious a priori, and their detection is often a challenge of both scientific and practical importance, requiring a clear understanding of component statistics. Importantly, some quantitative invariants appear to be common to many component systems, most notably a common broad distribution of component abundances, which often resembles the well-known Zipf's law. Such "laws" affect in a general and nontrivial way the component statistics, potentially hindering the identification of system-specific functional constraints or generative processes. Here, we specifically focus on the statistics of shared components, i.e., the distribution of the number of components shared by different system realizations, such as the common bricks found in different LEGO sets. To account for the effects of component heterogeneity, we consider a simple null model, which builds system realizations by random draws from a universe of possible components. Under general assumptions on abundance heterogeneity, we provide analytical estimates of component occurrence, which quantify exhaustively the statistics of shared components. Surprisingly, this simple null model can positively explain important features of empirical component-occurrence distributions obtained from large-scale data on bacterial genomes, LEGO sets, and book chapters. Specific architectural features and functional constraints can be detected from occurrence patterns as deviations from these null predictions, as we show for the illustrative case of the "core" genome in bacteria.

  11. Statistics of Shared Components in Complex Component Systems

    Directory of Open Access Journals (Sweden)

    Andrea Mazzolini

    2018-04-01

    Full Text Available Many complex systems are modular. Such systems can be represented as “component systems,” i.e., sets of elementary components, such as LEGO bricks in LEGO sets. The bricks found in a LEGO set reflect a target architecture, which can be built following a set-specific list of instructions. In other component systems, instead, the underlying functional design and constraints are not obvious a priori, and their detection is often a challenge of both scientific and practical importance, requiring a clear understanding of component statistics. Importantly, some quantitative invariants appear to be common to many component systems, most notably a common broad distribution of component abundances, which often resembles the well-known Zipf’s law. Such “laws” affect in a general and nontrivial way the component statistics, potentially hindering the identification of system-specific functional constraints or generative processes. Here, we specifically focus on the statistics of shared components, i.e., the distribution of the number of components shared by different system realizations, such as the common bricks found in different LEGO sets. To account for the effects of component heterogeneity, we consider a simple null model, which builds system realizations by random draws from a universe of possible components. Under general assumptions on abundance heterogeneity, we provide analytical estimates of component occurrence, which quantify exhaustively the statistics of shared components. Surprisingly, this simple null model can positively explain important features of empirical component-occurrence distributions obtained from large-scale data on bacterial genomes, LEGO sets, and book chapters. Specific architectural features and functional constraints can be detected from occurrence patterns as deviations from these null predictions, as we show for the illustrative case of the “core” genome in bacteria.

  12. Unblockable Compositions of Software Components

    DEFF Research Database (Denmark)

    Dong, Ruzhen; Faber, Johannes; Liu, Zhiming

    2012-01-01

    We present a new automata-based interface model describing the interaction behavior of software components. Contrary to earlier component- or interface-based approaches, the interface model we propose specifies all the non-blockable interaction behaviors of a component with any environment...... composition of interface models preserves unblockable sequences of provided services....

  13. Warm Water Pathways in the Northeastern North Atlantic ACCE RAFOS Float Data Report

    National Research Council Canada - National Science Library

    Furey, Heather

    2001-01-01

    ...). The RAFOS float component of ACCE, entitled "Warm Water Pathways and Intergyre Exchange in the Northeastern North Atlantic", was designed to measure the warm water currents entering the northeastern...

  14. Induction of cytoprotective pathways is central to the extension of lifespan conferred by multiple longevity pathways.

    Directory of Open Access Journals (Sweden)

    David E Shore

    Full Text Available Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 gene inactivations known to increase Caenorhabditis elegans longevity, including the mitochondrial UPR (hsp-6, hsp-60, the ER UPR (hsp-4, ROS response (sod-3, gst-4, and xenobiotic detoxification (gst-4. We then screened for other gene inactivations that disrupt the induction of these responses by xenobiotic or genetic triggers, identifying 29 gene inactivations required for cytoprotective gene expression. If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, caloric restriction, or the inhibition of mitochondrial function. We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension and identify a large set of new genetic components of the pathways that detect cellular damage and couple that detection to downstream cytoprotective effectors.

  15. Hydrogen fuel : well-to-pump pathways for 2050

    Energy Technology Data Exchange (ETDEWEB)

    Molburg, J. [Argonne National Lab., IL (United States); Mintz, M.; Folga, S.; Gillette, J.

    2002-07-01

    The authors discussed the topic of hydrogen fuels, and began the presentation by stating that the carbon intensity of world primary energy has been falling and hydrogen intensity has been rising. The declines in carbon can be explained by efficiency gains and fuel switches. There are several alternatives to gasoline fuel for vehicles, such as hydrogen, compressed natural gas, compressed natural gas/hydrogen. Emissions of greenhouse gases in the atmosphere represent a growing concern. The authors discussed four hydrogen pathways that have been modeled. They indicated that both natural gas pathways required additional natural gas transmission and storage. To better illustrate the hydrogen pathway, a conceptual representation of hydrogen pipeline loop supporting local hydrogen delivery was displayed. Some hydrogen distribution assumptions for centralized hydrogen production were examined. A cost modeling procedure was described, with the following topics: defining paths, determining tank-in fuel requirement, size pathway components, estimating component costs, and calculating pathway costs. The results indicated that the natural gas-based pathways were sensitive to feedstock cost, while coal and nuclear were not. Some of the conclusions that were arrived at were: (1) on a well-to-pump basis, with current technologies, the unit cost of hydrogen is expected to be 2 to 3 time that of gasoline, (2) the mpge of hydrogen-fueled vehicles must be more than double gasoline, and (3) hydrogen transport and production are the largest components of all pathways. For the future, the focus has to be on transition, including total and unit costs through study time frame, penetration of hydrogen blends, and niche markets. One must compare apples to apples, i e cost of infrastructure components over time, and learning curves. Pathways and scenarios must be re-examined, to include issues such as truck, rail marine market penetration; and hydrogen carrier pathways. Disruptive

  16. Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway

    DEFF Research Database (Denmark)

    Oka, Yasuyoshi; Bekker-Jensen, Simon; Mailand, Niels

    2015-01-01

    in promoting the function of the Fanconi anemia (FA) pathway for repair of DNA interstrand crosslinks (ICLs), mediated by a specific interaction with the central FA pathway component FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI protein stability, defective FANCI function...

  17. Pathways to man

    International Nuclear Information System (INIS)

    Harley, J.H.

    1980-01-01

    The study of radionuclide pathways leading to man generally has the goal of allowing us to predict human exposure from measurements of the radionuclide concentration in some segment of the environment. This modelling process provides a valuable tool in both the regulatory and health protection fields. However, most of the models in the regulatory field and in the health physics profession were designed to maximize exposure estimates. It is preferable to have scientifically defensible estimates and to add suitable safety factors at the end. Thus we are still faced with the development and validation of suitable models for many of the radionuclides of interest. The most useful models will include means of assessing variability and uncertainty. In this case variability might be considered as the differences in behavior due to age, sex or other factors in animals or man and those differences among plant species or animal species that determine their uptake factors. The uncertainty, on the other hand, would be the estimate of possible error in the experimental measurements. Model parameters would always have some variability even for site-specific cases and broad averages for population groups would have to include a factor expressing the possible variabilty and uncertainity. Thus any exposure calculation would have to be expressed with some range and valid assessments of this range are required

  18. PathNet: a tool for pathway analysis using topological information

    Directory of Open Access Journals (Sweden)

    Dutta Bhaskar

    2012-09-01

    Full Text Available Abstract Background Identification of canonical pathways through enrichment of differentially expressed genes in a given pathway is a widely used method for interpreting gene lists generated from high-throughput experimental studies. However, most algorithms treat pathways as sets of genes, disregarding any inter- and intra-pathway connectivity information, and do not provide insights beyond identifying lists of pathways. Results We developed an algorithm (PathNet that utilizes the connectivity information in canonical pathway descriptions to help identify study-relevant pathways and characterize non-obvious dependencies and connections among pathways using gene expression data. PathNet considers both the differential expression of genes and their pathway neighbors to strengthen the evidence that a pathway is implicated in the biological conditions characterizing the experiment. As an adjunct to this analysis, PathNet uses the connectivity of the differentially expressed genes among all pathways to score pathway contextual associations and statistically identify biological relations among pathways. In this study, we used PathNet to identify biologically relevant results in two Alzheimer’s disease microarray datasets, and compared its performance with existing methods. Importantly, PathNet identified de-regulation of the ubiquitin-mediated proteolysis pathway as an important component in Alzheimer’s disease progression, despite the absence of this pathway in the standard enrichment analyses. Conclusions PathNet is a novel method for identifying enrichment and association between canonical pathways in the context of gene expression data. It takes into account topological information present in pathways to reveal biological information. PathNet is available as an R workspace image from http://www.bhsai.org/downloads/pathnet/.

  19. Comparison of growth factor signalling pathway utilisation in cultured normal melanocytes and melanoma cell lines

    International Nuclear Information System (INIS)

    Kim, Ji Eun; Stones, Clare; Joseph, Wayne R; Leung, Euphemia; Finlay, Graeme J; Shelling, Andrew N; Phillips, Wayne A; Shepherd, Peter R; Baguley, Bruce C

    2012-01-01

    The phosphatidylinositol-3-kinase (PI3K-PKB), mitogen activated protein kinase (MEK-ERK) and the mammalian target of rapamycin (mTOR- p70S6K), are thought to regulate many aspects of tumour cell proliferation and survival. We have examined the utilisation of these three signalling pathways in a number of cell lines derived from patients with metastatic malignant melanoma of known PIK3CA, PTEN, NRAS and BRAF mutational status. Western blotting was used to compare the phosphorylation status of components of the PI3K-PKB, MEK-ERK and mTOR-p70S6K signalling pathways, as indices of pathway utilisation. Normal melanocytes could not be distinguished from melanoma cells on the basis of pathway utilisation when grown in the presence of serum, but could be distinguished upon serum starvation, where signalling protein phosphorylation was generally abrogated. Surprisingly, the differential utilisation of individual pathways was not consistently associated with the presence of an oncogenic or tumour suppressor mutation of genes in these pathways. Utilisation of the PI3K-PKB, MEK-ERK and mTOR-p70S6K signalling pathways in melanoma, as determined by phosphorylation of signalling components, varies widely across a series of cell lines, and does not directly reflect mutation of genes coding these components. The main difference between cultured normal melanocytes and melanoma cells is not the pathway utilisation itself, but rather in the serum dependence of pathway utilisation

  20. Novel metabolic pathways in Archaea.

    Science.gov (United States)

    Sato, Takaaki; Atomi, Haruyuki

    2011-06-01

    The Archaea harbor many metabolic pathways that differ to previously recognized classical pathways. Glycolysis is carried out by modified versions of the Embden-Meyerhof and Entner-Doudoroff pathways. Thermophilic archaea have recently been found to harbor a bi-functional fructose-1,6-bisphosphate aldolase/phosphatase for gluconeogenesis. A number of novel pentose-degrading pathways have also been recently identified. In terms of anabolic metabolism, a pathway for acetate assimilation, the methylaspartate cycle, and two CO2-fixing pathways, the 3-hydroxypropionate/4-hydroxybutyrate cycle and the dicarboxylate/4-hydroxybutyrate cycle, have been elucidated. As for biosynthetic pathways, recent studies have clarified the enzymes responsible for several steps involved in the biosynthesis of inositol phospholipids, polyamine, coenzyme A, flavin adeninedinucleotide and heme. By examining the presence/absence of homologs of these enzymes on genome sequences, we have found that the majority of these enzymes and pathways are specific to the Archaea. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Component Reification in Systems Modelling

    DEFF Research Database (Denmark)

    Bendisposto, Jens; Hallerstede, Stefan

    When modelling concurrent or distributed systems in Event-B, we often obtain models where the structure of the connected components is specified by constants. Their behaviour is specified by the non-deterministic choice of event parameters for events that operate on shared variables. From a certain......? These components may still refer to shared variables. Events of these components should not refer to the constants specifying the structure. The non-deterministic choice between these components should not be via parameters. We say the components are reified. We need to address how the reified components get...... reflected into the original model. This reflection should indicate the constraints on how to connect the components....

  2. Component Composition Using Feature Models

    DEFF Research Database (Denmark)

    Eichberg, Michael; Klose, Karl; Mitschke, Ralf

    2010-01-01

    interface description languages. If this variability is relevant when selecting a matching component then human interaction is required to decide which components can be bound. We propose to use feature models for making this variability explicit and (re-)enabling automatic component binding. In our...... approach, feature models are one part of service specifications. This enables to declaratively specify which service variant is provided by a component. By referring to a service's variation points, a component that requires a specific service can list the requirements on the desired variant. Using...... these specifications, a component environment can then determine if a binding of the components exists that satisfies all requirements. The prototypical environment Columbus demonstrates the feasibility of the approach....

  3. The resistance of the yeast Saccharomyces cerevisiae to the biocide polyhexamethylene biguanide: involvement of cell wall integrity pathway and emerging role for YAP1

    Directory of Open Access Journals (Sweden)

    de Morais Marcos A

    2011-08-01

    Full Text Available Abstract Background Polyhexamethylene biguanide (PHMB is an antiseptic polymer that is mainly used for cleaning hospitals and pools and combating Acantamoeba infection. Its fungicide activity was recently shown by its lethal effect on yeasts that contaminate the industrial ethanol process, and on the PE-2 strain of Saccharomyces cerevisiae, one of the main fermenting yeasts in Brazil. This pointed to the need to know the molecular mechanism that lay behind the cell resistance to this compound. In this study, we examined the factors involved in PHMB-cell interaction and the mechanisms that respond to the damage caused by this interaction. To achieve this, two research strategies were employed: the expression of some genes by RT-qPCR and the analysis of mutant strains. Results Cell Wall integrity (CWI genes were induced in the PHMB-resistant Saccharomyces cerevisiae strain JP-1, although they are poorly expressed in the PHMB-sensitive Saccharomyces cerevisiae PE2 strain. This suggested that PHMB damages the glucan structure on the yeast cell wall. It was also confirmed by the observed sensitivity of the yeast deletion strains, Δslg1, Δrom2, Δmkk2, Δslt2, Δknr4, Δswi4 and Δswi4, which showed that the protein kinase C (PKC regulatory mechanism is involved in the response and resistance to PHMB. The sensitivity of the Δhog1 mutant was also observed. Furthermore, the cytotoxicity assay and gene expression analysis showed that the part played by YAP1 and CTT1 genes in cell resistance to PHMB is unrelated to oxidative stress response. Thus, we suggested that Yap1p can play a role in cell wall maintenance by controlling the expression of the CWI genes. Conclusion The PHMB treatment of the yeast cells activates the PKC1/Slt2 (CWI pathway. In addition, it is suggested that HOG1 and YAP1 can play a role in the regulation of CWI genes.

  4. KeyPathwayMinerWeb

    DEFF Research Database (Denmark)

    List, Markus; Alcaraz, Nicolas; Dissing-Hansen, Martin

    2016-01-01

    , for instance), KeyPathwayMiner extracts connected sub-networks containing a high number of active or differentially regulated genes (proteins, metabolites) in the molecular profiles. The web interface at (http://keypathwayminer.compbio.sdu.dk) implements all core functionalities of the KeyPathwayMiner tool set......We present KeyPathwayMinerWeb, the first online platform for de novo pathway enrichment analysis directly in the browser. Given a biological interaction network (e.g. protein-protein interactions) and a series of molecular profiles derived from one or multiple OMICS studies (gene expression...... such as data integration, input of background knowledge, batch runs for parameter optimization and visualization of extracted pathways. In addition to an intuitive web interface, we also implemented a RESTful API that now enables other online developers to integrate network enrichment as a web service...

  5. Pathways Intern Report

    Science.gov (United States)

    Bell, Evan A.

    2015-01-01

    During my time at NASA, I worked with the Granular Mechanics and Regolith Organization (GMRO), better known as Swamp Works. The goal of the lab is to find ways to utilize resources found after the astronaut or robot has landed on another planet or asteroid. This concept is known as in-situ resource utilization and it is critical to long term missions such as those to Mars. During my time here I worked on the Asteroid and Lava Tube Free Flyer project (ALTFF). A lava tube, such as the one shown in figure 1, is a long tear drop shaped cavern that is produced when molten lava tunnels through the surrounding rock creating large unground pathways. Before mining for resources on Mars or on asteroids, a sampling mission must be done to scout out useful resource deposits. ALTFF's goal is to provide a low cost, autonomous scout robot that can sample the surface and return to the mother ship or lander for further processing of the samples. The vehicle will be looking for water ice in the regolith that can be processed into either potable water, hydrogen and oxygen fuel, or a binder material for 3D printing. By using a low cost craft to sample, there is much less risk to the more expensive mother ship or lander. While my main task was the construction of a simulation environment to test control code in and the construction of the asteroid free flyer prototype, there were other tasks that I performed relating to the ALTFF project.

  6. pathways in myogenesis

    Directory of Open Access Journals (Sweden)

    Marta Milewska

    2014-05-01

    Full Text Available The commitment of myogenic cells in skeletal muscle differentiation requires earlier irreversible interruption of the cell cycle. At the molecular level, several key regulators of the cell cycle have been identified: cyclin-dependent kinases and their cyclins stimulate the cell cycle progress and its arrest is determined by the activity of cdk inhibitors (Cip/Kip and INK protein families and pocket protein family: Rb, p107 and p130. The biological activity of cyclin/cdk complexes allows the successive phases of the cell cycle to occur. Myoblast specialization, differentiation and fusion require the activity of myogenic regulatory factors, which include MyoD, myogenin, Myf5 and MRF4. MyoD and Myf5 play a role in muscle cell specialization, myogenin controls the differentiation process, whereas MRF4 is involved in myotube maturation. The deregulation of the cell cycle leads to uncontrolled proliferation, which antagonizes the functions of myogenic factors and it explains the lack of differentiation-specific gene expression in dividing cells. Conversely, the myogenic factor MyoD seems to cooperate with cell cycle inhibitors leading to inhibition of cell cycle progress and commitment to the differentiation process. The hypophosphorylated form of Rb and cdk inhibitors play an important role in permanent arrest of the cell cycle in differentiated myotubes. Furthermore, cyclin/cdk complexes not only regulate cell division by phosphorylation of several substrates, but may also control other cellular processes such as signal transduction, differentiation and apoptosis. Beyond regulating the cell cycle, Cip/Kip proteins play an important role in cell death, transcription regulation, cell fate determination, cell migration and cytoskeletal dynamics. The article summarizes current knowledge concerning the interactions of intracellular signaling pathways controlling crucial stages of fetal and regenerative myogenesis.

