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Sample records for autophagic components contribute

  1. Autophagic degradation contributes to muscle wasting in cancer cachexia.

    Science.gov (United States)

    Penna, Fabio; Costamagna, Domiziana; Pin, Fabrizio; Camperi, Andrea; Fanzani, Alessandro; Chiarpotto, Elena M; Cavallini, Gabriella; Bonelli, Gabriella; Baccino, Francesco M; Costelli, Paola

    2013-04-01

    Muscle protein wasting in cancer cachexia is a critical problem. The underlying mechanisms are still unclear, although the ubiquitin-proteasome system has been involved in the degradation of bulk myofibrillar proteins. The present work has been aimed to investigate whether autophagic degradation also plays a role in the onset of muscle depletion in cancer-bearing animals and in glucocorticoid-induced atrophy and sarcopenia of aging. The results show that autophagy is induced in muscle in three different models of cancer cachexia and in glucocorticoid-treated mice. In contrast, autophagic degradation in the muscle of sarcopenic animals is impaired but can be reactivated by calorie restriction. These results further demonstrate that different mechanisms are involved in pathologic muscle wasting and that autophagy, either excessive or defective, contributes to the complicated network that leads to muscle atrophy. In this regard, particularly intriguing is the observation that in cancer hosts and tumor necrosis factor α-treated C2C12 myotubes, insulin can only partially blunt autophagy induction. This finding suggests that autophagy is triggered through mechanisms that cannot be circumvented by using classic upstream modulators, prompting us to identify more effective approaches to target this proteolytic system. PMID:23395093

  2. Autophagic components contribute to hypersensitive cell death in Arabidopsis

    DEFF Research Database (Denmark)

    Hofius, Daniel; Schultz-Larsen, Torsten; Joensen, Jan; Tsitsigiannis, Dimitrios I; Petersen, Nikolaj H T; Mattsson, Ole; Jørgensen, Lise Bolt; Jones, Jonathan D G; Mundy, John; Petersen, Morten

    2009-01-01

    Autophagy has been implicated as a prosurvival mechanism to restrict programmed cell death (PCD) associated with the pathogen-triggered hypersensitive response (HR) during plant innate immunity. This model is based on the observation that HR lesions spread in plants with reduced autophagy gene...

  3. Baicalein induces autophagic cell death through AMPK/ULK1 activation and downregulation of mTORC1 complex components in human cancer cells.

    Science.gov (United States)

    Aryal, Pramod; Kim, Kijoong; Park, Pil-Hoon; Ham, Seongho; Cho, Junghee; Song, Kyung

    2014-10-01

    Baicalein, a flavonoid and aglycon hydrolyzed from baicalin, has anticancer properties in several human carcinomas, but its molecular mechanisms of action remain unclear. Here, we show that baicalein leads to human cancer cell death by inducing autophagy rather than apoptosis, because cell death induced by baicalein was completely reversed by suppressing the expression levels of key molecules in autophagy such as Beclin 1, vacuolar protein sorting 34 (Vps34), autophagy-related (Atg)5 and Atg7, but not by pan-caspase inhibitor. Our data revealed that baicalein significantly increased the number of green fluorescence protein-cytosol-associated protein light chain 3 (GFP-LC3)-containing puncta and LC3B-II expression levels, which were further enhanced by chloroquine treatment. Furthermore, a luciferase-based reporter assay showed that the ratio of RLuc-LC3wt/RLuc-LC3G120A was greatly reduced. The data suggested that baicalein induced not only autophagosome formation, but also autophagic flux. Experiments using short interfering RNAs and pharmacological inhibitors revealed that Beclin 1, Vps34, Atg5, Atg7 and UNC-51 (Caenorhabditis elegans)-like kinase 1 (ULK1) play pivotal roles in mediating baicalein-induced autophagy. Moreover, baicalein activated AMP-activated protein kinase (AMPK)α, leading to ULK1 activation through phosphorylation at Ser555, whereas both protein and mRNA levels of mammalian target of rapamycin (mTOR) and Raptor, upstream inhibitors of ULK1 and autophagy, were markedly downregulated by baicalein. Our data suggest that the anticancer effects of baicalein are mainly due to autophagic cell death through activation of the AMPK/ULK1 pathway and inhibition of mTOR/Raptor complex 1 expression. These results provide new mechanistic insights into the anticancer functions of autophagy inducers, such as baicalein, which may be used as potential therapeutics for cancer treatment. PMID:25132405

  4. Epistasis and Its Contribution to Genetic Variance Components

    OpenAIRE

    Cheverud, J M; Routman, E J

    1995-01-01

    We present a new parameterization of physiological epistasis that allows the measurement of epistasis separate from its effects on the interaction (epistatic) genetic variance component. Epistasis is the deviation of two-locus genotypic values from the sum of the contributing single-locus genotypic values. This parameterization leads to statistical tests for epistasis given estimates of two-locus genotypic values such as can be obtained from quantitative trait locus studies. The contributions...

  5. NOTE - Contribution of components of production on snap bean yield

    Directory of Open Access Journals (Sweden)

    Rogério Figueiredo Daher

    2012-09-01

    Full Text Available Aiming to estimate the path coefficients among morphological traits and effects of production components on the yield of grains and pods, thirty snap bean genotypes (27 lines and three commercial controls were evaluated in Bom Jesus of Itabapoana-RJ. The experiments were carried out in a randomized block design, with four replications, from May to June, in 2009 and 2010. Eight traits were evaluated and the number of pods per plant, associated with high genetic correlation, is the character with the most significant direct effect on productivity. There is a high rate of genotypic association between the yields of pods and grains, as well as direct effects of high magnitude and positive signal between them, indicating that the selection for increased pod yield allows increased grain yield.

  6. Chikungunya triggers an autophagic process which promotes viral replication

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    Briant Laurence

    2011-09-01

    Full Text Available Abstract Background Chikungunya Virus (ChikV surprised by a massive re-emerging outbreak in Indian Ocean in 2006, reaching Europe in 2007 and exhibited exceptional severe physiopathology in infants and elderly patients. In this context, it is important to analyze the innate immune host responses triggered against ChikV. Autophagy has been shown to be an important component of the innate immune response and is involved in host defense elimination of different pathogens. However, the autophagic process was recently observed to be hijacked by virus for their own replication. Here we provide the first evidence that hallmarks of autophagy are specifically found in HEK.293 infected cells and are involved in ChikV replication. Methods To test the capacity of ChikV to mobilize the autophagic machinery, we performed fluorescence microscopy experiments on HEK.GFP.LC3 stable cells, and followed the LC3 distribution during the time course of ChikV infection. To confirm this, we performed electron microscopy on HEK.293 infected cells. To test the effect of ChikV-induced-autophagy on viral replication, we blocked the autophagic process, either by pharmacological (3-MA or genetic inhibition (siRNA against the transcript of Beclin 1, an autophagic protein, and analyzed the percentage of infected cells and the viral RNA load released in the supernatant. Moreover, the effect of induction of autophagy by Rapamycin on viral replication was tested. Results The increasing number of GFP-LC3 positive cells with a punctate staining together with the enhanced number of GFP-LC3 dots per cell showed that ChikV triggered an autophagic process in HEK.293 infected cells. Those results were confirmed by electron microscopy analysis since numerous membrane-bound vacuoles characteristic of autophagosomes were observed in infected cells. Moreover, we found that inhibition of autophagy, either by biochemical reagent and RNA interference, dramatically decreases ChikV replication

  7. The Autophagic Machinery in Enterovirus Infection

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    Jeffrey K. F. Lai

    2016-01-01

    Full Text Available The Enterovirus genus of the Picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus A71, and enterovirus D68. They cause a wide variety of diseases, ranging from mild to severe life-threatening diseases. Currently, no effective vaccine is available against enteroviruses except for poliovirus. Enteroviruses subvert the autophagic machinery to benefit their assembly, maturation, and exit from host. Some enteroviruses spread between cells via a process described as autophagosome-mediated exit without lysis (AWOL. The early and late phases of autophagy are regulated through various lipids and their metabolizing enzymes. Some of these lipids and enzymes are specifically regulated by enteroviruses. In the present review, we summarize the current understanding of the regulation of autophagic machinery by enteroviruses, and provide updates on recent developments in this field.

  8. Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation

    OpenAIRE

    Rong, Yueguang; McPhee, Christina K; Deng, Shuangshen; Huang, Lei; Chen, Lilian; Liu, Mei; Tracy, Kirsten; Baehrecke, Eric H.; Yu, Li; Lenardo, Michael J.

    2011-01-01

    Autophagy is a conserved cellular process to degrade and recycle cytoplasmic components. During autophagy, lysosomes fuse with an autophagosome to form an autolysosome. Sequestered components are degraded by lysosomal hydrolases and presumably released into the cytosol by lysosomal efflux permeases. Following starvation-induced autophagy, lysosome homeostasis is restored by autophagic lysosome reformation (ALR) requiring activation of the “target of rapamycin” (TOR) kinase. Spinster (Spin) en...

  9. MnSOD upregulation induces autophagic programmed cell death in senescent keratinocytes.

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    Emeric Deruy

    Full Text Available Senescence is a state of growth arrest resulting mainly from telomere attrition and oxidative stress. It ultimately leads to cell death. We have previously shown that, in keratinocytes, senescence is induced by NF-kappaB activation, MnSOD upregulation and H(2O(2 overproduction. We have also shown that senescent keratinocytes do not die by apoptosis but as a result of high macroautophagic activity that targets the primary vital cell components. Here, we investigated the mechanisms that activate this autophagic cell death program. We show that corpses occurring at the senescence plateau display oxidatively-damaged mitochondria and nucleus that colocalize with autophagic vacuoles. The occurrence of such corpses was decreased by specifically reducing the H(2O(2 level with catalase, and, conversely, reproduced by overexpressing MnSOD or applying subtoxic doses of H(2O(2. This H(2O(2-induced cell death did occur through autophagy since it was accompanied by an accumulation of autophagic vesicles as evidenced by Lysotracker staining, LC3 vesiculation and transmission electron microscopy. Most importantly, it was partly abolished by 3-methyladenine, the specific inhibitor of autophagosome formation, and by anti-Atg5 siRNAs. Taken together these results suggest that autophagic cell death is activated in senescent keratinocytes because of the upregulation of MnSOD and the resulting accumulation of oxidative damages to nucleus and mitochondria.

  10. How do different components of Effortful Control contribute to children’s mathematics achievement?

    OpenAIRE

    Sánchez-Pérez, Noelia; Luis J Fuentes; Pina, Violeta; López-López, Jose A.; González-Salinas, Carmen

    2015-01-01

    This work sought to investigate the specific contribution of two different components of Effortful Control (EC) -attentional focusing (AF) and inhibitory control- to children’s mathematics achievement. The sample was composed of 142 children aged 9–12 year-old. EC components were measured through the Temperament in Middle Childhood Questionnaire (TMCQ; parent’s report); math achievement was measured via teacher’s report and through the standard Woodcock–Johnson test. Additionally, the contrib...

  11. Evaluation of the Contributions of Four Components of Gross Domestic Product in Various Regions in China

    OpenAIRE

    Wu, Sanmang; Lei, Yalin; Li, Li

    2015-01-01

    Four major components influence the growth of the gross domestic product in Chinese provinces: consumption, investment, transnational exports, and inter-provincial exports. By splitting a competitive input-output table into a non-competitive input-output table, this study used an input-output model to measure the contributions of the four components of gross domestic product in various regions in China. We found that international exports drove the growth of the gross domestic product more st...

  12. Disentangling giant component and finite cluster contributions in sparse random matrix spectra

    Science.gov (United States)

    Kühn, Reimer

    2016-04-01

    We describe a method for disentangling giant component and finite cluster contributions to sparse random matrix spectra, using sparse symmetric random matrices defined on Erdős-Rényi graphs as an example and test bed. Our methods apply to sparse matrices defined in terms of arbitrary graphs in the configuration model class, as long as they have finite mean degree.

  13. How do different components of Effortful Control contribute to children's mathematics achievement?

    Science.gov (United States)

    Sánchez-Pérez, Noelia; Fuentes, Luis J; Pina, Violeta; López-López, Jose A; González-Salinas, Carmen

    2015-01-01

    This work sought to investigate the specific contribution of two different components of Effortful Control (EC) -attentional focusing (AF) and inhibitory control- to children's mathematics achievement. The sample was composed of 142 children aged 9-12 year-old. EC components were measured through the Temperament in Middle Childhood Questionnaire (TMCQ; parent's report); math achievement was measured via teacher's report and through the standard Woodcock-Johnson test. Additionally, the contribution of other cognitive and socio-emotional processes was taken into account. Our results showed that only AF significantly contributed to the variance of children's mathematics achievement; interestingly, mediational models showed that the relationship between effortful attentional self-regulation and mathematics achievement was mediated by academic peer popularity, as well as by intelligence and study skills. Results are discussed in the light of the current theories on the role of children's self-regulation abilities in the context of school. PMID:26441758

  14. Time-independent and time-dependent contributions to the unavailability of standby safety system components

    Energy Technology Data Exchange (ETDEWEB)

    Lofgren, E.V. [Science Applications International Corp., Fairfax Station, VA (United States); Uryasev, S.; Samanta, P. [Brookhaven National Lab., Upton, NY (United States)

    1997-02-01

    The unavailability of standby safety system components due to failures in nuclear power plants is considered to involve a time-independent and a time-dependent part. The former relates to the component`s unavailability from demand stresses due to usage, and the latter represents the component`s unavailability due to standby-time stresses related to the environment. In this paper, data from the nuclear plant reliability data system (NPRDS) were used to partition the component`s unavailability into the contributions from standby-time stress (i.e., due to environmental factors) and demand stress (i.e., due to usage). Analyses are presented of motor-operated valves (MOVs), motor-driven pumps (MDPs), and turbine-driven pumps (TDPs). MOVs fail predominantly (approx. 78 %) from environmental factors (standby-time stress failures). MDPs fail slightly more frequently from demand stresses (approx. 63 %) than standby-time stresses, while TDPs fail predominantly from standby-time stresses (approx. 78 %). Such partitions of component unavailability have many uses in risk-informed and performance-based regulation relating to modifications to Technical Specification, in-service testing, precise determination of dominant accident sequences, and implementation of maintenance rules.

  15. Updates from the Intestinal Front Line: Autophagic Weapons against Inflammation and Cancer

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    Cristiano Simone

    2012-08-01

    Full Text Available The intestine lies at the interface between the organism and its environment and responds to infection/inflammation in a multi-leveled manner, potentially leading to chronic inflammatory pathologies and cancer formation. Indeed, the immune response at the intestinal epithelium has been found to be involved in the origin and development of colorectal cancer, which is the third most commonly diagnosed neoplastic disease. Among the mechanisms induced upon inflammation, autophagy appears as a defensive strategy for the clearance of invading microbes and intracellular waste components. Autophagy has also been found to play an important role in colorectal cancer, where it seems to have a pro-survival or pro-death function depending on the stage of the neoplastic process. In this paper we discuss the dual role of autophagy in colorectal cancer and review evidence showing that modulation of autophagy affects the immune response and cancer biology. The study of key players involved in autophagy might contribute to the design of new approaches for colorectal cancer, consisting in combined therapies capable of modifying cancer-specific metabolism rather than simply evoking a generic apoptotic and/or autophagic response, thus enhancing the efficacy of currently used drugs and treatments.

  16. Contribution to the edaphic components definition in the desertification susceptibility index

    International Nuclear Information System (INIS)

    Many of the biophysical processes involved in the scope of desertification depend on the hydric characteristics of the soils the impact on vegetation cover. To protect soils against desertification, it is necessary to understand how some of these characteristics (such as water storage) interact in a complex and integrated chain of degradation processes. Several works have been developed to contribute to the definition of a Index of Desertification Susceptibility (DSI) expressed as a function of several components, climatic, edaphic, vegetative and slope. However, the various built-in edaphic components already defined, leave aside the water retention in soil. Furthermore, these components only focus on the characteristics of the uppermost surface soil layer (A-layer). In fact, desertification is simultaneously cause and consequence of the depleted soil water retention with a positive feedback of the plant life and on the hydrological cycle. (Author) 10 refs.

  17. How do different components of Effortful Control contribute to children's mathematics achievement?

    Directory of Open Access Journals (Sweden)

    Noelia eSánchez-Pérez

    2015-09-01

    Full Text Available This work sought to investigate the specific contribution of two different components of Effortful Control -attentional focusing and inhibitory control- to children’s mathematics achievement. The sample was composed of 142 children aged 9 to 12 years old. Effortful Control components were measured through the Temperament in Middle Childhood Questionnaire (TMCQ; parent´s report; math achievement was measured via teacher’s report and through the standard Woodcock-Johnson test. Additionally, the contribution of other cognitive and socio-emotional processes was taken into account. Our results showed that only attentional focusing significantly contributed to the variance of children’s mathematics achievement; interestingly, mediational models showed that the relationship between effortful attentional self-regulation and mathematics achievement was mediated by academic peer popularity, as well as by intelligence and study skills. Results are discussed in the light of the current theories on the role of children’ self-regulation abilities in the context of school.

  18. Epigallocatechin-3-gallate attenuates impairment of learning and memory in chronic unpredictable mild stress-treated rats by restoring hippocampal autophagic flux.

    Directory of Open Access Journals (Sweden)

    Hong-Feng Gu

    Full Text Available Epigallocatechin gallate (EGCG is a major polyphenol in green tea with beneficial effects on the impairment in learning and memory. Autophagy is a cellular process that protects neurons from stressful conditions. The present study was designed to investigate whether EGCG can rescue chronic unpredictable mild stress (CUMS-induced cognitive impairment in rats and whether its protective effect involves improvement of autophagic flux. As expected, our results showed that CUMS significantly impaired memory performance and inhibited autophagic flux as indicated by elevated LC3-II and p62 protein levels. At the same time, we observed an increased neuronal loss and activated mammalian target of rapamycin (mTOR/p70 ribosomal protein S6 kinase (p70S6k signaling in the CA1 regions. Interestingly, chronic treatment with EGCG (25 mg/kg, i.p. significantly improved those behavioral alterations, attenuated histopathological abnormalities in hippocampal CA1 regions, reduced amyloid beta1-42 (Aβ1-42 levels, and restored autophagic flux. However, blocking autophagic flux with chloroquine, an inhibitor of autophagic flux, reversed these effects of EGCG. Taken together, these findings suggest that the impaired autophagy in CA1 regions of CUMS rats may contribute to learning and memory impairment. Therefore, we conclude that EGCG attenuation of CUMS-induced learning and memory impairment may be through rescuing autophagic flux.

  19. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms

    OpenAIRE

    Mansilla Pareja, Maria Eugenia; Colombo, Maria I

    2013-01-01

    Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will d...

  20. Utilization of contribution margin in the costing system in production of components for wood working machines

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    Marek Potkány

    2009-06-01

    Full Text Available The aim of this paper is to propose optimization of costing method for planning a production-sales programme of the chosen engineering enterprise dealing with the production of components for wood working machines. This engineering company uses the calculation pattern methodology in the comprehensive cost accounting system. All costs components are absorbed by individual outputs in this cost calculation. The results of this calculation are not available for decision-making tasks. In order to solve the decision tasks relating to output assortment optimization, it is necessary to show separately variable costs influenced by changes in production volume and fixed costs not influenced by changes in production volume. For these reasons we propose a specific application of retrograde costing as a necessary condition for effective system of decision-making on the basis of contribution margin calculation. The contribution margin/standard hour is the criteria for the calculation in a critical place of production and this is very important information for developing an optimal production-sales programme.

  1. Deoxycholate, an Endogenous Cytotoxin/Genotoxin, Induces the Autophagic Stress-Survival Pathway: Implications for Colon Carcinogenesis

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    Claire M. Payne

    2009-01-01

    Full Text Available We report that deoxycholate (DOC, a hydrophobic bile acid associated with a high-fat diet, activates the autophagic pathway in non-cancer colon epithelial cells (NCM-460, and that this activation contributes to cell survival. The DOC-induced increase in autophagy was documented by an increase in autophagic vacuoles (detected using transmission electron microscopy, increased levels of LC3-I and LC3-II (western blotting, an increase in acidic vesicles (fluorescence spectroscopy of monodansycadaverine and lysotracker red probes, and increased expression of the autophagic protein, beclin-1 (immunohistochemistry/western blotting. The DOC-induced increase in beclin-1 expression was ROS-dependent. Rapamycin (activator of autophagy pre-treatment of NCM-460 cells significantly (P<.05 decreased, and 3-MA (inhibitor of autophagy significantly (P<.05 increased the cell loss caused by DOC treatment, alone. Rapamycin pre-treatment of the apoptosis-resistant colon cancer cell line, HCT-116RC (developed in our laboratory, resulted in a significant decrease in DOC-induced cell death. Bafilomycin A1 and hydroxychloroquine (inhibitors of the autophagic process increased the DOC-induced percentage of apoptotic cells in HCT-116RC cells. It was concluded that the activation of autophagy by DOC has important implications for colon carcinogenesis and for the treatment of colon cancer in conjunction with commonly used chemotherapeutic agents.

  2. Deoxycholate, an Endogenous Cytotoxin/Geno toxin, Induces the Autophagic Stress-Survival Pathway: Implications for Colon Carcinogenesis

    International Nuclear Information System (INIS)

    We report that deoxycholate (DOC), a hydrophobic bile acid associated with a high-fat diet, activates the autophagic pathway in non-cancer colon epithelial cells (NCM-460), and that this activation contributes to cell survival. The DOC-induced increase in autophagy was documented by an increase in autophagic vacuoles (detected using transmission electron microscopy, increased levels of LC3-I and LC3-II (western blotting), an increase in acidic vesicles (fluorescence spectroscopy of monodansylcadaverine and lyso tracker red probes), and increased expression of the autophagic protein, beclin-1 (immunohistochemistry/western blotting). The DOC-induced increase in beclin-1 expression was ROS-dependent. Rapa mycin (activator of autophagy) pre-treatment of NCM-460 cells significantly (P<.05) decreased, and 3-MA (inhibitor of autophagy) significantly (P<.05) increased the cell loss caused by DOC treatment, alone. Rapa mycin pre-treatment of the apoptosis-resistant colon cancer cell line, HCT-116RC (developed in our laboratory), resulted in a significant decrease in DOC-induced cell death. Bafilomycin A1 and hydroxychloroquine (inhibitors of the autophagic process) increased the DOC-induced percentage of apoptotic cells in HCT-116RC cells. It was concluded that the activation of autophagy by DOC has important implications for colon carcinogenesis and for the treatment of colon cancer in conjunction with commonly used chemotherapeutic agents.

  3. Soil CO2 efflux in a sand grassland: contribution by root, mycorrhizal and basal respiration components

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    Papp, Marianna; Balogh, János; Pintér, Krisztina; Cserhalmi, Dóra; Nagy, Zoltán

    2014-05-01

    Grasslands play an important role in global carbon cycle because of their remarkable extension and carbon storage capacity. Soil respiration takes a major part in the carbon cycle of the ecosystems; ratio of its autotrophic and heterotrophic components is important also when considering their sensitivity to environmental drivers. The aim of the study was to estimate the contribution by root, mycorrhizal and basal components to total soil CO2 efflux. The study was carried out in the semi-arid sandy grassland dominated by Festuca pseudovina at the Kiskunság National Park in Hungary (Bugac site) where C-flux measurements have been going on since 2002. The soil CO2 effluxes were measured in the following treatments: a./ control, b./ root-exclusion, c./ root and mycorrhiza exclusion by using 80 cm long 15 cm inner diameter PVC tubes and micro-pore inox meshes. Inox mesh was used to exclude roots, but let the mycorrhiza filaments to grow into the tubes. 10 soil cores were excavated, sieved, then root-free soil was packed back layer by layer into the cores giving 6 and 4 repetitions in b and c treatments respectively. Basal respiration is referred to as the heterotrophic respiration without influence of roots or mycorrhiza. Difference between root-exclusion and root and mycorrhiza exclusion treatment gave the value of mycorrhizal respiration and control (non-disturbed) plots the total soil CO2 efflux. The contribution by the above components was evaluated. Soil CO2 efflux was measured continuously by using an automated open system of 10 soil respiration chambers. Data was collected in every two hours from each treatment (one of the chambers recorded basal respiration, 3 chambers were settled on root-excluded treatments and 6 chambers measured control plots). Chambers were moved in every 2 weeks between the repetitions of the treatments. Soil CO2 efflux (mycorrhiza-free, root free, control) data were fitted using a soil respiration model, where soil temperature, soil

  4. Autophagic pathways in Parkinson disease and related disorders.

    Science.gov (United States)

    Xilouri, Maria; Stefanis, Leonidas

    2011-01-01

    Macroautophagy and chaperone-mediated autophagy (CMA) are the two main mammalian lysosomal proteolytic systems. In macroautophagy, double-membrane structures engulf organelles and other intracellular constituents through a highly regulated process that involves the formation of autophagic vacuoles and their fusion with lysosomes. In CMA, selected proteins are targeted through a nonvesicular pathway to a transport complex at the lysosomal membrane, through which they are threaded into the lysosomes and degraded. Autophagy is important in development, differentiation, cellular remodelling and survival during nutrient starvation. Increasing evidence suggests that autophagic dysregulation causes accumulation of abnormal proteins or damaged organelles, which is a characteristic of chronic neurodegenerative conditions, such as Parkinson disease (PD). Evidence from post-mortem material, transgenic mice, and animal and cellular models of PD suggests that both major autophagic pathways are malfunctioning. Numerous connections exist between proteins genetically linked to autosomal dominant PD, in particular α-synuclein and LRRK2, and autophagic pathways. However, proteins involved in recessive PD, such as PINK1 and Parkin (PINK2), function in the process of mitophagy, whereby damaged mitochondria are selectively engulfed by macroautophagy. This wealth of new data suggests that both autophagic pathways are potential targets for therapeutic intervention in PD and other related neurodegenerative conditions. PMID:21418705

  5. Estimation of Properties of Pure Components Using Improved Group-Contribution+ (GC+) Based Models and Uncertainty Analysis

    OpenAIRE

    Hukkerikar, Amol; Sarup, Bent; Abildskov, Jens; Sin, Gürkan; Gani, Rafiqul

    2012-01-01

    Physical and thermodynamic properties of pure components are needed to carry out tasks such as process design and computer aided molecular/mixture design among others. The experimental values of properties of many important pure components have not been measured due to many reasons, and hence they must be estimated. Predictive methods such as the group-contribution+ (GC+) method (combined group-contribution (GC) method and atom connectivity index (CI) method) are generally suitable to estimat...

  6. Nanoparticles modulate autophagic effect in a dispersity-dependent manner

    Science.gov (United States)

    Huang, Dengtong; Zhou, Hualu; Gao, Jinhao

    2015-09-01

    Autophagy plays a key role in human health and disease, especially in cancer and neurodegeneration. Many autophagy regulators are developed for therapy. Diverse nanomaterials have been reported to induce autophagy. However, the underlying mechanisms and universal rules remain unclear. Here, for the first time, we show a reliable and general mechanism by which nanoparticles induce autophagy and then successfully modulate autophagy via tuning their dispersity. Various well-designed univariate experiments demonstrate that nanomaterials induce autophagy in a dispersity-dependent manner. Aggregated nanoparticles induce significant autophagic effect in comparison with well-dispersed nanoparticles. As the highly stable nanoparticles may block autophagic degradation in autolysosomes, endocytosis and intracellular accumulation of nanoparticles can be responsible for this interesting phenomenon. Our results suggest dispersity-dependent autophagic effect as a common cellular response to nanoparticles, reveal the relationship between properties of nanoparticles and autophagy, and offer a new alternative way to modulate autophagy.

  7. Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

    Energy Technology Data Exchange (ETDEWEB)

    Tashiro, Kanae [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Shishido, Mayumi [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Fujimoto, Keiko [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Organelle Homeostasis Research Center, Kyushu University, Fukuoka (Japan); Hirota, Yuko [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Yo, Kazuyuki; Gomi, Takamasa [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Tanaka, Yoshitaka, E-mail: tanakay@bioc.phar.kyushu-u.ac.jp [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Organelle Homeostasis Research Center, Kyushu University, Fukuoka (Japan)

    2014-01-03

    Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.

  8. Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

    International Nuclear Information System (INIS)

    Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility

  9. AB158. Atorvastatin induces autophagic cell death in prostate cancer cells in vitro

    Science.gov (United States)

    He, Zhenhua; Wang, Zhiping

    2016-01-01

    Objective Although it is well known that apoptosis contributes to cancer cell death, the role of autophagy in cancer cell death has remained in dispute. Atorvastatin has been suggested to exhibit anti-cancer effects. The present study aimed to examine atorvastatin-induced autophagy-associated cell death and the autophagy-associated gene expression profile in the PC3 prostate carcinoma cell line. Methods The atorvastatin-induced process of autophagy in PC3 cells was determined via evaluation of the cellular expression levels of autophagosomal marker light-chain-3 (LC3)-II, using immunoblotting and counting of green fluorescent protein (GFP)-LC3-transfected autophagiccells. Apoptosis was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and an MTT assay was used to evaluate cell viability. Total RNA of PC3 cells was isolated for characterization of the gene expression profile following atorvastatin treatment. Results Atorvastatin treatment of PC3 cells for 24 h increased the expression of GFP-LC3-II by >25% and expression continued for >72 h, while apoptosis was not significantly induced within this time period. Four genes associated with the autophagy machinery were also significantly upregulated. Conclusions In the presence of atorvastatin, autophagy may be unable to abrogate cell damage and may therefore contribute to cellular dysfunction, leading to autophagic/type II programmed cell death. In response to atorvastatin treatment, the expression of genes involved in autophagic mediating pathways may have a role in tumor suppression.

  10. Research program Integrity of Components (FKS). A substantial contribution to component safety; Forschungsvorhaben Komponentensicherheit (FKS). Ein wesentlicher Beitrag zur Komponentensicherheit

    Energy Technology Data Exchange (ETDEWEB)

    Kussmaul, K.; Roos, E.; Foehl, J.

    1998-11-01

    The main objectives pursued are: (a) verify the quality of reactor pressure vessels in existing LWR-type reactors, and (b) quantify the safety margin using both specified and non-specified materials and welds. On the basis of knowledge obtained through earlier programmes, the research project was to examine in particular deviations from the specified materials properties, for more exact quantification of the safety margin before RPV failure. There are three major factors influencing the component performance until failure, which are aggregate material fatigue, flaws, loading conditions, and the research work was to focus on the materials properties. An item of main interest was to assess the impact of long service life on the materials properties, assuming particularly unfavourable boundary conditions for materials properties and operational loads. (orig./CB) [Deutsch] Die Hauptziele des Forschungsvorhabens Komponentensicherheit waren (a) die Qualitaet bestehender Reaktordruckbehaelter von Leichtwasserreaktoren zu verifizieren, und (b) den Sicherheitsabstand zu quantifizieren unter Verwendung von Werkstoffen und Schweissverbindungen, die innerhalb und ausserhalb der Spezifikation liegen. Gestuetzt auf Erkenntnisse aus frueheren Programmen sollten zur quantitativen Erfassung des Sicherheitsabstandes gegen Versagen des RDB`s insbesondere auch Abweichungen vom spezifikationsgemaessen Werkstoffzustand betrachtet werden. Von den drei Haupteinflussgroessen Werkstoffzustand, Fehlerzustand, Beanspruchungszustand, die das Versagensverhalten bestimmen, lag der Schwerpunkt des FKS auf der Untersuchung des Werkstoffeinflusses. Insbesondere sollte geprueft werden, wie sich der Langzeitbetrieb auf die Aenderung der Werkstoffeigenschaften auswirkt, wenn besonders unguenstige Randbedingungen von Werkstoffzustand und Betriebsbedingungen zugrunde gelegt werden. (orig./MM)

  11. Safety and reliability of pressure components with special emphasis on the contribution of component and large specimen testing to structural integrity assessment methodology. Vol. 1 and 2

    International Nuclear Information System (INIS)

    The 51 papers of the 13. MPA-seminar contribute to structural integrity assessment methodology with special emphasis on the component and large specimen testing. 8 of the papers deal with fracture mechanics, 6 papers with dynamic loading, 13 papers with nondestructive testing, 2 papers with radiation embrittlement, 5 papers with pipe failure, 4 papers with components, 2 papers with thermal shock loading, 5 papers with the high temperature behaviour, 4 papers with the integrity of vessels and 3 papers with the integrity of welded joints. Especially also the fracture behaviour of steel material is verificated. All papers are separately indexed and analysed for the database. (DG)

  12. Understanding Oral Reading Fluency among Adults with Low Literacy: Dominance Analysis of Contributing Component Skills

    Science.gov (United States)

    Mellard, Daryl F.; Anthony, Jason L.; Woods, Kari L.

    2012-01-01

    This study extends the literature on the component skills involved in oral reading fluency. Dominance analysis was applied to assess the relative importance of seven reading-related component skills in the prediction of the oral reading fluency of 272 adult literacy learners. The best predictors of oral reading fluency when text difficulty was…

  13. Comparison of the relative contributions of intra-abdominal and liver fat to components of the metabolic syndrome

    DEFF Research Database (Denmark)

    Kotronen, Anna; Yki-Järvinen, Hannele; Sevastianova, Ksenia; Bergholm, Robert; Hakkarainen, Antti; Pietiläinen, Kirsi H; Juurinen, Leena; Lundbom, Nina; Sørensen, Thorkild I A

    2011-01-01

    Abdominally obese individuals with the metabolic syndrome often have excess fat deposition both intra-abdominally (IA) and in the liver, but the relative contribution of these two deposits to variation in components of the metabolic syndrome remains unclear. We determined the mutually independent...

  14. Autophagic sequestration of [14C]sucrose, introduced into rat hepatocytes by reversible electro-permeabilization

    International Nuclear Information System (INIS)

    Isolated rat hepatocytes could be made permeable to small molecules such as [14C]sucrose (but not to proteins) but subjecting the cells to repeated discharges in a high-voltage field. During subsequent incubation at 370C, the permeability changes were reversed within 15 min, the electron-injected [14C]sucros remaining trapped inside the re-sealed plasma membrane. Autophagic sequestration of [14C]sucrose, i.e., the transfer of radioactivity from cytosol to sedimentable vesicles (autophagosomes and lysosomes), could be followed by incubating the [14C]sucrose-loaded hepatocytes for up to 2 h at 370C. After incubation, the cells were disrupted by a single high-voltage discharge in electrolyte-free medium (sucrose), and sedimentable cell components were separated from the cytosol by centrifugation through metrizamide. By the use of these methods, which are particularly suitable for the analysis of many small cell samples, it could be shown that [14C]sucros was autophagically sequestered in the hepatocytes at a rate of 4-5%/h. The sequestration was nearly completely inhibited by the specific autophagy inhibitor 3-methyladenine

  15. The role of autophagic and lysosomal pathways in ischemic brain injury******

    Institute of Scientific and Technical Information of China (English)

    Zhaohua Gu; Nan Shi; Qian Zhang; Wei Zhang; Meizhen Zhao; Xiaojiang Sun; Yinyi Sun; Kangyong Liu; Fen Wang; Ting Zhang; Qiang Li; Liwei Shen; Ling Zhou; Liang Dong

    2013-01-01

    Autophagy is involved in neural cel death after cerebral ischemia. Our previous studies showed that rapamycin-induced autophagy decreased the rate of apoptosis, but the rate of apoptosis was creased after the autophagy inhibitor, 3-methyladenine, was used. In this study, a suture-occluded method was performed to generate a rat model of brain ischemia. Under a transmission electron microscope, autophagic bodies and autophagy lysosomes were markedly accumulated in neurons at 4 hours post brain ischemic injury, with their numbers gradual y reducing over time. Western blotting demonstrated that protein levels of light chain 3-II and cathepsin B were significantly in-creased within 4 hours of ischemic injury, but these levels were not persistently upregulated over time. Confocal microscopy showed that autophagy was mainly found in neurons with positive light chain 3 signal. Injection of rapamycin via tail vein promoted the occurrence of autophagy in rat brain tissue after cerebral ischemia and elevated light chain 3 and cathepsin B expression. However, in-jection of 3-methyladenine significantly diminished light chain 3-II and cathepsin B expression. Results verified that autophagic and lysosomal activity is increased in ischemic neurons. Abnormal components in cel s can be eliminated through upregulating cel autophagy or inhibiting autophagy after ischemic brain injury, resulting in a dynamic balance of substances in cel s. Moreover, drugs that interfere with autophagy may be potential therapies for the treatment of brain injury.

  16. Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression

    International Nuclear Information System (INIS)

    Highlights: → Acidification of autophagosome was blunted in steatotic hepatocytes. → Hepatic steatosis did not disturb fusion of isolated autophagosome and lysosome. → Proteinase activity of cathepsin B and L in autolysosomes was inhibited by steatosis. → Hepatic expression of cathepsin B and L was suppressed by steatosis. -- Abstract: Autophagy, one of protein degradation system, contributes to maintain cellular homeostasis and cell defense. Recently, some evidences indicated that autophagy and lipid metabolism are interrelated. Here, we demonstrate that hepatic steatosis impairs autophagic proteolysis. Though accumulation of autophagosome is observed in hepatocytes from ob/ob mice, expression of p62 was augmented in liver from ob/ob mice more than control mice. Moreover, degradation of the long-lived protein leucine was significantly suppressed in hepatocytes isolated from ob/ob mice. More than 80% of autophagosomes were stained by LysoTracker Red (LTR) in hepatocytes from control mice; however, rate of LTR-stained autophagosomes in hepatocytes were suppressed in ob/ob mice. On the other hand, clearance of autolysosomes loaded with LTR was blunted in hepatocytes from ob/ob mice. Although fusion of isolated autophagosome and lysosome was not disturbed, proteinase activity of cathepsin B and L in autolysosomes and cathepsin B and L expression of liver were suppressed in ob/ob mice. These results indicate that lipid accumulation blunts autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression.

  17. Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression

    Energy Technology Data Exchange (ETDEWEB)

    Inami, Yoshihiro [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Yamashina, Shunhei, E-mail: syamashi@juntendo.ac.jp [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Izumi, Kousuke [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Ueno, Takashi [Department of Biochemistry, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Tanida, Isei [Department of Biochemistry and Cell Biology, Laboratory of Biomembranes, National Institute of Infectious Disease, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640 (Japan); Ikejima, Kenichi; Watanabe, Sumio [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2011-09-09

    Highlights: {yields} Acidification of autophagosome was blunted in steatotic hepatocytes. {yields} Hepatic steatosis did not disturb fusion of isolated autophagosome and lysosome. {yields} Proteinase activity of cathepsin B and L in autolysosomes was inhibited by steatosis. {yields} Hepatic expression of cathepsin B and L was suppressed by steatosis. -- Abstract: Autophagy, one of protein degradation system, contributes to maintain cellular homeostasis and cell defense. Recently, some evidences indicated that autophagy and lipid metabolism are interrelated. Here, we demonstrate that hepatic steatosis impairs autophagic proteolysis. Though accumulation of autophagosome is observed in hepatocytes from ob/ob mice, expression of p62 was augmented in liver from ob/ob mice more than control mice. Moreover, degradation of the long-lived protein leucine was significantly suppressed in hepatocytes isolated from ob/ob mice. More than 80% of autophagosomes were stained by LysoTracker Red (LTR) in hepatocytes from control mice; however, rate of LTR-stained autophagosomes in hepatocytes were suppressed in ob/ob mice. On the other hand, clearance of autolysosomes loaded with LTR was blunted in hepatocytes from ob/ob mice. Although fusion of isolated autophagosome and lysosome was not disturbed, proteinase activity of cathepsin B and L in autolysosomes and cathepsin B and L expression of liver were suppressed in ob/ob mice. These results indicate that lipid accumulation blunts autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression.

  18. Intraneuronal aggregation of the β-CTF fragment of APP (C99) induces Aβ-independent lysosomal-autophagic pathology.

    Science.gov (United States)

    Lauritzen, Inger; Pardossi-Piquard, Raphaëlle; Bourgeois, Alexandre; Pagnotta, Sophie; Biferi, Maria-Grazia; Barkats, Martine; Lacor, Pascale; Klein, William; Bauer, Charlotte; Checler, Frederic

    2016-08-01

    Endosomal-autophagic-lysosomal (EAL) dysfunction is an early and prominent neuropathological feature of Alzheimers's disease, yet the exact molecular mechanisms contributing to this pathology remain undefined. By combined biochemical, immunohistochemical and ultrastructural approaches, we demonstrate a link between EAL pathology and the intraneuronal accumulation of the β-secretase-derived βAPP fragment (C99) in two in vivo models, 3xTgAD mice and adeno-associated viral-mediated C99-infected mice. We present a pathological loop in which the accumulation of C99 is both the effect and causality of impaired lysosomal-autophagic function. The deleterious effect of C99 was found to be linked to its aggregation within EAL-vesicle membranes leading to disrupted lysosomal proteolysis and autophagic impairment. This effect was Aβ independent and was even exacerbated when γ-secretase was pharmacologically inhibited. No effect was observed in inhibitor-treated wild-type animals suggesting that lysosomal dysfunction was indeed directly linked to C99 accumulation. In some brain areas, strong C99 expression also led to inflammatory responses and synaptic dysfunction. Taken together, this work demonstrates a toxic effect of C99 which could underlie some of the early-stage anatomical hallmarks of Alzheimer's disease pathology. Our work also proposes molecular mechanisms likely explaining some of the unfavorable side-effects associated with γ-secretase inhibitor-directed therapies. PMID:27138984

  19. T315 Decreases Acute Myeloid Leukemia Cell Viability through a Combination of Apoptosis Induction and Autophagic Cell Death

    Science.gov (United States)

    Chiu, Chang-Fang; Weng, Jing-Ru; Jadhav, Appaso; Wu, Chia-Yung; Sargeant, Aaron M.; Bai, Li-Yuan

    2016-01-01

    T315, an integrin-linked kinase (ILK) inhibitor, has been shown to suppress the proliferation of breast cancer, stomach cancer and chronic lymphocytic leukemia cells. Here we demonstrate that T315 decreases cell viability of acute myeloid leukemia (AML) cell lines (HL-60 and THP-1) and primary leukemia cells from AML patients in a dose-responsive manner. Normal human bone marrow cells are less sensitive than leukemia cells to T315. T315 down regulates protein kinase B (Akt) and p-Akt and induces caspase activation, poly-ADP-ribose polymerase (PARP) cleavage, apoptosis and autophagy through an ILK-independent manner. Interestingly, pretreatment with autophagy inhibitors rescues cells from apoptosis and concomitant PARP cleavage, which implicates a key role of autophagic cell death in T315-mediated cytotoxicity. T315 also demonstrates efficacy in vivo, suppressing the growth of THP-1 xenograft tumors in athymic nude mice when administered intraperitoneally. This study shows that autophagic cell death and apoptosis cooperatively contribute to the anticancer activity of T315 in AML cells. In conclusion, the complementary roles of apoptotic and autophagic cell death should be considered in the future assessment of the translational value of T315 in AML therapy. PMID:27537872

  20. Autophagic machinery activated by dengue virus enhances virus replication

    International Nuclear Information System (INIS)

    Autophagy is a cellular response against stresses which include the infection of viruses and bacteria. We unravel that Dengue virus-2 (DV2) can trigger autophagic process in various infected cell lines demonstrated by GFP-LC3 dot formation and increased LC3-II formation. Autophagosome formation was also observed under the transmission electron microscope. DV2-induced autophagy further enhances the titers of extracellular and intracellular viruses indicating that autophagy can promote viral replication in the infected cells. Moreover, our data show that ATG5 protein is required to execute DV2-induced autophagy. All together, we are the first to demonstrate that DV can activate autophagic machinery that is favorable for viral replication

  1. Contribution to the determination of priority constructive influences on the hot crack initiation of welded components

    International Nuclear Information System (INIS)

    The previous research results do not allow a general hot crack characterisation although a variety of experimental and numerical knowledge is available. The reason for this is mainly the large number of influencing factors that complicate a complete description of the hot cracking phenomenon and especially solidification cracking. The hot crack formation and thus the solidification crack initiation can be described by the interaction of process, metallurgy and design. However, the literature examination shows that in the solidifaction crack characterisation the influence of the design aspect is often underestimated. The pre-stresses of the structural components is up to now not considered as an essential cause for the formation of solidification cracks. The evaluation of the influence of the various parameters is presented partly inconsistent. In addition, the targeted presentation of the design influence with respect to the solidification cracks in the weld is because the limited transferability of the various component-specific stresses on a laboratory scale and thus to the respective hot cracking tests restricted. Hence, the difficulty to transfer the results between laboratory specimen and component as well as the general hot crack characterisation is given. In this work the different types of stresses from the component welding in the laboratory and to quantify experimentally the solidification crack critical values, displacements and displacement rates were detected. In this regard external loaded hot cracking tests were carried out by using the advantages of contactless measurement techniques close to the weld and to analyse the welding process with respect to various local and global design-specific factors influencing the formation of solidification cracks in high alloyed steel. These investigations were performed on austenitic (1.4828) and ferritic (1.4509) materials with different mechanical and technological properties. To reflect the praxis relevant

  2. Contributions to theory and algorithms of independent component analysis and signal separation

    OpenAIRE

    Eriksson, Jan

    2004-01-01

    This thesis addresses the problem of blind signal separation (BSS) using independent component analysis (ICA). In blind signal separation, signals from multiple sources arrive simultaneously at a sensor array, so that each sensor array output contains a mixture of source signals. Sets of sensor outputs are processed to recover the source signals or to identify the mixing system. The term blind refers to the fact that no explicit knowledge of source signals or mixing system is available. Indep...

  3. What component of executive functions contributes to normal and impaired reading comprehension in young adults?

    Science.gov (United States)

    Georgiou, George K; Das, J P

    2016-01-01

    The purpose of this study was two-fold: (a) to examine what component of executive functions (EF) - planning and working memory - predicts reading comprehension in young adults (Study 1), and (b) to examine if less skilled comprehenders experience deficits in the EF components (Study 2). In Study 1, we assessed 178 university students (120 females; mean age=21.82 years) on planning (Planned Connections, Planned Codes, and Planned Patterns), working memory (Listening Span, Digit Span Backward, and Digit Memory), and reading comprehension (Nelson-Denny Reading Test). The results of structural equation modeling indicated that only planning was a significant predictor of reading comprehension. In Study 2, we assessed 30 university students with a specific reading comprehension deficit (19 females; mean age=23.01 years) and 30 controls (18 females; mean age=22.77 years) on planning (Planned Connections and Crack the Code) and working memory (Listening Span and Digit Span Backward). The results showed that less skilled comprehenders performed significantly poorer than controls only in planning. Taken together, the findings of both studies suggest that planning is the preeminent component of EF that is driving its relationship with reading comprehension in young adults. PMID:26704777

  4. The Contribution of Emotional Intelligence on the Components of Burnout : The Case of Health Care Sector Professionals

    OpenAIRE

    Merve Ünal, Zeynep

    2014-01-01

    The purpose of this study is to investigate the contribution of emotional intelligence on three components of burnout (emotional exhaustion, depersonalization, and reduced personal accomplishment) in health care professionals. Data were collected from a sample of 136 health care professionals (78 men, 58 women). The findings imply that the more emotionally intelligent health care professionals were, the less likely they were to experience emotional exhaustion and depersonalization whereas mor...

  5. Pb isotope evidence for contributions from different Iceland mantle components to Palaeogene East Greenland flood basalts

    DEFF Research Database (Denmark)

    Peate, David; Stecher, Ole

    2003-01-01

    We present new Pb isotope data on 21 samples of break-up-related flood basalts (56–54 Ma) from the Blosseville Kyst region of East Greenland. These samples show a considerable range in isotopic composition (206Pb/204Pb 17.6 to 19.3) that broadly correlates with compositional type. The ‘low-Ti’ ty...... to the break-up-related magmatism, at least close to the inferred plume track, suggesting that it has been an inherent component of the Iceland plume upwelling for the last 56 Myr or so, although perhaps absent earlier....

  6. The contribution of inflammasome components on macrophage response to surface nanotopography and chemistry

    Science.gov (United States)

    Christo, Susan; Bachhuka, Akash; Diener, Kerrilyn R.; Vasilev, Krasimir; Hayball, John D.

    2016-01-01

    Implantable devices have become an established part of medical practice. However, often a negative inflammatory host response can impede the integration and functionality of the device. In this paper, we interrogate the role of surface nanotopography and chemistry on the potential molecular role of the inflammasome in controlling macrophage responses. To achieve this goal we engineered model substrata having precisely controlled nanotopography of predetermined height and tailored outermost surface chemistry. Bone marrow derived macrophages (BMDM) were harvested from genetically engineered mice deficient in the inflammasome components ASC, NLRP3 and AIM2. These cells were then cultured on these nanoengineered substrata and assessed for their capacity to attach and express pro-inflammatory cytokines. Our data provide evidence that the inflammasome components ASC, NLRP3 and AIM2 play a role in regulating macrophage adhesion and activation in response to surface nanotopography and chemistry. The findings of this paper are important for understanding the inflammatory consequences caused by biomaterials and pave the way to the rational design of future implantable devices having controlled and predictable inflammatory outcomes. PMID:27188492

  7. The contribution of inflammasome components on macrophage response to surface nanotopography and chemistry

    Science.gov (United States)

    Christo, Susan; Bachhuka, Akash; Diener, Kerrilyn R.; Vasilev, Krasimir; Hayball, John D.

    2016-05-01

    Implantable devices have become an established part of medical practice. However, often a negative inflammatory host response can impede the integration and functionality of the device. In this paper, we interrogate the role of surface nanotopography and chemistry on the potential molecular role of the inflammasome in controlling macrophage responses. To achieve this goal we engineered model substrata having precisely controlled nanotopography of predetermined height and tailored outermost surface chemistry. Bone marrow derived macrophages (BMDM) were harvested from genetically engineered mice deficient in the inflammasome components ASC, NLRP3 and AIM2. These cells were then cultured on these nanoengineered substrata and assessed for their capacity to attach and express pro-inflammatory cytokines. Our data provide evidence that the inflammasome components ASC, NLRP3 and AIM2 play a role in regulating macrophage adhesion and activation in response to surface nanotopography and chemistry. The findings of this paper are important for understanding the inflammatory consequences caused by biomaterials and pave the way to the rational design of future implantable devices having controlled and predictable inflammatory outcomes.

  8. Some Statistical Procedures for Evaluation of the Relative Contribution for Yield Components in irradiated populations of Peanut (Arachis hypogaea L

    International Nuclear Information System (INIS)

    The present investigation was conducted at Ismaillia Research Station-Agricultural Research Center, Ismaillia Governorate, during the two successive seasons of 2000 and 2001. Two varieties of peanut (Arachis hypogaea L) namely Giza 4 and Giza 5 were treated with gamma ray doses; 10,15, 20, 25 Kr in order to induce genetic variability and to study the importance of the relative contribution of peanut yield components by employing some statistical procedures, i.e. simple correlation, multiple linear regression and stepwise regression analysis. The results showed that, there was significant positive correlation between seed yield/plant and no. of pods/plant, 100 seed weight, shelling percentage and pod yield/plant, and there was significant positive correlation between pod yield/plant and no of seed/plant,100 pod weight and 100 seed weight. The multiple linear regression analysis clearly showed that the relative contribution (R2%) of the yield components, no. of pods/plant, no. of seed/plant and shelling % were the most important variables contributing toward seed yield/plant (90.35%), meanwhile, no. of seeds/plant, shelling % and oil content % were the most important variables contributing toward pod yield/plant (82.36 %)

  9. YAP enhances autophagic flux to promote breast cancer cell survival in response to nutrient deprivation.

    Directory of Open Access Journals (Sweden)

    Qinghe Song

    Full Text Available The Yes-associated protein (YAP, a transcriptional coactivator inactivated by the Hippo tumor suppressor pathway, functions as an oncoprotein in a variety of cancers. However, its contribution to breast cancer remains controversial. This study investigated the role of YAP in breast cancer cells under nutrient deprivation (ND. Here, we show that YAP knockdown sensitized MCF7 breast cancer cells to nutrient deprivation-induced apoptosis. Furthermore, in response to ND, YAP increased the autolysosome degradation, thereby enhancing the cellular autophagic flux in breast cancer cells. Of note, autophagy is crucial for YAP to protect MCF7 cells from apoptosis under ND conditions. In addition, the TEA domain (TEAD family of growth-promoting transcription factors was indispensable for YAP-mediated regulation of autophagy. Collectively, our data reveal a role for YAP in promoting breast cancer cell survival upon ND stress and uncover an unappreciated function of YAP/TEAD in the regulation of autophagy.

  10. RNA is an integral component of chromatin that contributes to its structural organization.

    Directory of Open Access Journals (Sweden)

    Antonio Rodríguez-Campos

    Full Text Available Chromatin structure is influenced by multiples factors, such as pH, temperature, nature and concentration of counterions, post-translational modifications of histones and binding of structural non-histone proteins. RNA is also known to contribute to the regulation of chromatin structure as chromatin-induced gene silencing was shown to depend on the RNAi machinery in S. pombe, plants and Drosophila. Moreover, both in Drosophila and mammals, dosage compensation requires the contribution of specific non-coding RNAs. However, whether RNA itself plays a direct structural role in chromatin is not known. Here, we report results that indicate a general structural role for RNA in eukaryotic chromatin. RNA is found associated to purified chromatin prepared from chicken liver, or cultured Drosophila S2 cells, and treatment with RNase A alters the structural properties of chromatin. Our results indicate that chromatin-associated RNAs, which account for 2%-5% of total chromatin-associated nucleic acids, are polyA(- and show a size similar to that of the DNA contained in the corresponding chromatin fragments. Chromatin-associated RNA(s are not likely to correspond to nascent transcripts as they are also found bound to chromatin when cells are treated with alpha-amanitin. After treatment with RNase A, chromatin fragments of molecular weight >3.000 bp of DNA showed reduced sedimentation through sucrose gradients and increased sensitivity to micrococcal nuclease digestion. This structural transition, which is observed both at euchromatic and heterochromatic regions, proceeds without loss of histone H1 or any significant change in core-histone composition and integrity.

  11. The CpxRA two-component system contributes to Legionella pneumophila virulence.

    Science.gov (United States)

    Tanner, Jennifer R; Li, Laam; Faucher, Sébastien P; Brassinga, Ann Karen C

    2016-06-01

    The bacterium Legionella pneumophila is capable of intracellular replication within freshwater protozoa as well as human macrophages, the latter of which results in the serious pneumonia Legionnaires' disease. A primary factor involved in these host cell interactions is the Dot/Icm Type IV secretion system responsible for translocating effector proteins needed to establish and maintain the bacterial replicative niche. Several regulatory factors have been identified to control the expression of the Dot/Icm system and effectors, one of which is the CpxRA two-component system, suggesting essentiality for virulence. In this study, we generated cpxR, cpxA and cpxRA in-frame null mutant strains to further delineate the role of the CpxRA system in bacterial survival and virulence. We found that cpxR is essential for intracellular replication within Acanthamoeba castellanii, but not in U937-derived macrophages. Transcriptome analysis revealed that CpxRA regulates a large number of virulence-associated proteins including Dot/Icm effectors as well as Type II secreted substrates. Furthermore, the cpxR and cpxRA mutant strains were more sodium resistant than the parental strain Lp02, and cpxRA expression reaches maximal levels during postexponential phase. Taken together, our findings suggest the CpxRA system is a key contributor to L. pneumophila virulence in protozoa via virulence factor regulation. PMID:26934669

  12. The contribution of the nonporous distal stem to the stability of proximally porous-coated canine femoral components.

    Science.gov (United States)

    Jasty, M; Krushell, R; Zalenski, E; O'Connor, D; Sedlacek, R; Harris, W

    1993-02-01

    The contribution of the distal nonporous-coated stem to the stability of the uncemented femoral components, which were porous coated only proximally, was investigated under two conditions: (1) immediately after insertion and (2) at 6 months, 1 year, and 2 years after surgery in a canine model. The relative motion of the femoral components at the bone porous-coating interface under loads simulating the canine midstance was measured at these time periods using displacement transducers. The measurements were repeated after severing the connection between the porous-coated proximal body and the nonporous-coated distal stem through a small hole in the anterior cortex. The results showed that while the distal nonporous-coated stem enhanced the immediate stability of the proximally porous-coated uncemented femoral components, it contributed little to the long-term stability of the femoral components after bony ingrowth had occurred in vivo. The mean relative motion between the body of the prosthesis and the cortical bone increased from 12 microns (+/- 7 microns) to 31 microns (+/- 34 microns) in the posterior transverse direction when the stem was immediately severed after the surgery. However, at 6 months, 1 year, and 2 years after surgery, extensive bone ingrowth had occurred into the proximal porous-coated regions of the body and provided excellent stability to the femoral components. With bone ingrowth, the mean relative motion was less than 5 microns at any site. Under these conditions, severing the stem did not increase the relative motion of the prostheses significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8436987

  13. Pure phase-locking of beta/gamma oscillation contributes to the N30 frontal component of somatosensory evoked potentials

    Directory of Open Access Journals (Sweden)

    Leroy Axelle

    2007-09-01

    Full Text Available Abstract Background Evoked potentials have been proposed to result from phase-locking of electroencephalographic (EEG activities within specific frequency bands. However, the respective contribution of phasic activity and phase resetting of ongoing EEG oscillation remains largely debated. We here applied the EEGlab procedure in order to quantify the contribution of electroencephalographic oscillation in the generation of the frontal N30 component of the somatosensory evoked potentials (SEP triggered by median nerve electrical stimulation at the wrist. Power spectrum and intertrial coherence analysis were performed on EEG recordings in relation to median nerve stimulation. Results The frontal N30 component was accompanied by a significant phase-locking of beta/gamma oscillation (25–35 Hz and to a lesser extent of 80 Hz oscillation. After the selection in each subject of the trials for which the power spectrum amplitude remained unchanged, we found pure phase-locking of beta/gamma oscillation (25–35 Hz peaking about 30 ms after the stimulation. Transition across trials from uniform to normal phase distribution revealed temporal phase reorganization of ongoing 30 Hz EEG oscillations in relation to stimulation. In a proportion of trials, this phase-locking was accompanied by a spectral power increase peaking in the 30 Hz frequency band. This corresponds to the complex situation of 'phase-locking with enhancement' in which the distinction between the contribution of phasic neural event versus EEG phase resetting is hazardous. Conclusion The identification of a pure phase-locking in a large proportion of the SEP trials reinforces the contribution of the oscillatory model for the physiological correlates of the frontal N30. This may imply that ongoing EEG rhythms, such as beta/gamma oscillation, are involved in somatosensory information processing.

  14. Contributions of different biomass components to the sorption of 1,2,4-trichlorobenzene under a series of pyrolytic temperatures.

    Science.gov (United States)

    Han, Lu; Qian, Linbo; Yan, Jingchun; Chen, Mengfang

    2016-08-01

    In order to investigate contributions of cellulose (CEL), hemicellulose (HEM), lignin (LIG) to the sorption capacity of biochar derived from lignocellulose, the individual component and their artificially modeled biomass mixture (C-H-L) were pyrolyzed under oxygen-limited condition at various pyrolytic temperatures (i.e. 250, 350, 500, 700 °C). The characterization analysis of biochars and sorption batch experiments were carried out. Variations in physiochemical property of different component biochars resulted in discrepancies in their ability to function as sorbents to 1,2,4-trichlorobenzene (1,2,4-TCB). The maximum mass sorption capacity (Qfm) of 1,2,4-TCB was the greatest on CEL biochars ranging from 58.31 to 601.20 mg g(-1), and can be best explained by their huge surface area and micropore volume. Hydrophobic partitioning-sorption into 'soft' amorphous alkyl carbon may account for the second greatest Qfm (45.09-56.57 mg g(-1)) on HEM biochars under low pyrolytic temperatures (250-350 °C) with the lowest surface area. LIG biochars with more compact and smooth aromatic structure surface may undergo a surface monolayer specific adsorption. The Qfm (87.86-196.53 mg g(-1)) on C-H-L biochars were largely dependent on CEL and HEM components for their outstanding sorption capacity and higher content in biomass. Therefore, the results highlighted the importance of CEL and HEM components for 1,2,4-TCB sorption to biochar. PMID:27179244

  15. Autophagic response to cell culture stress in pluripotent stem cells.

    Science.gov (United States)

    Gregory, Siân; Swamy, Sushma; Hewitt, Zoe; Wood, Andrew; Weightman, Richard; Moore, Harry

    2016-05-01

    Autophagy is an important conserved cellular process, both constitutively as a recycling pathway for long lived proteins and as an upregulated stress response. Recent findings suggest a fundamental role for autophagic processes in the maintenance of pluripotent stem cell function. In human embryonic stem cells (hESCS), autophagy was investigated by transfection of LC3-GFP to visualize autophagosomes and with an antibody to LC3B protein. The presence of the primary cilium (PC) in hESCs as the site of recruitment of autophagy-related proteins was also assessed. HESCs (mShef11) in vitro displayed basal autophagy which was upregulated in response to deprivation of culture medium replacement. Significantly higher levels of autophagy were exhibited on spontaneous differentiation of hESCs in vitro. The PC was confirmed to be present in hESCs and therefore may serve to coordinate autophagy function. PMID:26385182

  16. Role of phosphoinositide 3-kinase in the autophagic death of serum-deprived PC12 cells.

    Science.gov (United States)

    Guillon-Munos, A; van Bemmelen, M X P; Clarke, P G H

    2005-10-01

    The death of serum-deprived undifferentiated PC12 cells shows both autophagic and apoptotic features. Since it is still controversial whether the autophagy is instrumental in the cell death or a mere epiphenomenon, we tested the effects of inhibiting the autophagy by a variety of phosphoinositide 3-kinase inhibitors, and provided evidence that the autophagy, or a related trafficking event, is indeed instrumental in the cell death. Furthermore, by comparing the effects of PI3-K inhibition and caspase-inhibition on autophagic and apoptotic cellular events, we showed that in this case the autophagic and apoptotic mechanisms mediate cell death by parallel pathways and do not act in series. PMID:16151638

  17. Seasonal contribution of mineral dust and other major components to particulate matter at two remote sites in Central Asia

    Science.gov (United States)

    Miller-Schulze, Justin P.; Shafer, Martin; Schauer, James J.; Heo, Jongbae; Solomon, Paul A.; Lantz, Jeffrey; Artamonova, Maria; Chen, Boris; Imashev, Sanjar; Sverdlik, Leonid; Carmichael, Greg; DeMinter, Jeff

    2015-10-01

    Dust storms are significant contributors to ambient levels of particulate matter (PM) in many areas of the world. Central Asia, an area that is relatively understudied in this regard, is anticipated to be affected by dust storms due to its proximity to several major deserts that are in and generally surround Central Asia (e.g., the Aral Sea region, the Taklimakan desert in Western China). To investigate the relative importance of mineral dust (dust specifically composed of soil related minerals and oxides) in Central Asia, PM10 and PM2.5, and by difference, coarse particles (particles with diameters between 2.5 and 10 μm) were measured at two sites, Bishkek and Lidar Station Teplokluchenka (Lidar), in the Kyrgyz Republic. Samples were collected every other day from July 2008 to July 2009. Daily samples were analyzed for mass and organic and elemental carbon. Samples were also composited on a bi-weekly basis and analyzed for elemental constituents and ionic components. In addition, samples collected on days with relatively high and low PM concentrations were analyzed before, and separately, from the biweekly composites to investigate the chemical differences between the episodic events. Data from the episodic samples were averaged into the composited averages. Using the elemental component data, several observational models were examined to estimate the contribution of mineral dust to ambient PM levels. A mass balance was also conducted. Results indicate that at both sites, mineral dust (as approximated by the "dust oxide" model) and organic matter (OM) were the dominant contributors to PM10 and PM2.5. Mineral dust was a more significant contributor to the coarse PM (PM10-2.5) during high event samples at both sites, although the relative contribution is greater at the Lidar site (average ± standard deviation = 42 ± 29%) as compared with the Bishkek site (26 ± 16%). Principal Components Analysis (PCA) was performed using data from both sites, and PCA indicated

  18. The contribution of dominance and inbreeding depression in estimating variance components for litter size in Pannon White rabbits.

    Science.gov (United States)

    Nagy, I; Gorjanc, G; Curik, I; Farkas, J; Kiszlinger, H; Szendrő, Zs

    2013-08-01

    In a synthetic closed population of Pannon White rabbits, additive (VA ), dominance (VD ) and permanent environmental (VPe ) variance components as well as doe (bF d ) and litter (bF l ) inbreeding depression were estimated for the number of kits born alive (NBA), number of kits born dead (NBD) and total number of kits born (TNB). The data set consisted of 18,398 kindling records of 3883 does collected from 1992 to 2009. Six models were used to estimate dominance and inbreeding effects. The most complete model estimated VA and VD to contribute 5.5 ± 1.1% and 4.8 ± 2.4%, respectively, to total phenotypic variance (VP ) for NBA; the corresponding values for NBD were 1.9 ± 0.6% and 5.3 ± 2.4%, for TNB, 6.2 ± 1.0% and 8.1 ± 3.2% respectively. These results indicate the presence of considerable VD . Including dominance in the model generally reduced VA and VPe estimates, and had only a very small effect on inbreeding depression estimates. Including inbreeding covariates did not affect estimates of any variance component. A 10% increase in doe inbreeding significantly increased NBD (bF d  = 0.18 ± 0.07), while a 10% increase in litter inbreeding significantly reduced NBA (bF l  = -0.41 ± 0.11) and TNB (bF l  = -0.34 ± 0.10). These findings argue for including dominance effects in models of litter size traits in populations that exhibit significant dominance relationships. PMID:23855632

  19. Changes in Autophagic Response in Patients with Chronic Hepatitis C Virus Infection

    OpenAIRE

    Rautou, Pierre-Emmanuel; Cazals-Hatem, Dominique; Feldmann, Gérard; Mansouri, Abdellah; Grodet, Alain; Barge, Sandrine; Martinot-Peignoux, Michèle; Duces, Aurélie; Bièche, Ivan; Lebrec, Didier; Bedossa, Pierre; Paradis, Valérie; Marcellin, Patrick; Valla, Dominique; Asselah, Tarik

    2011-01-01

    Autophagy is a regulated process that can be involved in the elimination of intracellular microorganisms and in antigen presentation. Some in vitro studies have shown an altered autophagic response in hepatitis C virus infected hepatocytes. The present study aimed at evaluating the autophagic process in the liver of chronic hepatitis C (CHC) patients. Fifty-six CHC patients and 47 control patients (8 with nonalcoholic steatohepatitis or alcoholic liver disease, 18 with chronic heptatitis B vi...

  20. Inhibition of HDAC6 modifies tau inclusion body formation and impairs autophagic clearance.

    Science.gov (United States)

    Leyk, Janina; Goldbaum, Olaf; Noack, Monika; Richter-Landsberg, Christiane

    2015-04-01

    of apoptotic cell death. Furthermore, the heat shock response is altered, and TST suppresses the MG-132-stimulated induction of HSP70. To test whether the alteration of protein aggregate formation is related to the influence of HDAC6 on the autophagic degradation system, an oligodendroglial cell line, i.e., OLN-93 cells stably expressing green fluorescent protein (GFP)-microtubule associated protein light chain 3 (LC3) and tau, was used. During autophagosome formation, endogenous LC3 is processed to LC3-I, which is then converted to LC3-II. An increase of LC3-II is used as a reliable marker for autophagosome formation and abundance. It is demonstrated that inhibition of HDAC6 leads to the accumulation of LC3-positive autophagosomal vacuoles and an increase in LC3-II immunoreactivity, but the autophagic flux is rather impaired. Hence, the inhibition or dysregulation of HDAC6 contributes to stress responses and pathological processes in oligodendrocytes. PMID:25434725

  1. Dose rate and contribution of the nuclides on the primary components during shutdown chemistry in Beznau NPP

    Energy Technology Data Exchange (ETDEWEB)

    Mailand, I.; Franz, P. [Axpo AG, Nuclear Power Plant Beznau, Dottingen (Switzerland)

    2010-07-01

    The Nuclear Power Plant Beznau consists of two identical 380 MWe PWR units with two loops each, commissioned in 1969 and 1971. Westinghouse was responsible for the primary part of the plant and BBC, nowadays ABB for the secondary one. In the last 20 years the plant has undergone an extensive modernisation programme in which about 1.5 billion Swiss Francs have been invested. One of the main measures was the replacement of the steam generators with Inconel 690 tube material, realized at unit 1 in 1993 and at unit 2 in 1999. To keep the dose rate at permanently low levels, the minimisation of activity build-up on the surfaces of the primary components is always the main focus of the chemistry and radiation protection. A large number of measures to decrease the dose rates have been realized in the past, which are connected with permanent improvements of the primary coolant and shutdown chemistry. The shutdown chemistry, which has been introduced at the beginning of the eighties, was improved continuously during the nineties. A further optimisation was elaborated in the last years and has been proved to be a beneficial procedure. It is capable to remove activated corrosion products as well as iodine and noble gases during shutdown before opening the primary system. This process is supported by dosing hydrogen peroxide at 80°C. Since the replacements of the steam generators special attention has been paid to the behaviour and inventory of main nuclides and their contribution to dose rate. The contamination level and the deposited activities have been measured by in-situ gamma spectrometry at several locations, like steam generator and main circulation pipe surfaces. A crucial factor of the personal dose of the maintenance workers is the dose rate of the closure (crossover) leg during outages. Therefore, additional in-situ gamma spectrometric measurements have been performed during shutdown chemistry at the closure leg. The results of these measurements demonstrate an

  2. p-Cresol mediates autophagic cell death in renal proximal tubular cells.