  7. Repression of germline RNAi pathways in somatic cells by retinoblastoma pathway chromatin complexes.

    Directory of Open Access Journals (Sweden)

    Xiaoyun Wu

    Full Text Available The retinoblastoma (Rb tumor suppressor acts with a number of chromatin cofactors in a wide range of species to suppress cell proliferation. The Caenorhabditis elegans retinoblastoma gene and many of these cofactors, called synMuv B genes, were identified in genetic screens for cell lineage defects caused by growth factor misexpression. Mutations in many synMuv B genes, including lin-35/Rb, also cause somatic misexpression of the germline RNA processing P granules and enhanced RNAi. We show here that multiple small RNA components, including a set of germline-specific Argonaute genes, are misexpressed in the soma of many synMuv B mutant animals, revealing one node for enhanced RNAi. Distinct classes of synMuv B mutants differ in the subcellular architecture of their misexpressed P granules, their profile of misexpressed small RNA and P granule genes, as well as their enhancement of RNAi and the related silencing of transgenes. These differences define three classes of synMuv B genes, representing three chromatin complexes: a LIN-35/Rb-containing DRM core complex, a SUMO-recruited Mec complex, and a synMuv B heterochromatin complex, suggesting that intersecting chromatin pathways regulate the repression of small RNA and P granule genes in the soma and the potency of RNAi. Consistent with this, the DRM complex and the synMuv B heterochromatin complex were genetically additive and displayed distinct antagonistic interactions with the MES-4 histone methyltransferase and the MRG-1 chromodomain protein, two germline chromatin regulators required for the synMuv phenotype and the somatic misexpression of P granule components. Thus intersecting synMuv B chromatin pathways conspire with synMuv B suppressor chromatin factors to regulate the expression of small RNA pathway genes, which enables heightened RNAi response. Regulation of small RNA pathway genes by human retinoblastoma may also underlie its role as a tumor suppressor gene.

  8. Characterization of the atmospheric pathway at hazardous waste sites

    International Nuclear Information System (INIS)

    Droppo, J.G. Jr.; Buck, J.W.

    1988-10-01

    Evaluation of potential health effects for populations surrounding hazardous waste sites requires consideration of all potential contaminant transport pathways through groundwater, surface water, and the atmosphere. A comprehensive pathway model that includes emission, dispersion, and deposition computations has been developed as a component of the Remedial Action Priority System (RAPS). RAPS is designed to assess the relative potential risks associated with hazardous and radioactive mixed-waste disposal sites. The atmospheric component includes optional volatilization and suspension emission routines. Atmospheric transport, dispersion, and deposition are computed using relatively standard modeling techniques expanded to incorporate topographical influences. This sector-averaged Gaussian model accounts for local channeling, terrain heights, and terrain roughness effects. Long-term total deposition is computed for the terrain surrounding the hazardous waste site. An example is given of applications at a US Department of Energy site, where atmospheric emissions are potentially important. The multiple applications of RAPS have provided information on the relative importance of different constitutent transport pathways from a potential population risk basis. Our results show that the atmospheric pathway is often equally as important as other pathways such as groundwater and direct soil ingestion. 6 refs., 3 figs., 4 tabs

  9. Two-Component Systems of Mycobacterium tuberculosis—Structure-Based Approaches

    DEFF Research Database (Denmark)

    Tucker, Paul; Nowak, Elzbieta; Morth, Jens Preben

    2007-01-01

    Mycobacterium tuberculosis contains few two‐component systems compared to many other bacteria, possibly because it has more serine/threonine signaling pathways. Even so, these two‐component systems appear to play an important role in early intracellular survival of the pathogen as well as in aspe...

  10. Protein design for pathway engineering.

    Science.gov (United States)

    Eriksen, Dawn T; Lian, Jiazhang; Zhao, Huimin

    2014-02-01

    Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Imprecise system reliability and component importance based on survival signature

    International Nuclear Information System (INIS)

    Feng, Geng; Patelli, Edoardo; Beer, Michael; Coolen, Frank P.A.

    2016-01-01

    The concept of the survival signature has recently attracted increasing attention for performing reliability analysis on systems with multiple types of components. It opens a new pathway for a structured approach with high computational efficiency based on a complete probabilistic description of the system. In practical applications, however, some of the parameters of the system might not be defined completely due to limited data, which implies the need to take imprecisions of component specifications into account. This paper presents a methodology to include explicitly the imprecision, which leads to upper and lower bounds of the survival function of the system. In addition, the approach introduces novel and efficient component importance measures. By implementing relative importance index of each component without or with imprecision, the most critical component in the system can be identified depending on the service time of the system. Simulation method based on survival signature is introduced to deal with imprecision within components, which is precise and efficient. Numerical example is presented to show the applicability of the approach for systems. - Highlights: • Survival signature is a novel way for system reliability and component importance • High computational efficiency based on a complete description of system. • Include explicitly the imprecision, which leads to bounds of the survival function. • A novel relative importance index is proposed as importance measure. • Allows to identify critical components depending on the service time of the system.

  12. SBA Network Components & Software Inventory

    Data.gov (United States)

    Small Business Administration — SBA’s Network Components & Software Inventory contains a complete inventory of all devices connected to SBA’s network including workstations, servers, routers,...

  13. IPAD: the Integrated Pathway Analysis Database for Systematic Enrichment Analysis.

    Science.gov (United States)

    Zhang, Fan; Drabier, Renee

    2012-01-01

    multiple available data sources.IPAD is a comprehensive database covering about 22,498 genes, 25,469 proteins, 1956 pathways, 6704 diseases, 5615 drugs, and 52 organs integrated from databases including the BioCarta, KEGG, NCI-Nature curated, Reactome, CTD, PharmGKB, DrugBank, PharmGKB, and HOMER. The database has a web-based user interface that allows users to perform enrichment analysis from genes/proteins/molecules and inter-association analysis from a pathway, disease, drug, and organ.Moreover, the quality of the database was validated with the context of the existing biological knowledge and a "gold standard" constructed from reputable and reliable sources. Two case studies were also presented to demonstrate: 1) self-validation of enrichment analysis and inter-association analysis on brain-specific markers, and 2) identification of previously undiscovered components by the enrichment analysis from a prostate cancer study. IPAD is a new resource for analyzing, identifying, and validating pathway, disease, drug, organ specificity and their inter-associations. The statistical method we developed for enrichment and similarity measurement and the two criteria we described for setting the threshold parameters can be extended to other enrichment applications. Enriched pathways, diseases, drugs, organs and their inter-associations can be searched, displayed, and downloaded from our online user interface. The current IPAD database can help users address a wide range of biological pathway related, disease susceptibility related, drug target related and organ specificity related questions in human disease studies.

  14. Retinoblastoma pathway defects show differential ability to activate the constitutive DNA damage response in human tumorigenesis

    DEFF Research Database (Denmark)

    Tort, F.; Bartkova, J.; Sehested, M.

    2006-01-01

    culture models with differential defects of retinoblastoma pathway components, as overexpression of cyclin D1 or lack of p16(Ink4a), either alone or combined, did not elicit detectable DDR. In contrast, inactivation of pRb, the key component of the pathway, activated the DDR in cultured human or mouse...... with their hierarchical positions along the retinoblastoma pathway. Our data provide new insights into oncogene-evoked DDR in human tumorigenesis, with potential implications for individualized management of tumors with elevated cyclin D1 versus cyclin E, due to their distinct clinical variables and biological behavior....

  15. WRKY Transcription Factors: Key Components in Abscisic Acid Signaling

    Science.gov (United States)

    2011-01-01

    networks that take inputs from numerous stimuli and that they are involved in mediating responses to numerous phytohormones including salicylic acid ... jasmonic acid , ABA and GA. These roles in multiple signalling pathways may in turn partly explain the pleiotropic effects commonly seen when TF genes are...Review article WRKY transcription factors: key components in abscisic acid signalling Deena L. Rushton1, Prateek Tripathi1, Roel C. Rabara1, Jun Lin1

  16. Hormetins as novel components of cosmeceuticals and aging interventions

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2015-01-01

    A promising strategy for maintaining a healthy and youthful phenotype during aging is that of mild stress-induced beneficial hormesis. The basis of hormesis lies in the molecular pathways of stress response, which are essential for the survival of a system by activation of maintenance and repair ...... in achieving various benefits including maintenance of the skin structure and function. Several polyphenols, flavonoids and other components from spices, algae and other sources are potential hormetins that may act via hormesis....

  17. Safety assessment for deep underground disposal vault-pathways analysis

    International Nuclear Information System (INIS)

    Lyon, R.B.; Rosinger, E.L.J.

    1980-01-01

    The concept verification phase of the Canadian programme for the disposal of nuclear fuel waste encompasses a period of about three years before the start of site selection. During this time, the methodology for Environmental and Safety Assessment studies is being developed by focusing on a model site. Pathways analysis is an important component of these studies. It involves the prediction of the rate at which radionuclides might be released from a disposal vault and travel through the geosphere and biosphere to reach man. The pathways analysis studies cover three major topics: geosphere pathways analysis, biosphere pathways analysis and potentially-disruptive-phenomena analysis. Geosphere pathways analysis includes a total systems analysis, using the computer program GARD2, vault analysis, which considers container failure and waste leaching, hydrogeological modelling and geochemical modelling. Biosphere pathways analysis incorporates a compartmental modelling approach using the computer program RAMM, and a food chain analysis using the computer program FOOD II. Potentially-disruptive-phenomena analysis involves the estimation of the probability and consequences of events such as earthquakes which might reduce the effectiveness of the barriers preventing the release of radionuclides. The current stage of development of the required methodology and data is discussed in each of the three areas and preliminary results are presented. (author)

  18. The genetic makeup of the Drosophila piRNA pathway.

    Science.gov (United States)

    Handler, Dominik; Meixner, Katharina; Pizka, Manfred; Lauss, Kathrin; Schmied, Christopher; Gruber, Franz Sebastian; Brennecke, Julius

    2013-06-06

    The piRNA (PIWI-interacting RNA) pathway is a small RNA silencing system that acts in animal gonads and protects the genome against the deleterious influence of transposons. A major bottleneck in the field is the lack of comprehensive knowledge of the factors and molecular processes that constitute this pathway. We conducted an RNAi screen in Drosophila and identified ~50 genes that strongly impact the ovarian somatic piRNA pathway. Many identified genes fall into functional categories that indicate essential roles for mitochondrial metabolism, RNA export, the nuclear pore, transcription elongation, and chromatin regulation in the pathway. Follow-up studies on two factors demonstrate that components acting at distinct hierarchical levels of the pathway were identified. Finally, we define CG2183/Gasz as an essential primary piRNA biogenesis factor in somatic and germline cells. Based on the similarities between insect and vertebrate piRNA pathways, our results have far-reaching implications for the understanding of this conserved genome defense system. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Components selection for ageing management

    International Nuclear Information System (INIS)

    Mingiuc, C.; Vidican, D.

    2002-01-01

    Full text: The paper presents a synthesis of methods and activities realized for the selection of critical components to assure plant safety and availability (as electricity supplier). There are presented main criteria for selection, screening process. For the resulted categories of components shall be applied different category of maintenance (condition oriented, scheduled or corrective), function of the importance and financial effort necessary to fulfil the task. 1. Systems and components screening for plant safety assurance For the systems selection, from Safety point of view, was necessary first, to define systems which are dangerous in case of failure (mainly by rupture/ release of radioactivity) and the safety systems which have to mitigate the effects. This is realized based on accident analysis (from Safety Report). Also where taken in to account the 4 basic Safety Principles: 'Reactor shut down; Residual heat removal; Radioactivity products confinement; NPP status monitoring in normal and accident conditions'. Following step is to establish safety support systems, which have to action to assure main safety systems operation. This could be realized based on engineering judgement, or on PSA Level I analysis. Finally shall be realized chains of the support systems, which have to work, till primary systems. For the critical components selection, was realized a Failure Mode and Effect Analysis (FMEA), considering the components effects of failures, on system safety function. 2. Systems and components screening for plant availability assurance The work was realized in two steps: Systems screening; Components screening The systems screening, included: General, analyze of the plant systems list and the definition of those which clearly have to run continue to assure the nominal power; Realization of a complex diagram to define interdependence between the systems (e.g. PHT and auxiliaries, moderator and auxiliaries, plant electrical diagram); Fill of special

  20. APS beamline standard components handbook

    International Nuclear Information System (INIS)

    Kuzay, T.M.

    1992-01-01

    It is clear that most Advanced Photon Source (APS) Collaborative Access Team (CAT) members would like to concentrate on designing specialized equipment related to their scientific programs rather than on routine or standard beamline components. Thus, an effort is in progress at the APS to identify standard and modular components of APS beamlines. Identifying standard components is a nontrivial task because these components should support diverse beamline objectives. To assist with this effort, the APS has obtained advice and help from a Beamline Standardization and Modularization Committee consisting of experts in beamline design, construction, and operation. The staff of the Experimental Facilities Division identified various components thought to be standard items for beamlines, regardless of the specific scientific objective of a particular beamline. A generic beamline layout formed the basis for this identification. This layout is based on a double-crystal monochromator as the first optical element, with the possibility of other elements to follow. Pre-engineering designs were then made of the identified standard components. The Beamline Standardization and Modularization Committee has reviewed these designs and provided very useful input regarding the specifications of these components. We realize that there will be other configurations that may require special or modified components. This Handbook in its current version (1.1) contains descriptions, specifications, and pre-engineering design drawings of these standard components. In the future, the APS plans to add engineering drawings of identified standard beamline components. Use of standard components should result in major cost reductions for CATs in the areas of beamline design and construction

  1. Pathway Design, Engineering, and Optimization.

    Science.gov (United States)

    Garcia-Ruiz, Eva; HamediRad, Mohammad; Zhao, Huimin

    The microbial metabolic versatility found in nature has inspired scientists to create microorganisms capable of producing value-added compounds. Many endeavors have been made to transfer and/or combine pathways, existing or even engineered enzymes with new function to tractable microorganisms to generate new metabolic routes for drug, biofuel, and specialty chemical production. However, the success of these pathways can be impeded by different complications from an inherent failure of the pathway to cell perturbations. Pursuing ways to overcome these shortcomings, a wide variety of strategies have been developed. This chapter will review the computational algorithms and experimental tools used to design efficient metabolic routes, and construct and optimize biochemical pathways to produce chemicals of high interest.

  2. Pathways of Unconventional Protein Secretion

    NARCIS (Netherlands)

    Rabouille, Catherine

    2017-01-01

    Secretory proteins are conventionally transported through the endoplasmic reticulum to the Golgi and then to the plasma membrane where they are released into the extracellular space. However, numerous substrates also reach these destinations using unconventional pathways. Unconventional protein

  3. Pathways of Unconventional Protein Secretion

    NARCIS (Netherlands)

    Rabouille, Catherine

    2016-01-01

    Secretory proteins are conventionally transported through the endoplasmic reticulum to the Golgi and then to the plasma membrane where they are released into the extracellular space. However, numerous substrates also reach these destinations using unconventional pathways. Unconventional protein

  4. Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

    Science.gov (United States)

    Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

    2014-06-01

    The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

  5. Secure coupling of hardware components

    NARCIS (Netherlands)

    Hoepman, J.H.; Joosten, H.J.M.; Knobbe, J.W.

    2011-01-01

    A method and a system for securing communication between at least a first and a second hardware components of a mobile device is described. The method includes establishing a first shared secret between the first and the second hardware components during an initialization of the mobile device and,

  6. Generic component failure data base

    International Nuclear Information System (INIS)

    Eide, S.A.; Calley, M.B.

    1992-01-01

    This report discusses comprehensive component generic failure data base which has been developed for light water reactor probabilistic risk assessments. The Nuclear Computerized Library for Assessing Reactor Reliability (NUCLARR) was used to generate component failure rates. Using this approach, most of the failure rates are based on actual plant data rather then existing estimates

  7. Active components in food supplements

    NARCIS (Netherlands)

    Siemelink M; Jansen EHJM; Piersma AH; Opperhuizen A; LEO

    2000-01-01

    The growing food supplement market, where supplements are both more diverse and more easily available (e.g. through Internet) formed the backdrop to the inventory of the active components in food supplements. The safety of an increased intake of food components via supplements was also at issue

  8. Component reliability for electronic systems

    CERN Document Server

    Bajenescu, Titu-Marius I

    2010-01-01

    The main reason for the premature breakdown of today's electronic products (computers, cars, tools, appliances, etc.) is the failure of the components used to build these products. Today professionals are looking for effective ways to minimize the degradation of electronic components to help ensure longer-lasting, more technically sound products and systems. This practical book offers engineers specific guidance on how to design more reliable components and build more reliable electronic systems. Professionals learn how to optimize a virtual component prototype, accurately monitor product reliability during the entire production process, and add the burn-in and selection procedures that are the most appropriate for the intended applications. Moreover, the book helps system designers ensure that all components are correctly applied, margins are adequate, wear-out failure modes are prevented during the expected duration of life, and system interfaces cannot lead to failure.

  9. Development, Implementation and Compliance of Treatment Pathways in Radiation Medicine

    Directory of Open Access Journals (Sweden)

    Louis ePotters

    2013-05-01

    Full Text Available INTRODUCTION: While much emphasis on safety in the radiation oncology clinic is placed on process, there remains considerable opportunity to increase safety, enhance outcomes and avoid ad-hoc care by instituting detailed treatment pathways. The purpose of this study was to review the process of developing evidence and consensus-based, outcomes-oriented treatment pathways that standardize treatment and patient management in a large multicenter radiation oncology practice. Further, we reviewed our compliance in incorporating these directives into our day-to-day clinical practice. METHODS: Using the Institute of Medicine guideline for developing treatment pathways, 87 disease specific pathways were developed and incorporated into the electronic medical system in our multi-facility radiation oncology department. Compliance in incorporating treatment pathways was assessed by mining our EMR data from January 1, 2010 through February 2012 for patients with breast and prostate cancer. RESULTS: This retrospective analysis of data from electronic medical records found overall compliance to breast and prostate cancer treatment pathways to be 97% and 99%, respectively. The reason for non-compliance proved to be either a failure to complete the prescribed care based on grade II or III toxicity (n=1 breast, 3 prostate or patient elected discontinuance of care (n=1 prostate or the physician chose a higher dose for positive/close margins (n=3 breast. CONCLUSION: This study demonstrates that consensus and evidence-based treatment pathways can be developed and implemented in a multi-center department of radiation oncology. And that for prostate and breast cancer there was a high degree of compliance using these directives. The development and implementation of these pathways serve as a key component of our safety program, most notably in our effort to facilitate consistent decision-making and reducing variation between physicians.

  10. Junction detection and pathway selection

    Science.gov (United States)

    Peck, Alex N.; Lim, Willie Y.; Breul, Harry T.

    1992-02-01

    The ability to detect junctions and make choices among the possible pathways is important for autonomous navigation. In our script-based navigation approach where a journey is specified as a script of high-level instructions, actions are frequently referenced to junctions, e.g., `turn left at the intersection.' In order for the robot to carry out these kind of instructions, it must be able (1) to detect an intersection (i.e., an intersection of pathways), (2) know that there are several possible pathways it can take, and (3) pick the pathway consistent with the high level instruction. In this paper we describe our implementation of the ability to detect junctions in an indoor environment, such as corners, T-junctions and intersections, using sonar. Our approach uses a combination of partial scan of the local environment and recognition of sonar signatures of certain features of the junctions. In the case where the environment is known, we use additional sensor information (such as compass bearings) to help recognize the specific junction. In general, once a junction is detected and its type known, the number of possible pathways can be deduced and the correct pathway selected. Then the appropriate behavior for negotiating the junction is activated.