    Science.gov (United States)

    Lin, Hsin-Hung; Huang, Chiu-Ching; Lin, Tze-Yi; Lin, Ching-Yuang

    2015-04-01

    Higher serum level of p-cresol (PC) in chronic kidney disease (CKD) patients has been linked with CKD progression. The toxic effect of PC on diverse cells has been reported by prior studies, except for renal tubular cells. Both autophagy and apoptosis contribute to renal tubular cell death, yet evidence of its response to PC is limited and their crosstalk is still unclear. Autophagy is an important cellular process involved in toxin-induced cell death. Renal tubular cell death in tubular injury is thought to be one of the key events causing the progression of CKD. Thus, we treated rat (NRK-52E) and human (HRPTEC) renal proximal tubular cells (RPTC) with PC and found the cell proliferation was significantly decreased. Cell apoptosis was significantly increased and accompanied with the activation of autophagy as evidenced by increases in LC3-II, beclin 1 and Atg 4. We also found an increase of p62 by c-Jun activation. p62 accumulation could mediate the activation of caspase 8-dependent cell apoptosis. Conversely, knockdown of p62 by siRNA of p62 had the opposite effect by arresting LC3-II accumulation and promoting increasing cell viability. We conclude that PC triggered autophagic RPTC death via JNK-mediated p62 accumulation and then activated caspase 8-dependent cell death pathway. PC can be considered as one of the key events causing progression of CKD, which might affect drug disposition in CKD cases. PMID:25668154

  3. Autophagic myelin destruction by schwann cells during wallerian degeneration and segmental demyelination.

    Science.gov (United States)

    Jang, So Young; Shin, Yoon Kyung; Park, So Young; Park, Joo Youn; Lee, Hye Jeong; Yoo, Young Hyun; Kim, Jong Kuk; Park, Hwan Tae

    2016-05-01

    As lysosomal hydrolysis has long been suggested to be responsible for myelin clearance after peripheral nerve injury, in this study, we investigated the possible role of autophagolysosome formation in myelin phagocytosis by Schwann cells and its final contribution to nerve regeneration. We found that the canonical formation of autophagolysosomes was induced in demyelinating Schwann cells after injury, and the inhibition of autophagy via Schwann cell-specific knockout of the atg7 gene or pharmacological intervention of lysosomal function caused a significant delay in myelin clearance. However, Schwann cell dedifferentiation, as demonstrated by extracellular signal-regulated kinase activation and c-Jun induction, and redifferentiation were not significantly affected, and thus the entire repair program progressed normally in atg7 knockout mice. Finally, autophagic Schwann cells were also found during segmental demyelination in a mouse model of inflammatory peripheral neuropathy. Together, our findings suggest that autophagy is the self-myelin destruction mechanism of Schwann cells, but mechanistically, it is a process distinct from Schwann cell plasticity for nerve repair. GLIA 2016;64:730-742. PMID:26712109

  4. Perceptual Correlates of Turkish Word Stress and Their Contribution to Automatic Lexical Access: Evidence from Early ERP Components.

    Science.gov (United States)

    Zora, Hatice; Heldner, Mattias; Schwarz, Iris-Corinna

    2016-01-01

    Perceptual correlates of Turkish word stress and their contribution to lexical access were studied using the mismatch negativity (MMN) component in event-related potentials (ERPs). The MMN was expected to indicate if segmentally identical Turkish words were distinguished on the sole basis of prosodic features such as fundamental frequency (f 0), spectral emphasis (SE), and duration. The salience of these features in lexical access was expected to be reflected in the amplitude of MMN responses. In a multi-deviant oddball paradigm, neural responses to changes in f 0, SE, and duration individually, as well as to all three features combined, were recorded for words and pseudowords presented to 14 native speakers of Turkish. The word and pseudoword contrast was used to differentiate language-related effects from acoustic-change effects on the neural responses. First and in line with previous findings, the overall MMN was maximal over frontal and central scalp locations. Second, changes in prosodic features elicited neural responses both in words and pseudowords, confirming the brain's automatic response to any change in auditory input. However, there were processing differences between the prosodic features, most significantly in f 0: While f 0 manipulation elicited a slightly right-lateralized frontally-maximal MMN in words, it elicited a frontal P3a in pseudowords. Considering that P3a is associated with involuntary allocation of attention to salient changes, the manipulations of f 0 in the absence of lexical processing lead to an intentional evaluation of pitch change. f 0 is therefore claimed to be lexically specified in Turkish. Rather than combined features, individual prosodic features differentiate language-related effects from acoustic-change effects. The present study confirms that segmentally identical words can be distinguished on the basis of prosodic information alone, and establishes the salience of f 0 in lexical access. PMID:26834534

  5. Lipid rafts participate in aberrant degradative autophagic-lysosomal pathway of amyloid-beta peptide in Alzheimer’s disease

    Institute of Scientific and Technical Information of China (English)

    Xin Zhou; Chun Yang; Yufeng Liu; Peng Li; Huiying Yang; Jingxing Dai; Rongmei Qu; Lin Yuan

    2014-01-01

    Amyloid-beta peptide is the main component of amyloid plaques, which are found in Alzhei-mer’s disease. The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzheimer’s disease. Lipid rafts are glycolipid-rich liquid domains of the plasma membrane, where certain types of protein tend to aggregate and intercalate. Lipid rafts are involved in the generation of amyloid-beta oligomers and the formation of amyloid-beta peptides. In this paper, we review the mechanism by which lipid rafts disturb the aberrant deg-radative autophagic-lysosomal pathway of amyloid-beta, which plays an important role in the pathological process of Alzheimer’s disease. Moreover, we describe this mechanism from the view of the Two-system Theory of fasciology and thus, suggest that lipid rafts may be a new target of Alzheimer’s disease treatment.

  6. Micromechanical modelling of heterogeneous materials in transient conditions: contributions for the study of the ageing of structural components under service

    International Nuclear Information System (INIS)

    The modelling of the mechanical behaviour of structural materials is increasingly based on microstructural parameters. Within this framework, homogenisation methods have the advantage of providing deductive methods which, starting from the properties and space distribution of each constituent, deduce the effective properties of the heterogeneous material. Nevertheless, many applications make still difficult the use of homogenisation methods. It is in particular the case of structural materials presenting elastic-viscoplastic behaviours and subjected to both non-monotone and ageing loadings. To progress on the treatment by homogenisation of these useful situations constitutes precisely the main idea of the various contributions presented in this work.For linear elasticity, new expressions for the computation of the Eshelby tensor are first of all established in order to improve the efficiency of homogenisation methods usually used. Always for linear behaviours but now viscoelastic, various approximations associated with the use of the theorem of correspondence are studied and compared. The equivalence of one of these approximations (the so-called 'collocation method') with an internal variables formulation of the effective behaviour is shown. This internal variables formulation leads to exact results in some situations and strongly simplifies the treatment of ageing linear viscoelastic behaviours. In the case of elastic-viscoplastic behaviours, is added to the previous difficulty (viscoelastic coupling) that of the treatment of nonlinear behaviour. Comparisons made between various families of estimates make it possible to determine the effects of the various approximations needed to deal with these nonlinearities. An improvement is also proposed and implemented in a particular case while the extension of this internal variable formulation to nonlinear behaviours is discussed. Finally, full-field computations of microstructures are also tackled by considering the

  7. Changes in autophagic response in patients with chronic hepatitis C virus infection.

    Science.gov (United States)

    Rautou, Pierre-Emmanuel; Cazals-Hatem, Dominique; Feldmann, Gérard; Mansouri, Abdellah; Grodet, Alain; Barge, Sandrine; Martinot-Peignoux, Michèle; Duces, Aurélie; Bièche, Ivan; Lebrec, Didier; Bedossa, Pierre; Paradis, Valérie; Marcellin, Patrick; Valla, Dominique; Asselah, Tarik; Moreau, Richard

    2011-06-01

    Autophagy is a regulated process that can be involved in the elimination of intracellular microorganisms and in antigen presentation. Some in vitro studies have shown an altered autophagic response in hepatitis C virus infected hepatocytes. The present study aimed at evaluating the autophagic process in the liver of chronic hepatitis C (CHC) patients. Fifty-six CHC patients and 47 control patients (8 with nonalcoholic steatohepatitis or alcoholic liver disease, 18 with chronic heptatitis B virus infection, and 21 with no or mild liver abnormalities at histological examination) were included. Autophagy was assessed by means of electron microscopy and microtubule-associated protein light chain 3 immunoblotting. Using light chain 3 immunoblotting, the form present on autophagic vesicle (light chain 3-II) was significantly higher in CHC patients than in controls (P < 0.05). Using quantitative electron microscopy analysis, the median number of autophagic vesicles observed in hepatocytes from CHC patients was sixfold higher than in overall controls (P < 0.001). In contrast, there was no difference between CHC patients and controls in the number of mature lysosomes with electron-dense contents arguing in favor of a lack of fusion between autophagosome and lysosome. Neither genotype nor viral load influenced the autophagy level. In conclusion, autophagy is altered in hepatocytes from CHC patients, likely due to a blockade of the last step of the autophagic process. PMID:21641393

  8. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death

    Energy Technology Data Exchange (ETDEWEB)

    Lyu, Qing [School of Life Sciences, Tsinghua University, Beijing, 100084 (China); Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055 (China); Tou, Fangfang [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China); Su, Hong; Wu, Xiaoyong [First Affiliated Hospital, Guiyang College of Traditional Chinese Medicine, Guiyang, 550002 (China); Chen, Xinyi [Department of Hematology and Oncology, Beijing University of Chinese Medicine, Beijing, 100029 (China); Zheng, Zhi, E-mail: zheng_sheva@hotmail.com [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China)

    2015-06-19

    Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway.

  9. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death

    International Nuclear Information System (INIS)

    Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway

  10. Lysosomal and autophagic reactions as predictive indicators of environmental impact in aquatic animals.

    Science.gov (United States)

    Moore, Michael N; Allen, J Icarus; McVeigh, Allan; Shaw, Jenny

    2006-01-01

    The lysosomal-autophagic system appears to be a common target for many environmental pollutants as lysosomes accumulate many toxic metals and organic xenobiotics, which perturb normal function and damage the lysosomal membrane. In fact, lysosomal membrane integrity or stability appears to be an effective generic indicator of cellular well-being in eukaryotes: in bivalve molluscs and fish, stability is correlated with many toxicological responses and pathological reactions. Prognostic use of adverse lysosomal and autophagic reactions to environmental pollutants has been explored in relation to predicting cellular dysfunction and health in marine mussels, which are extensively used as sensitive bioindicators in monitoring ecosystem health. Derivation of explanatory frameworks for prediction of pollutant impact on health is a major goal; and we have developed a conceptual mechanistic model linking lysosomal damage and autophagic dysfunction with injury to cells and tissues. This model has also complemented the creation of a cell-based computational model for molluscan hepatopancreatic cells that simulates lysosomal, autophagic and other cellular reactions to pollutants. Experimental and simulated results have also indicated that nutritional deprivation-induced autophagy has a protective function against toxic effects mediated by reactive oxygen species (ROS). Finally, coupled measurement of lysosomal-autophagic reactions and modelling is proposed as a practical toolbox for predicting toxic environmental risk. PMID:16874099

  11. Estimation of foetal dose and segregation of contributing scatter components during three-dimensional conformal radiation therapy (3DCRT) of a brain tumour during pregnancy

    International Nuclear Information System (INIS)

    The aim of this work is to measure the dose to foetus, both in vivo and in vitro, during three-dimensional conformal radiation therapy (3DCRT) in a pregnant patient with a pituitary adenoma. The study was then extended to assess the components contributing to the foetal dose, such as collimator scatter, internal scatter, head leakage, wedge scatter and MLC effect

  12. Potential contribution of planktonic components to ammonium cycling in the coastal area off central-southern Chile during non-upwelling conditions

    Science.gov (United States)

    Molina, Veronica; Morales, Carmen E.; Farías, Laura; Cornejo, Marcela; Graco, Michelle; Eissler, Yoanna; Cuevas, Luis A.

    2012-01-01

    The potential contributions of different microbial components (chemosynthesis (0.005 g C m -2 d -1) represented a large proportion (51%) of the total dark carbon fixation during the non-upwelling season when integrated rates of photosynthesis are relatively low (0.42 g C m -2 d -1) and microbial food webs dominate the transfer of carbon within this coastal system.

  13. Autophagic flux data in differentiated C2C12 myotubes following exposure to acetylcholine and caffeine

    Directory of Open Access Journals (Sweden)

    Darin Bloemberg

    2016-06-01

    Full Text Available The C2C12 line of mouse myoblasts is a useful cell culture model in which to conduct in vitro analyses related to skeletal muscle. Here we present data regarding the autophagic response induced by two chemicals known to influence calcium release and contraction in skeletal muscles and C2C12 cells: acetylcholine and caffeine. More specifically, by concurrently administering acetylcholine or caffeine along with chloroquine to differentiated myotubes for various amounts of time and assessing the protein expression of LC3 and p62, we report data on the relative level of autophagic flux induced by these two calcium- and contraction-regulating chemicals.

  14. Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

    Energy Technology Data Exchange (ETDEWEB)

    Zois, Christos E. [Department of Radiotherapy - Oncology, Democritus University of Thrace, Alexandroupolis 68100 (Greece); Giatromanolaki, Alexandra [Department of Pathology, Democritus University of Thrace, Alexandroupolis (Greece); Kainulainen, Heikki [Department of Biology of Physical Activity, University of Jyvaeskylae (Finland); Botaitis, Sotirios [Department of Experimental Surgery, Democritus University of Thrace, Alexandroupolis (Greece); Torvinen, Sira [Department of Biology of Physical Activity, University of Jyvaeskylae (Finland); Simopoulos, Constantinos [Department of Experimental Surgery, Democritus University of Thrace, Alexandroupolis (Greece); Kortsaris, Alexandros [Department of Biochemistry, Democritus University of Thrace, Alexandroupolis (Greece); Sivridis, Efthimios [Department of Pathology, Democritus University of Thrace, Alexandroupolis (Greece); Koukourakis, Michael I., E-mail: targ@her.forthnet.gr [Department of Radiotherapy - Oncology, Democritus University of Thrace, Alexandroupolis 68100 (Greece)

    2011-01-07

    Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response of normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body {gamma}-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function

  15. Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

    International Nuclear Information System (INIS)

    Research highlights: → We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. → Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. → The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. → Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response of normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body γ-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function. The LC3A and Beclin1 m

  16. Autophagic flux data in differentiated C2C12 myotubes following exposure to acetylcholine and caffeine.

    Science.gov (United States)

    Bloemberg, Darin; Quadrilatero, Joe

    2016-06-01

    The C2C12 line of mouse myoblasts is a useful cell culture model in which to conduct in vitro analyses related to skeletal muscle. Here we present data regarding the autophagic response induced by two chemicals known to influence calcium release and contraction in skeletal muscles and C2C12 cells: acetylcholine and caffeine. More specifically, by concurrently administering acetylcholine or caffeine along with chloroquine to differentiated myotubes for various amounts of time and assessing the protein expression of LC3 and p62, we report data on the relative level of autophagic flux induced by these two calcium- and contraction-regulating chemicals. PMID:27054179

  17. Conessine Interferes with Oxidative Stress-Induced C2C12 Myoblast Cell Death through Inhibition of Autophagic Flux.

    Directory of Open Access Journals (Sweden)

    Hyunju Kim

    Full Text Available Conessine, a steroidal alkaloid isolated from Holarrhena floribunda, has anti-malarial activity and interacts with the histamine H3 receptor. However, the cellular effects of conessine are poorly understood. Accordingly, we evaluated the involvement of conessine in the regulation of autophagy. We searched natural compounds that modulate autophagy, and conessine was identified as an inhibitor of autophagic flux. Conessine treatment induced the formation of autophagosomes, and p62, an autophagic adapter, accumulated in the autophagosomes. Reactive oxygen species such as hydrogen peroxide (H2O2 result in muscle cell death by inducing excessive autophagic flux. Treatment with conessine inhibited H2O2-induced autophagic flux in C2C12 myoblast cells and also interfered with cell death. Our results indicate that conessine has the potential effect to inhibit muscle cell death by interfering with autophagic flux.

  18. Conessine Interferes with Oxidative Stress-Induced C2C12 Myoblast Cell Death through Inhibition of Autophagic Flux

    Science.gov (United States)

    Kim, Hyunju; Lee, Kang Il; Jang, Minsu; Namkoong, Sim; Park, Rackhyun; Ju, Hyunwoo; Choi, Inho; Oh, Won Keun

    2016-01-01

    Conessine, a steroidal alkaloid isolated from Holarrhena floribunda, has anti-malarial activity and interacts with the histamine H3 receptor. However, the cellular effects of conessine are poorly understood. Accordingly, we evaluated the involvement of conessine in the regulation of autophagy. We searched natural compounds that modulate autophagy, and conessine was identified as an inhibitor of autophagic flux. Conessine treatment induced the formation of autophagosomes, and p62, an autophagic adapter, accumulated in the autophagosomes. Reactive oxygen species such as hydrogen peroxide (H2O2) result in muscle cell death by inducing excessive autophagic flux. Treatment with conessine inhibited H2O2-induced autophagic flux in C2C12 myoblast cells and also interfered with cell death. Our results indicate that conessine has the potential effect to inhibit muscle cell death by interfering with autophagic flux. PMID:27257813

  19. The contributions of $qqqq\\bar{q}$ components to the axial charges of proton and its resonances

    CERN Document Server

    Yuan, S G; He, Jun

    2009-01-01

    We calculate the axial charges of the proton and its resonances in the framework of the constituent quark model, which is extended to include the $qqqq\\bar{q}$ components. If 20% admixtures of the $qqqq\\bar{q}$ components in the proton are assumed, the theoretical value for the axial charge in our model is in good agreement with the empirical value, which can not be well reproduced in the traditional constituent quark model even though the $SU(6) \\bigotimes O(3)$ symmetry breaking or relativistic effect is taken into account. We also predict an unity axial charge for $N^{*}(1440)$ with 30% $qqqq\\bar{q}$ components constrained by the strong and electromagnetic decays.

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

    International Nuclear Information System (INIS)

    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

  1. A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects

    Science.gov (United States)

    Schaffner, Adam; Fedick, Anastasia; Kaye, Lauren E.; Liao, Jun; Yachelevich, Naomi; Chu, Mary-Lynn; Boles, Richard G.; Moran, Ellen; Tokita, Mari; Gorman, Elizabeth; Zhang, Wei; Xia, Fan; Leduc, Magalie; Yang, Yaping; Eng, Christine; Wong, Lee-Jun; Schiffmann, Raphael; Diaz, George A.; Kornreich, Ruth; Thummel, Ryan; Wasserstein, Melissa; Yue, Zhenyu; Edelmann, Lisa

    2016-01-01

    Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities affecting the central nervous system (CNS). The causative mutation in ~50% of gLEs is unknown. Using whole exome sequencing (WES), we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G), as the genetic cause of a leukoencephalopathy syndrome in five individuals from three unrelated Ashkenazi Jewish (AJ) families. All five patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures. The carrier frequency of the VPS11: c.2536T>G variant is 1:250 in the AJ population (n = 2,026). VPS11 protein is a core component of HOPS (homotypic fusion and protein sorting) and CORVET (class C core vacuole/endosome tethering) protein complexes involved in membrane trafficking and fusion of the lysosomes and endosomes. The cysteine 846 resides in an evolutionarily conserved cysteine-rich RING-H2 domain in carboxyl terminal regions of VPS11 proteins. Our data shows that the C846G mutation causes aberrant ubiquitination and accelerated turnover of VPS11 protein as well as compromised VPS11-VPS18 complex assembly, suggesting a loss of function in the mutant protein. Reduced VPS11 expression leads to an impaired autophagic activity in human cells. Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain. Thus, our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway. PMID:27120463

  2. Aging and Autophagic Function Influences the Progressive Decline of Adult Drosophila Behaviors.

    Directory of Open Access Journals (Sweden)

    Eric P Ratliff

    Full Text Available Multiple neurological disorders are characterized by the abnormal accumulation of protein aggregates and the progressive impairment of complex behaviors. Our Drosophila studies demonstrate that middle-aged wild-type flies (WT, ~4-weeks exhibit a marked accumulation of neural aggregates that is commensurate with the decline of the autophagy pathway. However, enhancing autophagy via neuronal over-expression of Atg8a (Atg8a-OE reduces the age-dependent accumulation of aggregates. Here we assess basal locomotor activity profiles for single- and group-housed male and female WT flies and observed that only modest behavioral changes occurred by 4-weeks of age, with the noted exception of group-housed male flies. Male flies in same-sex social groups exhibit a progressive increase in nighttime activity. Infrared videos show aged group-housed males (4-weeks are engaged in extensive bouts of courtship during periods of darkness, which is partly repressed during lighted conditions. Together, these nighttime courtship behaviors were nearly absent in young WT flies and aged Atg8a-OE flies. Previous studies have indicated a regulatory role for olfaction in male courtship partner choice. Coincidently, the mRNA expression profiles of several olfactory genes decline with age in WT flies; however, they are maintained in age-matched Atg8a-OE flies. Together, these results suggest that middle-aged male flies develop impairments in olfaction, which could contribute to the dysregulation of courtship behaviors during dark time periods. Combined, our results demonstrate that as Drosophila age, they develop early behavior defects that are coordinate with protein aggregate accumulation in the nervous system. In addition, the nighttime activity behavior is preserved when neuronal autophagy is maintained (Atg8a-OE flies. Thus, environmental or genetic factors that modify autophagic capacity could have a positive impact on neuronal aging and complex behaviors.

  3. Intense pseudotransport of a cationic drug mediated by vacuolar ATPase: Procainamide-induced autophagic cell vacuolization

    International Nuclear Information System (INIS)

    Cationic drugs frequently exhibit large apparent volumes of distribution, consistent with various forms of cellular sequestration. The contributions of organelles and metabolic processes that may mimic drug transport were defined in human vascular smooth muscle cells. We hypothesized that procainamide-induced vacuolar cytopathology is driven by intense pseudotransport mediated by the vacuolar (V)-ATPase and pursued the characterization of vesicular trafficking alterations in this model. Large amounts of procainamide were taken up by intact cells (maximal in 2 h, reversible upon washout, apparent KM 4.69 mM; fluorometric determination of cell-associated drug). Procainamide uptake was extensively prevented or reversed by pharmacological inhibition of the V-ATPase with bafilomycin A1 or FR 167356, decreased at low extracellular pH and preceded vacuolar cell morphology. However, the uptake of procainamide was unaffected by mitochondrial poisons that reduced the uptake of rhodamine 6G. Large vacuoles induced by millimolar procainamide were labeled with the late endosome/lysosome markers Rab7 and CD63 and the autophagy effector LC3; their osmotic formation (but not procainamide uptake) was reduced by extracellular mannitol and parallel to LC3 II formation. Procainamide-induced vacuolization is associated with defective endocytosis of fluorophore-labeled bovine serum albumin, but not with induction of the unfolded protein response. The contents of a vacuole subset slowly (≥ 24 h) become positive for Nile red staining (phospholipidosis-like response). V-ATPase-driven ion trapping is a form of intense cation pseudotransport that concerns the uncharged form of the drugs, and is associated with a vacuolar, autophagic and evolutive cytopathology and profound effects on vesicular trafficking

  4. Autophagic Cell Death and Apoptosis Jointly Mediate Cisatracurium Besylate-Induced Cell Injury

    Directory of Open Access Journals (Sweden)

    Haixia Zhuang

    2016-04-01

    Full Text Available Cisatracurium besylate is an ideal non-depolarizing muscle relaxant which is widely used in clinical application. However, some studies have suggested that cisatracurium besylate can affect cell proliferation. Moreover, its specific mechanism of action remains unclear. Here, we found that the number of GFP-LC3 (green fluoresent protein-light chain 3 positive autophagosomes and the rate of mitochondria fracture both increased significantly in drug-treated GFP-LC3 and MitoDsRed stable HeLa cells. Moreover, cisatracurium promoted the co-localization of LC3 and mitochondria and induced formation of autolysosomes. Levels of mitochondrial proteins decreased, which were reversed by the lysosome inhibitor Bafinomycin A1. Similar results with evidence of dose-dependent effects were found in both HeLa and Human Umbilical Vein Endothelial Cells (HUVECs. Cisatracurium lowered HUVEC viability to 0.16 (OD490 at 100 µM and to 0.05 (OD490 after 48 h in vitro; it increased the cell death rate to 56% at 100 µM and to 60% after 24 h in a concentration- and time-dependent manner (p < 0.01. Cell proliferation decreased significantly by four fold in Atg5 WT (wildtype MEF (mouse embryonic fibroblast (p < 0.01 but was unaffected in Atg5 KO (Knockout MEF, even upon treatment with a high dose of cisatracurium. Cisatracurium induced significant increase in cell death of wild-type MEFs even in the presence of the apoptosis inhibitor zVAD. Thus, we conclude that activation of both the autophagic cell death and cell apoptosis pathways contributes to cisatracurium-mediated cell injury.

  5. Investigating a two-component model of solid fuel organic aerosol in London: processes, PM1 contributions, and seasonality

    Science.gov (United States)

    Young, D. E.; Allan, J. D.; Williams, P. I.; Green, D. C.; Harrison, R. M.; Yin, J.; Flynn, M. J.; Gallagher, M. W.; Coe, H.

    2015-03-01

    Solid fuel emissions, including those from biomass burning, are increasing in urban areas across the European Union due to rising energy costs and government incentives to use renewable energy sources for heating. In order to help protect human health as well as to improve air quality and pollution abatement strategies, the sources of combustion aerosols, their contributions, and the processes they undergo need to be better understood. A high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) was therefore deployed at an urban background site between January and February 2012 to investigate solid fuel organic aerosols (SFOA) in London. The variability of SFOA was examined and the factors governing the split between the two SFOA factors derived from Positive Matrix Factorisation (PMF) were assessed. The concentrations of both factors were found to increase during the night and during cold periods, consistent with domestic space heating activities. The split between the two factors is likely governed predominantly by differences in burn conditions where SFOA1 best represents more efficient burns and SFOA2 best represents less efficient burns. The differences in efficiency may be due to burner types or burn phase, for example. Different fuel types and levels of atmospheric processing also likely contribute to the two factors. As the mass spectral profile of SFOA is highly variable, the findings from this study may have implications for improving future source apportionment and factorisation analyses. During the winter, SFOA was found to contribute 38% to the total non-refractory submicron organic aerosol (OA) mass, with similar contributions from both SFOA factors (20% from SFOA1 and 18% from SFOA2). A similar contribution of SFOA was derived for the same period from a compact time-of-flight AMS (cToF-AMS), which measured for a full calendar year at the same site. The seasonality of SFOA was investigated using the year-long data set where concentrations

  6. Investigating the two-component model of solid fuel organic aerosol in London: processes, PM1 contributions, and seasonality

    Science.gov (United States)

    Young, D. E.; Allan, J. D.; Williams, P. I.; Green, D. C.; Harrison, R. M.; Yin, J.; Flynn, M. J.; Gallagher, M. W.; Coe, H.

    2014-08-01

    Solid fuel emissions, including those from biomass burning, are increasing in urban areas across the European Union due to rising energy costs and government incentives to use renewable energy sources for heating. In order to help protect human health as well as to improve air quality and pollution abatement strategies, the sources of combustion aerosols, their contributions, and the processes they undergo need to be better understood. A high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) was therefore deployed at an urban background site between January and February 2012 to investigate solid fuel organic aerosols (SFOA) in London. The variability of SFOA was examined and the factors governing the split between the two SFOA factors derived from positive matrix factorisation (PMF) were assessed. The concentrations of both factors were found to increase during the night and during cold periods, consistent with domestic space heating activities. The split between the two factors is likely governed predominantly by differences in burn conditions where SFOA1 best represents more efficient burns in the south and SFOA2 best represents less efficient burns in the east and west. The differences in efficiency may be due to burner types or burn phase, for example. Different fuel types and levels of atmospheric processing also likely contribute to the two factors. As the mass spectral profile of SFOA is highly variable, the findings from this study have implications for improving future source apportionment and factorisation analyses. During the winter, SFOA was found to contribute 38% to the total submicron organic aerosol (OA) mass, with SFOA2 contributing slightly more than SFOA1 (20% compared to 18%). A similar contribution of SFOA was derived for the same period from compact time-of-flight AMS (cToF-AMS), which measured for a full calendar year at the same site. The seasonality of SFOA was investigated using the year-long data set where concentrations

  7. Ezrin Is a Component of the HIV-1 Virological Presynapse and Contributes to the Inhibition of Cell-Cell Fusion

    OpenAIRE

    Roy, Nathan H.; Lambelé, Marie; Chan, Jany; Symeonides, Menelaos; Thali, Markus

    2014-01-01

    During cell-to-cell transmission of HIV-1, viral and cellular proteins transiently accumulate at the contact zone between infected (producer) and uninfected (target) cells, forming the virological synapse. Rearrangements of the cytoskeleton in producer and target cells are required for proper targeting of viral and cellular components during synapse formation, yet little is known about how these processes are regulated, particularly within the producer cell. Since ezrin-radixin-moesin (ERM) p...

  8. Three-channel Lissajous' trajectories of auditory brainstem evoked potentials: contribution of fast and slow components to planar segment formation.

    Science.gov (United States)

    Pratt, H; Bleich, N; Feingold, K

    1990-01-01

    Three-Channel Lissajous' Trajectories (3CLT) of Auditory Brainstem Evoked Potentials (ABEP) to clicks were obtained after finite impulse response filtering in three frequency bands. These bands were chosen to replicate the widely used passband (100-3000 Hz) and to selectively enhance the definition of the 'pedestal' (10-240 Hz) or the first, third and fifth components (240-483 Hz). Quantitative measures of 3CLT were calculated to describe apex latencies, planar segment orientations, durations, trajectory amplitude peaks and their latencies. In addition, dipole moments at the latencies of apical points along 3-CLT were calculated. The planarity of ABEP 3-CLT segments persisted after selective enhancement of the 'pedestal' or the first, third and fifth components. These results rule out the suggestion that planarity of ABEP segments results from the interaction of the 'pedestal' with the superimposed faster components. These results demonstrate summation of 3-CLT planar segments ('a' 'c' and 'e' with the 'pedestal') to form new segments (wide-band 'a', 'c' and 'e'). With the exception of 'c', planar segments and the equivalent dipole moments associated with apexes did not change orientations across passbands. The effects of passband on the orientation of planar segment 'c' and the dipole moment of its apex are explained by its superimposition on the 'pedestal' in the wide-band records. A similar analysis of ABEP to clicks as compared to low-frequency stimuli (high-pass masked clicks) revealed no change in planarity nor in plane parameters. These results are compatible with the suggestion that the generators of the first, third and fifth ABEP components are curved fiber tracts. The planarity of the slow 'pedestal' may be due to the summation of slow synaptic potentials in auditory brainstem nuclei. These findings indicate that the generators of ABEP are composites that may be separated by selective lesion studies. PMID:2312411

  9. pH-Sensitive Polymeric Nanoparticles Modulate Autophagic Effect via Lysosome Impairment.

    Science.gov (United States)

    Lin, Yao-Xin; Wang, Yi; Qiao, Sheng-Lin; An, Hong-Wei; Zhang, Ruo-Xin; Qiao, Zeng-Ying; Rajapaksha, R P Y J; Wang, Lei; Wang, Hao

    2016-06-01

    In drug delivery systems, pH-sensitive polymers are commonly used as drug carriers, and significant efforts have been devoted to the aspects of controlled delivery and release of drugs. However, few studies address the possible autophagic effects on cells. Here, for the first time, using a fluorescent autophagy-reporting cell line, this study evaluates the autophagy-induced capabilities of four types of pH-sensitive polymeric nanoparticles (NPs) with different physical properties, including size, surface modification, and pH-sensitivity. Based on experimental results, this study concludes that pH-sensitivity is one of the most important factors in autophagy induction. In addition, this study finds that variation of concentration of NPs could cause different autophagic effect, i.e., low concentration of NPs induces autophagy in an mTOR-dependent manner, but high dose of NPs leads to autophagic cell death. Identification of this tunable autophagic effect offers a novel strategy for enhancing therapeutic effect in cancer therapy through modulation of autophagy. PMID:27120078

  10. The Regulation of the Autophagic Network and Its Implications for Human Disease

    NARCIS (Netherlands)

    Yang, Jing; Carra, Serena; Zhu, Wei-Guo; Kampinga, Harm H.

    2013-01-01

    Autophagy has attracted a lot of attention in recent years. More and more proteins and signaling pathways have been discovered that somehow feed into the autophagy regulatory pathways. Regulation of autophagy is complex and condition-specific, and in several diseases, autophagic fluxes are changed.