  11. Modelling and performance analysis of clinical pathways using the stochastic process algebra PEPA.

    Science.gov (United States)

    Yang, Xian; Han, Rui; Guo, Yike; Bradley, Jeremy; Cox, Benita; Dickinson, Robert; Kitney, Richard

    2012-01-01

    Hospitals nowadays have to serve numerous patients with limited medical staff and equipment while maintaining healthcare quality. Clinical pathway informatics is regarded as an efficient way to solve a series of hospital challenges. To date, conventional research lacks a mathematical model to describe clinical pathways. Existing vague descriptions cannot fully capture the complexities accurately in clinical pathways and hinders the effective management and further optimization of clinical pathways. Given this motivation, this paper presents a clinical pathway management platform, the Imperial Clinical Pathway Analyzer (ICPA). By extending the stochastic model performance evaluation process algebra (PEPA), ICPA introduces a clinical-pathway-specific model: clinical pathway PEPA (CPP). ICPA can simulate stochastic behaviours of a clinical pathway by extracting information from public clinical databases and other related documents using CPP. Thus, the performance of this clinical pathway, including its throughput, resource utilisation and passage time can be quantitatively analysed. A typical clinical pathway on stroke extracted from a UK hospital is used to illustrate the effectiveness of ICPA. Three application scenarios are tested using ICPA: 1) redundant resources are identified and removed, thus the number of patients being served is maintained with less cost; 2) the patient passage time is estimated, providing the likelihood that patients can leave hospital within a specific period; 3) the maximum number of input patients are found, helping hospitals to decide whether they can serve more patients with the existing resource allocation. ICPA is an effective platform for clinical pathway management: 1) ICPA can describe a variety of components (state, activity, resource and constraints) in a clinical pathway, thus facilitating the proper understanding of complexities involved in it; 2) ICPA supports the performance analysis of clinical pathway, thereby assisting

  12. Alternative Cell Death Pathways and Cell Metabolism

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2013-01-01

    Full Text Available While necroptosis has for long been viewed as an accidental mode of cell death triggered by physical or chemical damage, it has become clear over the last years that necroptosis can also represent a programmed form of cell death in mammalian cells. Key discoveries in the field of cell death research, including the identification of critical components of the necroptotic machinery, led to a revised concept of cell death signaling programs. Several regulatory check and balances are in place in order to ensure that necroptosis is tightly controlled according to environmental cues and cellular needs. This network of regulatory mechanisms includes metabolic pathways, especially those linked to mitochondrial signaling events. A better understanding of these signal transduction mechanisms will likely contribute to open new avenues to exploit our knowledge on the regulation of necroptosis signaling for therapeutic application in the treatment of human diseases.

  13. USP21 regulates Hippo pathway activity by mediating MARK protein turnover

    DEFF Research Database (Denmark)

    Nguyen, Thanh Hung; Kugler, Jan-Michael; Loya, Anand Chainsukh

    2017-01-01

    observed in cancer and often correlates with worse survival. The activity and stability of Hippo pathway components, including YAP/TAZ, AMOT and LATS1/2, are regulated by ubiquitin-mediated protein degradation. Aberrant expression of ubiquitin ligase complexes that regulate the turnover of Hippo components...

  14. Signaling pathways in a Citrus EST database

    Directory of Open Access Journals (Sweden)

    Angela Mehta

    2007-01-01

    Full Text Available Citrus spp. are economically important crops, which in Brazil are grown mainly in the State of São Paulo. Citrus cultures are attacked by several pathogens, causing severe yield losses. In order to better understand this culture, the Millenium Project (IAC Cordeirópolis was launched in order to sequence Citrus ESTs (expressed sequence tags from different tissues, including leaf, bark, fruit, root and flower. Plants were submitted to biotic and abiotic stresses and investigated under different development stages (adult vs. juvenile. Several cDNA libraries were constructed and the sequences obtained formed the Citrus ESTs database with almost 200,000 sequences. Searches were performed in the Citrus database to investigate the presence of different signaling pathway components. Several of the genes involved in the signaling of sugar, calcium, cytokinin, plant hormones, inositol phosphate, MAPKinase and COP9 were found in the citrus genome and are discussed in this paper. The results obtained may indicate that similar mechanisms described in other plants, such as Arabidopsis, occur in citrus. Further experimental studies must be conducted in order to understand the different signaling pathways present.

  15. Targeting Signaling Pathways in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Johannes Haybaeck

    2013-05-01

    Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are relevant for ovarian tumorigenesis. The understanding of these molecular pathways is essential for the development of novel therapeutic strategies. Purpose: We want to give an overview on the molecular genetic changes of the histopathological types of OC and their role as putative therapeutic targets. In Depth Review of Existing Data: In 2012, the vascular endothelial growth factor (VEGF inhibitor, bevacizumab, was approved for OC treatment. Bevacizumab has shown promising results as single agent and in combination with conventional chemotherapy, but its target is not distinctive when analyzed before treatment. At present, mammalian target of rapamycin (mTOR inhibitors, poly-ADP-ribose polymerase (PARP inhibitors and components of the EGFR pathway are in the focus of clinical research. Interestingly, some phytochemical substances show good synergistic effects when used in combination with chemotherapy. Conclusion: Ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative options to bevacizumab available for OC patients. Novel targets which can be assessed before therapy to predict efficacy are needed. The assessment of therapeutic targets is continuously improved by molecular pathological analyses on tumor tissue. A careful selection of patients for personalized treatment will help to reduce putative side effects and toxicity.

  16. Diverse exocytic pathways for mast cell mediators.

    Science.gov (United States)

    Xu, Hao; Bin, Na-Ryum; Sugita, Shuzo

    2018-04-17

    Mast cells play pivotal roles in innate and adaptive immunities but are also culprits in allergy, autoimmunity, and cardiovascular diseases. Mast cells respond to environmental changes by initiating regulated exocytosis/secretion of various biologically active compounds called mediators (e.g. proteases, amines, and cytokines). Many of these mediators are stored in granules/lysosomes and rely on intricate degranulation processes for release. Mast cell stabilizers (e.g. sodium cromoglicate), which prevent such degranulation processes, have therefore been clinically employed to treat asthma and allergic rhinitis. However, it has become increasingly clear that different mast cell diseases often involve multiple mediators that rely on overlapping but distinct mechanisms for release. This review illustrates existing evidence that highlights the diverse exocytic pathways in mast cells. We also discuss strategies to delineate these pathways so as to identify unique molecular components which could serve as new drug targets for more effective and specific treatments against mast cell-related diseases. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  17. [Advance in flavonoids biosynthetic pathway and synthetic biology].

    Science.gov (United States)

    Zou, Li-Qiu; Wang, Cai-Xia; Kuang, Xue-Jun; Li, Ying; Sun, Chao

    2016-11-01

    Flavonoids are the valuable components in medicinal plants, which possess a variety of pharmacological activities, including anti-tumor, antioxidant and anti-inflammatory activities. There is an unambiguous understanding about flavonoids biosynthetic pathway, that is,2S-flavanones including naringenin and pinocembrin are the skeleton of other flavonoids and they can transform to other flavonoids through branched metabolic pathway. Elucidation of the flavonoids biosynthetic pathway lays a solid foundation for their synthetic biology. A few flavonoids have been produced in Escherichia coli or yeast with synthetic biological technologies, such as naringenin, pinocembrin and fisetin. Synthetic biology will provide a new way to get valuable flavonoids and promote the research and development of flavonoid drugs and health products, making flavonoids play more important roles in human diet and health. Copyright© by the Chinese Pharmaceutical Association.

  18. Component Fragility Research Program: Phase 1 component prioritization

    International Nuclear Information System (INIS)

    Holman, G.S.; Chou, C.K.

    1987-06-01

    Current probabilistic risk assessment (PRA) methods for nuclear power plants utilize seismic ''fragilities'' - probabilities of failure conditioned on the severity of seismic input motion - that are based largely on limited test data and on engineering judgment. Under the NRC Component Fragility Research Program (CFRP), the Lawrence Livermore National Laboratory (LLNL) has developed and demonstrated procedures for using test data to derive probabilistic fragility descriptions for mechanical and electrical components. As part of its CFRP activities, LLNL systematically identified and categorized components influencing plant safety in order to identify ''candidate'' components for future NRC testing. Plant systems relevant to safety were first identified; within each system components were then ranked according to their importance to overall system function and their anticipated seismic capacity. Highest priority for future testing was assigned to those ''very important'' components having ''low'' seismic capacity. This report describes the LLNL prioritization effort, which also included application of ''high-level'' qualification data as an alternate means of developing probabilistic fragility descriptions for PRA applications

  19. Neem components as potential agents for cancer prevention and treatment

    Science.gov (United States)

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2016-01-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment. PMID:25016141

  20. Formalization in Component Based Development

    DEFF Research Database (Denmark)

    Holmegaard, Jens Peter; Knudsen, John; Makowski, Piotr

    2006-01-01

    We present a unifying conceptual framework for components, component interfaces, contracts and composition of components by focusing on the collection of properties or qualities that they must share. A specific property, such as signature, functionality behaviour or timing is an aspect. Each aspect...... may be specified in a formal language convenient for its purpose and, in principle, unrelated to languages for other aspects. Each aspect forms its own semantic domain, although a semantic domain may be parameterized by values derived from other aspects. The proposed conceptual framework is introduced...

  1. Dietary modification of metabolic pathways via nuclear hormone receptors.

    Science.gov (United States)

    Caiozzi, Gianella; Wong, Brian S; Ricketts, Marie-Louise

    2012-10-01

    Nuclear hormone receptors (NHRs), as ligand-dependent transcription factors, have emerged as important mediators in the control of whole body metabolism. Because of the promiscuous nature of several members of this superfamily that have been found to bind ligand with lower affinity than the classical steroid NHRs, they consequently display a broader ligand selectivity. This promiscuous nature has facilitated various bioactive dietary components being able to act as agonist ligands for certain members of the NHR superfamily. By binding to these NHRs, bioactive dietary components are able to mediate changes in various metabolic pathways, including, glucose, cholesterol and triglyceride homeostasis among others. This review will provide a general overview of the nuclear hormone receptors that have been shown to be activated by dietary components. The physiological consequences of such receptor activation by these dietary components will then be discussed in more detail. Copyright © 2012 John Wiley & Sons, Ltd.

  2. The Hippo pathway: key interaction and catalytic domains in organ growth control, stem cell self-renewal and tissue regeneration.

    Science.gov (United States)

    Cherrett, Claire; Furutani-Seiki, Makoto; Bagby, Stefan

    2012-01-01

    The Hippo pathway is a conserved pathway that interconnects with several other pathways to regulate organ growth, tissue homoeostasis and regeneration, and stem cell self-renewal. This pathway is unique in its capacity to orchestrate multiple processes, from sensing to execution, necessary for organ expansion. Activation of the Hippo pathway core kinase cassette leads to cytoplasmic sequestration of the nuclear effectors YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), consequently disabling their transcriptional co-activation function. Components upstream of the core kinase cassette have not been well understood, especially in vertebrates, but are gradually being elucidated and include cell polarity and cell adhesion proteins.

  3. Three-component homeostasis control

    Science.gov (United States)

    Xu, Jin; Hong, Hyunsuk; Jo, Junghyo

    2014-03-01

    Two reciprocal components seem to be sufficient to maintain a control variable constant. However, pancreatic islets adapt three components to control glucose homeostasis. They are α (secreting glucagon), β (insulin), and δ (somatostatin) cells. Glucagon and insulin are the reciprocal hormones for increasing and decreasing blood glucose levels, while the role of somatostatin is unknown. However, it has been known how each hormone affects other cell types. Based on the pulsatile hormone secretion and the cellular interactions, this system can be described as coupled oscillators. In particular, we used the Landau-Stuart model to consider both amplitudes and phases of hormone oscillations. We found that the presence of the third component, δ cell, was effective to resist under glucose perturbations, and to quickly return to the normal glucose level once perturbed. Our analysis suggested that three components are necessary for advanced homeostasis control.

  4. Component Processes in Analogical Reasoning

    Science.gov (United States)

    Sternberg, Robert J.

    1977-01-01

    Describes alternative theoretical positions regarding (a) the component information processes used in analogical reasoning and (b) strategies for combining these processes. Also presents results from three experiments on analogical reasoning. (Author/RK)

  5. Passive Microwave Components and Antennas

    DEFF Research Database (Denmark)

    State-of-the-art microwave systems always require higher performance and lower cost microwave components. Constantly growing demands and performance requirements of industrial and scientific applications often make employing traditionally designed components impractical. For that reason, the design...... and development process remains a great challenge today. This problem motivated intensive research efforts in microwave design and technology, which is responsible for a great number of recently appeared alternative approaches to analysis and design of microwave components and antennas. This book highlights...... techniques. Modelling and computations in electromagnetics is a quite fast-growing research area. The recent interest in this field is caused by the increased demand for designing complex microwave components, modeling electromagnetic materials, and rapid increase in computational power for calculation...

  6. Metallurgical Laboratory and Components Testing

    Data.gov (United States)

    Federal Laboratory Consortium — In the field of metallurgy, TTC is equipped to run laboratory tests on track and rolling stock components and materials. The testing lab contains scanning-electron,...

  7. Metal binding by food components

    DEFF Research Database (Denmark)

    Tang, Ning

    for zinc binding by the investigated amino acids, peptides and proteins. The thiol group or imidazole group containing amino acids, peptides and proteins which exhibited strong zinc binding ability were further selected for interacting with zinc salts in relation to zinc absorption. The interactions...... between the above selected food components and zinc citrate or zinc phytate will lead to the enhanced solubility of zinc citrate or zinc phytate. The main driving force for this observed solubility enhancement is the complex formation between zinc and investigated food components as revealed by isothermal...... titration calorimetry and quantum mechanical calculations. This is due to the zinc binding affinity of the relatively softer ligands (investigated food components) will become much stronger than citrate or phytate when they present together in aqueous solution. This mechanism indicates these food components...

  8. Comparative transcriptome and gene co-expression network analysis reveal genes and signaling pathways adaptively responsive to varied adverse stresses in the insect fungal pathogen, Beauveria bassiana.

    Science.gov (United States)

    He, Zhangjiang; Zhao, Xin; Lu, Zhuoyue; Wang, Huifang; Liu, Pengfei; Zeng, Fanqin; Zhang, Yongjun

    2018-01-01

    Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. Beauveria bassiana is an economically important insect-pathogenic fungus which is widely used as a biocontrol agent to control a variety of insect pests. The fungal pathogen unavoidably encounters a variety of adverse environmental stresses and defense response from the host insects during application of the fungal agents. However, few are known about the transcription response of the fungus to respond or adapt varied adverse stresses. Here, we comparatively analyzed the transcriptome of B. bassiana in globe genome under the varied stationary-phase stresses including osmotic agent (0.8 M NaCl), high temperature (32 °C), cell wall-perturbing agent (Congo red), and oxidative agents (H 2 O 2 or menadione). Total of 12,412 reads were obtained, and mapped to the 6767 genes of the B. bassiana. All of these stresses caused transcription responses involved in basal metabolism, cell wall construction, stress response or cell rescue/detoxification, signaling transduction and gene transcription regulation, and likely other cellular processes. An array of genes displayed similar transcription patterns in response to at least two of the five stresses, suggesting a shared transcription response to varied adverse stresses. Gene co-expression network analysis revealed that mTOR signaling pathway, but not HOG1 MAP kinase pathway, played a central role in regulation the varied adverse stress responses, which was verified by RNAi-mediated knockdown of TOR1. Our findings provided an insight of transcription response and gene co-expression network of B. bassiana in adaptation to varied environments. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Vibrational energy relaxation: proposed pathway of fast local chromatin denaturation

    International Nuclear Information System (INIS)

    Harder, D.; Greinert, R.

    2002-01-01

    The molecular mechanism responsible for the a component of exchange-type chromosome aberrations, of chromosome fragmentation and of reproductive cell death is one of the unsolved issues of radiation biology. Under review is whether vibrational energy relaxation in the constitutive biopolymers of chromatin, induced by inelastic energy deposition events and mediated via highly excited vibrational states, may provide a pathway of fast local chromatin denaturation, thereby producing the severe DNA lesion able to interact chemically with other, non-damaged chromatin. (author)

  10. Physics-Based Stress Corrosion Cracking Component Reliability Model cast in an R7-Compatible Cumulative Damage Framework

    Energy Technology Data Exchange (ETDEWEB)

    Unwin, Stephen D.; Lowry, Peter P.; Layton, Robert F.; Toloczko, Mychailo B.; Johnson, Kenneth I.; Sanborn, Scott E.

    2011-07-01

    This is a working report drafted under the Risk-Informed Safety Margin Characterization pathway of the Light Water Reactor Sustainability Program, describing statistical models of passives component reliabilities.

  11. PHOTOBIOMODULATION-MEDIATED PATHWAY DIAGNOSTICS

    Directory of Open Access Journals (Sweden)

    TIMON CHENG-YI LIU

    2013-01-01

    Full Text Available Cellular pathways are ordinarily diagnosed with pathway inhibitors, related gene regulation, or fluorescent protein markers. They are also suggested to be diagnosed with pathway activation modulation of photobiomodulation (PBM in this paper. A PBM on a biosystem function depends on whether the biosystem is in its function-specific homeostasis (FSH. An FSH, a negative feedback response for the function to be performed perfectly, is maintained by its FSH-essential subfunctions and its FSH-non-essential subfunctions (FNSs. A function in its FSH or far from its FSH is called a normal or dysfunctional function. A direct PBM may self-adaptatively modulate a dysfunctional function until it is normal so that it can be used to discover the optimum pathways for an FSH to be established. An indirect PBM may self-adaptatively modulate a dysfunctional FNS of a normal function until the FNS is normal, and the normal function is then upgraded so that it can be used to discover the redundant pathways for a normal function to be upgraded.

  12. Radiation effects in optical components

    International Nuclear Information System (INIS)

    Friebele, E.J.

    1987-01-01

    This report discusses components of high performance optical devices may be exposed to high energy radiation environments during their lifetime. The effect of these adverse environments depends upon a large number of parameters associated with the radiation (nature, energy, dose, dose rate, etc.) or the system (temperature, optical performance requirements, optical wavelength, optical power, path length, etc.), as well as the intrinsic susceptibility of the optical component itself to degradation

  13. Multiview Bayesian Correlated Component Analysis

    DEFF Research Database (Denmark)

    Kamronn, Simon Due; Poulsen, Andreas Trier; Hansen, Lars Kai

    2015-01-01

    are identical. Here we propose a hierarchical probabilistic model that can infer the level of universality in such multiview data, from completely unrelated representations, corresponding to canonical correlation analysis, to identical representations as in correlated component analysis. This new model, which...... we denote Bayesian correlated component analysis, evaluates favorably against three relevant algorithms in simulated data. A well-established benchmark EEG data set is used to further validate the new model and infer the variability of spatial representations across multiple subjects....

  14. Catalytic Hydrotreatment of Fast Pyrolysis Oil: Model Studies on Reaction Pathways for the Carbohydrate Fraction

    OpenAIRE

    Wildschut, J.; Arentz, J.; Rasrendra, C. B.; Venderbosch, R. H.; Heeres, H. J.

    2009-01-01

    Fast pyrolysis oil can be upgraded by a catalytic hydrotreatment (250-400 degrees C, 100-200 bar) using heterogeneous catalysts such as Ru/C to hydrocarbon-like products that can serve as liquid transportation fuels. Insight into the complex reaction pathways of the various component fractions during hydrotreatment is desirable to reduce the formation of by-products such as char and gaseous components. This paper deals with the catalytic hydrotreatment of representative model components for t...