  11. Fluorescence-based visualization of autophagic activity predicts mouse embryo viability

    Science.gov (United States)

    Tsukamoto, Satoshi; Hara, Taichi; Yamamoto, Atsushi; Kito, Seiji; Minami, Naojiro; Kubota, Toshiro; Sato, Ken; Kokubo, Toshiaki

    2014-03-01

    Embryo quality is a critical parameter in assisted reproductive technologies. Although embryo quality can be evaluated morphologically, embryo morphology does not correlate perfectly with embryo viability. To improve this, it is important to understand which molecular mechanisms are involved in embryo quality control. Autophagy is an evolutionarily conserved catabolic process in which cytoplasmic materials sequestered by autophagosomes are degraded in lysosomes. We previously demonstrated that autophagy is highly activated after fertilization and is essential for further embryonic development. Here, we developed a simple fluorescence-based method for visualizing autophagic activity in live mouse embryos. Our method is based on imaging of the fluorescence intensity of GFP-LC3, a versatile marker for autophagy, which is microinjected into the embryos. Using this method, we show that embryonic autophagic activity declines with advancing maternal age, probably due to a decline in the activity of lysosomal hydrolases. We also demonstrate that embryonic autophagic activity is associated with the developmental viability of the embryo. Our results suggest that embryonic autophagic activity can be utilized as a novel indicator of embryo quality.

  12. The Drosophila effector caspase Dcp-1 regulates mitochondrial dynamics and autophagic flux via SesB.

    Science.gov (United States)

    DeVorkin, Lindsay; Go, Nancy Erro; Hou, Ying-Chen Claire; Moradian, Annie; Morin, Gregg B; Gorski, Sharon M

    2014-05-26

    Increasing evidence reveals that a subset of proteins participates in both the autophagy and apoptosis pathways, and this intersection is important in normal physiological contexts and in pathological settings. In this paper, we show that the Drosophila effector caspase, Drosophila caspase 1 (Dcp-1), localizes within mitochondria and regulates mitochondrial morphology and autophagic flux. Loss of Dcp-1 led to mitochondrial elongation, increased levels of the mitochondrial adenine nucleotide translocase stress-sensitive B (SesB), increased adenosine triphosphate (ATP), and a reduction in autophagic flux. Moreover, we find that SesB suppresses autophagic flux during midoogenesis, identifying a novel negative regulator of autophagy. Reduced SesB activity or depletion of ATP by oligomycin A could rescue the autophagic defect in Dcp-1 loss-of-function flies, demonstrating that Dcp-1 promotes autophagy by negatively regulating SesB and ATP levels. Furthermore, we find that pro-Dcp-1 interacts with SesB in a nonproteolytic manner to regulate its stability. These data reveal a new mitochondrial-associated molecular link between nonapoptotic caspase function and autophagy regulation in vivo. PMID:24862573

  13. Changes in chemical components of aerosol particles in different haze regions in China from 2006 to 2013 and contribution of meteorological factors

    OpenAIRE

    Zhang, X. Y.; Wang, J. Z.; Wang, Y Q; Liu, H. L.; SUN J. Y.; Zhang, Y M

    2015-01-01

    Since there have been individual reports of persistent haze–fog events in January 2013 in central-eastern China, questions on factors causing the drastic differences in changes in 2013 from changes in adjacent years have been raised. Changes in major chemical components of aerosol particles over the years also remain unclear. The extent of meteorological factors contributing to such changes is yet to be determined. The study intends to present the changes in daily based majo...

  14. Changes in chemical components of aerosol particles in different haze regions in China from 2006 to 2013 and contribution of meteorological factors

    OpenAIRE

    Zhang, X. Y.; Wang, J. Z.; Wang, Y Q; Liu, H. L.; SUN J. Y.; Zhang, Y M

    2015-01-01

    Since individuals experienced persistent haze-fog events in January 2013 in central-eastern China, questions on factors causing differences in drastic changes in 2013 from those in adjacent years have been raised. Changes in major chemical components of aerosol particles over the years also remain unclear. The extent of meteorological factors contributed to such changes is yet to be determined. The study intends to present the changes in daily-based major wa...

  15. How much does ICT contribute to innovation output? An analysis of the ICT component in the innovation output indicator

    OpenAIRE

    PESOLE ANNAROSA

    2015-01-01

    During the past years, the role of ICT as key driver and enabler of innovation has been widely recognized. The advent and development of ICT transformed the economy and the society in an evident way. However, what and how ICT contributes to this value creation process and its full potential remains hard to detect. There is a need for continuous monitoring of ICT impacts in order to provide policy makers with appropriate tools to define the right policies to seize ICT benefits. In light of thi...

  16. Deletion of TOP3β, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders

    Science.gov (United States)

    Suvisaari, Jaana; Brosi, Cornelia; Hennah, William; Leppä, Virpi; Torniainen, Minna; Ripatti, Samuli; Ala-Mello, Sirpa; Plöttner, Oliver; Rehnström, Karola; Tuulio-Henriksson, Annamari; Varilo, Teppo; Tallila, Jonna; Kristiansson, Kati; Isohanni, Matti; Kaprio, Jaakko; Eriksson, Johan G.; Raitakari, Olli T.; Lehtimäki, Terho; Jarvelin, Marjo-Riitta; Salomaa, Veikko; Hurles, Matthew; Stefansson, Hreinn; Peltonen, Leena; Sullivan, Patrick F.; Paunio, Tiina; Lönnqvist, Jouko; Daly, Mark J.; Fischer, Utz; Freimer, Nelson B.; Palotie, Aarno

    2014-01-01

    Implicating particular genes in the generation of complex brain and behavior phenotypes requires multiple lines of evidence. The rarity of most high impact genetic variants typically precludes the possibility of accruing statistical evidence that they are associated with a given trait. We show here that the enrichment of a rare Chromosome 22q11.22 deletion in a recently expanded Northern Finnish sub-isolate enables the detection of association between TOP3β and both schizophrenia and cognitive impairment. Biochemical analysis of TOP3β revealed that this topoisomerase is a component of cytosolic messenger ribonucleoproteins (mRNPs) and is catalytically active on RNA. The recruitment of TOP3β to mRNPs was independent of RNA cis-elements and was coupled to the co-recruitment of FMRP, the disease gene product in fragile X mental retardation syndrome (FXS). Thus, we uncover a novel role for TOP3β in mRNA metabolism and provide several lines of evidence implicating it in neurodevelopmental disorders. PMID:23912948

  17. Peroxisome Proliferator-Activated Receptor γ Level Contributes to Structural Integrity and Component Production of Elastic Fibers in the Aorta.

    Science.gov (United States)

    Tai, Haw-Chih; Tsai, Pei-Jane; Chen, Ju-Yi; Lai, Chao-Han; Wang, Kuan-Chieh; Teng, Shih-Hua; Lin, Shih-Chieh; Chang, Alice Y W; Jiang, Meei-Jyh; Li, Yi-Heng; Wu, Hua-Lin; Maeda, Nobuyo; Tsai, Yau-Sheng

    2016-06-01

    Loss of integrity and massive disruption of elastic fibers are key features of abdominal aortic aneurysm (AAA). Peroxisome proliferator-activated receptor γ (PPARγ) has been shown to attenuate AAA through inhibition of inflammation and proteolytic degradation. However, its involvement in elastogenesis during AAA remains unclear. PPARγ was highly expressed in human AAA within all vascular cells, including inflammatory cells and fibroblasts. In the aortas of transgenic mice expressing PPARγ at 25% normal levels (Pparg(C) (/-) mice), we observed the fragmentation of elastic fibers and reduced expression of vital elastic fiber components of elastin and fibulin-5. These were not observed in mice with 50% normal PPARγ expression (Pparg(+/-) mice). Infusion of a moderate dose of angiotensin II (500 ng/kg per minute) did not induce AAA but Pparg(+/-) aorta developed flattened elastic lamellae, whereas Pparg(C/-) aorta showed severe destruction of elastic fibers. After infusion of angiotensin II at 1000 ng/kg per minute, 73% of Pparg(C/-) mice developed atypical suprarenal aortic aneurysms: superior mesenteric arteries were dilated with extensive collagen deposition in adventitia and infiltrations of inflammatory cells. Although matrix metalloproteinase inhibition by doxycycline somewhat attenuated the dilation of aneurysm, it did not reduce the incidence nor elastic lamella deterioration in angiotensin II-infused Pparg(C/-) mice. Furthermore, PPARγ antagonism downregulated elastin and fibulin-5 in fibroblasts, but not in vascular smooth muscle cells. Chromatin immunoprecipitation assay demonstrated PPARγ binding in the genomic sequence of fibulin-5 in fibroblasts. Our results underscore the importance of PPARγ in AAA development though orchestrating proper elastogenesis and preserving elastic fiber integrity. PMID:27045031

  18. Contribution of mantle components within juvenile lower-crust to collisional zone porphyry Cu systems in Tibet

    Science.gov (United States)

    Hou, Zengqian; Zheng, Yuanchuan; Yang, Zhiming; Rui, Zongyao; Zhao, Zhidan; Jiang, Sihong; Qu, Xiaoming; Sun, Qinzhong

    2013-02-01

    Most porphyry Cu-Mo-Au deposits are found in magmatic arcs worldwide, and are associated with hydrous, high- fO2, calc-alkaline magmas, derived from a mantle wedge that was metasomatized by the fluids from a subducted oceanic slab. Recently, such deposits have been documented as occurring widely in collisional settings, where they are associated with potassic magmas generated during the collisional process, but the genesis of the fertile magmas and the mechanism of metallic enrichment remain controversial. Here we present new geochemical and Sr-Nd-Hf isotopic data from the post-collisional fertile and barren porphyries of the Miocene Gangdese porphyry belt in the Tibetan orogen, an orogen formed by the collision of India and Asia in the early Cenozoic. Both types of porphyry are characterized by high K2O contents, and have geochemical affinities with adakite, but the fertile magmas were most likely derived from the melting of a thickened juvenile mafic lower-crust, formed by the underplating of earlier asthenospheric melts at the base of crust, whereas the derivation of the barren magmas involved variable amounts of old lower-crust in Tibet. The melting of sulfide-bearing phases in the juvenile mantle components of the Tibetan lower-crust probably provided Cu, Au, and S to the fertile magmas. The breakdown of amphibole during melting at the source released the fluids necessary for the formation of the porphyry Cu deposits in Tibet. The thickened crust (up to 70-80 km), due to collision, is thought to be responsible for a decrease in the fO2 of the fertile magmas during their ascent to the upper crust, thus preventing the generation of more porphyry Cu-Au and epithermal Au deposits in this collisional zone.

  19. Identification of the Streptococcus mutans LytST two-component regulon reveals its contribution to oxidative stress tolerance

    Directory of Open Access Journals (Sweden)

    Ahn Sang-Joon

    2012-09-01

    Full Text Available Abstract Background The S. mutans LrgA/B holin-like proteins have been shown to affect biofilm formation and oxidative stress tolerance, and are regulated by oxygenation, glucose levels, and by the LytST two-component system. In this study, we sought to determine if LytST was involved in regulating lrgAB expression in response to glucose and oxygenation in S. mutans. Results Real-time PCR revealed that growth phase-dependent regulation of lrgAB expression in response to glucose metabolism is mediated by LytST under low-oxygen conditions. However, the effect of LytST on lrgAB expression was less pronounced when cells were grown with aeration. RNA expression profiles in the wild-type and lytS mutant strains were compared using microarrays in early exponential and late exponential phase cells. The expression of 40 and 136 genes in early-exponential and late exponential phase, respectively, was altered in the lytS mutant. Although expression of comYB, encoding a DNA binding-uptake protein, was substantially increased in the lytS mutant, this did not translate to an effect on competence. However, a lrgA mutant displayed a substantial decrease in transformation efficiency, suggestive of a previously-unknown link between LrgA and S. mutans competence development. Finally, increased expression of genes encoding antioxidant and DNA recombination/repair enzymes was observed in the lytS mutant, suggesting that the mutant may be subjected to increased oxidative stress during normal growth. Although the intracellular levels of reaction oxygen species (ROS appeared similar between wild-type and lytS mutant strains after overnight growth, challenge of these strains with hydrogen peroxide (H2O2 resulted in increased intracellular ROS in the lytS mutant. Conclusions Overall, these results: (1 Reinforce the importance of LytST in governing lrgAB expression in response to glucose and oxygen, (2 Define a new role for LytST in global gene regulation and resistance

  20. Identification of novel autophagic Radix Polygalae fraction by cell membrane chromatography and UHPLC-(Q)TOF-MS for degradation of neurodegenerative disease proteins.

    Science.gov (United States)

    Wu, An-Guo; Wong, Vincent Kam-Wai; Zeng, Wu; Liu, Liang; Law, Betty Yuen-Kwan

    2015-01-01

    With its traditional use in relieving insomnia and anxiety, our previous study has identified onjisaponin B from Radix Polygalae (RP), as a novel autophagic enhancer with potential neuroprotective effects. In current study, we have further identified a novel active fraction from RP, contains 17 major triterpenoid saponins including the onjisaponin B, by the combinational use of cell membrane chromatography (CMC) and ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry {UHPLC-(Q)TOF-MS}. By exhibiting more potent autophagic effect in cells, the active fraction enhances the clearance of mutant huntingtin, and reduces protein level and aggregation of α-synuclein in a higher extent when compared with onjisaponin B. Here, we have reported for the first time the new application of cell-based CMC and UHPLC-(Q)TOF-MS analysis in identifying new autophagy inducers with neuroprotective effects from Chinese medicinal herb. This result has provided novel insights into the possible pharmacological actions of the active components present in the newly identified active fraction of RP, which may help to improve the efficacy of the traditional way of prescribing RP, and also provide new standard for the quality control of decoction of RP or its medicinal products in the future. PMID:26598009

  1. Cationic polystyrene nanospheres induce autophagic cell death through the induction of endoplasmic reticulum stress

    Science.gov (United States)

    Chiu, Hui-Wen; Xia, Tian; Lee, Yu-Hsuan; Chen, Chun-Wan; Tsai, Jui-Chen; Wang, Ying-Jan

    2014-12-01

    Nanoparticles (NPs) have been used to produce a wide range of products that have applications in imaging and drug delivery in medicine. Due to their chemical stability, well-controlled sizes and surface charges, polystyrene (PS) NPs have been developed as biosensors and drug delivery carriers. However, the possible adverse biological effects and underlying mechanisms are still unclear. Recently, autophagy has been implicated in the regulation of cell death. In this study, we evaluated a library of PS NPs with different surface charges. We found that NH2-labeled polystyrene (NH2-PS) nanospheres were highly toxic with enhanced uptake in macrophage (RAW 264.7) and lung epithelial (BEAS-2B) cells. Furthermore, NH2-PS could induce autophagic cell death. NH2-PS increased autophagic flux due to reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress caused by misfolded protein aggregation. The inhibition of ER stress decreased cytotoxicity and autophagy in the NH2-PS-treated cells. In addition, the Akt/mTOR and AMPK signaling pathways were involved in the regulation of NH2-PS-triggered autophagic cell death. These results suggest an important role of autophagy in cationic NP-induced cell death and provide mechanistic insights into the inhibition of the toxicity and safe material design.Nanoparticles (NPs) have been used to produce a wide range of products that have applications in imaging and drug delivery in medicine. Due to their chemical stability, well-controlled sizes and surface charges, polystyrene (PS) NPs have been developed as biosensors and drug delivery carriers. However, the possible adverse biological effects and underlying mechanisms are still unclear. Recently, autophagy has been implicated in the regulation of cell death. In this study, we evaluated a library of PS NPs with different surface charges. We found that NH2-labeled polystyrene (NH2-PS) nanospheres were highly toxic with enhanced uptake in macrophage (RAW 264.7) and lung

  2. Earth moving machine whole-body vibration and the contribution of Sub-1Hz components to ISO 2631-1 metrics.

    Science.gov (United States)

    Mansfield, Neil J; Newell, Geraldine S; Notini, Luca

    2009-08-01

    Exposure to whole-body vibration (WBV) is an occupational hazard for operators of industrial vehicles, such as earth-moving machines. Quantification of WBV exposure in terms of impact on health forms one aspect of the Standard ISO 2631-1 (1997). Regarding assessment of risk to health, ISO 2631-1 (1997) states that if WBV components below 1 Hz are not ;relevant nor important' then they can be excluded from the assessment. In this paper the influence of sub-1 Hz components in WBV acquired from a sample of 46 earth moving machines is evaluated in terms of their contribution to ISO 2631-1 WBV exposure dose metrics: frequency weighted r.m.s. and the vibration dose value (VDV). For the majority of machines, a high proportion of the horizontal (x- and y-axis) WBV r.m.s. and VDV values was generated by sub-1 Hz vibration components; there was a much lower proportion of the vertical (z-axis) vibration generated by such components. PMID:19672014

  3. Response curves of the surface modules of the Pierre Auger Observatory and the contribution of the hadronic component to the total signal of extensive showers

    International Nuclear Information System (INIS)

    Full text: At large distances from the shower's core, is generally said that the electromagnetic and muonic components are responsible for most of the signal detected and the contribution of hadrons is irrelevant. In fact, looking at the events generated by the simulations of showers, we see an average number of hadrons which is small compared to other components. On the other hand, the important factor to be considered is the fraction of energy they carry. Geant4 full simulations of shower particles interacting in the surface module are very time consuming. To overcome this difficulty, we produced a set of response curves that can replace the corresponding full simulations. To include albedo phenomena, we include a soil layer as a new target for hadronic interactions, with the detailed treatment of hadron interactions available in Geant4 tool kit. The response curves for each particle type were obtained with full runs of Geant4 in the new setup. We will present this parametrization, which reduce the processing time by factors larger than 1000 times. These response curves were implemented in the tool kit Offline, developed by the collaboration to simulate/reconstruct the development of air showers. The Geant4 class corresponding to the surface module was replaced by our parametrization, while the rest of the simulation chain remained unchanged. The main focus of this work are the interactions of the hadronic component, in the tank and in the soil target below the tank. Those were obtained with the new setup and compared to the results from the original version of Offline. To assess the contribution of hadrons, we also studied the contribution of other components under the same conditions, so we can to obtain always the effect of hadronic interactions compared with the other components. We make a comparison between the energy reconstructed by the original Offline (with no changes) and the Offline with the implementation of our parameterization. We can infer the

  4. Paternal mitochondrial destruction after fertilization is mediated by a common endocytic and autophagic pathway in Drosophila.

    Science.gov (United States)

    Politi, Yoav; Gal, Liron; Kalifa, Yossi; Ravid, Liat; Elazar, Zvulun; Arama, Eli

    2014-05-12

    Almost all animals contain mitochondria of maternal origin only, but the exact mechanisms underlying this phenomenon are still vague. We investigated the fate of Drosophila paternal mitochondria after fertilization. We demonstrate that the sperm mitochondrial derivative (MD) is rapidly eliminated in a stereotypical process dubbed paternal mitochondrial destruction (PMD). PMD is initiated by a network of vesicles resembling multivesicular bodies and displaying common features of the endocytic and autophagic pathways. These vesicles associate with the sperm tail and mediate the disintegration of its plasma membrane. Subsequently, the MD separates from the axoneme and breaks into smaller fragments, which are then sequestered by autophagosomes for degradation in lysosomes. We further provide evidence for the involvement of the ubiquitin pathway and the autophagy receptor p62 in this process. Finally, we show that the ubiquitin ligase Parkin is not involved in PMD, implying a divergence from the autophagic pathway of damaged mitochondria. PMID:24823375

  5. Analysis of Relevant Parameters for Autophagic Flux Using HeLa Cells Expressing EGFP-LC3.

    Science.gov (United States)

    Muñoz-Braceras, Sandra; Escalante, Ricardo

    2016-01-01

    Macroautophagy (called just autophagy hereafter) is an intracellular degradation machinery essential for cell survival under stress conditions and for the maintenance of cellular homeostasis. The hallmark of autophagy is the formation of double membrane vesicles that engulf cytoplasmic material. These vesicles, called autophagosomes, mature by fusion with endosomes and lysosomes that allows the degradation of the cargo. Autophagy is a dynamic process regulated at multiple steps. Assessment of autophagy is not trivial because the number autophagosomes might not necessarily reflect the real level of autophagic degradation, the so-called autophagic flux. Here, we describe an optimized protocol for the analysis of relevant parameters of autophagic flux using HeLa cells stably expressing EGFP-LC3. These cells are a convenient tool to determine the influence of the downregulation or overexpression of specific proteins in the autophagic flux as well as the analysis of autophagy-modulating compounds. Western blot analysis of relevant parameters, such as the levels of EGFP-LC3, free EGFP generated by autophagic degradation and endogenous LC3·I-II are analyzed in the presence and absence of the autophagic inhibitor chloroquine. PMID:27613046

  6. Normal autophagic activity in macrophages from mice lacking Gαi3, AGS3, or RGS19.

    Directory of Open Access Journals (Sweden)

    Ali Vural

    Full Text Available In macrophages autophagy assists antigen presentation, affects cytokine release, and promotes intracellular pathogen elimination. In some cells autophagy is modulated by a signaling pathway that employs Gαi3, Activator of G-protein Signaling-3 (AGS3/GPSM1, and Regulator of G-protein Signaling 19 (RGS19. As macrophages express each of these proteins, we tested their importance in regulating macrophage autophagy. We assessed LC3 processing and the formation of LC3 puncta in bone marrow derived macrophages prepared from wild type, Gnai3(-/-, Gpsm1(-/-, or Rgs19(-/- mice following amino acid starvation or Nigericin treatment. In addition, we evaluated rapamycin-induced autophagic proteolysis rates by long-lived protein degradation assays and anti-autophagic action after rapamycin induction in wild type, Gnai3(-/-, and Gpsm1(-/- macrophages. In similar assays we compared macrophages treated or not with pertussis toxin, an inhibitor of GPCR (G-protein couple receptor triggered Gαi nucleotide exchange. Despite previous findings, the level of basal autophagy, autophagic induction, autophagic flux, autophagic degradation and the anti-autophagic action in macrophages that lacked Gαi3, AGS3, or RGS19; or had been treated with pertussis toxin, were similar to controls. These results indicate that while Gαi signaling may impact autophagy in some cell types it does not in macrophages.

  7. A Cluster of Thin Tubular Structures Mediates Transformation of the Endoplasmic Reticulum to Autophagic Isolation Membrane

    OpenAIRE

    Uemura, Takefumi; Yamamoto, Masaya; Kametaka, Ai; Sou, Yu-shin; Yabashi, Atsuko; Yamada, Akane; Annoh, Hiromichi; Kametaka, Satoshi; Komatsu, Masaaki; Waguri, Satoshi

    2014-01-01

    Recent findings have suggested that the autophagic isolation membrane (IM) might originate from a domain of the endoplasmic reticulum (ER) called the omegasome. However, the morphological relationships between ER, omegasome, and IM remain unclear. In the present study, we found that hybrid structures composed of a double FYVE domain-containing protein 1 (DFCP1)-positive omegasome and the IM accumulated in Atg3-deficient mouse embryonic fibroblasts (MEFs). Moreover, correlative light and elect...

  8. WASH is required for lysosomal recycling and efficient autophagic and phagocytic digestion

    OpenAIRE

    King, Jason S.; Gueho, Aurélie; Hagedorn, Monica; Gopaldass, Navin Andréw; Leuba, Florence; Soldati, Thierry; Insall, Robert H.

    2013-01-01

    Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) is an important regulator of vesicle trafficking. By generating actin on the surface of intracellular vesicles, WASH is able to directly regulate endosomal sorting and maturation. We report that, in Dictyostelium, WASH is also required for the lysosomal digestion of both phagocytic and autophagic cargo. Consequently, Dictyostelium cells lacking WASH are unable to grow on many bacteria or to digest their own cytoplasm to survive starva...

  9. Naringin Attenuates Autophagic Stress and Neuroinflammation in Kainic Acid-Treated Hippocampus In Vivo

    OpenAIRE

    Kyoung Hoon Jeong; Un Ju Jung; Sang Ryong Kim

    2015-01-01

    Kainic acid (KA) is well known as a chemical compound to study epileptic seizures and neuronal excitotoxicity. KA-induced excitotoxicity causes neuronal death by induction of autophagic stress and microglia-derived neuroinflammation, suggesting that the control of KA-induced effects may be important to inhibit epileptic seizures with neuroprotection. Naringin, a flavonoid in grapefruit and citrus fruits, has anti-inflammatory and antioxidative activities, resulting in neuroprotection in anima...

  10. The Drosophila effector caspase Dcp-1 regulates mitochondrial dynamics and autophagic flux via SesB

    OpenAIRE

    DeVorkin, Lindsay; Go, Nancy Erro; Hou, Ying-Chen Claire; Moradian, Annie; Morin, Gregg B.; Gorski, Sharon M.

    2014-01-01

    Increasing evidence reveals that a subset of proteins participates in both the autophagy and apoptosis pathways, and this intersection is important in normal physiological contexts and in pathological settings. In this paper, we show that the Drosophila effector caspase, Drosophila caspase 1 (Dcp-1), localizes within mitochondria and regulates mitochondrial morphology and autophagic flux. Loss of Dcp-1 led to mitochondrial elongation, increased levels of the mitochondrial adenine nucleotide t...

  11. A thin diffuse component of the Galactic Ridge X-ray emission and heating of the interstellar medium contributed by the radiation of Galactic X-ray binaries

    CERN Document Server

    Molaro, Margherita; Sunyaev, Rashid

    2013-01-01

    We suggest a thin (scale height ~80 pc) diffuse component to the Galactic Ridge X-ray emission (GRXE) arising from the scattering of the radiation of bright X-ray binaries (XBs) by the interstellar medium. The morphology of the scattered component is expected to trace the clumpy molecular and HI clouds. We calculate this contribution to the GRXE from known Galactic XBs assuming that they are all persistent. The known XBs sample is however incomplete as it is flux-limited and spans the small lifetime of X-ray astronomy (~50 years), compared to the characteristic time of 1000-10000 years that would contribute to the diffuse emission observed today due to time delays. We therefore also use a simulated sample of sources, to estimate the diffuse emission we should expect in an optimistic case assuming that the X-ray luminosity of our Galaxy is on average similar to that of other galaxies. In the calculations we also take into account the enhancement of the total scattering cross section due to coherence effects in...

  12. Looking at the metabolic consequences of the colchicine-based in vivo autophagic flux assay.

    Science.gov (United States)

    Seiliez, Iban; Belghit, Ikram; Gao, Yujie; Skiba-Cassy, Sandrine; Dias, Karine; Cluzeaud, Marianne; Rémond, Didier; Hafnaoui, Nordine; Salin, Bénédicte; Camougrand, Nadine; Panserat, Stéphane

    2016-02-01

    Monitoring autophagic flux in vivo or in organs remains limited and the ideal methods relative to the techniques possible with cell culture may not exist. Recently, a few papers have demonstrated the feasibility of measuring autophagic flux in vivo by intraperitoneal (IP) injection of pharmacological agents (chloroquine, leupeptin, vinblastine, and colchicine). However, the metabolic consequences of the administration of these drugs remain largely unknown. Here, we report that 0.8 mg/kg/day IP colchicine increased LC3-II protein levels in the liver of fasted trout, supporting the usefulness of this drug for studying autophagic flux in vivo in our model organism. This effect was accompanied by a decrease of plasma glucose concentration associated with a fall in the mRNA levels of gluconeogenesis-related genes. Concurrently, triglycerides and lipid droplets content in the liver increased. In contrast, transcript levels of β-oxidation-related gene Cpt1a dropped significantly. Together, these results match with the reported role of autophagy in the regulation of glucose homeostasis and intracellular lipid stores, and highlight the importance of considering these effects when using colchicine as an in vivo "autophagometer." PMID:26902586

  13. Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2.

    Directory of Open Access Journals (Sweden)

    David Ramonet

    Full Text Available Mutations in the leucine-rich repeat kinase 2 (LRRK2 gene cause late-onset, autosomal dominant familial Parkinson's disease (PD and also contribute to idiopathic PD. LRRK2 mutations represent the most common cause of PD with clinical and neurochemical features that are largely indistinguishable from idiopathic disease. Currently, transgenic mice expressing wild-type or disease-causing mutants of LRRK2 have failed to produce overt neurodegeneration, although abnormalities in nigrostriatal dopaminergic neurotransmission have been observed. Here, we describe the development and characterization of transgenic mice expressing human LRRK2 bearing the familial PD mutations, R1441C and G2019S. Our study demonstrates that expression of G2019S mutant LRRK2 induces the degeneration of nigrostriatal pathway dopaminergic neurons in an age-dependent manner. In addition, we observe autophagic and mitochondrial abnormalities in the brains of aged G2019S LRRK2 mice and markedly reduced neurite complexity of cultured dopaminergic neurons. These new LRRK2 transgenic mice will provide important tools for understanding the mechanism(s through which familial mutations precipitate neuronal degeneration and PD.

  14. Changes in chemical components of aerosol particles in different haze regions in China from 2006 to 2013 and contribution of meteorological factors

    Science.gov (United States)

    Zhang, X. Y.; Wang, J. Z.; Wang, Y. Q.; Liu, H. L.; Sun, J. Y.; Zhang, Y. M.

    2015-11-01

    Since there have been individual reports of persistent haze-fog events in January 2013 in central-eastern China, questions on factors causing the drastic differences in changes in 2013 from changes in adjacent years have been raised. Changes in major chemical components of aerosol particles over the years also remain unclear. The extent of meteorological factors contributing to such changes is yet to be determined. The study intends to present the changes in daily based major water-soluble constituents, carbonaceous species, and mineral aerosol in PM10 at 13 stations within different haze regions in China from 2006 to 2013, which are associated with specific meteorological conditions that are highly related to aerosol pollution (parameterized as an index called Parameter Linking Aerosol Pollution and Meteorological Elements - PLAM). No obvious changes were found in annual mean concentrations of these various chemical components and PM10 in 2013, relative to 2012. By contrast, wintertime mass of these components was quite different. In Hua Bei Plain (HBP), sulfate, organic carbon (OC), nitrate, ammonium, element carbon (EC), and mineral dust concentrations in winter were approximately 43, 55, 28, 23, 21, and 130 μg m-3, respectively; these masses were approximately 2 to 4 times higher than those in background mass, which also exhibited a decline during 2006 to 2010 and then a rise till 2013. The mass of these concentrations and PM10, except minerals, respectively, increased by approximately 28 to 117 % and 25 % in January 2013 compared with that in January 2012. Thus, persistent haze-fog events occurred in January 2013, and approximately 60 % of this increase in component concentrations from 2012 to 2013 can be attributed to severe meteorological conditions in the winter of 2013. In the Yangtze River Delta (YRD) area, winter masses of these components, unlike HBP, have not significantly increase since 2010; PLAM were also maintained at a similar level without

  15. Changes in chemical components of aerosol particles in different haze regions in China from 2006 to 2013 and contribution of meteorological factors

    Directory of Open Access Journals (Sweden)

    X. Y. Zhang

    2015-07-01

    Full Text Available Since individuals experienced persistent haze-fog events in January 2013 in central-eastern China, questions on factors causing differences in drastic changes in 2013 from those in adjacent years have been raised. Changes in major chemical components of aerosol particles over the years also remain unclear. The extent of meteorological factors contributed to such changes is yet to be determined. The study intends to present the changes in daily-based major water-soluble constituents, carbonaceous species and mineral aerosol in PM10 at 13 stations within different haze regions in China from 2006 to 2013, associated with specific meteorological conditions that are highly related with aerosol pollution (parameterized as an index called "PLAM". No obvious changes were found in annual mean concentrations of these various chemical components and PM10 in 2013, relative to 2012. By contrast, wintertime mass of these components were quite different, in Hua Bei Plain (HBP, sulfate, OC, nitrate, ammonium, EC, and mineral dust concentrations in winter were approximately 43, 55, 28, 23, 21 and 130 μg m−3, respectively; these masses were approximately two to four times higher than those in background mass, also exhibiting a decline during 2006 to 2010, and then a rise till 2013. The mass of these concentrations and PM10, except mineral, respectively increased by approximately 28 to 117 and 25 % in January 2013 compared with that in January 2012. Thus, persistent haze-fog events occurred in January 2013, and approximately 60 % of this increase in component concentrations from 2012 to 2013 can be attributed to severe meteorological conditions in the winter of 2013. In Yangtzi River Delta (YRD area, winter masses of these components, unlike HBP, did not significantly increase since 2010; PLAM was also maintained at a similar level without significant changes. In the Pearl River Delta (PRD area, the regional background concentrations of the major chemical

  16. Contribution of individual components of a job cycle on overall severity of whole-body vibration exposure: a study in Indian mines.

    Science.gov (United States)

    Mandal, Bibhuti B; Mansfield, Neil J

    2016-01-01

    Drivers of earth-moving machines are exposed to whole-body vibration (WBV). In mining operations there can be a combination of relatively high magnitudes of vibration and long exposure times. Effective risk mitigation requires understanding of the main aspects of a task that pose a hazard to health. There are very few published studies of WBV exposure from India. This paper reports on a study that considered the contribution of the component phases of dumper operations, on the overall vibration exposure of the drivers. It shows that vibration magnitudes are relatively high, and that haulage tasks are the main contributor to the exposure. It is recommended that driver speed, haul road surfaces and vehicle maintenance/selection are optimized to ensure minimization of vibration. If this is not sufficient, operation times might need to be reduced in order to ensure that the health guidance caution zone from Standard No. ISO 2631-1:1997 is not exceeded. PMID:26652833

  17. Metabolic, autophagic, and mitophagic activities in cancer initiation and progression.

    Science.gov (United States)

    Hjelmeland, Anita; Zhang, Jianhua

    2016-04-01

    Cancer is a complex disease marked by uncontrolled cell growth and invasion. These processes are driven by the accumulation of genetic and epigenetic alterations that promote cancer initiation and progression. Contributing to genome changes are the regulation of oxidative stress and reactive species-induced damage to molecules and organelles. Redox regulation, metabolic plasticity, autophagy, and mitophagy play important and interactive roles in cancer hallmarks including sustained proliferation, activated invasion, and replicative immortality. However, the impact of these processes can differ depending on the signaling pathways altered in cancer, tumor type, tumor stage, and/or the differentiation state. Here, we highlight some of the representative studies on the impact of oxidative and nitrosative activities, mitochondrial bioenergetics, metabolism, and autophagy and mitophagy in the context of tumorigenesis. We discuss the implications of these processes for cellular activities in cancer for anti-cancer-based therapeutics. PMID:27372165

  18. SMCX and components of the TIP60 complex contribute to E2 regulation of the HPV E6/E7 promoter

    Science.gov (United States)

    Smith, Jennifer A.; Haberstroh, Friederike S.; White, Elizabeth A.; Livingston, David M.; DeCaprio, James A.; Howley, Peter M.

    2014-01-01

    An important step in the malignant progression of HPV-associated lesions is the dysregulation of expression of the viral E6 and E7 oncogenes. This is often achieved through the loss of expression of E2, which represses the HPV LCR promoter and E6/E7 expression. Our previous studies confirmed a role for Brd4 in mediating the E2 transcriptional repression function, and identified JARID1C/SMCX and EP400 as contributors to E2-mediated repression. Here we show that TIP60, a component of the TIP60/TRRAP histone acetyltransferase complex, also contributes to the E2 repression function, and we extend our studies on SMCX. Di- and tri-methyl marks on histone H3K4 are reduced in the presence of E2 and SMCX, suggesting a mechanism by which SMCX contributes to E2-mediated repression of the HPV LCR. Together, these findings lead us to hypothesize that E2 recruits histone-modifying cellular proteins to the HPV LCR, resulting in transcriptional repression of E6 and E7. PMID:25222147

  19. SMCX and components of the TIP60 complex contribute to E2 regulation of the HPV E6/E7 promoter.

    Science.gov (United States)

    Smith, Jennifer A; Haberstroh, Friederike S; White, Elizabeth A; Livingston, David M; DeCaprio, James A; Howley, Peter M

    2014-11-01

    An important step in the malignant progression of HPV-associated lesions is the dysregulation of expression of the viral E6 and E7 oncogenes. This is often achieved through the loss of expression of E2, which represses the HPV LCR promoter and E6/E7 expression. Our previous studies confirmed a role for Brd4 in mediating the E2 transcriptional repression function, and identified JARID1C/SMCX and EP400 as contributors to E2-mediated repression. Here we show that TIP60, a component of the TIP60/TRRAP histone acetyltransferase complex, also contributes to the E2 repression function, and we extend our studies on SMCX. Di- and tri-methyl marks on histone H3K4 are reduced in the presence of E2 and SMCX, suggesting a mechanism by which SMCX contributes to E2-mediated repression of the HPV LCR. Together, these findings lead us to hypothesize that E2 recruits histone-modifying cellular proteins to the HPV LCR, resulting in transcriptional repression of E6 and E7. PMID:25222147

  20. G9a Inhibition Induces Autophagic Cell Death via AMPK/mTOR Pathway in Bladder Transitional Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Feng Li

    Full Text Available G9a has been reported to highly express in bladder transitional cell carcinoma (TCC and G9a inhibition significantly attenuates cell proliferation, but the underlying mechanism is not fully understood. The present study aimed at examining the potential role of autophagy in the anti-proliferation effect of G9a inhibition on TCC T24 and UMUC-3 cell lines in vitro. We found that both pharmaceutical and genetical G9a inhibition significantly attenuated cell proliferation by MTT assay, Brdu incorporation assay and colony formation assay. G9a inhibition induced autophagy like morphology as determined by transmission electron microscope and LC-3 fluorescence assay. In addition, autophagy flux was induced by G9a inhibition in TCC cells, as determined by p62 turnover assay and LC-3 turnover assay. The autophagy induced positively contributed to the inhibition of cell proliferation because the growth attenuation capacity of G9a inhibition was reversed by autophagy inhibitors 3-MA. Mechanically, AMPK/mTOR pathway was identified to be involved in the regulation of G9a inhibition induced autophagy. Intensively activating mTOR by Rheb overexpression attenuated autophagy and autophagic cell death induced by G9a inhibition. In addition, pre-inhibiting AMPK by Compound C attenuated autophagy together with the anti-proliferation effect induced by G9a inhibition while pre-activating AMPK by AICAR enhanced them. In conclusion, our results indicate that G9a inhibition induces autophagy through activating AMPK/mTOR pathway and the autophagy induced positively contributes to the inhibition of cell proliferation in TCC cells. These findings shed some light on the functional role of G9a in cell metabolism and suggest that G9a might be a therapeutic target in bladder TCC in the future.

  1. The autophagic- lysosomal pathway determines the fate of glial cells under manganese- induced oxidative stress conditions.

    Science.gov (United States)

    Gorojod, R M; Alaimo, A; Porte Alcon, S; Pomilio, C; Saravia, F; Kotler, M L

    2015-10-01

    Manganese (Mn) overexposure is frequently associated with the development of a neurodegenerative disorder known as Manganism. The Mn-mediated generation of reactive oxygen species (ROS) promotes cellular damage, finally leading to apoptotic cell death in rat astrocytoma C6 cells. In this scenario, the autophagic pathway could play an important role in preventing cytotoxicity. In the present study, we found that Mn induced an increase in the amount and total volume of acidic vesicular organelles (AVOs), a process usually related to the activation of the autophagic pathway. Particularly, the generation of enlarged AVOs was a ROS- dependent event. In this report we demonstrated for the first time that Mn induces autophagy in glial cells. This conclusion emerged from the results obtained employing a battery of autophagy markers: a) the increase in LC3-II expression levels, b) the formation of autophagic vesicles labeled with monodansylcadaverine (MDC) or LC3 and, c) the increase in Beclin 1/ Bcl-2 and Beclin 1/ Bcl-X(L) ratio. Autophagy inhibition employing 3-MA and mAtg5(K130R) resulted in decreased cell viability indicating that this event plays a protective role in Mn- induced cell death. In addition, mitophagy was demonstrated by an increase in LC3 and TOM-20 colocalization. On the other hand, we proposed the occurrence of lysosomal membrane permeabilization (LMP) based in the fact that cathepsins B and D activities are essential for cell death. Both cathepsin B inhibitor (Ca-074 Me) or cathepsin D inhibitor (Pepstatin A) completely prevented Mn- induced cytotoxicity. In addition, low dose of Bafilomycin A1 showed a similar effect, a finding that adds evidence about the lysosomal role in Mn cytotoxicity. Finally, in vivo experiments demonstrated that Mn induces injury and alters LC3 expression levels in rat striatal astrocytes. In summary, our results demonstrated that autophagy is activated to counteract the harmful effect caused by Mn. These data is valuable to

  2. Disturbed Flow Induces Autophagy, but Impairs Autophagic Flux to Perturb Mitochondrial Homeostasis

    Science.gov (United States)

    Li, Rongsong; Jen, Nelson; Wu, Lan; Lee, Juhyun; Fang, Karen; Quigley, Katherine; Lee, Katherine; Wang, Sky; Zhou, Bill; Vergnes, Laurent; Chen, Yun-Ru; Li, Zhaoping; Reue, Karen; Ann, David K.

    2015-01-01

    Abstract Aim: Temporal and spatial variations in shear stress are intimately linked with vascular metabolic effects. Autophagy is tightly regulated in intracellular bulk degradation/recycling system for maintaining cellular homeostasis. We postulated that disturbed flow modulates autophagy with an implication in mitochondrial superoxide (mtO2•−) production. Results: In the disturbed flow or oscillatory shear stress (OSS)-exposed aortic arch, we observed prominent staining of p62, a reverse marker of autophagic flux, whereas in the pulsatile shear stress (PSS)-exposed descending aorta, p62 was attenuated. OSS significantly increased (i) microtubule-associated protein light chain 3 (LC3) II to I ratios in human aortic endothelial cells, (ii) autophagosome formation as quantified by green fluorescent protein (GFP)-LC3 dots per cell, and (iii) p62 protein levels, whereas manganese superoxide dismutase (MnSOD) overexpression by recombinant adenovirus, N-acetyl cysteine treatment, or c-Jun N-terminal kinase (JNK) inhibition reduced OSS-mediated LC3-II/LC3-I ratios and mitochondrial DNA damage. Introducing bafilomycin to Earle's balanced salt solution or to OSS condition incrementally increased both LC3-II/LC3-I ratios and p62 levels, implicating impaired autophagic flux. In the OSS-exposed aortic arch, both anti-phospho-JNK and anti-8-hydroxy-2′-deoxyguanosine (8-OHdG) staining for DNA damage were prominent, whereas in the PSS-exposed descending aorta, the staining was nearly absent. Knockdown of ATG5 with siRNA increased OSS-mediated mtO2•−, whereas starvation or rapamycin-induced autophagy reduced OSS-mediated mtO2•−, mitochondrial respiration, and complex II activity. Innovation: Disturbed flow-mediated oxidative stress and JNK activation induce autophagy. Conclusion: OSS impairs autophagic flux to interfere with mitochondrial homeostasis. Antioxid. Redox Signal. 23, 1207–1219. PMID:26120766

  3. Estimating the contribution of the authigenic mineral component to the long-term reactive silica accumulation on the western shelf of the Mississippi River Delta

    Science.gov (United States)

    Presti, Massimo; Michalopoulos, Panagiotis

    2008-04-01

    Previous studies have shown how biogenic silica particles undergo conversion to aluminosilicate phases in large tropical deltaic systems, thus affecting the world ocean budget of major seawater cations. This study tackles the important question of the silica budget in the coastal zone of the Mississippi River Delta, providing evidence for the role of biogenic silica diagenesis in this subtropical system from direct examination of individual diatom particles, sediment leachates and pore-water composition. The estimated reactive silica stored in the study area (5990 km 2) is based on operational leaches that account for altered biogenic silica particles and other authigenic aluminosilicate phases in addition to fresh biogenic silica. Early diagenesis of silica in the delta front occurs mainly where more siliceous material is deposited. An inner-shelf area, where hypoxic conditions are found, significantly contributes to the formation of authigenic products of Si alteration. Data suggest that the limiting factor of silica alteration processes is the availability of detrital phases such as Al and Fe. The estimated total reactive silica accumulation in the study area is 1.45×10 10 mol Si year -1, representing ˜2.2% of the long-term bulk sediment accumulation. On the basis of a conservative appraisal, the authigenic mineral components account for ˜40% of the long-term reactive silica storage. This study shows that non-tropical deltaic systems are significantly more important sinks of silica than previously thought and that, where conditions are favourable, a consistent portion of reactive silica not leaving the shelf is stored within the delta in the form of authigenic components.

  4. Fullerenol cytotoxicity in kidney cells is associated with cytoskeleton disruption, autophagic vacuole accumulation, and mitochondrial dysfunction

    International Nuclear Information System (INIS)

    Water soluble fullerenes, such as the hydroxylated fullerene, fullerenol (C60OHx), are currently under development for diagnostic and therapeutic biomedical applications in the field of nanotechnology. These molecules have been shown to undergo urinary clearance, yet there is limited data available on their renal biocompatibility. Here we examine the biological responses of renal proximal tubule cells (LLC-PK1) exposed to fullerenol. Fullerenol was found to be cytotoxic in the millimolar range, with viability assessed by the sulforhodamine B and trypan blue assays. Fullerenol-induced cell death was associated with cytoskeleton disruption and autophagic vacuole accumulation. Interaction with the autophagy pathway was evaluated in vitro by Lysotracker Red dye uptake, LC3-II marker expression and TEM. Fullerenol treatment also resulted in coincident loss of cellular mitochondrial membrane potential and ATP depletion, as measured by the Mitotracker Red dye and the luciferin-luciferase assays, respectively. Fullerenol-induced ATP depletion and loss of mitochondrial potential were partially ameliorated by co-treatment with the autophagy inhibitor, 3-methyladenine. In vitro fullerenol treatment did not result in appreciable oxidative stress, as measured by lipid peroxide and glutathione content. Based on these data, it is hypothesized that cytoskeleton disruption may be an initiating event in fullerenol cytotoxicity, leading to subsequent autophagy dysfunction and loss of mitochondrial capacity. As nanoparticle-induced cytoskeleton disruption, autophagic vacuole accumulation and mitochondrial dysfunction are commonly reported in the literature, the proposed mechanism may be relevant for a variety of nanomaterials.

  5. Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates.

    Science.gov (United States)

    Korac, Jelena; Schaeffer, Veronique; Kovacevic, Igor; Clement, Albrecht M; Jungblut, Benno; Behl, Christian; Terzic, Janos; Dikic, Ivan

    2013-01-15

    Aggregation of misfolded proteins and the associated loss of neurons are considered a hallmark of numerous neurodegenerative diseases. Optineurin is present in protein inclusions observed in various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Huntington's disease, Alzheimer's disease, Parkinson's disease, Creutzfeld-Jacob disease and Pick's disease. Optineurin deletion mutations have also been described in ALS patients. However, the role of optineurin in mechanisms of protein aggregation remains unclear. In this report, we demonstrate that optineurin recognizes various protein aggregates via its C-terminal coiled-coil domain in a ubiquitin-independent manner. We also show that optineurin depletion significantly increases protein aggregation in HeLa cells and that morpholino-silencing of the optineurin ortholog in zebrafish causes the motor axonopathy phenotype similar to a zebrafish model of ALS. A more severe phenotype is observed when optineurin is depleted in zebrafish carrying ALS mutations. Furthermore, TANK1 binding kinase 1 (TBK1) is colocalized with optineurin on protein aggregates and is important in clearance of protein aggregates through the autophagy-lysosome pathway. TBK1 phosphorylates optineurin at serine 177 and regulates its ability to interact with autophagy modifiers. This study provides evidence for a ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates as well as additional relevance for TBK1 as an upstream regulator of the autophagic pathway. PMID:23178947

  6. Increased autophagic activity in dorsal root ganglion attenuates neuropathic pain following peripheral nerve injury.

    Science.gov (United States)

    Guo, Jian-Shuang; Jing, Peng-Bo; Wang, Ji-An; Zhang, Rui; Jiang, Bao-Chun; Gao, Yong-Jing; Zhang, Zhi-Jun

    2015-07-10

    Autophagy is a process of cellular self-cannibalization, and provides an adaptive mechanism to protect cells against diverse pathological settings. Following peripheral nerve injury, autophagic process was changed in Schwann cells and spinal neurons and glial cells, implicating a vital role of autophagy in chronic pain. However, little is known about the role of autophagy in dorsal root ganglion (DRG) in neuropathic pain. In the present study, we investigated the autophagic process in DRG and its effect on neuropathic pain induced by L5 spinal nerve ligation (SNL). The level of microtubule associated protein 1 light chain 3 (LC3)-II, a general marker for autophagy, was increased in L5 DRG after SNL. Immunofluorescence staining showed that LC3-II puncta were observed in DRG neurons after SNL. Injection of autophagy inducer rapamycin into L5 DRG before or after SNL dose-dependently attenuated neuropathic pain. The expression of LC3 was enhanced in L5 DRG by rapamycin. These data suggest that the autophagy in L5 DRG neurons is a defensive reaction to L5 spinal nerve injury, and pharmacological enhancement of autophagy may be a potential treatment to prevent the onset and chronification of neuropathic pain. PMID:26021876

  7. Naringin Attenuates Autophagic Stress and Neuroinflammation in Kainic Acid-Treated Hippocampus In Vivo

    Directory of Open Access Journals (Sweden)

    Kyoung Hoon Jeong

    2015-01-01

    Full Text Available Kainic acid (KA is well known as a chemical compound to study epileptic seizures and neuronal excitotoxicity. KA-induced excitotoxicity causes neuronal death by induction of autophagic stress and microglia-derived neuroinflammation, suggesting that the control of KA-induced effects may be important to inhibit epileptic seizures with neuroprotection. Naringin, a flavonoid in grapefruit and citrus fruits, has anti-inflammatory and antioxidative activities, resulting in neuroprotection in animal models from neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. In the present study, we examined its beneficial effects involved in antiautophagic stress and antineuroinflammation in the KA-treated hippocampus. Our results showed that naringin treatment delayed the onset of KA-induced seizures and decreased the occurrence of chronic spontaneous recurrent seizures (SRS in KA-treated mice. Moreover, naringin treatment protected hippocampal CA1 neurons in the KA-treated hippocampus, ameliorated KA-induced autophagic stress, confirmed by the expression of microtubule-associated protein light chain 3 (LC3, and attenuated an increase in tumor necrosis factor-α (TNFα in activated microglia. These results suggest that naringin may have beneficial effects of preventing epileptic events and neuronal death through antiautophagic stress and antineuroinflammation in the hippocampus in vivo.

  8. Autophagic down-regulation in motor neurons remarkably prolongs the survival of ALS mice.

    Science.gov (United States)

    Hsueh, Kuo-Wei; Chiou, Tzyy-Wen; Chiang, Shu-Fen; Yamashita, Toru; Abe, Koji; Borlongan, Cesar V; Sanberg, Paul R; Huang, Angela Yu Hsuan; Lin, Shinn-Zong; Harn, Horng-Jyh

    2016-09-01

    Amyotrophic lateral sclerosis (ALS) is a lethal degenerating disease, characterized by progressive muscular atrophy without any effective treatment. Here, we demonstrated the efficacy of abrograting autophagy in motor neurons (MN) by treatment with n-butylidenephthalide (n-BP) in ALS transgenic mice (SOD1(G93A)). Pre-symptomatic oral administration of 250 mg/kg/bid n-BP significantly prolonged the survival period (203.9 ± 18.3 days), improved motor function, and attenuated MN loss compared to vehicle control (126.4 ± 7.2 days). This prolonged survival of ALS mice is much more robust than that reported with riluzole (140 days), which is an approved clinical therapy for ALS. The therapeutic mechanism targeted by n-BP involved the autophagic pathway as evidenced by decreased LC3-II expression (a biomarker of autophagy), enhanced mTOR levels, and attenuated autophagic activity, altogether increasing MN survival in a dose-dependent manner. This result was also confirmed by double transgenic mice (SOD1(G93A):LC3-GFP) which showed that oral administration of n-BP reduced GFP density and decreased caspase-3 expression. In addition, electron microscopy revealed that n-BP administration not only decreased autophagosome number but also reduced morphological dysfunction of mitochondria. In summary, these results indicate that down-regulation of autophagy activation via n-BP may pose as a therapeutic regimen for ALS and relevant neurodegenerative diseases. PMID:27059126

  9. Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Highlights: •Free fatty acids exposure induces elevated autophagy. •H2O2 inhibits autophagic flux through impairing the fusion between autophagosomes and lysosomes. •Inhibition of autophagy potentiates H2O2-induced cell death. -- Abstract: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H2O2 and TNF-α, two typical “second hit” factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD

  10. Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Pengtao [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101 (China); University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049 (China); Huang, Zhen [Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021 (China); Zhao, Hong, E-mail: zhaohong9@sina.com [Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021 (China); Wei, Taotao, E-mail: weitt@moon.ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101 (China)

    2013-04-19

    Highlights: •Free fatty acids exposure induces elevated autophagy. •H{sub 2}O{sub 2} inhibits autophagic flux through impairing the fusion between autophagosomes and lysosomes. •Inhibition of autophagy potentiates H{sub 2}O{sub 2}-induced cell death. -- Abstract: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H{sub 2}O{sub 2} and TNF-α, two typical “second hit” factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD.

  11. Staurosporine-induced cell death in Tetrahymena thermophila has mixed characteristics of both apoptotic and autophagic degeneration

    DEFF Research Database (Denmark)

    Christensen, S T; Chemnitz, J; Straarup, E M; Kristiansen, Karsten; Wheatley, D N; Rasmussen, L

    phosphorylation of the PKC-specific substrate, myelin basic protein fragment 4-14. Our results show that cell death in the presence of staurosporine is associated with morphological and ultrastructural changes similar to both apoptosis and autophagic degeneration, but these in turn can be postponed or prevented...

  12. Inhibition of UCH-L1 in oligodendroglial cells results in microtubule stabilization and prevents α-synuclein aggregate formation by activating the autophagic pathway: implications for multiple system atrophy

    Directory of Open Access Journals (Sweden)

    Katharina Pukaß

    2015-05-01

    Full Text Available α-Synuclein (α-syn positive glial cytoplasmic inclusions (GCI originating in oligodendrocytes are a characteristic hallmark in multiple system atrophy. Their occurrence may be linked to a failure of the ubiquitin proteasome system (UPS or the autophagic pathway. For proteasomal degradation, proteins need to be covalently modified by ubiquitin, and deubiquitinated by deubiquitinating enzymes before proteolytic degradation is performed. The deubiquitinating enzyme UCH-L1 is a component of the UPS, it is abundantly expressed in neuronal brain cells and has been connected to Parkinson`s disease. It interacts with α-syn and tubulin. The present study was undertaken to investigate whether UCH-L1 is a constituent of oligodendrocytes, the myelin forming cells of the CNS, and is associated with GCIs in MSA. Furthermore, LDN-57444 (LDN, a specific UCH-L1 inhibitor, was used to analyze its effects on cell morphology, microtubule organization and the proteolytic degradation system. Towards this an oligodendroglial cell line (OLN cells, stably transfected with α-syn or with α-syn and GFP-LC3, to monitor the autophagic flux, was used. The data show that UCHL-1 is expressed in oligodendrocytes derived from the brains of newborn rats and colocalizes with α-syn in GCIs of MSA brain sections. LDN treatment had a direct impact on the microtubule network by affecting tubulin posttranslational modifications, i.e. acetylation and tyrosination. An increase in α-tubulin detyrosination was observed and detyrosinated microtubules were abundantly recruited to the cellular extensions. Furthermore, small α-syn aggregates, which are constitutively expressed in OLN cells overexpressing α-syn, were abolished, and LDN caused the upregulation of the autophagic pathway. Our data add to the knowledge that the UPS and the autophagy-lysosomal pathway are tightly balanced, and that UCH-L1 and its regulation may play a role in neurodegenerative diseases with oligodendroglia

  13. Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells.

    Science.gov (United States)

    Yu, Xinfeng; Li, Ruilian; Shi, Wenna; Jiang, Tao; Wang, Yufei; Li, Cong; Qu, Xianjun

    2016-02-01

    Tamoxifen (TAM) and fulvestrant (FUL) represent the major adjuvant therapy to estrogen receptor-alpha positive (ER(+)) breast cancer patients. However, endocrine resistance to TAM and FUL is a great impediment for successful treatment. We hypothesized that miR-21 might alter the sensitivity of breast cancer cells to TAM or FUL by regulating cell autophagy. Using the ER(+) breast cancer cells, we knockdown miR-21.by transfection with miR-21 inhibitor, then the cells were exposed to TAM or FUL and the percentages of apoptosis and autophagy were determined. Knockdown of miR-21 significantly increased the TAM or FUL-induced apoptosis in ER(+) breast cancer cells. Further, silencing of miR-21 in MCF-7 cells enhanced cell autophagy at both basal and TAM or FUL-induced level. The increase of autophagy in miR-21-knockdown MCF-7 cells was also indicated by increase of beclin-1, LC3-II and increased GFP-LC3 dots. Importantly, knockdown of miR-21 contributed to autophagic cell death, which is responsible for part of TAM induced cell death in miR-21 inhibitor-transfected cells. Further analysis suggested that miR-21 inhibitor enhance autophagic cell death through inhibition of PI3K-AKT-mTOR pathway. MiR-21 coordinated the function of autophagy and apoptosis by targeting Phosphatase and tensin homolog (PTEN) through inhibition of PI3K-AKT-mTOR pathway. In conclusion, silencing of miR-21 increased the sensitivity of ER(+) breast cancer cells to TAM or FUL by increasing autophagic cell death. Targeting autophagy-related miRNAs is a potential strategy for overcoming endocrine resistance to TAM and FUL. PMID:26796263

  14. Group-contribution+ (GC+) based estimation of properties of pure components: Improved property estimation and uncertainty analysis

    DEFF Research Database (Denmark)

    Hukkerikar, Amol; Sarup, Bent; Ten Kate, Antoon;

    2012-01-01

    consistency of the predicted properties (such as, relation of normal boiling point versus critical temperature) are also analyzed and discussed. The developed methodology is simple, yet sound and effective and provides not only the estimated pure component property values but also the uncertainties (e...... of pure components of various classes (hydrocarbons, oxygenated components, nitrogenated components, poly-functional components, etc.) taken from the CAPEC database are used. In total 18 pure component properties are analyzed, namely normal boiling point, critical temperature, critical pressure, critical...... volume, normal melting point, standard Gibbs energy of formation, standard enthalpy of formation, normal enthalpy of fusion, enthalpy of vaporization at 298 K, enthalpy of vaporization at the normal boiling point, entropy of vaporization at the normal boiling point, flash point, auto ignition temperature...

  15. The convergent point of the endocytic and autophagic pathways in leydig cells

    Institute of Scientific and Technical Information of China (English)

    YIJING; XUEMINGTANG

    1999-01-01

    Endocytic tracers and marker enzyme of lysosomes were used in the present study to analyze the processes of autophagocytosis and endocytosis,and the convergent point of these two pathways in Leydig cells.The endocytic and autophagic compartments can be easily identified in Leydig cells,which makes easier to difine the stages of two pathways than was possible before.The evidences indicated that late endosomes (dense MVBs) deliver their endocytosed gold tracers together with lysosomal enzymes to the early autophagosomes and they are the convergent point of the two pathways.During this convergent process,the early autophadosomes transform into late autophagosomes and the late endosomes transform into mature lysosomes.

  16. Mesenchymal Stromal Cells Differentiating to Adipocytes Accumulate Autophagic Vesicles Instead of Functional Lipid Droplets.

    Science.gov (United States)

    Gruia, Alexandra T; Suciu, Maria; Barbu-Tudoran, Lucian; Azghadi, Seyed Mohammad Reza; Cristea, Mirabela I; Nica, Dragos V; Vaduva, Adrian; Muntean, Danina; Mic, Ani Aurora; Mic, Felix A

    2016-04-01

    Adult bone marrow mesenchymal stromal cells (BMSCs) can easily be differentiated into a variety of cells. In vivo transplantation of BMSCs-differentiated cells has had limited success, suggesting that these cells may not be fully compatible with the cells they are intended to replace in vivo. We investigated the structural and functional features of BMSCs-derived adipocytes as compared with adipocytes from adipose tissue, and the structure and functionality of lipid vesicles formed during BMSCs differentiation to adipocytes. Gas chromatography-mass spectrometry showed fatty acid composition of BMSCs-derived adipocytes and adipocytes from the adipose tissue to be very different, as is the lipid rafts composition, caveolin-1 expression, caveolae distribution in their membranes, and the pattern of expression of fatty acid elongases. Confocal microscopy confirmed the absence from BMSCs-derived adipocytes of markers of lipid droplets. BMSCs-derived adipocytes cannot convert deuterated glucose into deuterated species of fatty acids and cannot uptake the deuterated fatty acid-bovine serum albumin complexes from the culture medium, suggesting that intra-cellular accumulation of lipids does not occur by lipogenesis. We noted that BMSCs differentiation to adipocytes is accompanied by an increase in autophagy. Autophagic vesicles accumulate in the cytoplasm of BMSCs-derived adipocytes and their size and distribution resembles that of Nile Red-stained lipid vesicles. Stimulation of autophagy in BMSCs triggers the intra-cellular accumulation of lipids, while inhibition of autophagy prevents this accumulation. In conclusion, differentiation of BMSCs-derived adipocytes leads to intra-cellular accumulation of autophagic vesicles rather than functional lipid droplets, suggesting that these cells are not authentic adipocytes. J. Cell. Physiol. 231: 863-875, 2016. © 2015 Wiley Periodicals, Inc. PMID:26332160

  17. Advantages and limitations of different p62-based assays for estimating autophagic activity in Drosophila.

    Directory of Open Access Journals (Sweden)

    Karolina Pircs

    Full Text Available Levels of the selective autophagy substrate p62 have been established in recent years as a specific readout for basal autophagic activity. Here we compared different experimental approaches for using this assay in Drosophila larvae. Similar to the more commonly used western blots, quantifying p62 dots in immunostained fat body cells of L3 stage larvae detected a strong accumulation of endogenous p62 aggregates in null mutants for Atg genes and S6K. Importantly, genes whose mutation or silencing results in early stage lethality can only be analyzed by microscopy using clonal analysis. The loss of numerous general housekeeping genes show a phenotype in large-scale screens including autophagy, and the p62 assay was potentially suitable for distinguishing bona fide autophagy regulators from silencing of a DNA polymerase subunit or a ribosomal gene that likely has a non-specific effect on autophagy. p62 accumulation upon RNAi silencing of known autophagy regulators was dependent on the duration of the knockdown effect, unlike in the case of starvation-induced autophagy. The endogenous p62 assay was more sensitive than a constitutively overexpressed p62-GFP reporter, which showed self-aggregation and large-scale accumulation even in control cells. We recommend western blots for following the conversion of overexpressed p62-GFP reporters to estimate autophagic activity if sample collection from mutant larvae or adults is possible. In addition, we also showed that overexpressed p62 or Atg8 reporters can strongly influence the phenotypes of each other, potentially giving rise to false or contradicting results. Overexpressed p62 aggregates also incorporated Atg8 reporter molecules that might lead to a wrong conclusion of strongly enhanced autophagy, whereas expression of an Atg8 reporter transgene rescued the inhibitory effect of a dominant-negative Atg4 mutant on basal and starvation-induced autophagy.

  18. Identification of neural networks that contribute to motion sickness through principal components analysis of fos labeling induced by galvanic vestibular stimulation.

    Science.gov (United States)

    Balaban, Carey D; Ogburn, Sarah W; Warshafsky, Susan G; Ahmed, Abdul; Yates, Bill J

    2014-01-01

    Motion sickness is a complex condition that includes both overt signs (e.g., vomiting) and more covert symptoms (e.g., anxiety and foreboding). The neural pathways that mediate these signs and symptoms are yet to identified. This study mapped the distribution of c-fos protein (Fos)-like immunoreactivity elicited during a galvanic vestibular stimulation paradigm that is known to induce motion sickness in felines. A principal components analysis was used to identify networks of neurons activated during this stimulus paradigm from functional correlations between Fos labeling in different nuclei. This analysis identified five principal components (neural networks) that accounted for greater than 95% of the variance in Fos labeling. Two of the components were correlated with the severity of motion sickness symptoms, and likely participated in generating the overt signs of the condition. One of these networks included neurons in locus coeruleus, medial, inferior and lateral vestibular nuclei, lateral nucleus tractus solitarius, medial parabrachial nucleus and periaqueductal gray. The second included neurons in the superior vestibular nucleus, precerebellar nuclei, periaqueductal gray, and parabrachial nuclei, with weaker associations of raphe nuclei. Three additional components (networks) were also identified that were not correlated with the severity of motion sickness symptoms. These networks likely mediated the covert aspects of motion sickness, such as affective components. The identification of five statistically independent component networks associated with the development of motion sickness provides an opportunity to consider, in network activation dimensions, the complex progression of signs and symptoms that are precipitated in provocative environments. Similar methodology can be used to parse the neural networks that mediate other complex responses to environmental stimuli. PMID:24466215

  19. Identification of neural networks that contribute to motion sickness through principal components analysis of fos labeling induced by galvanic vestibular stimulation.

    Directory of Open Access Journals (Sweden)

    Carey D Balaban

    Full Text Available Motion sickness is a complex condition that includes both overt signs (e.g., vomiting and more covert symptoms (e.g., anxiety and foreboding. The neural pathways that mediate these signs and symptoms are yet to identified. This study mapped the distribution of c-fos protein (Fos-like immunoreactivity elicited during a galvanic vestibular stimulation paradigm that is known to induce motion sickness in felines. A principal components analysis was used to identify networks of neurons activated during this stimulus paradigm from functional correlations between Fos labeling in different nuclei. This analysis identified five principal components (neural networks that accounted for greater than 95% of the variance in Fos labeling. Two of the components were correlated with the severity of motion sickness symptoms, and likely participated in generating the overt signs of the condition. One of these networks included neurons in locus coeruleus, medial, inferior and lateral vestibular nuclei, lateral nucleus tractus solitarius, medial parabrachial nucleus and periaqueductal gray. The second included neurons in the superior vestibular nucleus, precerebellar nuclei, periaqueductal gray, and parabrachial nuclei, with weaker associations of raphe nuclei. Three additional components (networks were also identified that were not correlated with the severity of motion sickness symptoms. These networks likely mediated the covert aspects of motion sickness, such as affective components. The identification of five statistically independent component networks associated with the development of motion sickness provides an opportunity to consider, in network activation dimensions, the complex progression of signs and symptoms that are precipitated in provocative environments. Similar methodology can be used to parse the neural networks that mediate other complex responses to environmental stimuli.

  20. Combined aerobic exercise and enzyme replacement therapy rejuvenates the mitochondrial-lysosomal axis and alleviates autophagic blockage in Pompe disease.