  15. MoCha: Molecular Characterization of Unknown Pathways.

    Science.gov (United States)

    Lobo, Daniel; Hammelman, Jennifer; Levin, Michael

    2016-04-01

    Automated methods for the reverse-engineering of complex regulatory networks are paving the way for the inference of mechanistic comprehensive models directly from experimental data. These novel methods can infer not only the relations and parameters of the known molecules defined in their input datasets, but also unknown components and pathways identified as necessary by the automated algorithms. Identifying the molecular nature of these unknown components is a crucial step for making testable predictions and experimentally validating the models, yet no specific and efficient tools exist to aid in this process. To this end, we present here MoCha (Molecular Characterization), a tool optimized for the search of unknown proteins and their pathways from a given set of known interacting proteins. MoCha uses the comprehensive dataset of protein-protein interactions provided by the STRING database, which currently includes more than a billion interactions from over 2,000 organisms. MoCha is highly optimized, performing typical searches within seconds. We demonstrate the use of MoCha with the characterization of unknown components from reverse-engineered models from the literature. MoCha is useful for working on network models by hand or as a downstream step of a model inference engine workflow and represents a valuable and efficient tool for the characterization of unknown pathways using known data from thousands of organisms. MoCha and its source code are freely available online under the GPLv3 license.

  16. Psychophysical and physiological responses to gratings with luminance and chromatic components of different spatial frequencies.

    Science.gov (United States)

    Cooper, Bonnie; Sun, Hao; Lee, Barry B

    2012-02-01

    Gratings that contain luminance and chromatic components of different spatial frequencies were used to study the segregation of signals in luminance and chromatic pathways. Psychophysical detection and discrimination thresholds to these compound gratings, with luminance and chromatic components of the one either half or double the spatial frequency of the other, were measured in human observers. Spatial frequency tuning curves for detection of compound gratings followed the envelope of those for luminance and chromatic gratings. Different grating types were discriminable at detection threshold. Fourier analysis of physiological responses of macaque retinal ganglion cells to compound waveforms showed chromatic information to be restricted to the parvocellular pathway and luminance information to the magnocellular pathway. Taken together, the human psychophysical and macaque physiological data support the strict segregation of luminance and chromatic information in independent channels, with the magnocellular and parvocellular pathways, respectively, serving as likely the physiological substrates. © 2012 Optical Society of America

  17. New Pathways for Alimentary Mucositis

    Directory of Open Access Journals (Sweden)

    Joanne M. Bowen

    2008-01-01

    Full Text Available Alimentary mucositis is a major dose-limiting toxicity associated with anticancer treatment. It is responsible for reducing patient quality of life and represents a significant economic burden in oncology. The pathobiology of alimentary mucositis is extremely complex, and an increased understanding of mechanisms and pathway interactions is required to rationally design improved therapies. This review describes the latest advances in defining mechanisms of alimentary mucositis pathobiology in the context of pathway activation. It focuses particularly on the recent genome-wide analyses of regimen-related mucosal injury and the identification of specific regulatory pathways implicated in mucositis development. This review also discusses the currently known alimentary mucositis risk factors and the development of novel treatments. Suggestions for future research directions have been raised.

  18. Aberrant Signaling Pathways in Glioma

    International Nuclear Information System (INIS)

    Nakada, Mitsutoshi; Kita, Daisuke; Watanabe, Takuya; Hayashi, Yutaka; Teng, Lei; Pyko, Ilya V.; Hamada, Jun-Ichiro

    2011-01-01

    Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults; few treatments are available. Median survival rates range from 12–15 months. The biological characteristics of this tumor are exemplified by prominent proliferation, active invasiveness, and rich angiogenesis. This is mainly due to highly deregulated signaling pathways in the tumor. Studies of these signaling pathways have greatly increased our understanding of the biology and clinical behavior of GBM. An integrated view of signal transduction will provide a more useful approach in designing novel therapies for this devastating disease. In this review, we summarize the current understanding of GBM signaling pathways with a focus on potential molecular targets for anti-signaling molecular therapies

  19. Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair.

    Science.gov (United States)

    Nakanishi, Koji; Yang, Yun-Gui; Pierce, Andrew J; Taniguchi, Toshiyasu; Digweed, Martin; D'Andrea, Alan D; Wang, Zhao-Qi; Jasin, Maria

    2005-01-25

    Fanconi anemia (FA) is a recessive disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. Cells from FA patients are hypersensitive to agents that produce DNA crosslinks and, after treatment with these agents, have pronounced chromosome breakage and other cytogenetic abnormalities. Eight FANC genes have been cloned, and the encoded proteins interact in a common cellular pathway. DNA-damaging agents activate the monoubiquitination of FANCD2, resulting in its targeting to nuclear foci that also contain BRCA1 and BRCA2/FANCD1, proteins involved in homology-directed DNA repair. Given the interaction of the FANC proteins with BRCA1 and BRCA2, we tested whether cells from FA patients (groups A, G, and D2) and mouse Fanca-/- cells with a targeted mutation are impaired for this repair pathway. We find that both the upstream (FANCA and FANCG) and downstream (FANCD2) FA pathway components promote homology-directed repair of chromosomal double-strand breaks (DSBs). The FANCD2 monoubiquitination site is critical for normal levels of repair, whereas the ATM phosphorylation site is not. The defect in these cells, however, is mild, differentiating them from BRCA1 and BRCA2 mutant cells. Surprisingly, we provide evidence that these proteins, like BRCA1 but unlike BRCA2, promote a second DSB repair pathway involving homology, i.e., single-strand annealing. These results suggest an early role for the FANC proteins in homologous DSB repair pathway choice.

  20. Pathview Web: user friendly pathway visualization and data integration.

    Science.gov (United States)

    Luo, Weijun; Pant, Gaurav; Bhavnasi, Yeshvant K; Blanchard, Steven G; Brouwer, Cory

    2017-07-03

    Pathway analysis is widely used in omics studies. Pathway-based data integration and visualization is a critical component of the analysis. To address this need, we recently developed a novel R package called Pathview. Pathview maps, integrates and renders a large variety of biological data onto molecular pathway graphs. Here we developed the Pathview Web server, as to make pathway visualization and data integration accessible to all scientists, including those without the special computing skills or resources. Pathview Web features an intuitive graphical web interface and a user centered design. The server not only expands the core functions of Pathview, but also provides many useful features not available in the offline R package. Importantly, the server presents a comprehensive workflow for both regular and integrated pathway analysis of multiple omics data. In addition, the server also provides a RESTful API for programmatic access and conveniently integration in third-party software or workflows. Pathview Web is openly and freely accessible at https://pathview.uncc.edu/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Nomenclature for Members of the Two-Component Signaling Pathway of Plants

    Czech Academy of Sciences Publication Activity Database

    Heyl, A.; Brault, M.; Frugier, F.; Kuderová, A.; Lindner, A.C.; Motyka, Václav; Rashotte, A.M.; von Schwartzenberg, K.; Vaňková, Radomíra; Schaller, G.E.

    2013-01-01

    Roč. 161, č. 3 (2013), s. 1063-1065 ISSN 0032-0889 Institutional research plan: CEZ:AV0Z50380511 Keywords : LIGAND-BINDING * CHASE DOMAIN * TRANSDUCTION Subject RIV: ED - Physiology Impact factor: 7.394, year: 2013

  2. Tolerance of Escherichia coli to fluoroquinolone antibiotics depends on specific components of the SOS response pathway.

    Science.gov (United States)

    Theodore, Alyssa; Lewis, Kim; Vulic, Marin

    2013-12-01

    Bacteria exposed to bactericidal fluoroquinolone (FQ) antibiotics can survive without becoming genetically resistant. Survival of these phenotypically resistant cells, commonly called "persisters," depends on the SOS gene network. We have examined mutants in all known SOS-regulated genes to identify functions essential for tolerance in Escherichia coli. The absence of DinG and UvrD helicases and the Holliday junction processing enzymes RuvA and RuvB leads to a decrease in survival. Analysis of the respective mutants indicates that, in addition to repair of double-strand breaks, tolerance depends on the repair of collapsed replication forks and stalled transcription complexes. Mutation in recF results in increased survival, which identifies RecAF recombination as a poisoning mechanism not previously linked to FQ lethality. DinG acts upstream of SOS promoting its induction, whereas RuvAB participates in repair only. UvrD directly promotes all repair processes initiated by FQ-induced damage and prevents RecAF-dependent misrepair, making it one of the crucial SOS functions required for tolerance.

  3. Identification and Characterization of Components of the Mitotic Spindle Checkpoint Pathway in Fission Yeast

    National Research Council Canada - National Science Library

    Kadura, Sheila

    2003-01-01

    .... For example, mutations in human Bub1 p have been identified in cancer cell lines and altered expression of the bub1 gene has been shown to correlate with tumor cell proliferation and chromosomal instability...

  4. Targeting the GPI biosynthetic pathway.

    Science.gov (United States)

    Yadav, Usha; Khan, Mohd Ashraf

    2018-02-27

    The GPI (Glycosylphosphatidylinositol) biosynthetic pathway is a multistep conserved pathway in eukaryotes that culminates in the generation of GPI glycolipid which in turn anchors many proteins (GPI-APs) to the cell surface. In spite of the overall conservation of the pathway, there still exist subtle differences in the GPI pathway of mammals and other eukaryotes which holds a great promise so far as the development of drugs/inhibitors against specific targets in the GPI pathway of pathogens is concerned. Many of the GPI structures and their anchored proteins in pathogenic protozoans and fungi act as pathogenicity factors. Notable examples include GPI-anchored variant surface glycoprotein (VSG) in Trypanosoma brucei, GPI-anchored merozoite surface protein 1 (MSP1) and MSP2 in Plasmodium falciparum, protein-free GPI related molecules like lipophosphoglycans (LPGs) and glycoinositolphospholipids (GIPLs) in Leishmania spp., GPI-anchored Gal/GalNAc lectin and proteophosphoglycans in Entamoeba histolytica or the GPI-anchored mannoproteins in pathogenic fungi like Candida albicans. Research in this active area has already yielded encouraging results in Trypanosoma brucei by the development of parasite-specific inhibitors of GlcNCONH 2 -β-PI, GlcNCONH 2 -(2-O-octyl)-PI and salicylic hydroxamic acid (SHAM) targeting trypanosomal GlcNAc-PI de-N-acetylase as well as the development of antifungal inhibitors like BIQ/E1210/gepinacin/G365/G884 and YW3548/M743/M720 targeting the GPI specific fungal inositol acyltransferase (Gwt1) and the phosphoethanolamine transferase-I (Mcd4), respectively. These confirm the fact that the GPI pathway continues to be the focus of researchers, given its implications for the betterment of human life.

  5. Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies.

    Science.gov (United States)

    Iurescia, Sandra; Fioretti, Daniela; Rinaldi, Monica

    2018-01-01

    The innate immune system provides the first line of defense against pathogen infection though also influences pathways involved in cancer immunosurveillance. The innate immune system relies on a limited set of germ line-encoded sensors termed pattern recognition receptors (PRRs), signaling proteins and immune response factors. Cytosolic receptors mediate recognition of danger damage-associated molecular patterns (DAMPs) signals. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Recent studies revealed that PRRs respond to nucleic acids (NA) released by dying, damaged, cancer cells, as danger DAMPs signals, and presence of signaling proteins across cancer types suggests that these signaling mechanisms may be involved in cancer biology. DAMPs play important roles in shaping adaptive immune responses through the activation of innate immune cells and immunological response to danger DAMPs signals is crucial for the host response to cancer and tumor rejection. Furthermore, PRRs mediate the response to NA in several vaccination strategies, including DNA immunization. As route of double-strand DNA intracellular entry, DNA immunization leads to expression of key components of cytosolic NA-sensing pathways. The involvement of NA-sensing mechanisms in the antitumor response makes these pathways attractive drug targets. Natural and synthetic agonists of NA-sensing pathways can trigger cell death in malignant cells, recruit immune cells, such as DCs, CD8 + T cells, and NK cells, into the tumor microenvironment and are being explored as promising adjuvants in cancer immunotherapies. In this minireview, we discuss how cGAS-STING and RIG-I-MAVS pathways have been targeted for cancer treatment in preclinical translational researches. In addition, we present a targeted selection of recent clinical trials employing agonists of cytosolic NA-sensing pathways showing how these pathways

  6. Component protection based automatic control

    International Nuclear Information System (INIS)

    Otaduy, P.J.

    1992-01-01

    Control and safety systems as well as operation procedures are designed on the basis of critical process parameters limits. The expectation is that short and long term mechanical damage and process failures will be avoided by operating the plant within the specified constraints envelopes. In this paper, one of the Advanced Liquid Metal Reactor (ALMR) design duty cycles events is discussed to corroborate that the time has come to explicitly make component protection part of the control system. Component stress assessment and aging data should be an integral part of the control system. Then transient trajectory planning and operating limits could be aimed at minimizing component specific and overall plant component damage cost functions. The impact of transients on critical components could then be managed according to plant lifetime design goals. The need for developing methodologies for online transient trajectory planning and assessment of operating limits in order to facilitate the explicit incorporation of damage assessment capabilities to the plant control and protection systems is discussed. 12 refs

  7. The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.

    Directory of Open Access Journals (Sweden)

    Ian R Kelsall

    Full Text Available The many proteins that function in the Fanconi anaemia (FA monoubiquitylation pathway initiate replicative DNA crosslink repair. However, it is not clear whether individual FA genes participate in DNA repair pathways other than homologous recombination and translesion bypass. Here we show that avian DT40 cell knockouts of two integral FA genes--UBE2T and FANCM are unexpectedly sensitive to UV-induced DNA damage. Comprehensive genetic dissection experiments indicate that both of these FA genes collaborate to promote nucleotide excision repair rather than translesion bypass to protect cells form UV genotoxicity. Furthermore, UBE2T deficiency impacts on the efficient removal of the UV-induced photolesion cyclobutane pyrimidine dimer. Therefore, this work reveals that the FA pathway shares two components with nucleotide excision repair, intimating not only crosstalk between the two major repair pathways, but also potentially identifying a UBE2T-mediated ubiquitin-signalling response pathway that contributes to nucleotide excision repair.

  8. Mechanical design of machine components

    CERN Document Server

    Ugural, Ansel C

    2015-01-01

    Mechanical Design of Machine Components, Second Edition strikes a balance between theory and application, and prepares students for more advanced study or professional practice. It outlines the basic concepts in the design and analysis of machine elements using traditional methods, based on the principles of mechanics of materials. The text combines the theory needed to gain insight into mechanics with numerical methods in design. It presents real-world engineering applications, and reveals the link between basic mechanics and the specific design of machine components and machines. Divided into three parts, this revised text presents basic background topics, deals with failure prevention in a variety of machine elements and covers applications in design of machine components as well as entire machines. Optional sections treating special and advanced topics are also included.Key Features of the Second Edition:Incorporates material that has been completely updated with new chapters, problems, practical examples...

  9. Towards Prognostics for Electronics Components

    Science.gov (United States)

    Saha, Bhaskar; Celaya, Jose R.; Wysocki, Philip F.; Goebel, Kai F.

    2013-01-01

    Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is becoming a very important research field as a result of the need to provide aircraft systems with system level health management information. This paper focuses on a prognostics application for electronics components within avionics systems, and in particular its application to an Isolated Gate Bipolar Transistor (IGBT). This application utilizes the remaining useful life prediction, accomplished by employing the particle filter framework, leveraging data from accelerated aging tests on IGBTs. These tests induced thermal-electrical overstresses by applying thermal cycling to the IGBT devices. In-situ state monitoring, including measurements of steady-state voltages and currents, electrical transients, and thermal transients are recorded and used as potential precursors of failure.

  10. Automated cleaning of electronic components

    International Nuclear Information System (INIS)

    Drotning, W.; Meirans, L.; Wapman, W.; Hwang, Y.; Koenig, L.; Petterson, B.

    1994-01-01

    Environmental and operator safety concerns are leading to the elimination of trichloroethylene and chlorofluorocarbon solvents in cleaning processes that remove rosin flux, organic and inorganic contamination, and particulates from electronic components. Present processes depend heavily on these solvents for manual spray cleaning of small components and subassemblies. Use of alternative solvent systems can lead to longer processing times and reduced quality. Automated spray cleaning can improve the quality of the cleaning process, thus enabling the productive use of environmentally conscious materials, while minimizing personnel exposure to hazardous materials. We describe the development of a prototype robotic system for cleaning electronic components in a spray cleaning workcell. An important feature of the prototype system is the capability to generate the robot paths and motions automatically from the CAD models of the part to be cleaned, and to embed cleaning process knowledge into the automatically programmed operations

  11. Two component systems: physiological effect of a third component.

    Directory of Open Access Journals (Sweden)

    Baldiri Salvado

    Full Text Available Signal transduction systems mediate the response and adaptation of organisms to environmental changes. In prokaryotes, this signal transduction is often done through Two Component Systems (TCS. These TCS are phosphotransfer protein cascades, and in their prototypical form they are composed by a kinase that senses the environmental signals (SK and by a response regulator (RR that regulates the cellular response. This basic motif can be modified by the addition of a third protein that interacts either with the SK or the RR in a way that could change the dynamic response of the TCS module. In this work we aim at understanding the effect of such an additional protein (which we call "third component" on the functional properties of a prototypical TCS. To do so we build mathematical models of TCS with alternative designs for their interaction with that third component. These mathematical models are analyzed in order to identify the differences in dynamic behavior inherent to each design, with respect to functionally relevant properties such as sensitivity to changes in either the parameter values or the molecular concentrations, temporal responsiveness, possibility of multiple steady states, or stochastic fluctuations in the system. The differences are then correlated to the physiological requirements that impinge on the functioning of the TCS. This analysis sheds light on both, the dynamic behavior of synthetically designed TCS, and the conditions under which natural selection might favor each of the designs. We find that a third component that modulates SK activity increases the parameter space where a bistable response of the TCS module to signals is possible, if SK is monofunctional, but decreases it when the SK is bifunctional. The presence of a third component that modulates RR activity decreases the parameter space where a bistable response of the TCS module to signals is possible.

  12. Career Technical Education Pathways Initiative

    Science.gov (United States)

    California Community Colleges, Chancellor's Office, 2013

    2013-01-01

    California's education system--the largest in the United States--is an essential resource for ensuring strong economic growth in the state. The Career Technical Education Pathways Initiative (referred to as the Initiative in this report), which became law in 2005, brings together community colleges, K-12 school districts, employers, organized…

  13. Diverse Pathways in Children's Learning.

    Science.gov (United States)

    Lambert, Beverley

    1996-01-01

    Used a Partially Ordered Scaling of Items method to analyze block construction play in a replication of Innes and King-Shaw's 1985 study. Found several developmental pathways for block play, illustrating the web-like nature of conceptual development. Results suggest a contextual developmental approach to better acknowledge individual diversity in…

  14. Critical nodes in signalling pathways

    DEFF Research Database (Denmark)

    Taniguchi, Cullen M; Emanuelli, Brice; Kahn, C Ronald

    2006-01-01

    Physiologically important cell-signalling networks are complex, and contain several points of regulation, signal divergence and crosstalk with other signalling cascades. Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role...... using insulin signalling as a model system....