    Science.gov (United States)

    Nilsson, M I; MacNeil, L G; Kitaoka, Y; Suri, R; Young, S P; Kaczor, J J; Nates, N J; Ansari, M U; Wong, T; Ahktar, M; Brandt, L; Hettinga, B P; Tarnopolsky, M A

    2015-10-01

    A unifying feature in the pathogenesis of aging, neurodegenerative disease, and lysosomal storage disorders is the progressive deposition of macromolecular debris impervious to enzyme catalysis by cellular waste disposal mechanisms (e.g., lipofuscin). Aerobic exercise training (AET) has pleiotropic effects and stimulates mitochondrial biogenesis, antioxidant defense systems, and autophagic flux in multiple organs and tissues. Our aim was to explore the therapeutic potential of AET as an ancillary therapy to mitigate autophagic buildup and oxidative damage and rejuvenate the mitochondrial-lysosomal axis in Pompe disease (GSD II/PD). Fourteen weeks of combined recombinant acid α-glucosidase (rhGAA) and AET polytherapy attenuated mitochondrial swelling, fortified antioxidant defense systems, reduced oxidative damage, and augmented glycogen clearance and removal of autophagic debris/lipofuscin in fast-twitch skeletal muscle of GAA-KO mice. Ancillary AET potently augmented the pool of PI4KA transcripts and exerted a mild restorative effect on Syt VII and VAMP-5/myobrevin, collectively suggesting improved endosomal transport and Ca(2+)- mediated lysosomal exocytosis. Compared with traditional rhGAA monotherapy, AET and rhGAA polytherapy effectively mitigated buildup of protein carbonyls, autophagic debris/lipofuscin, and P62/SQSTM1, while enhancing MnSOD expression, nuclear translocation of Nrf-2, muscle mass, and motor function in GAA-KO mice. Combined AET and rhGAA therapy reactivates cellular clearance pathways, mitigates mitochondrial senescence, and strengthens antioxidant defense systems in GSD II/PD. Aerobic exercise training (or pharmacologic targeting of contractile-activity-induced pathways) may have therapeutic potential for mitochondrial-lysosomal axis rejuvenation in lysosomal storage disorders and related conditions (e.g., aging and neurodegenerative disease). PMID:26001726

  1. Autophagy initiation correlates with the autophagic flux in 3D models of mesothelioma and with patient outcome.

    Science.gov (United States)

    Follo, Carlo; Barbone, Dario; Richards, William G; Bueno, Raphael; Broaddus, V Courtney

    2016-07-01

    Understanding the role of autophagy in cancer has been limited by the inability to measure this dynamic process in formalin-fixed tissue. We considered that 3-dimensional models including ex vivo tumor, such as we have developed for studying mesothelioma, would provide valuable insights. Using these models, in which we could use lysosomal inhibitors to measure the autophagic flux, we sought a marker of autophagy that would be valid in formalin-fixed tumor and be used to assess the role of autophagy in patient outcome. Autophagy was studied in mesothelioma cell lines, as 2-dimensional (2D) monolayers and 3-dimensional (3D) multicellular spheroids (MCS), and in tumor from 25 chemonaive patients, both as ex vivo 3D tumor fragment spheroids (TFS) and as formalin-fixed tissue. Autophagy was evaluated as autophagic flux by detection of the accumulation of LC3 after lysosomal inhibition and as autophagy initiation by detection of ATG13 puncta. We found that autophagic flux in 3D, but not in 2D, correlated with ATG13 positivity. In each TFS, ATG13 positivity was similar to that of the original tumor. When tested in tissue microarrays of 109 chemonaive patients, higher ATG13 positivity correlated with better prognosis and provided information independent of known prognostic factors. Our results show that ATG13 is a static marker of the autophagic flux in 3D models of mesothelioma and may also reflect autophagy levels in formalin-fixed tumor. If confirmed, this marker would represent a novel prognostic factor for mesothelioma, supporting the notion that autophagy plays an important role in this cancer. PMID:27097020

  2. Autophagic signaling and proteolytic enzyme activity in cardiac and skeletal muscle of spontaneously hypertensive rats following chronic aerobic exercise.

    Directory of Open Access Journals (Sweden)

    Elliott M McMillan

    Full Text Available Hypertension is a cardiovascular disease associated with deleterious effects in skeletal and cardiac muscle. Autophagy is a degradative process essential to muscle health. Acute exercise can alter autophagic signaling. Therefore, we aimed to characterize the effects of chronic endurance exercise on autophagy in skeletal and cardiac muscle of normotensive and hypertensive rats. Male Wistar Kyoto (WKY and spontaneously hypertensive rats (SHR were assigned to a sedentary condition or 6 weeks of treadmill running. White gastrocnemius (WG of hypertensive rats had higher (p<0.05 caspase-3 and proteasome activity, as well as elevated calpain activity. In addition, skeletal muscle of hypertensive animals had elevated (p<0.05 ATG7 and LC3I protein, LAMP2 mRNA, and cathepsin activity, indicative of enhanced autophagic signaling. Interestingly, chronic exercise training increased (p<0.05 Beclin-1, LC3, and p62 mRNA as well as proteasome activity, but reduced (p<0.05 Beclin-1 and ATG7 protein, as well as decreased (p<0.05 caspase-3, calpain, and cathepsin activity. Left ventricle (LV of hypertensive rats had reduced (p<0.05 AMPKα and LC3II protein, as well as elevated (p<0.05 p-AKT, p-p70S6K, LC3I and p62 protein, which collectively suggest reduced autophagic signaling. Exercise training had little effect on autophagy-related signaling factors in LV; however, exercise training increased (p<0.05 proteasome activity but reduced (p<0.05 caspase-3 and calpain activity. Our results suggest that autophagic signaling is altered in skeletal and cardiac muscle of hypertensive animals. Regular aerobic exercise can effectively alter the proteolytic environment in both cardiac and skeletal muscle, as well as influence several autophagy-related factors in skeletal muscle of normotensive and hypertensive rats.

  3. Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia

    Directory of Open Access Journals (Sweden)

    Chen YJ

    2016-07-01

    Full Text Available Yu-Jen Chen,1–4 Li-Wen Fang,5 Wen-Chi Su,6,7 Wen-Yi Hsu,1 Kai-Chien Yang,1 Huey-Lan Huang8 1Department of Medical Research, 2Department of Radiation Oncology, Mackay Memorial Hospital, 3Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 4Institute of Pharmacology, Taipei Medical University, Taipei, 5Department of Nutrition, I-Shou University, Kaohsiung, 6Research Center for Emerging Viruses, China Medical University Hospital, 7Graduate Institute of Clinical Medical Science, China Medical University, Taichung, 8Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan, Taiwan, Republic of China Abstract: Lapatinib is an oral-form dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR or ErbB/Her superfamily members with anticancer activity. In this study, we examined the effects and mechanism of action of lapatinib on several human leukemia cells lines, including acute myeloid leukemia (AML, chronic myeloid leukemia (CML, and acute lymphoblastic leukemia (ALL cells. We found that lapatinib inhibited the growth of human AML U937, HL-60, NB4, CML KU812, MEG-01, and ALL Jurkat T cells. Among these leukemia cell lines, lapatinib induced apoptosis in HL-60, NB4, and Jurkat cells, but induced nonapoptotic cell death in U937, K562, and MEG-01 cells. Moreover, lapatinib treatment caused autophagic cell death as shown by positive acridine orange staining, the massive formation of vacuoles as seen by electronic microscopy, and the upregulation of LC3-II, ATG5, and ATG7 in AML U937 cells. Furthermore, autophagy inhibitor 3-methyladenine and knockdown of ATG5, ATG7, and Beclin-1 using short hairpin RNA (shRNA partially rescued lapatinib-induced cell death. In addition, the induction of phagocytosis and ROS production as well as the upregulation of surface markers CD14 and CD68 was detected in lapatinib-treated U937 cells, suggesting the induction of

  4. AMPK activation protects cells from oxidative stress-induced senescence via autophagic flux restoration and intracellular NAD(+) elevation.

    Science.gov (United States)

    Han, Xiaojuan; Tai, Haoran; Wang, Xiaobo; Wang, Zhe; Zhou, Jiao; Wei, Xiawei; Ding, Yi; Gong, Hui; Mo, Chunfen; Zhang, Jie; Qin, Jianqiong; Ma, Yuanji; Huang, Ning; Xiang, Rong; Xiao, Hengyi

    2016-06-01

    AMPK activation is beneficial for cellular homeostasis and senescence prevention. However, the molecular events involved in AMPK activation are not well defined. In this study, we addressed the mechanism underlying the protective effect of AMPK on oxidative stress-induced senescence. The results showed that AMPK was inactivated in senescent cells. However, pharmacological activation of AMPK by metformin and berberine significantly prevented the development of senescence and, accordingly, inhibition of AMPK by Compound C was accelerated. Importantly, AMPK activation prevented hydrogen peroxide-induced impairment of the autophagic flux in senescent cells, evidenced by the decreased p62 degradation, GFP-RFP-LC3 cancellation, and activity of lysosomal hydrolases. We also found that AMPK activation restored the NAD(+) levels in the senescent cells via a mechanism involving mostly the salvage pathway for NAD(+) synthesis. In addition, the mechanistic relationship of autophagic flux and NAD(+) synthesis and the involvement of mTOR and Sirt1 activities were assessed. In summary, our results suggest that AMPK prevents oxidative stress-induced senescence by improving autophagic flux and NAD(+) homeostasis. This study provides a new insight for exploring the mechanisms of aging, autophagy and NAD(+) homeostasis, and it is also valuable in the development of innovative strategies to combat aging. PMID:26890602

  5. Contribution to the determination of priority constructive influences on the hot crack initiation of welded components; Beitrag zur Ermittlung vorrangig konstruktiver Einflussgroessen auf die Heissrissinitiierung an geschweissten Bauteilen

    Energy Technology Data Exchange (ETDEWEB)

    Gollnow, Christian

    2015-07-01

    The previous research results do not allow a general hot crack characterisation although a variety of experimental and numerical knowledge is available. The reason for this is mainly the large number of influencing factors that complicate a complete description of the hot cracking phenomenon and especially solidification cracking. The hot crack formation and thus the solidification crack initiation can be described by the interaction of process, metallurgy and design. However, the literature examination shows that in the solidifaction crack characterisation the influence of the design aspect is often underestimated. The pre-stresses of the structural components is up to now not considered as an essential cause for the formation of solidification cracks. The evaluation of the influence of the various parameters is presented partly inconsistent. In addition, the targeted presentation of the design influence with respect to the solidification cracks in the weld is because the limited transferability of the various component-specific stresses on a laboratory scale and thus to the respective hot cracking tests restricted. Hence, the difficulty to transfer the results between laboratory specimen and component as well as the general hot crack characterisation is given. In this work the different types of stresses from the component welding in the laboratory and to quantify experimentally the solidification crack critical values, displacements and displacement rates were detected. In this regard external loaded hot cracking tests were carried out by using the advantages of contactless measurement techniques close to the weld and to analyse the welding process with respect to various local and global design-specific factors influencing the formation of solidification cracks in high alloyed steel. These investigations were performed on austenitic (1.4828) and ferritic (1.4509) materials with different mechanical and technological properties. To reflect the praxis relevant

  6. Identification of Neural Networks That Contribute to Motion Sickness through Principal Components Analysis of Fos Labeling Induced by Galvanic Vestibular Stimulation

    OpenAIRE

    Balaban, Carey D.; Sarah W Ogburn; Warshafsky, Susan G.; Abdul Ahmed; Bill J Yates

    2014-01-01

    Motion sickness is a complex condition that includes both overt signs (e.g., vomiting) and more covert symptoms (e.g., anxiety and foreboding). The neural pathways that mediate these signs and symptoms are yet to identified. This study mapped the distribution of c-fos protein (Fos)-like immunoreactivity elicited during a galvanic vestibular stimulation paradigm that is known to induce motion sickness in felines. A principal components analysis was used to identify networks of neurons activate...

  7. CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia.

    Science.gov (United States)

    Mogami, Sachiko; Sadakane, Chiharu; Nahata, Miwa; Mizuhara, Yasuharu; Yamada, Chihiro; Hattori, Tomohisa; Takeda, Hiroshi

    2016-01-01

    Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities. PMID:27273195

  8. CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

    Science.gov (United States)

    Mogami, Sachiko; Sadakane, Chiharu; Nahata, Miwa; Mizuhara, Yasuharu; Yamada, Chihiro; Hattori, Tomohisa; Takeda, Hiroshi

    2016-01-01

    Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities. PMID:27273195

  9. The Protective Effect of Gangliosides on Lead (Pb)-Induced Neurotoxicity Is Mediated by Autophagic Pathways.

    Science.gov (United States)

    Meng, Hongtao; Wang, Lan; He, Junhong; Wang, Zhufeng

    2016-01-01

    Lead (Pb) is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS) from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions. PMID:27023584

  10. The Protective Effect of Gangliosides on Lead (Pb-Induced Neurotoxicity Is Mediated by Autophagic Pathways

    Directory of Open Access Journals (Sweden)

    Hongtao Meng

    2016-03-01

    Full Text Available Lead (Pb is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions.

  11. BH3 Mimetics Reactivate Autophagic Cell Death in Anoxia-Resistant Malignant Glioma Cells

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    Holger Hetschko

    2008-08-01

    Full Text Available Here, we investigated the specific roles of Bcl-2 family members in anoxia tolerance of malignant glioma. Flow cytometry analysis of cell death in 17 glioma cell lines revealed drastic differences in their sensitivity to oxygen withdrawal (<0.1% O2. Cell death correlated with mitochondrial depolarization, cytochrome C release, and translocation of green fluorescent protein (GFP-tagged light chain 3 to autophagosomes but occurred in the absence of caspase activation or phosphatidylserine exposure. In both sensitive and tolerant glioma cell lines, anoxia caused a significant up-regulation of BH3-only genes previously implicated in mediating anoxic cell death in other cell types (BNIP3, NIX, PUMA, and Noxa. In contrast, we detected a strong correlation between anoxia resistance and high expression levels of antiapoptotic Bcl-2 family proteins Bcl-xL, Bcl-2, and Mcl-1 that function to neutralize the proapoptotic activity of BH3-only proteins. Importantly, inhibition of both Bcl-2 and Bcl-xL with the small-molecule BH3 mimetics HA14-1 and BH3I-2′ and by RNA interference reactivated anoxia-induced autophagic cell death in previously resistant glioma cells. Our data suggest that endogenous BH3-only protein induction may not be able to compensate for the high expression of antiapoptotic Bcl-2 family proteins in anoxia-resistant astrocytomas. They also support the conjecture that BH3 mimetics may represent an exciting new approach for the treatment of malignant glioma.

  12. TNFα Impairs Rhabdoviral Clearance by Inhibiting the Host Autophagic Antiviral Response

    Science.gov (United States)

    Roca, Francisco J.; López-Muñoz, Azucena; Tyrkalska, Sylwia D.; Candel, Sergio; García-Moreno, Diana; Falco, Alberto; Meseguer, José

    2016-01-01

    TNFα is a pleiotropic pro-inflammatory cytokine with a key role in the activation of the immune system to fight viral infections. Despite its antiviral role, a few viruses might utilize the host produced TNFα to their benefit. Some recent reports have shown that anti-TNFα therapies could be utilized to treat certain viral infections. However, the underlying mechanisms by which TNFα can favor virus replication have not been identified. Here, a rhabdoviral infection model in zebrafish allowed us to identify the mechanism of action by which Tnfa has a deleterious role for the host to combat certain viral infections. Our results demonstrate that Tnfa signals through its receptor Tnfr2 to enhance viral replication. Mechanistically, Tnfa does not affect viral adhesion and delivery from endosomes to the cytosol. In addition, the host interferon response was also unaffected by Tnfa levels. However, Tnfa blocks the host autophagic response, which is required for viral clearance. This mechanism of action provides new therapeutic targets for the treatment of SVCV-infected fish, and advances our understanding of the previously enigmatic deleterious role of TNFα in certain viral infections. PMID:27351838

  13. Morin hydrate augments phagocytosis mechanism and inhibits LPS induced autophagic signaling in murine macrophage.

    Science.gov (United States)

    Jakhar, Rekha; Paul, Souren; Chauhan, Anil Kumar; Kang, Sun Chul

    2014-10-01

    Morin, a natural flavonoid that is the primary bioactive constituent of the family Moraceae, has been found to be associated with many therapeutic properties. In this study, we evaluated the immunomodulatory activities of increasing concentration of morin hydrate in vitro. Three different concentrations of morin hydrate (5, 10, and 15μM) were used to evaluate their effect on splenocyte proliferation, phagocytic activity of macrophages, cytokine secretion and complement inhibition. We also evaluated the role of morin hydrate on lipopolysaccharide (LPS) induced autophagy. Our study demonstrated that morin hydrate elicited a significant increase in splenocyte proliferation, phagocytic capacity and suppressed the production of cytokines and nitric oxide in activated macrophages. Humoral immunity measured by anti-complement activity showed an increase in inhibition of the complement system after the addition of morin hydrate, where morin hydrate at 15μM concentration induced a significant inhibition. Depending on our results, we can also conclude that morin hydrate protects macrophages from LPS induced autophagic cell death. Our findings suggest that morin hydrate represents a structurally diverse class of flavonoid and this structural variability can profoundly affect its cell-type specificity and its biological activities. Supplementation of immune cells with morin hydrate has an upregulating and immunoprotective effect that shows potential as a countermeasure to the immune dysfunction and suggests an interesting use in inflammation related diseases. PMID:25068824

  14. Ethambutol induces impaired autophagic flux and apoptosis in the rat retina

    Directory of Open Access Journals (Sweden)

    Shun-Ping Huang

    2015-08-01

    Full Text Available Ethambutol (EMB, an effective first-line antituberculosis agent, can cause serious visual impairment or irreversible vision loss in a significant number of patients. However, the mechanism underlying this ocular cytotoxicity remains to be elucidated. In this study, we found that there were statistically significant dose- and time-dependent increases in the number of cytoplasmic vacuoles and the level of cell death in EMB-treated RGC-5 cells (retinal ganglion cells. The protein kinase C (PKCδ inhibitor rottlerin markedly reduced the EMB-induced activation of caspase-3 and the subsequent apoptosis of RGC-5 cells. Western blot analysis revealed that the expression levels of class III PI3K, Beclin-1, p62 and LC3-II were upregulated, and LC3 immunostaining results showed activation of the early phase and inhibition of the late stage of autophagy in retinas of the EMB-intraperitoneal (IP-injected rat model. We further demonstrated that exposure to EMB induces autophagosome accumulation, which results from the impaired autophagic flux that is mediated by a PKCδ-dependent pathway, inhibits the PI3K/Akt/mTOR signaling pathway and leads to apoptotic death in retina neuronal cells. These results indicate that autophagy dysregulation in retinal neuronal cells might play a substantial role in EMB-induced optic neuroretinopathy.

  15. Interleukin-22 Ameliorates Cerulein-Induced Pancreatitis in Mice by Inhibiting the Autophagic Pathway

    Directory of Open Access Journals (Sweden)

    Dechun Feng, Ogyi Park, Svetlana Radaeva, Hua Wang, Shi Yin, Xiaoni Kong, Mingquan Zheng, Sam Zakhari, Jay K. Kolls, Bin Gao

    2012-01-01

    Full Text Available Pancreatitis occurs when digestive enzymes are activated in the pancreas. Severe pancreatitis has a 10-30% mortality rate. No specific treatments for pancreatitis exist now. Here, we discovered that interleukin-22 (IL-22 may have therapeutic potential in treating acute and chronic pancreatitis. Wild-type and IL-22 knockout mice were equally susceptible to cerulein-induced acute and chronic pancreatitis, whereas liver-specific IL-22 transgenic mice were completely resistant to cerulein-induced elevation of serum digestive enzymes, pancreatic necrosis and apoptosis, and inflammatory cell infiltration. Treatment of wild-type mice with recombinant IL-22 or adenovirus IL-22 markedly attenuated the severity of cerulein-induced acute and chronic pancreatitis. Mechanistically, we show that the protective effect of IL-22 on pancreatitis was mediated via the induction of Bcl-2 and Bcl-XL, which bind to Beclin-1 and subsequently inhibit autophagosome formation to ameliorate pancreatitis. In conclusion, IL-22 ameliorates cerulein-induced pancreatitis by inhibiting the autophagic pathway. IL-22 could be a promising therapeutic drug to treat pancreatitis.

  16. SMCX and components of the TIP60 complex contribute to E2 regulation of the HPV E6/E7 promoter

    OpenAIRE

    Smith, Jennifer A.; Haberstroh, Friederike S.; White, Elizabeth A.; Livingston, David M.; DeCaprio, James A.; Howley, Peter M.

    2014-01-01

    An important step in the malignant progression of HPV-associated lesions is the dysregulation of expression of the viral E6 and E7 oncogenes. This is often achieved through the loss of expression of E2, which represses the HPV LCR promoter and E6/E7 expression. Our previous studies confirmed a role for Brd4 in mediating the E2 transcriptional repression function, and identified JARID1C/SMCX and EP400 as contributors to E2-mediated repression. Here we show that TIP60, a component of the TIP60/...

  17. Cocaine elicits autophagic cytotoxicity via a nitric oxide-GAPDH signaling cascade.

    Science.gov (United States)

    Guha, Prasun; Harraz, Maged M; Snyder, Solomon H

    2016-02-01

    Cocaine exerts its behavioral stimulant effects by facilitating synaptic actions of neurotransmitters such as dopamine and serotonin. It is also neurotoxic and broadly cytotoxic, leading to overdose deaths. We demonstrate that the cytotoxic actions of cocaine reflect selective enhancement of autophagy, a process that physiologically degrades metabolites and cellular organelles, and that uncontrolled autophagy can also lead to cell death. In brain cultures, cocaine markedly increases levels of LC3-II and depletes p62, both actions characteristic of autophagy. By contrast, cocaine fails to stimulate cell death processes reflecting parthanatos, monitored by cleavage of poly(ADP ribose)polymerase-1 (PARP-1), or necroptosis, assessed by levels of phosphorylated mixed lineage kinase domain-like protein. Pharmacologic inhibition of autophagy protects neurons against cocaine-induced cell death. On the other hand, inhibition of parthanatos, necroptosis, or apoptosis did not change cocaine cytotoxicity. Depletion of ATG5 or beclin-1, major mediators of autophagy, prevents cocaine-induced cell death. By contrast, depleting caspase-3, whose cleavage reflects apoptosis, fails to alter cocaine cytotoxicity, and cocaine does not alter caspase-3 cleavage. Moreover, depleting PARP-1 or RIPK1, key mediators of parthanatos and necroptosis, respectively, did not prevent cocaine-induced cell death. Autophagic actions of cocaine are mediated by the nitric oxide-glyceraldehyde-3-phosphate dehydrogenase signaling pathway. Thus, cocaine-associated autophagy is abolished by depleting GAPDH via shRNA; by the drug CGP3466B, which prevents GAPDH nitrosylation; and by mutating cysteine-150 of GAPDH, its site of nitrosylation. Treatments that selectively influence cocaine-associated autophagy may afford therapeutic benefit. PMID:26787898

  18. Contribution to the study of recovery mechanisms to be considered in the selection of MOS-type components used in radiative environments

    International Nuclear Information System (INIS)

    The generalized use of commercial devices in a radiative environment (nuclear power plant, spatial) raises the problem of the sensitivity of electronic equipment to the radiation induced dose effect. Irradiation of electronic devices has varying impact on their electrical characteristics, according to the concomitant bias scenario. Under bias, there is a process of continuous degradation; but recovery will occur if subsequent irradiation is performed without bias voltage. This phenomenon is known as RICN (Radiation-Induced Charge Neutralization). On the other hand, increasingly widespread use of radiation-sensitive commercial off-the-shelf components (COTS) has raised interest in exploring the degradation and recovery phenomena encountered during the irradiation as a function of bias. In this work, a general method for selecting MOS devices is presented which takes into account their operating conditions (temperature, bias). After a description of the physical phenomena responsible for the oxide-trapped charge evolution, we present the RICN annealing and their implications on devices selection in a radiative environment. The tests describes in this study were performed on SRAMs and on a set of CMOS inverts from three manufacturers. In the last section, we compare our analytical model of RICN annealing with experimental data. (authors)

  19. Two overlapping two-component systems in Xanthomonas oryzae pv. oryzae contribute to full fitness in rice by regulating virulence factors expression.

    Science.gov (United States)

    Zheng, Dehong; Yao, Xiaoyan; Duan, Meng; Luo, Yufeng; Liu, Biao; Qi, Pengyuan; Sun, Ming; Ruan, Lifang

    2016-01-01

    Two-component signal transduction systems (TCSs) are widely used by bacteria to adapt to the environment. In the present study, StoS (stress tolerance-related oxygen sensor) and SreKRS (salt response kinase, regulator, and sensor) were found to positively regulate extracellular polysaccharide (EPS) production and swarming in the rice pathogen Xanthomonas oryzae pv. oryzae (Xoo). Surprisingly, the absence of stoS or sreKRS did not attenuate virulence. To better understand the intrinsic functions of StoS and SreKRS, quantitative proteomics isobaric tags for relative and absolute quantitation (iTRAQ) was employed. Consistent with stoS and sreK mutants exhibiting a similar phenotype, the signalling circuits of StoS and SreKRS overlapped. Carbohydrate metabolism proteins and chemotaxis proteins, which could be responsible for EPS and swarming regulation, respectively, were reprogrammed in stoS and sreK mutants. Moreover, StoS and SreKRS demonstrated moderate expression of the major virulence factor, hypersensitive response and pathogenicity (Hrp) proteins through the HrpG-HrpX circuit. Most importantly, Xoo equipped with StoS and SreKRS outcompetes strains without StoS or SreKRS in co-infected rice and grows outside the host. Therefore, we propose that StoS and SreKRS adopt a novel strategy involving the moderation of Hrp protein expression and the promotion of EPS and motility to adapt to the environment. PMID:26957113

  20. Dynein disruption perturbs post-synaptic components and contributes to impaired MuSK clustering at the NMJ: implication in ALS.

    Science.gov (United States)

    Vilmont, Valérie; Cadot, Bruno; Vezin, Elsa; Le Grand, Fabien; Gomes, Edgar R

    2016-01-01

    The neuromuscular junction (NMJ) allows the transformation of a neuronal message into a mechanical force by muscle contraction and is the target of several neuromuscular disorders. While the neuronal side is under extensive research, the muscle appeared recently to have a growing role in the formation and integrity of the neuromuscular junction. We used an in vitro model of mature myofibers to study the role of dynein on major postsynaptic proteins. We found that dynein affects the expression and the clustering of acetylcholine receptors (AChRs), muscle specific tyrosine kinase (MuSK) and Rapsyn. We also show that myofibers with dynein impairment or from an amyotrophic lateral sclerosis (ALS) model (SOD1(G93A)) show similar defects in myofiber formation and agrin-induced AChR clustering suggesting a role for dynein impairment in ALS progression. Finally, we found that dynein can affect MuSK traffic through the endosomal pathway. Collectively, our studies show that defects in dynein can lead to impairment of muscle NMJ components' expression and clustering. We propose that NMJ defects could happen via defective MuSK traffic and that this could be one of the pathological features involved in neurodegeneration such as ALS. PMID:27283349

  1. Contribution of the autophagy-lysosomal and ubiquitin-proteasomal proteolytic systems to total proteolysis in rainbow trout (Oncorhynchus mykiss) myotubes

    Science.gov (United States)

    Two major proteolytic systems are thought to (co-) operate in the skeletal muscle of vertebrates, the ubiquitin-proteasomal system (UPS) and the autophagic/lysosomal system (ALS). While their relative contribution to muscle loss has been already well documented in mammals, little is known in fish sp...

  2. The Root Hair Specific SYP123 Regulates the Localization of Cell Wall Components and Contributes to Rizhobacterial Priming of Induced Systemic Resistance.

    Science.gov (United States)

    Rodriguez-Furlán, Cecilia; Salinas-Grenet, Hernán; Sandoval, Omar; Recabarren, Camilo; Arraño-Salinas, Paulina; Soto-Alvear, Sylvana; Orellana, Ariel; Blanco-Herrera, Francisca

    2016-01-01

    Root hairs are important for nutrient and water uptake and are also critically involved the interaction with soil inhabiting microbiota. Root hairs are tubular-shaped outgrowths that emerge from trichoblasts. This polarized elongation is maintained and regulated by a robust mechanism involving the endomembrane secretory and endocytic system. Members of the syntaxin family of SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) in plants (SYP), have been implicated in regulation of the fusion of vesicles with the target membranes in both exocytic and endocytic pathways. One member of this family, SYP123, is expressed specifically in the root hairs and accumulated in the growing tip region. This study shows evidence of the SYP123 role in polarized trafficking using knockout insertional mutant plants. We were able to observe defects in the deposition of cell wall proline rich protein PRP3 and cell wall polysaccharides. In a complementary strategy, similar results were obtained using a plant expressing a dominant negative soluble version of SYP123 (SP2 fragment) lacking the transmembrane domain. The evidence presented indicates that SYP123 is also regulating PRP3 protein distribution by recycling by endocytosis. We also present evidence that indicates that SYP123 is necessary for the response of roots to plant growth promoting rhizobacterium (PGPR) in order to trigger trigger induced systemic response (ISR). Plants with a defective SYP123 function were unable to mount a systemic acquired resistance in response to bacterial pathogen infection and ISR upon interaction with rhizobacteria. These results indicated that SYP123 was involved in the polarized localization of protein and polysaccharides in growing root hairs and that this activity also contributed to the establishment of effective plant defense responses. Root hairs represent very plastic structures were many biotic and abiotic factors can affect the number, anatomy and physiology of

  3. Interference with the Autophagic Process as a Viral Strategy to Escape from the Immune Control: Lesson from Gamma Herpesviruses

    Directory of Open Access Journals (Sweden)

    Roberta Santarelli

    2015-01-01

    Full Text Available We summarized the most recent findings on the role of autophagy in antiviral immune response. We described how viruses have developed strategies to subvert the autophagic process. A particular attention has been given to Epstein-Barr and Kaposi’s sarcoma associated Herpesvirus, viruses studied for many years in our laboratory. These two viruses belong to γ-Herpesvirus subfamily and are associated with several human cancers. Besides the effects on the immune response, we have described how autophagy subversion by viruses may also concur to the enhancement of their replication and to viral tumorigenesis.

  4. Phospholipase C-related catalytically inactive protein participates in the autophagic elimination of Staphylococcus aureus infecting mouse embryonic fibroblasts.

    Directory of Open Access Journals (Sweden)

    Kae Harada-Hada

    Full Text Available Autophagy is an intrinsic host defense system that recognizes and eliminates invading bacterial pathogens. We have identified microtubule-associated protein 1 light chain 3 (LC3, a hallmark of autophagy, as a binding partner of phospholipase C-related catalytically inactive protein (PRIP that was originally identified as an inositol trisphosphate-binding protein. Here, we investigated the involvement of PRIP in the autophagic elimination of Staphylococcus aureus in infected mouse embryonic fibroblasts (MEFs. We observed significantly more LC3-positive autophagosome-like vacuoles enclosing an increased number of S. aureus cells in PRIP-deficient MEFs than control MEFs, 3 h and 4.5 h post infection, suggesting that S. aureus proliferates in LC3-positive autophagosome-like vacuoles in PRIP-deficient MEFs. We performed autophagic flux analysis using an mRFP-GFP-tagged LC3 plasmid and found that autophagosome maturation is significantly inhibited in PRIP-deficient MEFs. Furthermore, acidification of autophagosomes was significantly inhibited in PRIP-deficient MEFs compared to the wild-type MEFs, as determined by LysoTracker staining and time-lapse image analysis performed using mRFP-GFP-tagged LC3. Taken together, our data show that PRIP is required for the fusion of S. aureus-containing autophagosome-like vacuoles with lysosomes, indicating that PRIP is a novel modulator in the regulation of the innate immune system in non-professional phagocytic host cells.

  5. Some autophagic and apoptotic features of programmed cell death in the anterior silk glands of the silkworm, Bombyx mori.

    Science.gov (United States)

    Goncu, Ebru; Parlak, Osman

    2008-11-01

    Programmed cell death has been subdivided into two major groups: apoptosis and autophagic cell death. The anterior silk gland of Bombyx mori degenerates during larval-pupal metamorphosis. Our findings indicate that two types of programmed cell death features are observed during this physiological process. During the prepupal period, pyknosis of the nucleus, cell detachment,and membrane blebbing occur and they are the first signs of programmed cell death in the anterior silk glands. According to previous studies, all of these morphological appearances are common for both cell-death types. Autophagy features are also exhibited during the prepupal period. Levels of one of the lysosomal marker enzymes-acid phosphatase-are high during this period then decrease gradually. Vacuole formation begins to appear first at the basal surface of the cell, then expands to the apical surface just before the larval pupal ecdysis. After larval-pupal ecdysis, DNA fragmentation, which is the obvious biochemical marker of apoptosis, is detected in agarose gel electrophoresis, which also shows that caspase-like enzyme activities occur during the programmed cell death process of the anterior silk glands. Apoptosis and autophagic cell death interact with each other during the degeneration process of the anterior silk gland in Bombyx mori and this interaction occurs at a late phase of cell death. We suggest that apoptotic cell death only is not enough for whole gland degeneration and that more effective degeneration occurs with this cooperation. PMID:18838861

  6. Removal of the BH4 Domain from Bcl-2 Protein Triggers an Autophagic Process that Impairs Tumor Growth12

    Science.gov (United States)

    Trisciuoglio, Daniela; De Luca, Teresa; Desideri, Marianna; Passeri, Daniela; Gabellini, Chiara; Scarpino, Stefania; Liang, Chengyu; Orlandi, Augusto; Del Bufalo, Donatella

    2013-01-01

    Here, we show that forced expression of a B-cell lymphoma 2 (bcl-2) protein lacking residues 1 to 36 at the N-terminal, including the entire Bcl-2 homology 4 (BH4) domain, determines reduction of in vitro and in vivo human melanoma growth. Noteworthy, melanoma cells in vivo exhibit markedly increased autophagy, as response to expression of bcl-2 protein deleted of its BH4 domain. This observation led to the identification of a novel gain of function for bcl-2 protein lacking the BH4 domain. In particular, upon different autophagic stimuli in vitro, overexpression of bcl-2 protein deleted of BH4 domain induces autophagosome accumulation, conversion of microtubule-associated protein 1 light chain 3B-II, reduced expression of p62/SQSTM1 protein, and thereby enhanced autophagic flux. The relevance of Beclin-1 is evidenced by the fact that 1) the autophagy-promoting and growth-inhibiting properties are partially rescued by Beclin-1 knockdown in cells expressing bcl-2 protein lacking the BH4 domain, 2) Beclin-1 only interacts with wild-type but not with deleted bcl-2, and 3) BH4 domain removal from bcl-2 protein does not influence in vitro and in vivo growth of tumor cells expressing low levels of endogenous Beclin-1. These results provide new insight into molecular mechanism of bcl-2 functions and represent a rationale for the development of agents interfering with the BH4 domain of bcl-2 protein. PMID:23479509

  7. Removal of the BH4 Domain from Bcl-2 Protein Triggers an Autophagic Process that Impairs Tumor Growth

    Directory of Open Access Journals (Sweden)

    Daniela Trisciuoglio

    2013-03-01

    Full Text Available Here, we show that forced expression of a B-cell lymphoma 2 (bcl-2 protein lacking residues 1 to 36 at the N-terminal, including the entire Bcl-2 homology 4 (BH4 domain, determines reduction of in vitro and in vivo human melanoma growth. Noteworthy, melanoma cells in vivo exhibit markedly increased autophagy, as response to expression of bcl-2 protein deleted of its BH4 domain. This observation led to the identification of a novel gain of function for bcl-2 protein lacking the BH4 domain. In particular, upon different autophagic stimuli in vitro, overexpression of bcl-2 protein deleted of BH4 domain induces autophagosome accumulation, conversion of microtubule-associated protein 1 light chain 3B-II, reduced expression of p62/SQSTM1 protein, and thereby enhanced autophagic flux. The relevance of Beclin-1 is evidenced by the fact that 1 the autophagy-promoting and growth-inhibiting properties are partially rescued by Beclin-1 knockdown in cells expressing bcl-2 protein lacking the BH4 domain, 2 Beclin-1 only interacts with wild-type but not with deleted bcl-2, and 3 BH4 domain removal from bcl-2 protein does not influence in vitro and in vivo growth of tumor cells expressing low levels of endogenous Beclin-1. These results provide new insight into molecular mechanism of bcl-2 functions and represent a rationale for the development of agents interfering with the BH4 domain of bcl-2 protein.

  8. Removal of the BH4 domain from Bcl-2 protein triggers an autophagic process that impairs tumor growth.

    Science.gov (United States)

    Trisciuoglio, Daniela; De Luca, Teresa; Desideri, Marianna; Passeri, Daniela; Gabellini, Chiara; Scarpino, Stefania; Liang, Chengyu; Orlandi, Augusto; Del Bufalo, Donatella

    2013-03-01

    Here, we show that forced expression of a B-cell lymphoma 2 (bcl-2) protein lacking residues 1 to 36 at the N-terminal, including the entire Bcl-2 homology 4 (BH4) domain, determines reduction of in vitro and in vivo human melanoma growth. Noteworthy, melanoma cells in vivo exhibit markedly increased autophagy, as response to expression of bcl-2 protein deleted of its BH4 domain. This observation led to the identification of a novel gain of function for bcl-2 protein lacking the BH4 domain. In particular, upon different autophagic stimuli in vitro, overexpression of bcl-2 protein deleted of BH4 domain induces autophagosome accumulation, conversion of microtubule-associated protein 1 light chain 3B-II, reduced expression of p62/SQSTM1 protein, and thereby enhanced autophagic flux. The relevance of Beclin-1 is evidenced by the fact that 1) the autophagy-promoting and growth-inhibiting properties are partially rescued by Beclin-1 knockdown in cells expressing bcl-2 protein lacking the BH4 domain, 2) Beclin-1 only interacts with wild-type but not with deleted bcl-2, and 3) BH4 domain removal from bcl-2 protein does not influence in vitro and in vivo growth of tumor cells expressing low levels of endogenous Beclin-1. These results provide new insight into molecular mechanism of bcl-2 functions and represent a rationale for the development of agents interfering with the BH4 domain of bcl-2 protein. PMID:23479509

  9. ESCRT-0 dysfunction compromises autophagic degradation of protein aggregates and facilitates ER stress-mediated neurodegeneration via apoptotic and necroptotic pathways

    Science.gov (United States)

    Oshima, Ryuji; Hasegawa, Takafumi; Tamai, Keiichi; Sugeno, Naoto; Yoshida, Shun; Kobayashi, Junpei; Kikuchi, Akio; Baba, Toru; Futatsugi, Akira; Sato, Ikuro; Satoh, Kennichi; Takeda, Atsushi; Aoki, Masashi; Tanaka, Nobuyuki

    2016-01-01

    Endosomal sorting required for transport (ESCRT) complexes orchestrate endo-lysosomal sorting of ubiquitinated proteins, multivesicular body formation and autophagic degradation. Defects in the ESCRT pathway have been implicated in many neurodegenerative diseases, but the underlying molecular mechanisms that link them to neurodegeneration remain unknown. In this study, we showed that forebrain-specific ablation of ESCRT-0/Hrs induced marked hippocampal neuronal cell loss accompanied by the accumulation of ubiquitinated proteins, including α-synuclein, TDP-43 and huntingtin as well as the autophagic substrate SQSTM1/p62. Consistent with this, silencing of Hrs in cultured cells not only led to α-synuclein and TDP-43 accumulation in addition to impaired autophagic flux but also suppressed cell viability through the induction of ER stress followed by the activation of JNK and RIPK1, a key regulator of necroptosis. Moreover, necrostatin-1, a specific inhibitor of RIPK1, and pan-caspase inhibitors partially reduced the neurotoxicity in the Hrs-silenced cells. Altogether, these findings suggest that the disruption of ESCRT-0/Hrs in the nervous system compromises autophagic/lysosomal degradation of neurodegenerative disease-related proteins, which thereby triggers ER stress-mediated apoptotic and necroptotic cell death. PMID:27112194

  10. Autophagic flux inhibition and lysosomogenesis ensuing cellular capture and retention of the cationic drug quinacrine in murine models.

    Science.gov (United States)

    Parks, Alexandre; Charest-Morin, Xavier; Boivin-Welch, Michael; Bouthillier, Johanne; Marceau, Francois

    2015-01-01

    The proton pump vacuolar (V)-ATPase is the driving force that mediates the concentration of cationic drugs (weak bases) in the late endosome-lysosome continuum; secondary cell reactions include the protracted transformation of enlarged vacuoles into autophagosomes. We used the inherently fluorescent tertiary amine quinacrine in murine models to further assess the accumulation and signaling associated with cation trapping. Primary fibroblasts concentrate quinacrine ∼5,000-fold from their culture medium (KM 9.8 µM; transport studies). The drug is present in perinuclear granules that are mostly positive for Rab7 and LAMP1 (microscopy). Both drug uptake and retention are extensively inhibited by treatments with the V-ATPase inhibitor bafilomycin A1. The H(+) ionophore monensin also prevented quinacrine concentration by fibroblasts. However, inhibition of plasma membrane transporters or of the autophagic process with spautin-1 did not alter quinacrine transport parameters. Ancillary experiments did not support that low micromolar concentrations of quinacrine are substrates for organic cation transporters-1 to -3 or P-glycoprotein. The secondary autophagy induced by quinacrine in cells may derive from the accumulation of incompetent autophagolysosomes, as judged from the accumulation of p62/SQSTM1 and LC3 II (immunoblots). Accordingly, protracted lysosomogenesis is evidenced by increased expression of LAMP1 and LAMP2 in quinacrine-treated fibroblasts (48 h, immunoblots), a response that follows the nuclear translocation of the lysosomal genesis transcription factor TFEB and upregulation of LAMP1 and -2 mRNAs (24 h). Quinacrine administration to live mice evidenced variable distribution to various organs and heterogeneous accumulation within the lung (stereo-microscopy, extraction). Dose-dependent in vivo autophagic and lysosomal accumulation was observed in the lung (immunoblots). No evidence has been found for transport or extrusion mechanisms modulating the cellular

  11. In vivo effect of an antilipolytic drug (3,5'-dimethylpyrazole) on autophagic proteolysis and autophagy-related gene expression in rat liver

    International Nuclear Information System (INIS)

    Autophagy is an intracellular pathway induced by starvation, inhibited by nutrients, that is responsible for degradation of long-lived proteins and altered cell organelles. This process is involved in cell maintenance could be induced by antilipolytic drugs and may have anti-aging effects [A. Donati, The involvement of macroautophagy in aging and anti-aging interventions, Mol. Aspects Med. 27 (2006) 455-470]. We analyzed the effect of an intraperitoneal injection of an antilipolytic agent (3,5'-dimethylpyrazole, DMP, 12 mg/kg b.w.), that mimics nutrient shortage on autophagy and expression of autophagic genes in the liver of male 3-month-old Sprague-Dawley albino rats. Autophagy was evaluated by observing electron micrographs of the liver autophagosomal compartment and by monitoring protein degradation assessed by the release of valine into the bloodstream. LC3 gene expression, whose product is one of the best known markers of autophagy, was also monitored. As expected, DMP decreased the plasma levels of free fatty acids, glucose, and insulin and increased autophagic vacuoles and proteolysis. DMP treatment caused an increase in the expression of the LC3 gene although this occurred later than the induction of authophagic proteolysis caused by DMP. Glucose treatment rescued the effects caused by DMP on glucose and insulin plasma levels and negatively affected the rate of autophagic proteolysis, but did not suppress the positive regulatory effect on LC3 mRNA levels. In conclusion, antilipolytic drugs may induce both autophagic proteolysis and higher expression of an autophagy-related gene and the effect on autophagy gene expression might not be secondary to the stimulation of autophagic proteolysis

  12. Using isotope, hydrochemical methods and energy-balance modelling to estimate contribution of different components to flow forming process in a high-altitude catchment (Dzhancuat river basin case study)

    Science.gov (United States)

    Rets, Ekaterina; Loshakova, Nadezhda; Chizhova, Julia; Kireeva, Maria; Frolova, Natalia; Tokarev, Igor; Budantseva, Nadine; Vasilchuk, Yurij

    2016-04-01

    A multicomponent structure of sources of river runoff formation is characteristic of high-altitude territories: ice and firn melting; seasonal snow melting on glacier covered and non-glacier area of a watershed; liquid precipitation; underground waters. In addition, each of these components can run off the watershed surface in different ways. Use of isotopic, hydrochemical methods and energy balance modelling provides possibility to estimate contribution of different components to river runoff that is an essential to understand the mechanism of flow formation in mountainious areas. A study was carried out for Dzhancuat river basin that was chosen as representative for North Caucasus in course of the International Hydrological Decade. Complex glaciological, hydrological and meteorological observation have been carried in the basin since 1965. In years 2013-2015 the program also included daily collecting of water samples on natural stable isotopes on the Dzhancuat river gauging station, and sampling water nourishment sources (ice, snow, firn, liquid precipitation) within the study area. More then 800 water samples were collected. Application of an energy balance model of snow and ice melt with distributed parameters provided an opportunity to identify Dzhancuat river runoff respond to glaciers melt regime and seasonal redistribution of melt water. The diurnal amplitude of oscillation of the Dzhakuat river runoff in the days without precipitation is formed by melting at almost snow-free areas of the Dzhancuat glacier tongues. Snowmelt water from the non-glacierized part contributes to the formation of the next day runoff. A wave of snow and firn melt in upper zones of glacier flattens considerably during filtration through snow and run-off over the surface and in the body of the glacier. This determines a general significant inertia of the Dzhacuat river runoff. Some part of melt water is stored into natural regulating reservoirs of the watershed that supply the

  13. The tyrosine kinase inhibitor, sunitinib malate, induces cognitive impairment in vivo via dysregulating VEGFR signaling, apoptotic and autophagic machineries.

    Science.gov (United States)

    Abdel-Aziz, Amal Kamal; Mantawy, Eman M; Said, Riham Soliman; Helwa, Reham

    2016-09-01

    Chemobrain refers to a cluster of cognitive deficits which affects almost 4-75% of chemotherapy-treated cancer patients. Sunitinib, an FDA-approved multityrosine kinase inhibitor, is currently used in treating different types of tumors. Despite being regarded as targeted therapy which blunts sustained angiogenesis in cancer milieu through inhibiting vascular endothelial growth factor receptor 2 (VEGFR2) signaling, the latter has a cardinal role in cognition. Recent clinical reports warned that sunitinib adversely affected memory processing in cancer patients. Nevertheless, the underlying mechanisms have not been investigated yet. Hence, we explored the impact of a clinically relevant dose of sunitinib on memory processing in vivo and questioned the implication of VEGFR2 signaling, autophagy and apoptosis. Strikingly, sunitinib preferentially impaired spatial cognition as evidenced in Morris water maze, T-maze and passive avoidance task. Consistently, sunitinib degenerated cortical and hippocampal neurons as assessed by histopathological examination and toluidine blue staining. Ultrastructural examination also depicted chromatin condensation, mitochondrial damage and accumulated autophagosomes. Digging deeper, central VEGF/VEGFR2/mTOR signaling was robustly suppressed. Besides, sunitinib boosted cortical and hippocampal p53 and executioner caspase-3 and decreased nuclear factor kappa B and Bcl-2 levels promoting apoptotic cell death. It also profoundly impeded neuronal autophagic flux as shown by decreased beclin-1 and Atg5 and increased p62/SQTSM1 levels. To our knowledge, this is the first study to provide molecular insights into sunitinib-induced chemofog where impeded VEGFR2 signaling and autophagic and hyperactivated apoptotic machineries act in neurodegenerative concert. Importantly, our findings shed light on potential therapeutic strategies to be exploited in the management of sunitinib-induced chemobrain. PMID:27288242

  14. SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario

    International Nuclear Information System (INIS)

    We hypothesized that SET, a protein accumulated in some cancer types and Alzheimer disease, is involved in cell death through mitochondrial mechanisms. We addressed the mRNA and protein levels of the mitochondrial uncoupling proteins UCP1, UCP2 and UCP3 (S and L isoforms) by quantitative real-time PCR and immunofluorescence as well as other mitochondrial involvements, in HEK293 cells overexpressing the SET protein (HEK293/SET), either in the presence or absence of oxidative stress induced by the pro-oxidant t-butyl hydroperoxide (t-BHP). SET overexpression in HEK293 cells decreased UCP1 and increased UCP2 and UCP3 (S/L) mRNA and protein levels, whilst also preventing lipid peroxidation and decreasing the content of cellular ATP. SET overexpression also (i) decreased the area of mitochondria and increased the number of organelles and lysosomes, (ii) increased mitochondrial fission, as demonstrated by increased FIS1 mRNA and FIS-1 protein levels, an apparent accumulation of DRP-1 protein, and an increase in the VDAC protein level, and (iii) reduced autophagic flux, as demonstrated by a decrease in LC3B lipidation (LC3B-II) in the presence of chloroquine. Therefore, SET overexpression in HEK293 cells promotes mitochondrial fission and reduces autophagic flux in apparent association with up-regulation of UCP2 and UCP3; this implies a potential involvement in cellular processes that are deregulated such as in Alzheimer's disease and cancer. - Highlights: • SET, UCPs and autophagy prevention are correlated. • SET action has mitochondrial involvement. • UCP2/3 may reduce ROS and prevent autophagy. • SET protects cell from ROS via UCP2/3

  15. The M2 macrophages induce autophagic vascular disorder and promote mouse sensitivity to urethane-related lung carcinogenesis.

    Science.gov (United States)

    Li, G-G; Guo, Z-Z; Ma, X-F; Cao, N; Geng, S-N; Zheng, Y-Q; Meng, M-J; Lin, H-H; Han, G; Du, G-J

    2016-06-01

    Tumor vessels are known to be abnormal, with typically aberrant, leaky and disordered vessels. Here, we investigated whether polarized macrophage phenotypes are involved in tumor abnormal angiogenesis and what is its mechanism. We found that there was no difference in chemotaxis of polarized M1 and M2 macrophages to lewis lung carcinoma (LLC) cells and that either M1 or M2 macrophage-conditioned media had no effect on LLC cell proliferation. Unexpectedly, the M2 but not M1 macrophage-conditioned media promoted the proliferation of human umbilical vein endothelial cells (HUVECs) and simultaneously increased endothelial cell permeability in vitro and angiogenic index in the chick embryo chorioallantoic membrane (CAM). The treatment with M2 but not M1 macrophage-conditioned media increased autophagosomes as well as microtubule-associated protein light chain 3B (LC3-B) expression (a robust marker of autophagosomes) but decreased p62 protein expression (a selective autophagy substrate) in HUVECs, the treatment with chloroquine that blocked autophagy abrogated the abnormal angiogenic efficacy of M2 macrophage-conditioned media. These results were confirmed in urethane-induced lung carcinogenic progression. Urethane-induced lung carcinogenesis led to more M2 macrophage phenotype and increased abnormal angiogenesis concomitant with the upregulation of LC3-B and the downregulation of p62. Clodronate liposome-induced macrophage depletion, chloroquine-induced autophagic prevention or salvianolic acid B-induced vascular protection decreased abnormal angiogenesis and lung carcinogenesis. In addition, we found that the tendency of age-related M2 macrophage polarization also promoted vascular permeability and carcinogenesis in urethane carcinogenic progression. These findings indicate that the M2 macrophages induce autophagic vascular disorder to promote lung cancer progression, and the autophagy improvement represents an efficacious strategy for abnormal angiogenesis and cancer

  16. SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luciana O.; Goto, Renata N. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Neto, Marinaldo P.C. [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Sousa, Lucas O. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Curti, Carlos [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Leopoldino, Andréia M., E-mail: andreiaml@usp.br [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    2015-03-06

    We hypothesized that SET, a protein accumulated in some cancer types and Alzheimer disease, is involved in cell death through mitochondrial mechanisms. We addressed the mRNA and protein levels of the mitochondrial uncoupling proteins UCP1, UCP2 and UCP3 (S and L isoforms) by quantitative real-time PCR and immunofluorescence as well as other mitochondrial involvements, in HEK293 cells overexpressing the SET protein (HEK293/SET), either in the presence or absence of oxidative stress induced by the pro-oxidant t-butyl hydroperoxide (t-BHP). SET overexpression in HEK293 cells decreased UCP1 and increased UCP2 and UCP3 (S/L) mRNA and protein levels, whilst also preventing lipid peroxidation and decreasing the content of cellular ATP. SET overexpression also (i) decreased the area of mitochondria and increased the number of organelles and lysosomes, (ii) increased mitochondrial fission, as demonstrated by increased FIS1 mRNA and FIS-1 protein levels, an apparent accumulation of DRP-1 protein, and an increase in the VDAC protein level, and (iii) reduced autophagic flux, as demonstrated by a decrease in LC3B lipidation (LC3B-II) in the presence of chloroquine. Therefore, SET overexpression in HEK293 cells promotes mitochondrial fission and reduces autophagic flux in apparent association with up-regulation of UCP2 and UCP3; this implies a potential involvement in cellular processes that are deregulated such as in Alzheimer's disease and cancer. - Highlights: • SET, UCPs and autophagy prevention are correlated. • SET action has mitochondrial involvement. • UCP2/3 may reduce ROS and prevent autophagy. • SET protects cell from ROS via UCP2/3.

  17. Aurantiamide acetate suppresses the growth of malignant gliomas in vitro and in vivo by inhibiting autophagic flux.

    Science.gov (United States)

    Yang, Yi; Zhang, Li-hui; Yang, Bing-xian; Tian, Jin-kui; Zhang, Lin

    2015-05-01

    We aim to investigate the effect of aurantiamide acetate isolated from the aerial parts of Clematis terniflora DC against gliomas. Human malignant glioma U87 and U251 cells were incubated with different concentrations (0-100 μM) of aurantiamide acetate. Aurantiamide acetate greatly decreased the cell viability in a dose- and time-dependent manner. It induced moderate mitochondrial fragmentation and the loss of mitochondrial membrane potential. No significant difference was found in the alternation of other intracellular organelles, although F-actin structure was slightly disturbed. Apparent ultrastructure alternation with increased autophagosome and autolysosome accumulation was observed in aurantiamide acetate-treated cells. The expression of LC3-II was greatly up-regulated in cells exposed to aurantiamide acetate (P < 0.05 compared with control). The cytoplasmic accumulation of autophagosomes and autolysosomes induced by aurantiamide acetate treatment was confirmed by fluorescent reporter protein labelling. Administration of chloroquine (CQ), which inhibits the fusion step of autophagosomes, further increased the accumulation of autophagosomes in the cytoplasm of U87 cells. Autophagy inhibition by 3-methyladenine, Bafilomycin A1 or CQ had no influence on aurantiamide acetate-induced cytotoxicity, whereas autophagy stimulator rapamycin significantly suppressed aurantiamide acetate-induced cell death. The anti-tumour effects of aurantiamide acetate were further evaluated in tumour-bearing nude mice. Intratumoural injection of aurantiamide acetate obviously suppressed tumour growth, and increased number of autophagic vacuoles was observed in tumour tissues of animals receiving aurantiamide acetate. Our findings suggest that aurantiamide acetate may suppress the growth of malignant gliomas by blocking autophagic flux. PMID:25704599

  18. In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11.

    Directory of Open Access Journals (Sweden)

    Rita-Eva Varga

    2015-08-01

    Full Text Available Hereditary spastic paraplegia (HSP is characterized by a dying back degeneration of corticospinal axons which leads to progressive weakness and spasticity of the legs. SPG11 is the most common autosomal-recessive form of HSPs and is caused by mutations in SPG11. A recent in vitro study suggested that Spatacsin, the respective gene product, is needed for the recycling of lysosomes from autolysosomes, a process known as autophagic lysosome reformation. The relevance of this observation for hereditary spastic paraplegia, however, has remained unclear. Here, we report that disruption of Spatacsin in mice indeed causes hereditary spastic paraplegia-like phenotypes with loss of cortical neurons and Purkinje cells. Degenerating neurons accumulate autofluorescent material, which stains for the lysosomal protein Lamp1 and for p62, a marker of substrate destined to be degraded by autophagy, and hence appears to be related to autolysosomes. Supporting a more generalized defect of autophagy, levels of lipidated LC3 are increased in Spatacsin knockout mouse embryonic fibrobasts (MEFs. Though distinct parameters of lysosomal function like processing of cathepsin D and lysosomal pH are preserved, lysosome numbers are reduced in knockout MEFs and the recovery of lysosomes during sustained starvation impaired consistent with a defect of autophagic lysosome reformation. Because lysosomes are reduced in cortical neurons and Purkinje cells in vivo, we propose that the decreased number of lysosomes available for fusion with autophagosomes impairs autolysosomal clearance, results in the accumulation of undegraded material and finally causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells in knockout mice.

  19. Andrographolide alleviates imiquimod-induced psoriasis in mice via inducing autophagic proteolysis of MyD88.

    Science.gov (United States)

    Shao, Fenli; Tan, Tao; Tan, Yang; Sun, Yang; Wu, Xingxin; Xu, Qiang

    2016-09-01

    Psoriasis is a chronic inflammatory skin disease with excessive activation of toll-like receptors (TLRs), which play important roles in developing psoriasis. Targeting TLR signaling remains a challenge for treating psoriasis. Here, we found that andrographolide (Andro), a small-molecule natural product, alleviated imiquimod- but not interleukin 23 (IL-23)-induced psoriasis in mice with reducing expressions of IL-23 and IL-1β in the skin. The improvement in imiquimod-induced psoriasis by Andro was not observed in microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) knockout mice. Furthermore, Andro inhibited mRNA expressions of IL-23, IL-6 and IL-1β but not CD80 and CD86 in bone-marrow derived dendritic cells (BMDCs) treated with lipopolysaccharide (LPS) in a MAP1LC3B-dependent manner. In addition, Andro inhibited imiquimod-induced mRNA expressions of IL-23, IL-6, IL-1β, CD80 and CD86 in BMDCs from mice. Interestingly, Andro induced a degradation of myeloid differentiation factor 88 (MyD88) and blocked the recruitment of TNF receptor-associated factor 6 (TRAF6) to MyD88 upon LPS stimulation in BMDCs from mice. Blockade of autophagic proteolysis using NH4Cl or MAP1LC3B(-/-) BMDCs abolished the Andro-induced MyD88 degradation. In conclusion, Andro controls activation of MyD88-dependent cytokines and alleviates psoriasis in mice via inducing autophagic proteolysis of MyD88, which could be a novel strategy to treat psoriasis. PMID:27265145

  20. Increased levels of reduced cytochrome b and mitophagy components are required to trigger nonspecific autophagy following induced mitochondrial dysfunction

    OpenAIRE

    Deffieu, Maika; Bhatia-Kiššová, Ingrid; Salin, Bénédicte; Daniel J Klionsky; Pinson, Benoît; Manon, Stéphen; Camougrand, Nadine

    2013-01-01

    Mitochondria are essential organelles producing most of the energy required for the cell. A selective autophagic process called mitophagy removes damaged mitochondria, which is critical for proper cellular homeostasis; dysfunctional mitochondria can generate excess reactive oxygen species that can further damage the organelle as well as other cellular components. Although proper cell physiology requires the maintenance of a healthy pool of mitochondria, little is known about the mechanism und...

  1. Novel pure component contribution, mean centering of ratio spectra and factor based algorithms for simultaneous resolution and quantification of overlapped spectral signals: An application to recently co-formulated tablets of chlorzoxazone, aceclofenac and paracetamol

    Science.gov (United States)

    Toubar, Safaa S.; Hegazy, Maha A.; Elshahed, Mona S.; Helmy, Marwa I.

    2016-06-01

    In this work, resolution and quantitation of spectral signals are achieved by several univariate and multivariate techniques. The novel pure component contribution algorithm (PCCA) along with mean centering of ratio spectra (MCR) and the factor based partial least squares (PLS) algorithms were developed for simultaneous determination of chlorzoxazone (CXZ), aceclofenac (ACF) and paracetamol (PAR) in their pure form and recently co-formulated tablets. The PCCA method allows the determination of each drug at its λmax. While, the mean centered values at 230, 302 and 253 nm, were used for quantification of CXZ, ACF and PAR, respectively, by MCR method. Partial least-squares (PLS) algorithm was applied as a multivariate calibration method. The three methods were successfully applied for determination of CXZ, ACF and PAR in pure form and tablets. Good linear relationships were obtained in the ranges of 2-50, 2-40 and 2-30 μg mL- 1 for CXZ, ACF and PAR, in order, by both PCCA and MCR, while the PLS model was built for the three compounds each in the range of 2-10 μg mL- 1. The results obtained from the proposed methods were statistically compared with a reported one. PCCA and MCR methods were validated according to ICH guidelines, while PLS method was validated by both cross validation and an independent data set. They are found suitable for the determination of the studied drugs in bulk powder and tablets.

  2. Novel pure component contribution, mean centering of ratio spectra and factor based algorithms for simultaneous resolution and quantification of overlapped spectral signals: An application to recently co-formulated tablets of chlorzoxazone, aceclofenac and paracetamol.

    Science.gov (United States)

    Toubar, Safaa S; Hegazy, Maha A; Elshahed, Mona S; Helmy, Marwa I

    2016-06-15

    In this work, resolution and quantitation of spectral signals are achieved by several univariate and multivariate techniques. The novel pure component contribution algorithm (PCCA) along with mean centering of ratio spectra (MCR) and the factor based partial least squares (PLS) algorithms were developed for simultaneous determination of chlorzoxazone (CXZ), aceclofenac (ACF) and paracetamol (PAR) in their pure form and recently co-formulated tablets. The PCCA method allows the determination of each drug at its λmax. While, the mean centered values at 230, 302 and 253nm, were used for quantification of CXZ, ACF and PAR, respectively, by MCR method. Partial least-squares (PLS) algorithm was applied as a multivariate calibration method. The three methods were successfully applied for determination of CXZ, ACF and PAR in pure form and tablets. Good linear relationships were obtained in the ranges of 2-50, 2-40 and 2-30μgmL(-1) for CXZ, ACF and PAR, in order, by both PCCA and MCR, while the PLS model was built for the three compounds each in the range of 2-10μgmL(-1). The results obtained from the proposed methods were statistically compared with a reported one. PCCA and MCR methods were validated according to ICH guidelines, while PLS method was validated by both cross validation and an independent data set. They are found suitable for the determination of the studied drugs in bulk powder and tablets. PMID:27038581

  3. ER Stress and Autophagic Perturbations Lead to Elevated Extracellular α-Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons.

    Science.gov (United States)

    Fernandes, Hugo J R; Hartfield, Elizabeth M; Christian, Helen C; Emmanoulidou, Evangelia; Zheng, Ying; Booth, Heather; Bogetofte, Helle; Lang, Charmaine; Ryan, Brent J; Sardi, S Pablo; Badger, Jennifer; Vowles, Jane; Evetts, Samuel; Tofaris, George K; Vekrellis, Kostas; Talbot, Kevin; Hu, Michele T; James, William; Cowley, Sally A; Wade-Martins, Richard

    2016-03-01

    Heterozygous mutations in the glucocerebrosidase gene (GBA) represent the strongest common genetic risk factor for Parkinson's disease (PD), the second most common neurodegenerative disorder. However, the molecular mechanisms underlying this association are still poorly understood. Here, we have analyzed ten independent induced pluripotent stem cell (iPSC) lines from three controls and three unrelated PD patients heterozygous for the GBA-N370S mutation, and identified relevant disease mechanisms. After differentiation into dopaminergic neurons, we observed misprocessing of mutant glucocerebrosidase protein in the ER, associated with activation of ER stress and abnormal cellular lipid profiles. Furthermore, we observed autophagic perturbations and an enlargement of the lysosomal compartment specifically in dopamine neurons. Finally, we found increased extracellular α-synuclein in patient-derived neuronal culture medium, which was not associated with exosomes. Overall, ER stress, autophagic/lysosomal perturbations, and elevated extracellular α-synuclein likely represent critical early cellular phenotypes of PD, which might offer multiple therapeutic targets. PMID:26905200

  4. Identification of novel autophagic Radix Polygalae fraction by cell membrane chromatography and UHPLC-(Q)TOF-MS for degradation of neurodegenerative disease proteins

    OpenAIRE

    Wu, An-Guo; Kam-Wai Wong, Vincent; Zeng, Wu; Liang LIU; Yuen-Kwan Law, Betty

    2015-01-01

    With its traditional use in relieving insomnia and anxiety, our previous study has identified onjisaponin B from Radix Polygalae (RP), as a novel autophagic enhancer with potential neuroprotective effects. In current study, we have further identified a novel active fraction from RP, contains 17 major triterpenoid saponins including the onjisaponin B, by the combinational use of cell membrane chromatography (CMC) and ultra-performance liquid chromatography coupled to (quadrupole) time-of-fligh...

  5. Effects of hypoxia-inducible factor-1α on radiation-induced autophagic cell death in breast cancer cells

    International Nuclear Information System (INIS)

    Objective: To study the effects of hypoxia-inducible factor-1α (HIF-1α) on radiation-induced autophagic cell death in breast cancer cells. Methods: MCF-7 cells were divided into four groups:control (normoxia,21% Oxygen),irradiation (8 Gy X-rays), hypoxia (Cobalt chloride, CoCl2) and irradiation with hypoxia (CoCl2). 150 μmol/L CoCl2 was utilized to induce hypoxic conditions. Western blot was applied to detect the expression of HIF-1α and MAPLC3. MDC and Hoechst staining were used to detect autophagy and apoptosis. Radiosensitivity was detected by cloning formation. The short hairpin interfering RNA (shRNA) retroviral transduction particles targeting HIF-1α was transfected into MCF-7 cells to establish HIF-1α knockdown cells, then the radiosensibility, autophagy and apoptosis were detected. Results: Compared with control group and irradiation group,the protein level of HIF-1 increased obviously in the normoxia, irradiation, hypoxia and irradiation with hypoxia groups, and the values were 0, 0, 1.00, 1.89, respectively. The expression levels of MAPLC3 were markedly up-regulated in irradiation, hypoxia and irradiation with hypoxia groups as compared with control, and the ratios of LC3Ⅱ/LC3Ⅰ were 1.15, 1.73, 2.38 and 3.60, respectively. The radiosensitivity of MCF-7 cells decreased in the following order:normoxia with 3MA > normoxia > hypoxia with 3MA > hypoxia. HIF-1α knockdown cell (pSUPER-HIF-1α Ri) and vector control were constructed. After treatment with CoCl2, survival fraction of MCF-7-pSUPER was significantly higher than that of control (t=3.080, 6.946, 6.658, 6.380, P<0.05), and radiosensitivity was down-regulated after irradiation,but there was no significant difference between normoxia and hypoxia in survival fraction of MCF-7-pSUPER-HIF-1α Ri. After treatment of irradiation or hypoxia, the autophagic fractions in MCF-7-pSUPER-HIF-1α Ri significantly decreased, reduced by 21.1%, 25.5%, 15.5%, respectively (t=4.635, 4.738, 6.354, P<0.05) as

  6. Autophagic Killing Effects against Mycobacterium tuberculosis by Alveolar Macrophages from Young and Aged Rhesus Macaques

    OpenAIRE

    Pacheco, Sophia A.; Powers, Katelyn M.; Engelmann, Flora; Messaoudi, Ilhem; Purdy, Georgiana E.

    2013-01-01

    Non-human primates, notably rhesus macaques (Macaca mulatta, RM), provide a robust experimental model to investigate the immune response to and effective control of Mycobacterium tuberculosis infections. Changes in the function of immune cells and immunosenescence may contribute to the increased susceptibility of the elderly to tuberculosis. The goal of this study was to examine the impact of age on M. tuberculosis host-pathogen interactions following infection of primary alveolar macrophages...

  7. Synergistic chemopreventive effects of curcumin and berberine on human breast cancer cells through induction of apoptosis and autophagic cell death.

    Science.gov (United States)

    Wang, Kai; Zhang, Chao; Bao, Jiaolin; Jia, Xuejing; Liang, Yeer; Wang, Xiaotong; Chen, Meiwan; Su, Huanxing; Li, Peng; Wan, Jian-Bo; He, Chengwei

    2016-01-01

    Curcumin (CUR) and berberine (BBR) are renowned natural compounds that exhibit potent anticancer activities through distinct molecular mechanisms. However, the anticancer capacity of either CUR or BBR is limited. This prompted us to investigate the chemopreventive potential of co-treatment of CUR and BBR against breast cancers. The results showed that CUR and BBR in combination synergistically inhibited the growth of both MCF-7 and MDA-MB-231 breast cancer cells than the compounds used alone. Further study confirmed that synergistic anti-breast cancer activities of co-treatment of these two compounds was through inducing more apoptosis and autophagic cell death (ACD). The co-treatment-induced apoptosis was caspase-dependent and through activating ERK pathways. Our data also demonstrated that co-treatment of CUR and BBR strongly up-regulated phosphorylation of JNK and Beclin1, and decreased phosphorylated Bcl-2. Inhibition of JNK by SP600125 markedly decreased LC3-II and Beclin1, restored phosphorylated Bcl-2, and reduced the cytotoxicity induced by the two compounds in combination. These results strongly suggested that JNK/Bcl-2/Beclin1 pathway played a key role in the induction of ACD in breast cancer cells by co-treatment of CUR and BBR. This study provides an insight into the potential application of curcumin and berberine in combination for the chemoprevention and treatment of breast cancers. PMID:27263652

  8. Betanin-Enriched Red Beetroot (Beta vulgaris L.) Extract Induces Apoptosis and Autophagic Cell Death in MCF-7 Cells.

    Science.gov (United States)

    Nowacki, Laëtitia; Vigneron, Pascale; Rotellini, Laura; Cazzola, Hélène; Merlier, Franck; Prost, Elise; Ralanairina, Robert; Gadonna, Jean-Pierre; Rossi, Claire; Vayssade, Muriel

    2015-12-01

    Recent studies have pointed out the preventive role of beetroot extracts against cancers and their cytotoxic activity on cancer cells. Among many different natural compounds, these extracts contained betanin and its stereoisomer isobetanin, which belongs to the betalain group of highly bioavailable antioxidants. However, a precise identification of the molecules responsible for this tumor-inhibitory effect was still required. We isolated a betanin/isobetanin concentrate from fresh beetroots, corresponding to the highest purified betanin extract used for studying anticancer activities of these molecules. The cytotoxicity of this betanin-enriched extract was then characterized on cancer and normal cells and we highlighted the death signalling pathways involved. Betanin/isobetanin concentrate significantly decreased cancer cell proliferation and viability. Particularly in MCF-7-treated cells, the expressions of apoptosis-related proteins (Bad, TRAILR4, FAS, p53) were strongly increased and the mitochondrial membrane potential was altered, demonstrating the involvement of both intrinsic and extrinsic apoptotic pathways. Autophagosome vesicles in MCF-7-treated cells were observed, also suggesting autophagic cell death upon betanin/isobetanin treatment. Importantly, the betanin-enriched extract had no obvious effect towards normal cell lines. Our data bring new insight to consider the betanin/isobetanin mix as therapeutic anticancer compound, alone or in combination with classical chemotherapeutic drugs, especially in functional p53 tumors. PMID:26463240

  9. Tribenuron-Methyl Induces Male Sterility through Anther-Specific Inhibition of Acetolactate Synthase Leading to Autophagic Cell Death.