  15. The oxylipin pathway in Arabidopsis.

    Science.gov (United States)

    Creelman, Robert A; Mulpuri, Rao

    2002-01-01

    Oxylipins are acyclic or cyclic oxidation products derived from the catabolism of fatty acids which regulate many defense and developmental pathways in plants. The dramatic increase in the volume of publications and reviews on these compounds since 1997 documents the increasing interest in this compound and its role in plants. Research on this topic has solidified our understanding of the chemistry and biosynthetic pathways for oxylipin production. However, more information is still needed on how free fatty acids are produced and the role of beta-oxidation in the biosynthetic pathway for oxylipins. It is also becoming apparent that oxylipin content and composition changes during growth and development and during pathogen or insect attack. Oxylipins such as jasmonic acid (JA) or 12-oxo-phytodienoic acid modulate the expression of numerous genes and influence specific aspects of plant growth, development and responses to abiotic and biotic stresses. Although oxylipins are believed to act alone, several examples were presented to illustrate that JA-induced responses are modulated by the type and the nature of crosstalk with other signaling molecules such as ethylene and salicylic acid. How oxylipins cause changes in gene expression and instigate a physiological response is becoming understood with the isolation of mutations in both positive and negative regulators in the jasmonate signaling pathway and the use of cDNA microarrays.

  16. Explanation components as interactive tools

    Energy Technology Data Exchange (ETDEWEB)

    Wahlster, W.

    1983-01-01

    The ability to explain itself is probably the most important criterion of the user-friendliness of interactive systems. Explanation aids in the form of simple help functions do not meet this criterion. The reasons for this are outlined. More promising is an explanation component which can give the user intelligible and context-oriented explanations. The essential requirement for this is the development of knowledge-based interactive systems using artificial intelligence methods and techniques. The authors report on experiences with the development of explanation components, in particular a number of examples from the HAM-ANS project. 12 references.

  17. Radioactive resistance of EEPROM components

    International Nuclear Information System (INIS)

    Loncar, B.; Novakovic, D.; Stankovic, S.; Osmokrovic, P.

    1999-01-01

    The aim of this paper is to examine the resistance of EEPROM components under the influence of gamma radiation. This paper is significant for military industry and space technology. Therefore the analysis of the degradation mechanisms of these components as well as the possibilities to increase their radiation resistance have been considered by many authors. Total dose results are presented for 28C64C EEPROM there is evidence that the first failure appeared for 1000 Gy total dose level. The obtained result are analyzed and explained theoretically via the interaction of gamma radiation with oxide layer. (author)

  18. Space storable propulsion components development

    Science.gov (United States)

    Hagler, R., Jr.

    1982-01-01

    The current development status of components to control the flow of propellants (liquid fluorine and hydrazine) in a demonstration space storable propulsion system is discussed. The criteria which determined the designs for the pressure regulator, explosive-actuated valves, propellant shutoff valve, latching solenoid-actuated valve and propellant filter are presented. The test philosophy that was followed during component development is outlined. The results from compatibility demonstrations for reusable connectors, flange seals, and CRES/Ti-6Al4V transition tubes and the evaluations of processes for welding (hand-held TIG, automated TIG, and EB), cleaning for fluorine service, and decontamination after fluorine exposure are described.

  19. Radiation effects on eye components

    Science.gov (United States)

    Durchschlag, H.; Fochler, C.; Abraham, K.; Kulawik, B.

    1999-08-01

    The most important water-soluble components of the vertebrate eye (lens proteins, aqueous humor, vitreous, hyaluronic acid, ascorbic acid) have been investigated in aqueous solution, after preceding X- or UV-irradiation. Spectroscopic, chromatographic, electrophoretic, hydrodynamic and analytic techniques have been applied, to monitor several radiation damages such as destruction of aromatic and sulfur-containing amino acids, aggregation, crosslinking, dissociation, fragmentation, and partial unfolding. Various substances were found which were able to protect eye components effectively against radiation, some of them being also of medical relevance.

  20. Latent semantics as cognitive components

    DEFF Research Database (Denmark)

    Petersen, Michael Kai; Mørup, Morten; Hansen, Lars Kai

    2010-01-01

    Cognitive component analysis, defined as an unsupervised learning of features resembling human comprehension, suggests that the sensory structures we perceive might often be modeled by reducing dimensionality and treating objects in space and time as linear mixtures incorporating sparsity...... emotional responses can be encoded in words, we propose a simplified cognitive approach to model how we perceive media. Representing song lyrics in a vector space of reduced dimensionality using LSA, we combine bottom-up defined term distances with affective adjectives, that top-down constrain the latent......, which we suggest might function as cognitive components for perceiving the underlying structure in lyrics....

  1. Two-Electron Transfer Pathways.

    Science.gov (United States)

    Lin, Jiaxing; Balamurugan, D; Zhang, Peng; Skourtis, Spiros S; Beratan, David N

    2015-06-18

    The frontiers of electron-transfer chemistry demand that we develop theoretical frameworks to describe the delivery of multiple electrons, atoms, and ions in molecular systems. When electrons move over long distances through high barriers, where the probability for thermal population of oxidized or reduced bridge-localized states is very small, the electrons will tunnel from the donor (D) to acceptor (A), facilitated by bridge-mediated superexchange interactions. If the stable donor and acceptor redox states on D and A differ by two electrons, it is possible that the electrons will propagate coherently from D to A. While structure-function relations for single-electron superexchange in molecules are well established, strategies to manipulate the coherent flow of multiple electrons are largely unknown. In contrast to one-electron superexchange, two-electron superexchange involves both one- and two-electron virtual intermediate states, the number of virtual intermediates increases very rapidly with system size, and multiple classes of pathways interfere with one another. In the study described here, we developed simple superexchange models for two-electron transfer. We explored how the bridge structure and energetics influence multielectron superexchange, and we compared two-electron superexchange interactions to single-electron superexchange. Multielectron superexchange introduces interference between singly and doubly oxidized (or reduced) bridge virtual states, so that even simple linear donor-bridge-acceptor systems have pathway topologies that resemble those seen for one-electron superexchange through bridges with multiple parallel pathways. The simple model systems studied here exhibit a richness that is amenable to experimental exploration by manipulating the multiple pathways, pathway crosstalk, and changes in the number of donor and acceptor species. The features that emerge from these studies may assist in developing new strategies to deliver multiple

  2. Collateralization of descending spinal pathways from red nucleus and other brainstem cell groups in rat, cat and monkey

    NARCIS (Netherlands)

    A.M. Huisman (Margriet)

    1983-01-01

    textabstractThe somatotopically organized rubrospinal pathway is the major component of the laterally descending brainstem pathways, and is especially involved in steering of fractionated movements of the distal parts of the limbs. Electrophysiological studies in cat showed that this fiber

  3. cPath: open source software for collecting, storing, and querying biological pathways

    Directory of Open Access Journals (Sweden)

    Gross Benjamin E

    2006-11-01

    Full Text Available Abstract Background Biological pathways, including metabolic pathways, protein interaction networks, signal transduction pathways, and gene regulatory networks, are currently represented in over 220 diverse databases. These data are crucial for the study of specific biological processes, including human diseases. Standard exchange formats for pathway information, such as BioPAX, CellML, SBML and PSI-MI, enable convenient collection of this data for biological research, but mechanisms for common storage and communication are required. Results We have developed cPath, an open source database and web application for collecting, storing, and querying biological pathway data. cPath makes it easy to aggregate custom pathway data sets available in standard exchange formats from multiple databases, present pathway data to biologists via a customizable web interface, and export pathway data via a web service to third-party software, such as Cytoscape, for visualization and analysis. cPath is software only, and does not include new pathway information. Key features include: a built-in identifier mapping service for linking identical interactors and linking to external resources; built-in support for PSI-MI and BioPAX standard pathway exchange formats; a web service interface for searching and retrieving pathway data sets; and thorough documentation. The cPath software is freely available under the LGPL open source license for academic and commercial use. Conclusion cPath is a robust, scalable, modular, professional-grade software platform for collecting, storing, and querying biological pathways. It can serve as the core data handling component in information systems for pathway visualization, analysis and modeling.

  4. Phylogenetic diversity of stress signalling pathways in fungi

    Directory of Open Access Journals (Sweden)

    Stansfield Ian

    2009-02-01

    Full Text Available Abstract Background Microbes must sense environmental stresses, transduce these signals and mount protective responses to survive in hostile environments. In this study we have tested the hypothesis that fungal stress signalling pathways have evolved rapidly in a niche-specific fashion that is independent of phylogeny. To test this hypothesis we have compared the conservation of stress signalling molecules in diverse fungal species with their stress resistance. These fungi, which include ascomycetes, basidiomycetes and microsporidia, occupy highly divergent niches from saline environments to plant or mammalian hosts. Results The fungi displayed significant variation in their resistance to osmotic (NaCl and sorbitol, oxidative (H2O2 and menadione and cell wall stresses (Calcofluor White and Congo Red. There was no strict correlation between fungal phylogeny and stress resistance. Rather, the human pathogens tended to be more resistant to all three types of stress, an exception being the sensitivity of Candida albicans to the cell wall stress, Calcofluor White. In contrast, the plant pathogens were relatively sensitive to oxidative stress. The degree of conservation of osmotic, oxidative and cell wall stress signalling pathways amongst the eighteen fungal species was examined. Putative orthologues of functionally defined signalling components in Saccharomyces cerevisiae were identified by performing reciprocal BLASTP searches, and the percent amino acid identities of these orthologues recorded. This revealed that in general, central components of the osmotic, oxidative and cell wall stress signalling pathways are relatively well conserved, whereas the sensors lying upstream and transcriptional regulators lying downstream of these modules have diverged significantly. There was no obvious correlation between the degree of conservation of stress signalling pathways and the resistance of a particular fungus to the corresponding stress. Conclusion Our

  5. Environmental Forces - Some Esthetic Components.

    Science.gov (United States)

    Severino, D. Alexander

    Although our system of mass culture has raised our civilization to an extremely high level of material success and affluence, the fact remains that this system has the inherent flaw of not fully recognizing the esthetic needs of man. To overcome this weakness we need to re-introduce into the system a sizable component of first-hand experience…

  6. Components in the interstellar medium

    International Nuclear Information System (INIS)

    Martin, E.R.

    1981-01-01

    An analysis is made of the lines of sight toward 32 stars with a procedure that gives velocity components for various interstellar ions. The column densities found for species expected to be relatively undepleted are used to estimate the column density of neutral hydrogen in each component. Whenever possible, the molecular hydrogen excitation temperature, abundances (relative to S II), electron density, and hydrogen volume density are calculated for each component. The results for each star are combined to give total HI column density as a function of (LSR) velocity. The derived velocities correspond well with those found in optical studies. The mean electron density is found to be approximately constant with velocity, but the mean hydrogen volume density is found to vary. The data presented here are consistent with the assumption that some of the velocity components are due to circumstellar material. The total HI column density toward a given star is generally in agreement with Lyman alpha measurements, but ionization and abundance effects are important toward some stars. The total HI column density is found to vary exponentially with velocity (for N(HI)> 10 17 cm -2 ), with an indication that the velocity dispersion at low column densities (N(HI) 17 cm -2 ) is approximately constant. An estimate is made of the kinetic energy density due to cloud motion which depends only on the total HI column density as a function of velocity. The value of 9 x 10 42 erg/pc 3 is in good agreement with a theoretical prediction

  7. Embedded 100 Gbps Photonic Components:

    Energy Technology Data Exchange (ETDEWEB)

    Kuznia, Charlie

    2018-04-26

    This innovation to fiber optic component technology increases the performance, reduces the size and reduces the power consumption of optical communications within dense network systems, such as advanced distributed computing systems and data centers. VCSEL technology is enabling short-reach (< 100 m) and >100 Gbps optical interconnections over multi-mode fiber in commercial applications.

  8. Inspection of disposal canisters components

    International Nuclear Information System (INIS)

    Pitkaenen, J.

    2013-12-01

    This report presents the inspection techniques of disposal canister components. Manufacturing methods and a description of the defects related to different manufacturing methods are described briefly. The defect types form a basis for the design of non-destructive testing because the defect types, which occur in the inspected components, affect to choice of inspection methods. The canister components are to nodular cast iron insert, steel lid, lid screw, metal gasket, copper tube with integrated or separate bottom, and copper lid. The inspection of copper material is challenging due to the anisotropic properties of the material and local changes in the grain size of the copper material. The cast iron insert has some acoustical material property variation (attenuation, velocity changes, scattering properties), which make the ultrasonic inspection demanding from calibration point of view. Mainly three different methods are used for inspection. Ultrasonic testing technique is used for inspection of volume, eddy current technique, for copper components only, and visual testing technique are used for inspection of the surface and near surface area

  9. Component effects in mixture experiments

    International Nuclear Information System (INIS)

    Piepel, G.F.

    1980-01-01

    In a mixture experiment, the response to a mixture of q components is a function of the proportions x 1 , x 2 , ..., x/sub q/ of components in the mixture. Experimental regions for mixture experiments are often defined by constraints on the proportions of the components forming the mixture. The usual (orthogonal direction) definition of a factor effect does not apply because of the dependence imposed by the mixture restriction, /sup q/Σ/sub i=1/ x/sub i/ = 1. A direction within the experimental region in which to compute a mixture component effect is presented and compared to previously suggested directions. This new direction has none of the inadequacies or errors of previous suggestions while having a more meaningful interpretation. The distinction between partial and total effects is made. The uses of partial and total effects (computed using the new direction) in modification and interpretation of mixture response prediction equations are considered. The suggestions of the paper are illustrated in an example from a glass development study in a waste vitrification program. 5 figures, 3 tables

  10. Modelling Livestock Component in FSSIM

    NARCIS (Netherlands)

    Thorne, P.J.; Hengsdijk, H.; Janssen, S.J.C.; Louhichi, K.; Keulen, van H.; Thornton, P.K.

    2009-01-01

    This document summarises the development of a ruminant livestock component for the Farm System Simulator (FSSIM). This includes treatments of energy and protein transactions in ruminant livestock that have been used as a basis for the biophysical simulations that will generate the input production

  11. A forgotten component of biodiversity

    Indian Academy of Sciences (India)

    2011-07-08

    Jul 8, 2011 ... Home; Journals; Journal of Biosciences; Volume 36; Issue 4. Clipboard: Helminth richness in Arunachal Pradesh fishes: A forgotten component of biodiversity. Amit Tripathi. Volume 36 Issue 4 September 2011 pp 559-561. Fulltext. Click here to view fulltext PDF. Permanent link:

  12. Detecting decay in wood components

    Science.gov (United States)

    R.J. Ross; X. Wang; B.K. Brashaw

    2005-01-01

    This chapter presents a summary of the Wood and Timber Condition Assessment Manual. It focuses on current inspection techniques for decay detection and provides guidelines on the use of various non-destructive evaluation (NDE) methods in locating and defining areas of deterioration in timber bridge components and other civil structures.

  13. A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

    Science.gov (United States)

    Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

    2017-09-01

    The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

  14. Cold component flow in a two-component mirror machine

    International Nuclear Information System (INIS)

    Rognlien, T.D.

    1975-12-01

    Steady-state solutions are given for the flow characteristics along the magnetic field of the cold plasma component in a two-component mirror machine. The hot plasma component is represented by a fixed density profile. The fluid equations are used to describe the cold plasma, which is assumed to be generated in a localized region at one end of the machine. The ion flow speed, v/sub i/, is required to satisfy the Bohm sheath condition at the end walls, i.e., v/sub i/ greater than or equal to c/sub s/, where c/sub s/ is the ion-acoustic speed. For the case when the cold plasma density, n/sub c/, is much less than the hot plasma density, n/sub h/, the cold plasma is stagnant and does not penetrate through the machine in the zero temperature case. The effect of a finite temperature is to allow for the penetration of a small amount of cold plasma through the machine. For the density range n/sub c/ approximately n/sub h/, the flow solutions are asymmetric about the midplane and have v/sub i/ = c/sub s/ near the midplane. Finally, for n/sub c/ much greater than n/sub h/, the solutions become symmetric about the midplane and approach the Lee--McNamara type solutions with v/sub i/ = c/sub s/ near the mirror throats

  15. Alternative pathways to antimatter containment

    International Nuclear Information System (INIS)

    Rejcek, J.M.; Browder, M.K.; Fry, J.L.; Koymen, A.; Weiss, A.H.

    2003-01-01

    Antimatter containment is a gateway technology for future advancements in many areas. Immediate applications in propulsion, medicine, and instrumentation have already been envisioned and many others are yet to be considered. Key to this technological advance is identifying one or more pathways to achieve safe reliable containment of antimatter in sufficient quantities to be useful on an engineering and industrial scale. The goal of this paper is to review current approaches and discuss possible alternative pathways to antimatter containment. Specifically, this paper will address the possibility of designing a solid-state containment system that will safely hold antimatter in quantities dense enough to be of any engineering utility. A discussion of the current research, the needed engineering requirements, and a survey of current research is presented

  16. Molecular pathways towards psychiatric disorders

    International Nuclear Information System (INIS)

    Chela-Flores, J.

    1987-07-01

    The observed fibrillar-neuronal organization of the cerebral cortex suggests that in the aetiology of certain psychiatric disorders the genomic response of the neuron to the challenge presented by stress or insults at various stages of development, is to set off a programmed chain of molecular events (or ''pathways''), as demonstrated in previous genetic studies. The understanding of these pathways is important in order to enhance our ability to influence these illnesses, and are hypothesized to be initiated by a nucleolar mechanism for inducing abnormal synthesis of the nerve growth factor (NGF). The hypothesis is used to approach tentatively the still open question regarding the pathogenesis of mental retardation (MR) and senile dementia (SD). (author). 25 refs

  17. Floral pathway integrator gene expression mediates gradual transmission of environmental and endogenous cues to flowering time.

    Science.gov (United States)

    van Dijk, Aalt D J; Molenaar, Jaap

    2017-01-01

    The appropriate timing of flowering is crucial for the reproductive success of plants. Hence, intricate genetic networks integrate various environmental and endogenous cues such as temperature or hormonal statues. These signals integrate into a network of floral pathway integrator genes. At a quantitative level, it is currently unclear how the impact of genetic variation in signaling pathways on flowering time is mediated by floral pathway integrator genes. Here, using datasets available from literature, we connect Arabidopsis thaliana flowering time in genetic backgrounds varying in upstream signalling components with the expression levels of floral pathway integrator genes in these genetic backgrounds. Our modelling results indicate that flowering time depends in a quite linear way on expression levels of floral pathway integrator genes. This gradual, proportional response of flowering time to upstream changes enables a gradual adaptation to changing environmental factors such as temperature and light.

  18. Floral pathway integrator gene expression mediates gradual transmission of environmental and endogenous cues to flowering time

    Directory of Open Access Journals (Sweden)

    Aalt D.J. van Dijk

    2017-04-01

    Full Text Available The appropriate timing of flowering is crucial for the reproductive success of plants. Hence, intricate genetic networks integrate various environmental and endogenous cues such as temperature or hormonal statues. These signals integrate into a network of floral pathway integrator genes. At a quantitative level, it is currently unclear how the impact of genetic variation in signaling pathways on flowering time is mediated by floral pathway integrator genes. Here, using datasets available from literature, we connect Arabidopsis thaliana flowering time in genetic backgrounds varying in upstream signalling components with the expression levels of floral pathway integrator genes in these genetic backgrounds. Our modelling results indicate that flowering time depends in a quite linear way on expression levels of floral pathway integrator genes. This gradual, proportional response of flowering time to upstream changes enables a gradual adaptation to changing environmental factors such as temperature and light.

  19. Cylinder components properties, applications, materials

    CERN Document Server

    2016-01-01

    Owing to the ever-increasing requirements to be met by gasoline and diesel engines in terms of CO2 reduction, emission behavior, weight, and service life, a comprehensive understanding of combustion engine components is essential today. It is no longer possible for professionals in automotive engineering to manage without the corresponding expertise, whether they work in the field of design, development, testing, or maintenance. This technical book provides in-depth answers to questions about design, production, and machining of cylinder components. In this second edition, every section has been revised and expanded to include the latest developments in the combustion engine. Content Piston rings Piston pins and piston pin circlips Bearings Connecting rods Crankcase and cylinder liners Target audience Engineers in the field of engine development and maintenanceLecturers and students in the areas of mechanical engineering, engine technology, and vehicle constructionAnyone interested in technology Publisher MAH...

  20. Tritium in fusion reactor components

    International Nuclear Information System (INIS)

    Watson, J.S.; Fisher, P.W.; Talbot, J.B.

    1980-01-01

    When tritium is used in a fusion energy experiment or reactor, several implications affect and usually restrict the design and operation of the system and involve questions of containment, inventory, and radiation damage. Containment is expected to be particularly important both for high-temperature components and for those components that are prone to require frequent maintenance. Inventory is currently of major significance in cases where safety and environmental considerations limit the experiments to very low levels of tritium. Fewer inventory restrictions are expected as fusion experiments are placed in more-remote locations and as the fusion community gains experience with the use of tritium. However, the advent of power-producing experiments with high-duty cycle will again lead to serious difficulties based principally on tritium availability; cyclic operations with significant regeneration times are the principal problems

  1. HG ion thruster component testing

    Science.gov (United States)

    Mantenieks, M. A.

    1979-01-01

    Cathodes, isolators, and vaporizers are critical components in determining the performance and lifetime of mercury ion thrusters. The results of life tests of several of these components are reported. A 30-cm thruster CIV test in a bell jar has successfully accumulated over 26,000 hours. The cathode has undergone 65 restarts during the life test without requiring any appreciable increases in starting power. Recently, all restarts have been achieved with only the 44 volt keeper supply with no change required in the starting power. Another ongoing 30-cm Hg thruster cathode test has successfully passed the 10,000 hour mark. A solid-insert, 8-cm thruster cathode has accumulated over 4,000 hours of thruster operation. All starts have been achieved without the use of a high voltage ignitor. The results of this test indicate that the solid impregnated insert is a viable neutralizer cathode for the 8-cm thruster.

  2. Component processes underlying future thinking.

    Science.gov (United States)

    D'Argembeau, Arnaud; Ortoleva, Claudia; Jumentier, Sabrina; Van der Linden, Martial

    2010-09-01

    This study sought to investigate the component processes underlying the ability to imagine future events, using an individual-differences approach. Participants completed several tasks assessing different aspects of future thinking (i.e., fluency, specificity, amount of episodic details, phenomenology) and were also assessed with tasks and questionnaires measuring various component processes that have been hypothesized to support future thinking (i.e., executive processes, visual-spatial processing, relational memory processing, self-consciousness, and time perspective). The main results showed that executive processes were correlated with various measures of future thinking, whereas visual-spatial processing abilities and time perspective were specifically related to the number of sensory descriptions reported when specific future events were imagined. Furthermore, individual differences in self-consciousness predicted the subjective feeling of experiencing the imagined future events. These results suggest that future thinking involves a collection of processes that are related to different facets of future-event representation.

  3. Nuclear power plant component protection

    International Nuclear Information System (INIS)

    Michel, E.; Ruf, R.; Dorner, H.

    1976-01-01

    Described is a nuclear power plant installation which includes a concrete biological shield forming a pit in which a reactor pressure vessel is positioned. A steam generator on the outside of the shield is connected with the pressure vessel via coolant pipe lines which extend through the shield, the coolant circulation being provided by a coolant pump which is also on the outside of the shield. To protect these components on the outside of the shield and which are of mainly or substantially cylindrical shape, semicylindrical concrete segments are interfitted around them to form complete outer cylinders which are retained against outward separation radially from the components, by rings of high tensile steel which may be interspaced so closely that they provide, in effect, an outer steel cylinder. The invention is particularly applicable to pressurized-water coolant reactor installations

  4. Vanillin biosynthetic pathways in plants.

    Science.gov (United States)

    Kundu, Anish

    2017-06-01

    The present review compiles the up-to-date knowledge on vanillin biosynthesis in plant systems to focus principally on the enzymatic reactions of in planta vanillin biosynthetic pathway and to find out its impact and prospect in future research in this field. Vanillin, a very popular flavouring compound, is widely used throughout the world. The principal natural resource of vanillin is the cured vanilla pods. Due to the high demand of vanillin as a flavouring agent, it is necessary to explore its biosynthetic enzymes and genes, so that improvement in its commercial production can be achieved through metabolic engineering. In spite of significant advancement in elucidating vanillin biosynthetic pathway in the last two decades, no conclusive demonstration had been reported yet for plant system. Several biosynthetic enzymes have been worked upon but divergences in published reports, particularly in characterizing the crucial biochemical steps of vanillin biosynthesis, such as side-chain shortening, methylation, and glucoside formation and have created a space for discussion. Recently, published reviews on vanillin biosynthesis have focused mainly on the biotechnological approaches and bioconversion in microbial systems. This review, however, aims to compile in brief the overall vanillin biosynthetic route and present a comparative as well as comprehensive description of enzymes involved in the pathway in Vanilla planifolia and other plants. Special emphasis has been given on the key enzymatic biochemical reactions that have been investigated extensively. Finally, the present standpoint and future prospects have been highlighted.

  5. Dual Pathways to Prospective Remembering

    Directory of Open Access Journals (Sweden)

    Mark A Mcdaniel

    2015-07-01

    Full Text Available According to the multiprocess framework (McDaniel & Einstein, 2000, the cognitive system can support prospective memory (PM retrieval through two general pathways. One pathway depends on top-down attentional control processes that maintain activation of the intention and/or monitor the environment for the triggering or target cues that indicate that the intention should be executed. A second pathway depends on (bottom-up spontaneous retrieval processes, processes that are often triggered by a PM target cue; critically spontaneous retrieval is assumed to not require monitoring or active maintenance of the intention. Given demand characteristics associated with experimental settings, however, participants are often inclined to monitor, thereby potentially masking discovery of bottom-up spontaneous retrieval processes. In this article, we discuss parameters of laboratory PM paradigms to discourage monitoring and review recent behavioral evidence from such paradigms that implicate spontaneous retrieval in PM. We then re-examine the neuro-imaging evidence from the lens of the multiprocess framework and suggest some critical modifications to existing neuro-cognitive interpretations of the neuro-imaging results. These modifications illuminate possible directions and refinements for further neuro-imaging investigations of PM.

  6. Dual pathways to prospective remembering

    Science.gov (United States)

    McDaniel, Mark A.; Umanath, Sharda; Einstein, Gilles O.; Waldum, Emily R.

    2015-01-01

    According to the multiprocess framework (McDaniel and Einstein, 2000), the cognitive system can support prospective memory (PM) retrieval through two general pathways. One pathway depends on top–down attentional control processes that maintain activation of the intention and/or monitor the environment for the triggering or target cues that indicate that the intention should be executed. A second pathway depends on (bottom–up) spontaneous retrieval processes, processes that are often triggered by a PM target cue; critically, spontaneous retrieval is assumed not to require monitoring or active maintenance of the intention. Given demand characteristics associated with experimental settings, however, participants are often inclined to monitor, thereby potentially masking discovery of bottom–up spontaneous retrieval processes. In this article, we discuss parameters of laboratory PM paradigms to discourage monitoring and review recent behavioral evidence from such paradigms that implicate spontaneous retrieval in PM. We then re-examine the neuro-imaging evidence from the lens of the multiprocess framework and suggest some critical modifications to existing neuro-cognitive interpretations of the neuro-imaging results. These modifications illuminate possible directions and refinements for further neuro-imaging investigations of PM. PMID:26236213

  7. Imbalanced Kynurenine Pathway in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Magdalena E. Kegel

    2014-01-01

    Full Text Available Several studies suggest a role for kynurenic acid (KYNA in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN. Here we investigate the levels of QUIN in cerebrospinal fluid (CSF of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22 and those of controls (n = 26 were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36. CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls ( P = 0.027. In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

  8. Maternal smoking and the retinoid pathway in the developing lung

    Directory of Open Access Journals (Sweden)

    Manoli Sara E

    2012-06-01

    Full Text Available Abstract Background Maternal smoking is a risk factor for pediatric lung disease, including asthma. Animal models suggest that maternal smoking causes defective alveolarization in the offspring. Retinoic acid signaling modulates both lung development and postnatal immune function. Thus, abnormalities in this pathway could mediate maternal smoking effects. We tested whether maternal smoking disrupts retinoic acid pathway expression and functioning in a murine model. Methods Female C57Bl/6 mice with/without mainstream cigarette smoke exposure (3 research cigarettes a day, 5 days a week were mated to nonsmoking males. Cigarette smoke exposure continued throughout the pregnancy and after parturition. Lung tissue from the offspring was examined by mean linear intercept analysis and by quantitative PCR. Cell culture experiments using the type II cell-like cell line, A549, tested whether lipid-soluble cigarette smoke components affected binding and activation of retinoic acid response elements in vitro. Results Compared to tobacco-naïve mice, juvenile mice with tobacco toxin exposure had significantly (P  Conclusions A murine model of maternal cigarette smoking causes abnormal alveolarization in association with altered retinoic acid pathway element expression in the offspring. An in vitro cell culture model shows that lipid-soluble components of cigarette smoke decrease retinoic acid response element activation. It is feasible that disruption of retinoic acid signaling contributes to the pediatric lung dysfunction caused by maternal smoking.

  9. Genetic screens to identify new Notch pathway mutants in Drosophila.

    Science.gov (United States)

    Giagtzoglou, Nikolaos

    2014-01-01

    Notch signaling controls a wide range of developmental processes, including proliferation, apoptosis, and cell fate specification during both development and adult tissue homeostasis. The functional versatility of the Notch signaling pathway is tightly linked with the complexity of its regulation in different cellular contexts. To unravel the complexity of Notch signaling, it is important to identify the different components of the Notch signaling pathway. A powerful strategy to accomplish this task is based on genetic screens. Given that the developmental context of signaling is important, these screens should be customized to specific cell populations or tissues. Here, I describe how to perform F1 clonal forward genetic screens in Drosophila to identify novel components of the Notch signaling pathway. These screens combine a classical EMS (ethyl methanesulfonate) chemical mutagenesis protocol along with clonal analysis via FRT-mediated mitotic recombination. These F1 clonal screens allow rapid phenotypic screening within clones of mutant cells induced at specific developmental stages and in tissues of interest, bypassing the pleiotropic effects of isolated mutations. More importantly, since EMS mutations have been notoriously difficult to map to specific genes in the past, I briefly discuss mapping methods that allow rapid identification of the causative mutations.

  10. Open Component Portability Infrastructure (OPENCPI)

    Science.gov (United States)

    2013-03-01

    declaration of the authored worker that must be implemented . If there is existing legacy VHDL entity architecture, then it is wrapped or modified to...that the software implementations were written to. Since all of the original code was VHDL , the HDL Authoring Model for VHDL was enhanced to meet...engineering process. This application was completed for the execution of all the components, the software implementations , and the VHDL skeletons for the

  11. Behavior Protocols for Software Components

    Czech Academy of Sciences Publication Activity Database

    Plášil, František; Višňovský, Stanislav

    2002-01-01

    Roč. 28, č. 11 (2002), s. 1056-1076 ISSN 0098-5589 R&D Projects: GA AV ČR IAA2030902; GA ČR GA201/99/0244 Grant - others:Eureka(XE) Pepita project no.2033 Institutional research plan: AV0Z1030915 Keywords : behavior protocols * component-based programming * software architecture Subject RIV: JC - Computer Hardware ; Software Impact factor: 1.170, year: 2002

  12. Chemical decontamination of reactor components

    International Nuclear Information System (INIS)

    Riess, R.; Berthold, H.O.

    1977-08-01

    A solution for the decontamination of reactor components of the primary system was developed. This solution is a modification of the APAC- (Alkaline Permanganate Ammonium Citrate) system described in the literature. The most important advantage of the present solution over the APAC-method is that it does not induce any selective corrosion attack on materials like stainless steel (austenitic), Inconel 600 and Incoloy 800. (orig.) [de

  13. The risk components of liquidity

    OpenAIRE

    Chollete, Lorán; Næs, Randi; Skjeltorp, Johannes A.

    2008-01-01

    Does liquidity risk differ depending on our choice of liquidity proxy? Unlike literature that considers common liquidity variation, we focus on identifying different components of liquidity, statistically and economically, using more than a decade of US transaction data. We identify three main statistical liquidity factors which are utilized in a linear asset pricing framework. We motivate a correspondence of the statistical factors to traditional dimensions of liquidity as well as the notion...

  14. New Jersey's experience with implementing Protective Action Guides during the 1988 Salem ingestion pathway exercise

    International Nuclear Information System (INIS)

    White, Duncan

    1989-01-01

    On November 30 and December 1, 1988, the New Jersey Department of Environmental Protection (DEP) and three other State agencies (Health, Agriculture and State Police) participated in the ingestion pathway portion of the 1988 Salem Nuclear Generating Station Emergency Exercise. The purpose of this phase of the exercise was to demonstrate the ingestion pathway components of the State's Radiological Emergency Response Plan (RERP) to the Federal Emergency Management Agency (FEMA). The intent of this paper is to provide a summary of difficulties and some lessons learned in implementing the DEP's ingestion pathway Protective Action Guides (PAGs) during the exercise as well as during the preparation of a total population dose estimate (TPDE)

  15. New Jersey's experience with implementing Protective Action Guides during the 1988 Salem ingestion pathway exercise

    Energy Technology Data Exchange (ETDEWEB)

    White, Duncan [New Jersey Department of Environmental Protection, Trenton, NJ (United States)

    1989-09-01

    On November 30 and December 1, 1988, the New Jersey Department of Environmental Protection (DEP) and three other State agencies (Health, Agriculture and State Police) participated in the ingestion pathway portion of the 1988 Salem Nuclear Generating Station Emergency Exercise. The purpose of this phase of the exercise was to demonstrate the ingestion pathway components of the State's Radiological Emergency Response Plan (RERP) to the Federal Emergency Management Agency (FEMA). The intent of this paper is to provide a summary of difficulties and some lessons learned in implementing the DEP's ingestion pathway Protective Action Guides (PAGs) during the exercise as well as during the preparation of a total population dose estimate (TPDE)

  16. Reformulating Component Identification as Document Analysis Problem

    NARCIS (Netherlands)

    Gross, H.G.; Lormans, M.; Zhou, J.

    2007-01-01

    One of the first steps of component procurement is the identification of required component features in large repositories of existing components. On the highest level of abstraction, component requirements as well as component descriptions are usually written in natural language. Therefore, we can

  17. Coherent systems with multistate components

    International Nuclear Information System (INIS)

    Caldarola, L.

    1980-01-01

    The basic rules of the Boolean algebra with restrictions on variables are briefly recalled. This special type of Boolean algebra allows one to handle fault trees of systems made of multistate (two or more than two states) components. Coherent systems are defined in the case of multistate components. This definition is consistent with that originally suggested by Barlow in the case of binary (two states) components. The basic properties of coherence are described and discussed. Coherent Boolean functions are also defined. It is shown that these functions are irredundant, that is they have only one base which is at the same time complete and irredundant. However, irredundant functions are not necessarily coherent. Finally a simplified algorithm for the calculation of the base of a coherent function is described. In the case that the function is not coherent, the algorithm can be used to reduce the size of the normal disjunctive form of the function. This in turn eases the application of the Nelson algorithm to calculate the complete base of the function. The simplified algorithm has been built in the computer program MUSTAFA-1. In a sample case the use of this algorithm caused a reduction of the CPU time by a factor of about 20. (orig.)

  18. Radiation damage to electronic components

    International Nuclear Information System (INIS)

    Battisti, S.; Bossart, R.; Schoenbacher, H.; Van de Voorde, M.

    1975-01-01

    Characteristic properties are presented of some 40 different electronic components (resistors, capacitors, diodes, transistors, and integrated circuits) which were irradiated in a nuclear reactor up to 1015 n/cm 2 (E > 1 MeV). Complete circuits (e.g. RF amplifiers and detectors, mixers, differential amplifiers, voltage-to-frequency converters, oscillators, power supplies) were irradiated near the CERN Intersecting Storage Rings up to 106 rad(RPL) (dose measured with radiophotoluminescent dosimeters) under simulated operational conditions. Representative measured parameters, such as resistance, capacitance, forward voltage, reverse current, toggle frequencies, are given in graphs as a function of radiation dose. The results are discussed in detail and lead to the over-all conclusion that the operation of electronic components and circuits is seriously affected by radiation environments with doses in the order of 10 13 n/cm 2 or 10 4 rad(RPL); some components and circuits fail completely at doses of 10 14 n/cm 2 or 10 5 rad(RPL). (Author)

  19. Fusion-component lifetime analysis

    International Nuclear Information System (INIS)

    Mattas, R.F.

    1982-09-01

    A one-dimensional computer code has been developed to examine the lifetime of first-wall and impurity-control components. The code incorporates the operating and design parameters, the material characteristics, and the appropriate failure criteria for the individual components. The major emphasis of the modeling effort has been to calculate the temperature-stress-strain-radiation effects history of a component so that the synergystic effects between sputtering erosion, swelling, creep, fatigue, and crack growth can be examined. The general forms of the property equations are the same for all materials in order to provide the greatest flexibility for materials selection in the code. The individual coefficients within the equations are different for each material. The code is capable of determining the behavior of a plate, composed of either a single or dual material structure, that is either totally constrained or constrained from bending but not from expansion. The code has been utilized to analyze the first walls for FED/INTOR and DEMO and to analyze the limiter for FED/INTOR

  20. Radiation effects on eye components

    International Nuclear Information System (INIS)

    Durchschlag, H.; Fochler, C.; Abraham, K.; Kulawik, B.

    1998-01-01

    The radiation damage (X-ray, UV light) of the most important components of the vertebrate eye (crystallins and other proteins, hyaluronic acid, vitreous, aqueous humour, ascorbic acid) has been investigated by various methods of physical chemistry. UV absorption and fluorescence spectroscopy as well as circular dichroism unveiled changes of the chromophores/fluorophores of the constituent biopolymers and low-molecular components, together with alterations of helix content and the occurrence of aggregation. Size-exclusion chromatography, analytical ultracentrifugation, densimetry, viscometry and light scattering experiments monitored changes of the global structure of proteins and polysaccharides involved. Electrophoreses allowed conclusions on fragmentation, unfolding and crosslinking. Analytical methods provided information regarding the integrity of groups of special concern (SH, SS) and revealed the existence of stable noxious species (H 2 O 2 ). By means of various measures and additives, manifold modifications of the impact of both ionizing and nonionizing radiation may be achieved. Caused by differences in the primary reactions, eye polymers are protected efficaciously by typical OH radical scavengers against X-irradiation, whereas compounds which exhibit absorption behavior in the UV range turn out to act as potent protectives ('chemical filters') against UV light. A few substances, such as ascorbate, are able to provide protection against both sorts of radiation and are even able to exhibit a slight chemical repair of already damaged particles. The results obtained are of importance for understanding pathological alterations of the eye (loss of transparency, cataractogenesis) and for developing new strategies for protection and repair of eye components. (author)

  1. Intercellular signaling pathways active during intervertebral disc growth, differentiation, and aging.

    Science.gov (United States)

    Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

    2009-03-01

    Intervertebral discs at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the signaling pathways active in the postnatal intervertebral disc (IVD). The postnatal IVD is a complex structure, consisting of 3 histologically distinct components, the nucleus pulposus, fibrous anulus fibrosus, and endplate. These differentiate and grow during the first 9 weeks of age in the mouse. Identification of the major signaling pathways active during and after the growth and differentiation period will allow functional analysis using mouse genetics and identify targets for therapy for individual components of the disc. Antibodies specific for individual cell signaling pathways were used on cryostat sections of IVD at different postnatal ages to identify which components of the IVD were responding to major classes of intercellular signal, including sonic hedgehog, Wnt, TGFbeta, FGF, and BMPs. We present a spatial/temporal map of these signaling pathways during growth, differentiation, and aging of the disc. During growth and differentiation of the disc, its different components respond at different times to different intercellular signaling ligands. Most of these are dramatically downregulated at the end of disc growth.

  2. Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

    Science.gov (United States)

    Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

    2017-06-01

    Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RPpathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RPpathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017

  3. Activation of DNA damage repair pathways by murine polyomavirus

    Energy Technology Data Exchange (ETDEWEB)

    Heiser, Katie; Nicholas, Catherine; Garcea, Robert L., E-mail: Robert.Garcea@Colorado.edu

    2016-10-15

    Nuclear replication of DNA viruses activates DNA damage repair (DDR) pathways, which are thought to detect and inhibit viral replication. However, many DNA viruses also depend on these pathways in order to optimally replicate their genomes. We investigated the relationship between murine polyomavirus (MuPyV) and components of DDR signaling pathways including CHK1, CHK2, H2AX, ATR, and DNAPK. We found that recruitment and retention of DDR proteins at viral replication centers was independent of H2AX, as well as the viral small and middle T-antigens. Additionally, infectious virus production required ATR kinase activity, but was independent of CHK1, CHK2, or DNAPK signaling. ATR inhibition did not reduce the total amount of viral DNA accumulated, but affected the amount of virus produced, indicating a defect in virus assembly. These results suggest that MuPyV may utilize a subset of DDR proteins or non-canonical DDR signaling pathways in order to efficiently replicate and assemble. -- Highlights: •Murine polyomavirus activates and recruits DNA damage repair (DDR) proteins to replication centers. •Large T-antigen mediates recruitment of DDR proteins to viral replication centers. •Inhibition or knockout of CHK1, CHK2, DNA-PK or H2AX do not affect viral titers. •Inhibition of ATR activity reduces viral titers, but not viral DNA accumulation.

  4. Alternative pathways for angiotensin II generation in the cardiovascular system

    Directory of Open Access Journals (Sweden)

    C. Becari

    2011-09-01

    Full Text Available The classical renin-angiotensin system (RAS consists of enzymes and peptides that regulate blood pressure and electrolyte and fluid homeostasis. Angiotensin II (Ang II is one of the most important and extensively studied components of the RAS. The beneficial effects of angiotensin converting enzyme (ACE inhibitors in the treatment of hypertension and heart failure, among other diseases, are well known. However, it has been reported that patients chronically treated with effective doses of these inhibitors do not show suppression of Ang II formation, suggesting the involvement of pathways alternative to ACE in the generation of Ang II. Moreover, the finding that the concentration of Ang II is preserved in the kidney, heart and lungs of mice with an ACE deletion indicates the important role of alternative pathways under basal conditions to maintain the levels of Ang II. Our group has characterized the serine protease elastase-2 as an alternative pathway for Ang II generation from Ang I in rats. A role for elastase-2 in the cardiovascular system was suggested by studies performed in heart and conductance and resistance vessels of normotensive and spontaneously hypertensive rats. This mini-review will highlight the pharmacological aspects of the RAS, emphasizing the role of elastase-2, an alternative pathway for Ang II generation.

  5. Method for determining heterologous biosynthesis pathways

    KAUST Repository

    Gao, Xin; Kuwahara, Hiroyuki; Alazmi, Meshari Saud; Cui, Xuefeng

    2017-01-01

    suitable pathways for the endogenous metabolism of a host organism because the efficacy of heterologous biosynthesis is affected by competing endogenous pathways. The present invention is called MRE (Metabolic Route Explorer), and it was conceived

  6. Primary Metabolic Pathways and Metabolic Flux Analysis

    DEFF Research Database (Denmark)

    Villadsen, John

    2015-01-01

    his chapter introduces the metabolic flux analysis (MFA) or stoichiometry-based MFA, and describes the quantitative basis for MFA. It discusses the catabolic pathways in which free energy is produced to drive the cell-building anabolic pathways. An overview of these primary pathways provides...... the reader who is primarily trained in the engineering sciences with atleast a preliminary introduction to biochemistry and also shows how carbon is drained off the catabolic pathways to provide precursors for cell mass building and sometimes for important industrial products. The primary pathways...... to be examined in the following are: glycolysis, primarily by the EMP pathway, but other glycolytic pathways is also mentioned; fermentative pathways in which the redox generated in the glycolytic reactions are consumed; reactions in the tricarboxylic acid (TCA) cycle, which produce biomass precursors and redox...

  7. CD137 pathway: immunology and diseases

    National Research Council Canada - National Science Library

    Chen, Lieping

    2006-01-01

    ... may work in either interconnected or linear fashion. Therefore, the combined understanding of each pathway, their interactions with other pathways, and the functional consequence, is a cornerstone for our interpretation of pathological basis of diseases and future treatments. It is important to stay abreast on the pace of progress, which I refer to as periodic summary of incremental and breakthrough discoveries in each pathway by the experts and the leader in the field. The CD137 Pathway: Immu...

  8. Certification Criteria for Linked Learning Pathways

    Science.gov (United States)

    ConnectEd: The California Center for College and Career, 2010

    2010-01-01

    Pathways offer a promising strategy for transforming high schools and improving student outcomes. However, to achieve these desired results, pathways must be of high quality. To guide sites in planning and implementing such pathways, a design team of experts developed the criteria outlined in this document. Sites can choose to go through a…

  9. A long slanted transseptal accessory pathway

    Directory of Open Access Journals (Sweden)

    Hui-Min Wang

    2011-05-01

    Full Text Available A 63-year-old male with Wolff-Parkinson-White syndrome was admitted for ablation of accessory pathway. Intracardiac electrogram revealed a left-side accessory pathway during tachycardia, which was successfully ablated from the right posterior tricuspid annulus because of a long slanted transseptal accessory pathway (2.2 cm.

  10. Web components and the semantic web

    OpenAIRE

    Casey, Maire; Pahl, Claus

    2003-01-01

    Component-based software engineering on the Web differs from traditional component and software engineering. We investigate Web component engineering activites that are crucial for the development,com position, and deployment of components on the Web. The current Web Services and Semantic Web initiatives strongly influence our work. Focussing on Web component composition we develop description and reasoning techniques that support a component developer in the composition activities,fo cussing...

  11. Efficient algorithms for extracting biological key pathways with global constraints

    DEFF Research Database (Denmark)

    Baumbach, Jan; Friedrich, T.; Kötzing, T.

    2012-01-01

    The integrated analysis of data of different types and with various interdependencies is one of the major challenges in computational biology. Recently, we developed KeyPathwayMiner, a method that combines biological networks modeled as graphs with disease-specific genetic expression data gained....... Here we present an alternative approach that avoids a certain bias towards hub nodes: We now aim for extracting all maximal connected sub-networks where all but at most K nodes are expressed in all cases but in total (!) at most L, i.e. accumulated over all cases and all nodes in a solution. We call...... this strategy GLONE (global node exceptions); the previous problem we call INES (individual node exceptions). Since finding GLONE-components is computationally hard, we developed an Ant Colony Optimization algorithm and implemented it with the KeyPathwayMiner Cytoscape framework as an alternative to the INES...

  12. Bonding pathways of high-pressure chemical transformations

    International Nuclear Information System (INIS)

    Hu Anguang; Zhang Fan

    2013-01-01

    A three-stage bonding pathway towards high-pressure chemical transformations from molecular precursors or intermediate states has been identified by first-principles simulations. With the evolution of principal stress tensor components in the response of chemical bonding to compressive loading, the three stages can be defined as the van der Waals bonding destruction, a bond breaking and forming reaction, and equilibrium of new bonds. The three-stage bonding pathway leads to the establishment of a fundamental principle of chemical bonding under compression. It reveals that during high-pressure chemical transformation, electrons moving away from functional groups follow anti-addition, collision-free paths to form new bonds in counteracting the local stress confinement. In applying this principle, a large number of molecular precursors were identified for high-pressure chemical transformations, resulting in new materials. (fast track communication)

  13. Text mining in cancer gene and pathway prioritization.

    Science.gov (United States)

    Luo, Yuan; Riedlinger, Gregory; Szolovits, Peter

    2014-01-01

    Prioritization of cancer implicated genes has received growing attention as an effective way to reduce wet lab cost by computational analysis that ranks candidate genes according to the likelihood that experimental verifications will succeed. A multitude of gene prioritization tools have been developed, each integrating different data sources covering gene sequences, differential expressions, function annotations, gene regulations, protein domains, protein interactions, and pathways. This review places existing gene prioritization tools against the backdrop of an integrative Omic hierarchy view toward cancer and focuses on the analysis of their text mining components. We explain the relatively slow progress of text mining in gene prioritization, identify several challenges to current text mining methods, and highlight a few directions where more effective text mining algorithms may improve the overall prioritization task and where prioritizing the pathways may be more desirable than prioritizing only genes.

  14. mc1r Pathway regulation of zebrafish melanosome dispersion

    DEFF Research Database (Denmark)

    Richardson, Jennifer; Lundegaard, Pia Rengtved; Reynolds, Natalie L

    2008-01-01

    Zebrafish rapidly alter their pigmentation in response to environmental changes. For black melanocytes, this change is due to aggregation or dispersion of melanin in the cell. Dispersion and aggregation are controlled by intracellular cyclic adenosine monophosphate (cAMP) levels, which increase...... in mammals, and melanosome dispersal in cold-blood vertebrates, the pathway components are highly conserved. However, it has only been assumed that mc1r mediates melanosome dispersal in fish. Here, using morpholino oligonucleotides designed to knockdown mc1r expression, we find that mc1r morphants are unable...... to disperse melanosomes when grown in dark conditions. We also use chemical modifiers of the cAMP pathway, and find an unexpected response to the specific phosphodiesterase 4 (PDE4) inhibitor, rolipram, in melanosome dispersal. When treated with the drug, melanosomes fail to fully disperse in dark conditions...

  15. A novel dysregulated pathway-identification analysis based on global influence of within-pathway effects and crosstalk between pathways

    Science.gov (United States)

    Han, Junwei; Li, Chunquan; Yang, Haixiu; Xu, Yanjun; Zhang, Chunlong; Ma, Jiquan; Shi, Xinrui; Liu, Wei; Shang, Desi; Yao, Qianlan; Zhang, Yunpeng; Su, Fei; Feng, Li; Li, Xia

    2015-01-01

    Identifying dysregulated pathways from high-throughput experimental data in order to infer underlying biological insights is an important task. Current pathway-identification methods focus on single pathways in isolation; however, consideration of crosstalk between pathways could improve our understanding of alterations in biological states. We propose a novel method of pathway analysis based on global influence (PAGI) to identify dysregulated pathways, by considering both within-pathway effects and crosstalk between pathways. We constructed a global gene–gene network based on the relationships among genes extracted from a pathway database. We then evaluated the extent of differential expression for each gene, and mapped them to the global network. The random walk with restart algorithm was used to calculate the extent of genes affected by global influence. Finally, we used cumulative distribution functions to determine the significance values of the dysregulated pathways. We applied the PAGI method to five cancer microarray datasets, and compared our results with gene set enrichment analysis and five other methods. Based on these analyses, we demonstrated that PAGI can effectively identify dysregulated pathways associated with cancer, with strong reproducibility and robustness. We implemented PAGI using the freely available R-based and Web-based tools (http://bioinfo.hrbmu.edu.cn/PAGI). PMID:25551156

  16. Hierarchical modularization of biochemical pathways using fuzzy-c means clustering.

    Science.gov (United States)

    de Luis Balaguer, Maria A; Williams, Cranos M

    2014-08-01

    Biological systems that are representative of regulatory, metabolic, or signaling pathways can be highly complex. Mathematical models that describe such systems inherit this complexity. As a result, these models can often fail to provide a path toward the intuitive comprehension of these systems. More coarse information that allows a perceptive insight of the system is sometimes needed in combination with the model to understand control hierarchies or lower level functional relationships. In this paper, we present a method to identify relationships between components of dynamic models of biochemical pathways that reside in different functional groups. We find primary relationships and secondary relationships. The secondary relationships reveal connections that are present in the system, which current techniques that only identify primary relationships are unable to show. We also identify how relationships between components dynamically change over time. This results in a method that provides the hierarchy of the relationships among components, which can help us to understand the low level functional structure of the system and to elucidate potential hierarchical control. As a proof of concept, we apply the algorithm to the epidermal growth factor signal transduction pathway, and to the C3 photosynthesis pathway. We identify primary relationships among components that are in agreement with previous computational decomposition studies, and identify secondary relationships that uncover connections among components that current computational approaches were unable to reveal.

  17. Component Control System for a Vehicle

    Science.gov (United States)

    Fraser-Chanpong, Nathan (Inventor); Spain, Ivan (Inventor); Dawson, Andrew D. (Inventor); Bluethmann, William J. (Inventor); Lee, Chunhao J. (Inventor); Vitale, Robert L. (Inventor); Guo, Raymond (Inventor); Waligora, Thomas M. (Inventor); Akinyode, Akinjide Akinniyi (Inventor); Reed, Ryan M. (Inventor)

    2016-01-01

    A vehicle includes a chassis, a modular component, and a central operating system. The modular component is supported by the chassis. The central operating system includes a component control system, a primary master controller, and a secondary master controller. The component control system is configured for controlling the modular component. The primary and secondary master controllers are in operative communication with the component control system. The primary and secondary master controllers are configured to simultaneously transmit commands to the component control system. The component control system is configured to accept commands from the secondary master controller only when a fault occurs in the primary master controller.

  18. Epigenetic Pathways of Oncogenic Viruses: Therapeutic Promises.

    Science.gov (United States)

    El-Araby, Amr M; Fouad, Abdelrahman A; Hanbal, Amr M; Abdelwahab, Sara M; Qassem, Omar M; El-Araby, Moustafa E

    2016-02-01

    Cancerous transformation comprises different events that are both genetic and epigenetic. The ultimate goal for such events is to maintain cell survival and proliferation. This transformation occurs as a consequence of different features such as environmental and genetic factors, as well as some types of infection. Many viral infections are considered to be causative agents of a number of different malignancies. To convert normal cells into cancerous cells, oncogenic viruses must function at the epigenetic level to communicate with their host cells. Oncogenic viruses encode certain epigenetic factors that lead to the immortality and proliferation of infected cells. The epigenetic effectors produced by oncogenic viruses constitute appealing targets to prevent and treat malignant diseases caused by these viruses. In this review, we highlight the importance of epigenetic reprogramming for virus-induced oncogenesis, with special emphasis on viral epigenetic oncoproteins as therapeutic targets. The discovery of molecular components that target epigenetic pathways, especially viral factors, is also discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Towards integrating extracellular matrix and immunological pathways.

    Science.gov (United States)

    Boyd, David F; Thomas, Paul G

    2017-10-01

    The extracellular matrix (ECM) is a complex and dynamic structure made up of an estimated 300 different proteins. The ECM is also a rich source of cytokines and growth factors in addition to numerous bioactive ECM degradation products that influence cell migration, proliferation, and differentiation. The ECM is constantly being remodeled during homeostasis and in a wide range of pathological contexts. Changes in the ECM modulate immune responses, which in turn regulate repair and regeneration of tissues. Here, we review the many components of the ECM, enzymes involved in ECM remodeling, and the signals that feed into immunological pathways in the context of a dynamic ECM. We highlight studies that have taken an integrative approach to studying immune responses in the context of the ECM and studies that use novel proteomic strategies. Finally, we discuss research challenges relevant to the integration of immune and ECM networks and propose experimental and translational approaches to resolve these issues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Making Sense of the Yeast Sphingolipid Pathway.

    Science.gov (United States)

    Megyeri, Márton; Riezman, Howard; Schuldiner, Maya; Futerman, Anthony H

    2016-12-04

    Sphingolipids (SL) and their metabolites play key roles both as structural components of membranes and as signaling molecules. Many of the key enzymes and regulators of SL metabolism were discovered using the yeast Saccharomyces cerevisiae, and based on the high degree of conservation, a number of mammalian homologs were identified. Although yeast continues to be an important tool for SL research, the complexity of SL structure and nomenclature often hampers the ability of new researchers to grasp the subtleties of yeast SL biology and discover new modulators of this intricate pathway. Moreover, the emergence of lipidomics by mass spectrometry has enabled the rapid identification of SL species in yeast and rendered the analysis of SL composition under various physiological and pathophysiological conditions readily amenable. However, the complex nomenclature of the identified species renders much of the data inaccessible to non-specialists. In this review, we focus on parsing both the classical SL nomenclature and the nomenclature normally used during mass spectrometry analysis, which should facilitate the understanding of yeast SL data and might shed light on biological processes in which SLs are involved. Finally, we discuss a number of putative roles of various yeast SL species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Modeling biological pathway dynamics with timed automata.

    Science.gov (United States)

    Schivo, Stefano; Scholma, Jetse; Wanders, Brend; Urquidi Camacho, Ricardo A; van der Vet, Paul E; Karperien, Marcel; Langerak, Rom; van de Pol, Jaco; Post, Janine N

    2014-05-01

    Living cells are constantly subjected to a plethora of environmental stimuli that require integration into an appropriate cellular response. This integration takes place through signal transduction events that form tightly interconnected networks. The understanding of these networks requires capturing their dynamics through computational support and models. ANIMO (analysis of Networks with Interactive Modeling) is a tool that enables the construction and exploration of executable models of biological networks, helping to derive hypotheses and to plan wet-lab experiments. The tool is based on the formalism of Timed Automata, which can be analyzed via the UPPAAL model checker. Thanks to Timed Automata, we can provide a formal semantics for the domain-specific language used to represent signaling networks. This enforces precision and uniformity in the definition of signaling pathways, contributing to the integration of isolated signaling events into complex network models. We propose an approach to discretization of reaction kinetics that allows us to efficiently use UPPAAL as the computational engine to explore the dynamic behavior of the network of interest. A user-friendly interface hides the use of Timed Automata from the user, while keeping the expressive power intact. Abstraction to single-parameter kinetics speeds up construction of models that remain faithful enough to provide meaningful insight. The resulting dynamic behavior of the network components is displayed graphically, allowing for an intuitive and interactive modeling experience.

  2. Experimental qualification of nuclear components

    Energy Technology Data Exchange (ETDEWEB)

    Alliot, P; Fronte, T; Genty, F [FRAMATOME - Cedex 16, Paris la Defense (France)

    1988-07-01

    In the process of showing the adequacy of the seismic design of French PWR reactor, Fermat has repeatedly used dynamic testing on actual nuclear reactor components both on site and in manufacturing shops. The objective and results of a few representative examples of this on-site experimental verification are presented in this paper: the experimental dynamic analysis of a manipulator crane; the investigation of the seismic behaviour of fuel storage racks equipped with aseismic bearing devices. Difficulties to select satisfactory testing methods are also discussed for the particular case of the electrical cabinets. (author)

  3. Lifetime of superheated steam components

    International Nuclear Information System (INIS)

    Stoklossa, K.H.; Oude-Hengel, H.H.; Kraechter, H.J.

    1974-01-01

    The current evaluation schemes in use for judging the lifetime expectations of superheated steam components are compared with each other. The influence of pressure and temperature fluctuations, the differences in the strength of the wall, and the spread band of constant-strainrates are critically investigated. The distribution of these contributory effects are demonstrated in the hight of numerous measuring results. As an important supplement to these evaluation schemes a newly developed technique is introduced which is designed to calculate failure probabilities. (orig./RW) [de

  4. Cooling concepts for HTS components

    International Nuclear Information System (INIS)

    Binneberg, A.; Buschmann, H.; Neubert, J.

    1993-01-01

    HTS components require that low-cost, reliable cooling systems be used. There are no general solutions to such systems. Any cooling concept has to be tailored to the specific requirements of a system. The following has to he taken into consideration when designing cooling concepts: - cooling temperature - constancy and controllability of the cooling temperature - cooling load and refrigerating capacity - continuous or discontinuous mode - degree of automation - full serviceability or availability before evacuation -malfunctions caused by microphonic, thermal or electromagnetic effects -stationary or mobile application - investment and operating costs (orig.)

  5. Bioactivity of Minor Milk Components

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh

    . In particular, 3-15% of very low birth weight preterm infants suffer from the most servere form of intestinal inflammation, known as necrotizing enterocolitis (NEC). This disease is incurable with a high mortality rate of 15-30%. Mother’s breast milk consists of different bioactive constituents...... of infant formula. Thereafter, bioactive milk components which were preserved in gently-processed infant formula were selected for further investigation of their immunomodulatory activity in cell and preterm pig models. We hope this project will contribute to the research on the development of new...

  6. Experimental qualification of nuclear components

    International Nuclear Information System (INIS)

    Alliot, P.; Fronte, T.; Genty, F.

    1988-01-01

    In the process of showing the adequacy of the seismic design of French PWR reactor, Fermat has repeatedly used dynamic testing on actual nuclear reactor components both on site and in manufacturing shops. The objective and results of a few representative examples of this on-site experimental verification are presented in this paper: the experimental dynamic analysis of a manipulator crane; the investigation of the seismic behaviour of fuel storage racks equipped with aseismic bearing devices. Difficulties to select satisfactory testing methods are also discussed for the particular case of the electrical cabinets. (author)

  7. Failures on stainless steel components

    International Nuclear Information System (INIS)

    Haenninen, H.

    1994-01-01

    Economic losses due to failure mainly by corrosion in process and nuclear industries are considered. In these industries the characteristics of different forms of corrosion and their economic effects are fairly well known and, especially, in nuclear industry the assessment of corrosion related costs has been comprehensive. In both industries the economic losses resulting from environmentally enhanced cracking of stainless steel components and the accompanying failures and outages have been considerable, owing as much to the frequency as the unpredictability of such occurrences. (orig.)

  8. Anthropological Component of Descartes’ Ontology

    Directory of Open Access Journals (Sweden)

    Anatolii M. Malivskyi

    2014-06-01

    Full Text Available The purpose of the article is to outline and comprehend the Descartes’ theory about anthropological component of ontology as the most important part of his philosophy. The accomplishment of this purpose covers the successive solution of the following tasks: 1 review of the research literature concerning the problem of human’s presence and the individual nature of truth; 2 emphasize the ambivalence of the basic intention of his legacy; 3 justify the thesis about constitutivity of human’s presence and comprehend passions as the form of disclosure of ontology’s anthropological component. Methodology. The use of the euristic potential of phenomenology, postpositivism and postmodernism makes it possible to emphasize the multiple-layer and multiple-meaning classical philosophy works, to comprehend the limitation and scarcity of the naïve-enlightening vision of human nature and to look for a new reception of European classics that provides the overcoming of established nihilism and pessimism concerning the interpretation of human nature. Scientific novelty. It is the first time that anthropological component of Descartes’ ontology became an object of particular attention. It previously lacked attention because of following main reasons: 1 traditional underestimating of the fact of Descartes’ legacy incompleteness as an unrealized anthropological project and 2 lack of proper attention to the individual nature of truth. The premise for its constructive overcoming is the attention to ambivalence of the basic intention and the significance of ethics in the philosopher’s legacy. His texts and research literature allow confirming the constitutive nature of human’s presence and passions as the key form of disclosure of the ontology anthropological component. Conclusions. The established tradition of interpretation the Descartes’ philosophizing nature as the filiation process of impersonal knowledge loses its cogency these days. The

  9. ANTHROPOLOGICAL COMPONENT OF DESCARTES’ ONTOLOGY

    Directory of Open Access Journals (Sweden)

    Anatolii M. Malivskyi

    2014-06-01

    Full Text Available The purpose of the article is to outline and comprehend the Descartes’ theory about anthropological component of ontology as the most important part of his philosophy. The accomplishment of this purpose covers the successive solution of the following tasks: 1 review of the research literature concerning the problem of human’s presence and the individual nature of truth; 2 emphasize the ambivalence of the basic intention of his legacy; 3 justify the thesis about constitutivity of human’s presence and comprehend passions as the form of disclosure of ontology’s anthropological component. Methodology. The use of the euristic potential of phenomenology, postpositivism and postmodernism makes it possible to emphasize the multiple-layer and multiple-meaning classical philosophy works, to comprehend the limitation and scarcity of the naïve-enlightening vision of human nature and to look for a new reception of European classics that provides the overcoming of established nihilism and pessimism concerning the interpretation of human nature. Scientific novelty. It is the first time that anthropological component of Descartes’ ontology became an object of particular attention. It previously lacked attention because of following main reasons: 1 traditional underestimating of the fact of Descartes’ legacy incompleteness as an unrealized anthropological project and 2 lack of proper attention to the individual nature of truth. The premise for its constructive overcoming is the attention to ambivalence of the basic intention and the significance of ethics in the philosopher’s legacy. His texts and research literature allow confirming the constitutive nature of human’s presence and passions as the key form of disclosure of the ontology anthropological component. Conclusions. The established tradition of interpretation the Descartes’ philosophizing nature as the filiation process of impersonal knowledge loses its cogency these days. The

  10. Gene set analysis using variance component tests.

    Science.gov (United States)

    Huang, Yen-Tsung; Lin, Xihong

    2013-06-28

    Gene set analyses have become increasingly important in genomic research, as many complex diseases are contributed jointly by alterations of numerous genes. Genes often coordinate together as a functional repertoire, e.g., a biological pathway/network and are highly correlated. However, most of the existing gene set analysis methods do not fully account for the correlation among the genes. Here we propose to tackle this important feature of a gene set to improve statistical power in gene set analyses. We propose to model the effects of an independent variable, e.g., exposure/biological status (yes/no), on multiple gene expression values in a gene set using a multivariate linear regression model, where the correlation among the genes is explicitly modeled using a working covariance matrix. We develop TEGS (Test for the Effect of a Gene Set), a variance component test for the gene set effects by assuming a common distribution for regression coefficients in multivariate linear regression models, and calculate the p-values using permutation and a scaled chi-square approximation. We show using simulations that type I error is protected under different choices of working covariance matrices and power is improved as the working covariance approaches the true covariance. The global test is a special case of TEGS when correlation among genes in a gene set is ignored. Using both simulation data and a published diabetes dataset, we show that our test outperforms the commonly used approaches, the global test and gene set enrichment analysis (GSEA). We develop a gene set analyses method (TEGS) under the multivariate regression framework, which directly models the interdependence of the expression values in a gene set using a working covariance. TEGS outperforms two widely used methods, GSEA and global test in both simulation and a diabetes microarray data.

  11. Apoptotic engulfment pathway and schizophrenia.

    LENUS (Irish Health Repository)

    Chen, Xiangning

    2009-01-01

    BACKGROUND: Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease. METHODOLOGY\\/PRINCIPAL FINDINGS: Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and 0.0437 respectively). We sought replication in independent samples for this marker and found highly significant association (p = 0.0003) in 3 Caucasian replication samples. But it was not significant in the 2 Chinese replication samples. In addition, we found a significant 2-marker (rs2242436 * rs3858075) interaction between the ABCA1 and ABCA7 genes in the ISHDSF sample (p = 0.0022) and a 3-marker interaction (rs246896 * rs4522565 * rs3858075) amongst the MEGF10, GULP1 and ABCA1 genes in the ICCSS sample (p = 0.0120). Rs3858075 in the ABCA1 gene was involved in both 2- and 3-marker interactions in the two samples. CONCLUSIONS\\/SIGNIFICANCE: From these data, we concluded that the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry and multiple genes in the pathway may interactively increase the risks to the disease.

  12. Nutrition pathways in consequence modeling

    International Nuclear Information System (INIS)

    Tveten, U.

    1982-01-01

    During 1979-1980 calculations of risk from waste transportation by truck (fire following collision) and fire in temporary storage for waste were performed. A modified version of the consequence model of WASH-1400 (CRAC) was used. Two exposure pathways dominated the results: external exposure from material on the ground and exposure via nutrition. Many of the parameters entering into the nutrition calculations will depend upon local conditions, like soil composition, crop yield, etc. It was decided to collect detailed comments upon the CRAC nutritions model and parameter values from radioecologists in the four Nordic countries. Four alternate sets of parameter values were derived from these comments, and new risk calculations were performed

  13. Bioactive Components in Fish Venoms

    Science.gov (United States)

    Ziegman, Rebekah; Alewood, Paul

    2015-01-01

    Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

  14. Safety engineering with COTS components

    International Nuclear Information System (INIS)

    O'Halloran, Mark; Hall, Jon G.; Rapanotti, Lucia

    2017-01-01

    Safety-critical systems are becoming more widespread, complex and reliant on software. Increasingly they are engineered through (COTS) (Commercial Off The Shelf) components to alleviate the spiralling costs and development time, often in the context of complex supply chains. A parallel increased concern for safety has resulted in a variety of safety standards, with a growing consensus that a safety life cycle is needed which is fully integrated with the design and development life cycle, to ensure that safety has appropriate influence on the design decisions as system development progresses. In this article we explore the application of an integrated approach to safety engineering in which assurance drives the engineering process. The paper reports on the outcome of a case study on a live industrial project with a view to evaluate: its suitability for application in a real-world safety engineering setting; its benefits and limitations in counteracting some of the difficulties of safety engineering with (COTS) components across supply chains; and, its effectiveness in generating evidence which can contribute directly to the construction of safety cases. - Highlights: • Assurance as effective driver for COTS-based safety-critical system development. • Engages stakeholders, captures requirements and provides rich traceability. • Shares appropriate safety requirements across the supply chain.

  15. Tipping device for large components

    International Nuclear Information System (INIS)

    Guigon, J.P.; Beraudier, D.

    1984-01-01

    For large components machining as components of a pressurized water reactor, it is necessary to have means allowing to present them in a position determined with regard to the machine tool used. The aim of the invention is a tipping device which consists of a base resting on the ground, a support-table mounted on this base, moving in rotation with the aid of at least a pivot joint of which axis is horizontal and parallel to the table and a gear pivot allowing to get a very good precision for the orientation of the piece and a very good stability whatever the orientation may be. The output shaft pinion of the base meshes with a gear wheel segment fixed to the table structure. Safety straps fasten the table structure to the base, as they are secured by horizontal pins. The toe pins run in straight slot holes incorporated in base jaws. The table rotation may be controlled by a spring-loaded braking mechanism which acts on the pivot axis and can be released by a hydraulic jack. The hydraulic pressure is used to prevent motor operation, unless the brakes have been released [fr

  16. Food components with anticaries activity.

    Science.gov (United States)

    Gazzani, Gabriella; Daglia, Maria; Papetti, Adele

    2012-04-01

    Caries is the most common oral infectious disease in the world. Its development is influenced also by diet components that interfere with pathogen mutans group Streptococci (MGS) activity. A very active research to identify functional foods and their components that are generally recognised as safe has been ongoing, with the aim of developing alternative approaches, to the use of synthetic chlorhexidine, and at the reduction or prevention of caries. Until now convincing evidence exists only for green tea as a functional food for oral health, partly owing to its high content of catechins, especially epigallocatechin-gallate. A number of other foods showed potential anticaries activity. Some other foods able to act against MGS growth and/or their virulence factors in in vitro tests are: apple, red grape seeds, red wine (proanthocyanidins), nutmeg (macelignan), ajowan caraway (nafthalen-derivative), coffee (trigonelline, nicotinic and chlorogenic acids, melanoidins), barley coffee (melanoidins), chicory and mushroom (quinic acid). In vivo anticaries activity has been shown by cranberry (procyanidins), glycyrrhiza root (glycyrrhizol-A), myrtus ethanolic extract, garlic aqueous extract, cocoa extracts (procyanidins), and propolis (apigenin, tt-farnesol). Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Interpretable functional principal component analysis.

    Science.gov (United States)

    Lin, Zhenhua; Wang, Liangliang; Cao, Jiguo

    2016-09-01

    Functional principal component analysis (FPCA) is a popular approach to explore major sources of variation in a sample of random curves. These major sources of variation are represented by functional principal components (FPCs). The intervals where the values of FPCs are significant are interpreted as where sample curves have major variations. However, these intervals are often hard for naïve users to identify, because of the vague definition of "significant values". In this article, we develop a novel penalty-based method to derive FPCs that are only nonzero precisely in the intervals where the values of FPCs are significant, whence the derived FPCs possess better interpretability than the FPCs derived from existing methods. To compute the proposed FPCs, we devise an efficient algorithm based on projection deflation techniques. We show that the proposed interpretable FPCs are strongly consistent and asymptotically normal under mild conditions. Simulation studies confirm that with a competitive performance in explaining variations of sample curves, the proposed FPCs are more interpretable than the traditional counterparts. This advantage is demonstrated by analyzing two real datasets, namely, electroencephalography data and Canadian weather data. © 2015, The International Biometric Society.

  18. GMES Space Component: Programme overview

    Science.gov (United States)

    Aschbacher, J.; Milagro-Perez, M. P.

    2012-04-01

    The European Union (EU) and the European Space Agency (ESA) have developed the Global Monitoring for Environment and Security (GMES) programme as Europe's answer to the vital need for joined-up data about our climate, environment and security. Through a unique combination of satellite, atmospheric and Earth-based monitoring systems, the initiative will provide new insight into the state of the land, sea and air, providing policymakers, scientists, businesses and the public with accurate and timely information. GMES capabilities include monitoring and forecasting of climatic change, flood risks, soil and coastal erosion, crop and fish resources, air pollution, greenhouse gases, iceberg distribution and snow cover, among others. To accomplish this, GMES has been divided into three main components: Space, In-situ and Services. The Space Component, led by ESA, comprises five types of new satellites called Sentinels that are being developed by ESA specifically to meet the needs of GMES, the first of which to be launched in 2013. These missions carry a range of technologies, such as radar and multi-spectral imaging instruments for land, ocean and atmospheric monitoring. In addition, access to data from the so-called Contributing Missions guarantees that European space infrastructure is fully used for GMES. An integrated Ground Segment ensures access to Sentinels and Contributing Missions data. The in-situ component, under the coordination of the European Environment Agency (EEA), is composed of atmospheric and Earth based monitoring systems, and based on established networks and programmes at European and international levels. The European Commission is in charge of implementing the services component of GMES and of leading GMES overall. GMES services, fed with data from the Space and In-situ components, will provide essential information in five main domains, atmosphere, ocean and land monitoring as well as emergency response and security. Climate change has been added

  19. Porcine Circovirus-Like Virus P1 Inhibits Wnt Signaling Pathway in Vivo and in Vitro.

    Science.gov (United States)

    Zhu, Xuejiao; Wen, Libin; Sheng, Shaoyang; Wang, Wei; Xiao, Qi; Qu, Meng; Hu, Yiyi; Liu, Chuanmin; He, Kongwang

    2018-01-01

    Porcine circovirus-like virus P1 is an important pathogen of the current pig industry, the infection mechanism is not entirely clear. Wnt signaling pathway plays an important role in the growth of young animals and infection of some viruses. This study was designed to demonstrate the effects of P1 infection on the Wnt signaling pathway. In vivo experiments, we demonstrated the down-regulatory effects of P1 infection in piglets and mice on the downstream components expression levels of Wnt signaling pathway, and the effects of Wnt signaling pathway activation on the pathogenesis of P1. In vitro studies, we found P1 infection down-regulated protein level of β-catenin and mRNA level of mmp2, prevented the β-catenin from entering into nucleus, abolished the TCF/LEF promoter activity, proved that P1 could inhibit the activation of Wnt signaling pathway in vitro . Finally, we found that VP1 of P1 virus also had the inhibitory effects on Wnt signaling pathway in vitro , elucidated the mechanism of P1's inhibitory effects on the Wnt signaling pathway and offered the possibility that the suppression of Wnt signaling pathway was involved in the post-weaning multisystemic wasting syndrome (PMWS), laying a foundation for elucidating the pathogenesis of P1.

  20. Porcine Circovirus-Like Virus P1 Inhibits Wnt Signaling Pathway in Vivo and in Vitro

    Directory of Open Access Journals (Sweden)

    Xuejiao Zhu

    2018-03-01

    Full Text Available Porcine circovirus-like virus P1 is an important pathogen of the current pig industry, the infection mechanism is not entirely clear. Wnt signaling pathway plays an important role in the growth of young animals and infection of some viruses. This study was designed to demonstrate the effects of P1 infection on the Wnt signaling pathway. In vivo experiments, we demonstrated the down-regulatory effects of P1 infection in piglets and mice on the downstream components expression levels of Wnt signaling pathway, and the effects of Wnt signaling pathway activation on the pathogenesis of P1. In vitro studies, we found P1 infection down-regulated protein level of β-catenin and mRNA level of mmp2, prevented the β-catenin from entering into nucleus, abolished the TCF/LEF promoter activity, proved that P1 could inhibit the activation of Wnt signaling pathway in vitro. Finally, we found that VP1 of P1 virus also had the inhibitory effects on Wnt signaling pathway in vitro, elucidated the mechanism of P1’s inhibitory effects on the Wnt signaling pathway and offered the possibility that the suppression of Wnt signaling pathway was involved in the post-weaning multisystemic wasting syndrome (PMWS, laying a foundation for elucidating the pathogenesis of P1.