    Science.gov (United States)

    Zhao, Lun; Jing, Xue; Chen, Li; Liu, Yingjun; Su, Yanan; Liu, Tingting; Gao, Changbin; Yi, Bin; Wen, Jing; Ma, Chaozhi; Tu, Jinxing; Zou, Jitao; Fu, Tingdong; Shen, Jinxiong

    2015-12-01

    Tribenuron-methyl (TM) is a powerful sulfonylurea herbicide that inhibits branched-chain amino acid (BCAA) biosynthesis by targeting the catalytic subunit (CSR1) of acetolactate synthase (ALS). Selective induction of male sterility by foliar spraying of TM at low doses has been widely used for hybrid seed production in rapeseed (Brassica napus); however, the underlying mechanism remains unknown. Here, we report greater TM accumulation and subsequent stronger ALS inhibition and BCAA starvation in anthers than in leaves and stems after TM application. Constitutive or anther-specific expression of csr1-1D (a CSR1 mutant) eliminated anther-selective ALS inhibition and reversed the TM-induced male sterile phenotype in both rapeseed and Arabidopsis. The results of TM daub-stem experiments, combined with the observations of little TM accumulation in anthers and reversion of TM-induced male sterility by targeted expression of the TM metabolism gene Bel in either the mesophyll or phloem, suggested that foliar-sprayed TM was polar-transported to anthers mainly through the mesophyll and phloem. Microscopy and immunoblotting revealed that autophagy, a bulk degradation process induced during cell death, was elevated in TM-induced male sterile anthers and by anther-specific knockdown of ALS. Moreover, TM-induced pollen abortion was significantly inhibited by the autophagy inhibitor 3-MA. These data suggested that TM was polar-transported to anthers, resulting in BCAA starvation via anther-specific ALS inhibition and, ultimately, autophagic cell death in anthers. PMID:26362932

  10. Ultracytochemical localization of H+—adenosine triphosphatase activity in autophagic vacuoles induced by vinblastine in rat liver

    Institute of Scientific and Technical Information of China (English)

    LUOSHENQIU; MASAHIROSAKAI; 等

    1990-01-01

    H-adenosine triphosphatase (H+-ATPase) activity was demonstrated cytochemically in autophagic vacuoles(AVs) of rat hepatocytes using a modification of the method for the demonstration of neutral p-nitrophenyl phosphatase(p-NPPase) activity[1].When an inhibitor of H+-ATPase,N-ethylmaleimide (NEM) or 4,4'-diisothiocyanostilbene-2,2'disulfonic acid,disodium salt (DIDS) was included in the incubation medium the enyzme activity was abolished indicating that p-NPPase demonstrated in this study represents H+-ATPase.Autophagy was induced by a single intraperitoneal injection of vinblastine sulfate(VBL).The number of AVs increased remarkably in hepatocytes from 40 min after VBL treatment.H+-ATPase activity was observed mainly on the membranes of lysosomes and AVs.However,early forms of AVs containing only incompletely digested material showed no H+-ATPase activity.Most AVs revealing a positive reaction seemed to be in advanced stages of development.Acid phosphatase acticity was demonstrable in mature but not in early forms of AVs.The present investigation showed that membranes of advanced stage AVs possess an H+-ATPase which may be derived from lysosomal membranes.

  11. LMFBR fuel component costs

    International Nuclear Information System (INIS)

    A significant portion of the cost of fabricating LMFBR fuels is in the non-fuel components such as fuel pin cladding, fuel assembly ducts and end fittings. The contribution of these to fuel fabrication costs, based on FFTF experience and extrapolated to large LMFBR fuel loadings, is discussed. The extrapolation considers the expected effects of LMFBR development programs in progress on non-fuel component costs

  12. 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

  13. Inhibition of autophagic flux by ROS promotes apoptosis during DTT-induced ER/oxidative stress in HeLa cells.

    Science.gov (United States)

    Xiang, Xi-Yan; Yang, Xiao-Chun; Su, Jin; Kang, Jing-Song; Wu, Yao; Xue, Ya-Nan; Dong, Yu-Tong; Sun, Lian-Kun

    2016-06-01

    As targets for cancer therapy, endoplasmic reticulum (ER) stress and autophagy are closely linked. However, the signaling pathways responsible for induction of autophagy in response to ER stress and its cellular consequences appear to vary with cell type and stimulus. In the present study, we showed that dithiothreitol (DTT) induced ER stress in HeLa cells in a time- and dose-dependent fashion. With increased ER stress, reactive oxygen species (ROS) production increased and autophagy flux, assessed by intracellular accumulation of LC3B-II and p62, was inhibited. N-acetyl-L-cysteine (NAC), a classic antioxidant, exacerbated cell death induced by 3.2 mM of DTT, but attenuated that induced by 6.4 mM DTT. Low cytotoxic doses of DTT transiently activated c-JNU N-terminal kinase (JNK) and p38, whereas high dose of DTT persistently activated JNK and p38 and simultaneously reduced extracellular signal-regulated kinase (ERK) activity. Combined treatment with DTT and U0126, an inhibitor of ERK upstream activators mitogen-activated protein kinase (MAPK) kinase 1 and 2 (MEK1/2), blocked autophagy flux in HeLa cells. This effect was similar to that caused by a combination of DTT and chloroquine (CQ). These data suggested that insufficient autophagy was accompanied by increased ROS production during DTT-induced ER stress. ROS appeared to regulate MAPK signaling, switching from a pro-survival to a pro-apoptotic signal as ER stress increased. ERK inhibition by ROS during severe ER stress blocked autophagic flux. Impaired autophagic flux, in turn, aggravated ER stress, ultimately leading to cell death. Taken together, our data provide the first reported evidence that ROS may control cell fate through regulating the MAPK pathways and autophagic flux during DTT-induced ER/oxidative stress. PMID:27035858

  14. Nuclear components

    International Nuclear Information System (INIS)

    The main features of the EPR concerning the fabrication of the reactor are: -) the size of the components, -) the modification of the design compared with classical PWR, and -) an intensive use of forging (in particular the cold and hot legs of the primary circuit are forged). This series of slides overviews the fabrication of the components for the EPR by highlighting the differences with the previous generation of reactors. 4 types of components are reviewed: the reactor vessel and internals, steam generators, primary circuit pipes, and primary coolant pumps. (A.C.)

  15. Multilevel Contracts for Trusted Components

    Directory of Open Access Journals (Sweden)

    Mohamed Messabihi

    2010-10-01

    Full Text Available This article contributes to the design and the verification of trusted components and services. The contracts are declined at several levels to cover then different facets, such as component consistency, compatibility or correctness. The article introduces multilevel contracts and a design+verification process for handling and analysing these contracts in component models. The approach is implemented with the COSTO platform that supports the Kmelia component model. A case study illustrates the overall approach.

  16. Cilostazol Modulates Autophagic Degradation of β-Amyloid Peptide via SIRT1-Coupled LKB1/AMPKα Signaling in Neuronal Cells

    Science.gov (United States)

    Lee, Won Suk; Shin, Hwa Kyoung; Kim, Hye Young; Hong, Ki Whan; Kim, Chi Dae

    2016-01-01

    A neuroprotective role of autophagy mediates the degradation of β-amyloid peptide (Aβ) in Alzheimer’s disease (AD). The previous study showed cilostazol modulates autophagy by increasing beclin1, Atg5 and LC3-II expressions, and depletes intracellular Aβ accumulation. This study elucidated the mechanisms through which cilostazol modulates the autophagic degradation of Aβ in neurons. In N2a cells, cilostazol (10–30 μM), significantly increased the expression of P-AMPKα (Thr 172) and downstream P-ACC (acetyl-CoA carboxylase) (Ser 79) as did resveratrol (SIRT1 activator), or AICAR (AMPK activator), which were blocked by KT5720, compound C (AMPK inhibitor), or sirtinol. Furthermore, phosphorylated-mTOR (Ser 2448) and phosphorylated-P70S6K (Thr 389) expressions were suppressed, and LC3-II levels were elevated in association with decreased P62/Sqstm1 by cilostazol. Cilostazol increased cathepsin B activity and decreased p62/SQSTM 1, consequently decreased accumulation of Aβ1–42 in the activated N2aSwe cells, and these results were blocked by sirtinol, compound C and bafilomycin A1 (autophagosome blocker), suggesting enhanced autophagosome formation by cilostazol. In SIRT1 gene-silenced N2a cells, cilostazol failed to increase the expressions of P-LKB1 (Ser 428) and P-AMPKα, which contrasted with its effect in negative control cells transfected with scrambled siRNA duplex. Further, N2a cells transfected with expression vectors encoding pcDNA SIRT1 showed increased P-AMPKα expression, which mimicked the effect of cilostazol in N2a cells; suggesting cilostazol-stimulated expressions of P-LKB1 and P-AMPKα were SIRT1-dependent. Unlike their effects in N2a cells, in HeLa cells, which lack LKB1, cilostazol and resveratrol did not elevate SIRT1 or P-AMPKα expression, indicating cilostazol and resveratrol-stimulated expressions of SIRT1 and P-AMPKα are LKB1-dependent. In conclusion, cilostazol upregulates autophagy by activating SIRT1-coupled P-LKB1/P-AMPKα and

  17. Studying p53 family proteins in yeast: Induction of autophagic cell death and modulation by interactors and small molecules

    International Nuclear Information System (INIS)

    In this work, the yeast Saccharomyces cerevisiae was used to individually study human p53, p63 (full length and truncated forms) and p73. Using this cell system, the effect of these proteins on cell proliferation and death, and the influence of MDM2 and MDMX on their activities were analyzed. When expressed in yeast, wild-type p53, TAp63, ΔNp63 and TAp73 induced growth inhibition associated with S-phase cell cycle arrest. This growth inhibition was accompanied by reactive oxygen species production and autophagic cell death. Furthermore, they stimulated rapamycin-induced autophagy. On the contrary, none of the tested p53 family members induced apoptosis either per se or after apoptotic stimuli. As previously reported for p53, also TAp63, ΔNp63 and TAp73 increased actin expression levels and its depolarization, suggesting that ACT1 is also a p63 and p73 putative yeast target gene. Additionally, MDM2 and MDMX inhibited the activity of all tested p53 family members in yeast, although the effect was weaker on TAp63. Moreover, Nutlin-3a and SJ-172550 were identified as potential inhibitors of the p73 interaction with MDM2 and MDMX, respectively. Altogether, the yeast-based assays herein developed can be envisaged as a simplified cell system to study the involvement of p53 family members in autophagy, the modulation of their activities by specific interactors (MDM2 and MDMX), and the potential of new small molecules to modulate these interactions. - Highlights: • p53, p63 and p73 are individually studied in the yeast S. cerevisiae. • p53 family members induce ROS production, cell cycle arrest and autophagy in yeast. • p53 family members increase actin depolarization and expression levels in yeast. • MDM2 and MDMX inhibit the activity of p53 family members in yeast. • Yeast can be a useful tool to study the biology and drugability of p53, p63 and p73

  18. Studying p53 family proteins in yeast: Induction of autophagic cell death and modulation by interactors and small molecules

    Energy Technology Data Exchange (ETDEWEB)

    Leão, Mariana; Gomes, Sara; Bessa, Cláudia; Soares, Joana; Raimundo, Liliana [REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n. 164, 4050-313 Porto (Portugal); Monti, Paola; Fronza, Gilberto [Mutagenesis Unit, Istituto di Ricerca e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro, 16132 Genoa (Italy); Pereira, Clara [REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n. 164, 4050-313 Porto (Portugal); Saraiva, Lucília, E-mail: lucilia.saraiva@ff.up.pt [REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n. 164, 4050-313 Porto (Portugal)

    2015-01-01

    In this work, the yeast Saccharomyces cerevisiae was used to individually study human p53, p63 (full length and truncated forms) and p73. Using this cell system, the effect of these proteins on cell proliferation and death, and the influence of MDM2 and MDMX on their activities were analyzed. When expressed in yeast, wild-type p53, TAp63, ΔNp63 and TAp73 induced growth inhibition associated with S-phase cell cycle arrest. This growth inhibition was accompanied by reactive oxygen species production and autophagic cell death. Furthermore, they stimulated rapamycin-induced autophagy. On the contrary, none of the tested p53 family members induced apoptosis either per se or after apoptotic stimuli. As previously reported for p53, also TAp63, ΔNp63 and TAp73 increased actin expression levels and its depolarization, suggesting that ACT1 is also a p63 and p73 putative yeast target gene. Additionally, MDM2 and MDMX inhibited the activity of all tested p53 family members in yeast, although the effect was weaker on TAp63. Moreover, Nutlin-3a and SJ-172550 were identified as potential inhibitors of the p73 interaction with MDM2 and MDMX, respectively. Altogether, the yeast-based assays herein developed can be envisaged as a simplified cell system to study the involvement of p53 family members in autophagy, the modulation of their activities by specific interactors (MDM2 and MDMX), and the potential of new small molecules to modulate these interactions. - Highlights: • p53, p63 and p73 are individually studied in the yeast S. cerevisiae. • p53 family members induce ROS production, cell cycle arrest and autophagy in yeast. • p53 family members increase actin depolarization and expression levels in yeast. • MDM2 and MDMX inhibit the activity of p53 family members in yeast. • Yeast can be a useful tool to study the biology and drugability of p53, p63 and p73.

  19. ER Stress and Autophagic Perturbations Lead to Elevated Extracellular α-Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons

    Directory of Open Access Journals (Sweden)

    Hugo J.R. Fernandes

    2016-03-01

    Full Text Available Heterozygous mutations in the glucocerebrosidase gene (GBA represent the strongest common genetic risk factor for Parkinson's disease (PD, the second most common neurodegenerative disorder. However, the molecular mechanisms underlying this association are still poorly understood. Here, we have analyzed ten independent induced pluripotent stem cell (iPSC lines from three controls and three unrelated PD patients heterozygous for the GBA-N370S mutation, and identified relevant disease mechanisms. After differentiation into dopaminergic neurons, we observed misprocessing of mutant glucocerebrosidase protein in the ER, associated with activation of ER stress and abnormal cellular lipid profiles. Furthermore, we observed autophagic perturbations and an enlargement of the lysosomal compartment specifically in dopamine neurons. Finally, we found increased extracellular α-synuclein in patient-derived neuronal culture medium, which was not associated with exosomes. Overall, ER stress, autophagic/lysosomal perturbations, and elevated extracellular α-synuclein likely represent critical early cellular phenotypes of PD, which might offer multiple therapeutic targets.

  20. cAMP and EPAC are key players in the regulation of the signal transduction pathway involved in the α-hemolysin autophagic response.

    Directory of Open Access Journals (Sweden)

    María Belén Mestre

    Full Text Available Staphylococcus aureus is a microorganism that causes serious diseases in the human being. This microorganism is able to escape the phagolysosomal pathway, increasing intracellular bacterial survival and killing the eukaryotic host cell to spread the infection. One of the key features of S. aureus infection is the production of a series of virulence factors, including secreted enzymes and toxins. We have shown that the pore-forming toxin α-hemolysin (Hla is the S. aureus-secreted factor responsible for the activation of the autophagic pathway and that this response occurs through a PI3K/Beclin1-independent form. In the present report we demonstrate that cAMP has a key role in the regulation of this autophagic response. Our results indicate that cAMP is able to inhibit the autophagy induced by Hla and that PKA, the classical cAMP effector, does not participate in this regulation. We present evidence that EPAC and Rap2b, through calpain activation, are the proteins involved in the regulation of Hla-induced autophagy. Similar results were obtained in cells infected with different S. aureus strains. Interestingly, in this report we show, for the first time to our knowledge, that both EPAC and Rap2b are recruited to the S. aureus-containing phagosome. We believe that our findings have important implications in understanding innate immune processes involved in intracellular pathogen invasion of the host cell.

  1. Component Rhinoplasty

    OpenAIRE

    Mohmand, Muhammad Humayun; Ahmad, Muhammad

    2014-01-01

    BACKGROUND According to statistics of American Society of Plastic Surgeons, cosmetic rhinoplasty was the second most frequently performed cosmetic surgery. This study shares the experiences with component rhinoplasty. METHODS From 2004 to 2010, all patients underwent aesthetic nasal surgery were enrolled. The patients requiring only correction of septal deviation and those presenting with cleft lip nasal deformity were excluded. All procedures were performed under general anaesthesia with ope...

  2. Component Separations

    OpenAIRE

    Heller, Lior; McNichols, Colton H.; Ramirez, Oscar M.

    2012-01-01

    Component separation is a technique used to provide adequate coverage for midline abdominal wall defects such as a large ventral hernia. This surgical technique is based on subcutaneous lateral dissection, fasciotomy lateral to the rectus abdominis muscle, and dissection on the plane between external and internal oblique muscles with medial advancement of the block that includes the rectus muscle and its fascia. This release allows for medial advancement of the fascia and closure of up to 20-...

  3. Component separations.

    Science.gov (United States)

    Heller, Lior; McNichols, Colton H; Ramirez, Oscar M

    2012-02-01

    Component separation is a technique used to provide adequate coverage for midline abdominal wall defects such as a large ventral hernia. This surgical technique is based on subcutaneous lateral dissection, fasciotomy lateral to the rectus abdominis muscle, and dissection on the plane between external and internal oblique muscles with medial advancement of the block that includes the rectus muscle and its fascia. This release allows for medial advancement of the fascia and closure of up to 20-cm wide defects in the midline area. Since its original description, components separation technique underwent multiple modifications with the ultimate goal to decrease the morbidity associated with the traditional procedure. The extensive subcutaneous lateral dissection had been associated with ischemia of the midline skin edges, wound dehiscence, infection, and seroma. Although the current trend is to proceed with minimally invasive component separation and to reinforce the fascia with mesh, the basic principles of the techniques as described by Ramirez et al in 1990 have not changed over the years. Surgeons who deal with the management of abdominal wall defects are highly encouraged to include this technique in their collection of treatment options. PMID:23372455

  4. Micromechanical modelling of heterogeneous materials in transient conditions: contributions for the study of the ageing of structural components under service; Modelisation micromecanique des materiaux heterogenes en regimes transitoires: contributions en vue de l'etude du vieillissement des structures en service

    Energy Technology Data Exchange (ETDEWEB)

    Masson, R.

    2010-12-20

    considering the particular situation where regions of the representative volume element have ill-defined mechanical properties. In the linear elastic case, new bounds for the effective behaviour are derived by marrying the structural analysis and a variational approach. This last work opens on important prospects for further works: more tightened bounds, nonlinear behaviours,... Considering homogenisation methods, further works are precisely defined, in particular for polycrystalline materials. In that situation, the field of investigation widens clearly (Fatigue, Large strains,...) thanks to the internal variables formulation proposed. Lastly, the simulation of irradiation effects constitutes the third topic of interest for the years to come, the general objective being to better predict the effects of the swelling strains induced by irradiation on the behaviour of structural components under service. (author) [French] La modelisation du comportement mecanique des materiaux de structure se nourrit de plus en plus de parametres microstructuraux. Dans ce cadre, les methodes d'homogeneisation presentent l'avantage de fournir des methodes deductives qui, a partir des proprietes et de la repartition spatiale des heterogeneites, deduisent les proprietes effectives du materiau considere. Neanmoins de nombreuses applications soulevent encore des difficultes. C'est en particulier le cas des materiaux de structure presentant un comportement elasto-viscoplastique et soumis a un trajet de chargement non monotone et non isotherme. Progresser sur le traitement par homogeneisation de ces situations concretes constitue precisement le fil conducteur des differentes contributions presentees dans ce memoire d'HDR. Dans le cas elastique lineaire, de nouvelles expressions pour le calcul du tenseur d'Eshelby sont tout d'abord etablies afin d'ameliorer l'efficacite des methodes d'homogeneisation habituellement proposees. Toujours pour des comportements

  5. Components of QCD

    International Nuclear Information System (INIS)

    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 Z0 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

  6. PAMAM Nanoparticles Promote Acute Lung Injury by Inducing Autophagic Cell Death through the Akt-TSC2-mTOR Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    Chenggang Li; Haolin Liu; Yang Sun; Hongliang Wang; Feng Guo; Shuan Rao; Jiejie Deng; Yanli Zhang; Yufa Miao; Chenying Guo; Jie Meng; Xiping Chen; Limin Li; Dangsheng Li; Haiyan Xu; Heng Wang; Bo Li; Chengyu Jiang

    2009-01-01

    Nanotechnology is an important and emerging industry with a projected annual market of around one trillion US dollars by 2011–2015. Concerns about the toxicity of nanomaterials in humans, however, have recently been raised. Although studies of nanoparticle toxicity have focused on lung disease the molecular link between nanoparticle exposure and lung injury remained unclear. In this report, we show that cationic Starburst polyamidoamine dendrimer (PAMAM), a class of nanomaterials that are being widely developed for clinical applications can induce acute lung injury in vivo. PAMAM triggers autophagic cell death by deregulating the Akt-TSC2-mTOR signaling pathway. The autophagy inhibitor 3-methyladenine rescued PAMAM dendrimer-induced cell death and ameliorated acute lung injury caused by PAMAM in mice. Our data provide a molecular explanation for nanoparticle-induced lung injury, and suggest potential remedies to address the growing concerns of nanotechnology safety.

  7. Poster contributions

    International Nuclear Information System (INIS)

    This document gathers the poster contributions among which 11 are relevant for fusion plasmas or particle acceleration: 1) the spectral study of a micro plasma from an X-pinch explosion; 2) experiments with a plasma density greater than the Greenwald value via the injection of icicles in Tore-Supra; 3) Bezier's surfaces and finite elements method for non-linear MHD; 4) 2-dimensional simulation of the RF casings before the ICRF antennas in tokamaks; 5) negative ion sources for ITER; 6) experimental characterization of electron heat transport on the laser integration line; 7) comparison of fluctuation measurement methods of plasma density via reflectometry in mode-o and mode-x in Tore-Supra; 8) water-bag model applied to kinetics equations of magnetic fusion plasmas; 9) computerized simulation of electron acceleration in plasma waves generated in a capillary pipe through laser wakefield; 10) the slowing-down of an alpha particle in a strongly magnetized dense plasma; and 11) stochastic processes of particle trapping by a wave in a magnetized plasma. (A.C.)

  8. The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages

    Directory of Open Access Journals (Sweden)

    Paola Maroni

    2016-03-01

    Full Text Available Autophagy favours metastatic growth through fuelling energy and nutrients and resistance to anoikis, typical of disseminated-tumour cells. The autophagic process, mediated by a unique organelle, the autophagosome, which fuses with lysosomes, is divided into three steps. Several stages, especially early omegasome formation and isolation-membrane initiation, remain controversial; molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle traffic for autophagosome formation. We examined Rab5a involvement in the function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated, interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was performed in human specimens of bone metastasis and pair-matched breast carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231 cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were exposed to two inhibitors of autolysosome function, and LC3II and p62 expression was measured. We showed basal autophagy in bone-metastatic cells and the pivotal role of Rab5a together with Beclin 1 between the early stages, elongation of isolation membrane/closed autophagosome mediated by Atg7, and the late-degradative stages. This regulatory network might occur in bone-metastasis and in high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring phenotypic characteristics for dissemination.

  9. The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages.

    Science.gov (United States)

    Maroni, Paola; Bendinelli, Paola; Resnati, Massimo; Matteucci, Emanuela; Milan, Enrico; Desiderio, Maria Alfonsina

    2016-01-01

    Autophagy favours metastatic growth through fuelling energy and nutrients and resistance to anoikis, typical of disseminated-tumour cells. The autophagic process, mediated by a unique organelle, the autophagosome, which fuses with lysosomes, is divided into three steps. Several stages, especially early omegasome formation and isolation-membrane initiation, remain controversial; molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle traffic for autophagosome formation. We examined Rab5a involvement in the function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated, interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was performed in human specimens of bone metastasis and pair-matched breast carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231 cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were exposed to two inhibitors of autolysosome function, and LC3II and p62 expression was measured. We showed basal autophagy in bone-metastatic cells and the pivotal role of Rab5a together with Beclin 1 between the early stages, elongation of isolation membrane/closed autophagosome mediated by Atg7, and the late-degradative stages. This regulatory network might occur in bone-metastasis and in high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring phenotypic characteristics for dissemination. PMID:27023526

  10. Graphite components

    International Nuclear Information System (INIS)

    The reflector of the AVR reactor consists of needle coke graphite ARS/AMT made by the firm of Sigri GmbH. Although its orientation anisotropy is greater than those of materials developed in the last few years, the reflector graphite shows comparatively good dimensional stability in the conditions prevailing in the AVR reactor, as shown by tests on irradiation samples. It was also found that the strength increased. No damage was found during inspections in 1984 of the upper side and ceiling reflector. After a 20 year operating period, the graphite components of the AVR reactor should be in an excellent state. This will be possible to prove when samples are taken from the graphite reflector and examined in the context of a dismantling program. (orig.)

  11. Component Compatibility in Component Based Development

    OpenAIRE

    Dr. Hardeep Singh; Anitpal Kaur

    2014-01-01

    This paper presents a research on component compatibility in component based development. Component-based software engineering is a process that emphasizes the design and construction of computer-based systems using reusable software components. Commercial components repositories contain hundred thousand components that make component selection an extremely difficult and time expensive task. Often component selected by functional features are incompatible or the integration effort...

  12. Contribution of Water-soluble Components in Lipids to Flavor of Cooked Rongchang Pork%荣昌猪脂质中水溶性成分对肉品风味的作用

    Institute of Scientific and Technical Information of China (English)

    王庭; 李洪军; 贺稚非; 黄业传; 秦刚

    2011-01-01

    Chloroform-methanol(2:1,V/V) extracts from longissimus dorsi muscle and subcutaneous fat of Rongchang pig with and without water-soluble fraction were compared for their differences in odor and volatile composition,measured by electronic nose,sensory evaluation and headspace solid-phase microextraction(HS-SPME) coupled with GC-MS.Lipid differences before and after secondary aqueous extraction of chloroform-methanol extract from the lean meat of Rongchang pig were effectively detected by electronic nose and sensory evaluation.Thus,water-soluble lipids greatly contribute the flavor of lean pork.In addition,various volatile compounds including furans,alcohols,esters,sulphur-containing compounds and aldehydes derived from Maillard reaction revealed an obviously higher level before econdary aqueous extraction.However,electronic nose and sensory evaluation could not clearly differentiate lipid differences between chloroform-methanol extracts from the fat meat of Rongchang pig with and without secondary aqueous extraction.As a result,there was no significant difference in volatile compounds,which is due to a smaller amount of water-soluble lipids in the fat meat of Rongchang pig.%以荣昌猪瘦肉和肥肉为原料,采用电子鼻、感官实验、气相-质谱联用仪(GC-MS)分别对比经氯仿甲醇萃取的脂质以及其水洗后的脂质。感官实验和电子鼻可以将氯仿甲醇萃取瘦肉中的脂质(对照瘦肉中脂质)以及其水洗后的瘦肉中脂质很好的区分,表明瘦肉脂质中的水溶性成分对肉香有显著贡献,且各类挥发性成分含量前者都显著大于后者,呋喃类、醇类、酯类、含硫化合物以及美拉德反应衍生的醛类比例也大于后者;感官实验和电子鼻不能将氯仿甲醇萃取肥肉中的脂质(对照肥肉中脂质)以及其水洗后的肥肉中的脂质很好的区分,各类挥发性成分含量差异也不显著,原因是肥肉脂质中本身水溶性成分含量就比较少。

  13. Attenuation of Aβ25–35-induced parallel autophagic and apoptotic cell death by gypenoside XVII through the estrogen receptor-dependent activation of Nrf2/ARE pathways

    International Nuclear Information System (INIS)

    Amyloid-beta (Aβ) has a pivotal function in the pathogenesis of Alzheimer's disease. To investigate Aβ neurotoxicity, we used an in vitro model that involves Aβ25–35-induced cell death in the nerve growth factor-induced differentiation of PC12 cells. Aβ25–35 (20 μM) treatment for 24 h caused apoptotic cell death, as evidenced by significant cell viability reduction, LDH release, phosphatidylserine externalization, mitochondrial membrane potential disruption, cytochrome c release, caspase-3 activation, PARP cleavage, and DNA fragmentation in PC12 cells. Aβ25–35 treatment led to autophagic cell death, as evidenced by augmented GFP-LC3 puncta, conversion of LC3-I to LC3-II, and increased LC3-II/LC3-I ratio. Aβ25–35 treatment induced oxidative stress, as evidenced by intracellular ROS accumulation and increased production of mitochondrial superoxide, malondialdehyde, protein carbonyl, and 8-OHdG. Phytoestrogens have been proved to be protective against Aβ-induced neurotoxicity and regarded as relatively safe targets for AD drug development. Gypenoside XVII (GP-17) is a novel phytoestrogen isolated from Gynostemma pentaphyllum or Panax notoginseng. Pretreatment with GP-17 (10 μM) for 12 h increased estrogen response element reporter activity, activated PI3K/Akt pathways, inhibited GSK-3β, induced Nrf2 nuclear translocation, augmented antioxidant responsive element enhancer activity, upregulated heme oxygenase 1 (HO-1) expression and activity, and provided protective effects against Aβ25–35-induced neurotoxicity, including oxidative stress, apoptosis, and autophagic cell death. In conclusion, GP-17 conferred protection against Aβ25–35-induced neurotoxicity through estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3β and activation of Nrf2/ARE/HO-1 pathways. This finding might provide novel insights into understanding the mechanism for neuroprotective effects of phytoestrogens or gypenosides. - Highlights:

  14. Fucosylation of LAMP-1 and LAMP-2 by FUT1 correlates with lysosomal positioning and autophagic flux of breast cancer cells.

    Science.gov (United States)

    Tan, Keng-Poo; Ho, Ming-Yi; Cho, Huan-Chieh; Yu, John; Hung, Jung-Tung; Yu, Alice Lin-Tsing

    2016-01-01

    Alpha1,2-fucosyltransferases, FUT1 and FUT2, which transfer fucoses onto the terminal galactose of N-acetyl-lactosamine via α1,2-linkage have been shown to be highly expressed in various types of cancers. A few studies have shown the involvement of FUT1 substrates in tumor cell proliferation and migration. Lysosome-associated membrane protein 1, LAMP-1, has been reported to carry alpha1,2-fucosylated Lewis Y (LeY) antigens in breast cancer cells, however, the biological functions of LeY on LAMP-1 remain largely unknown. Whether or not its family member, LAMP-2, displays similar modifications and functions as LAMP-1 has not yet been addressed. In this study, we have presented evidence supporting that both LAMP-1 and 2 are substrates for FUT1, but not FUT2. We have also demonstrated the presence of H2 and LeY antigens on LAMP-1 by a targeted nanoLC-MS(3) and the decreased levels of fucosylation on LAMP-2 by MALDI-TOF analysis upon FUT1 knockdown. In addition, we found that the expression of LeY was substantial in less invasive ER+/PR+/HER- breast cancer cells (MCF-7 and T47D) but negligible in highly invasive triple-negative MDA-MB-231 cells, of which LeY levels were correlated with the levels of LeY carried by LAMP-1 and 2. Intriguingly, we also observed a striking change in the subcellular localization of lysosomes upon FUT1 knockdown from peripheral distribution of LAMP-1 and 2 to a preferential perinuclear accumulation. Besides that, knockdown of FUT1 led to an increased rate of autophagic flux along with diminished activity of mammalian target of rapamycin complex 1 (mTORC1) and enhanced autophagosome-lysosome fusion. This may be associated with the predominantly perinuclear distribution of lysosomes mediated by FUT1 knockdown as lysosomal positioning has been reported to regulate mTOR activity and autophagy. Taken together, our results suggest that downregulation of FUT1, which leads to the perinuclear localization of LAMP-1 and 2, is correlated with increased

  15. A contribution to NPP component strength and lifetime assessment

    International Nuclear Information System (INIS)

    Standards for NPPs contain both a proposal for the basic dimensions using simple relationships and a control calculation demonstrating resistance of the material against damage by operation loads. Use of the finite element method (FEM) when setting up the proposal for the basic dimensions is inappropriate. Attention must be focused on the influence of the environment, to multiaxial stress and to thermal fatigue, although the fact must also be borne in mind the real NPP facilities are, in addition, subject to overpressure. It is necessary to experimentally determine the fatigue strength reduction factor under the combined effect of various influences on the degradation of the material properties. (orig.)

  16. The contribution of fat component to gestational weight gain

    Directory of Open Access Journals (Sweden)

    V N Pokusaeva

    2013-12-01

    Full Text Available Objective: to estimate the role of adipose tissue in gestational weight gain (GWG and preferential fat deposition among normal-weight women. Subjects and methods: prospective cohort study of 84 pregnancies: maternal body mass index 18,5–24,9 kg/m2, singleton term pregnancy, nondiabetic women, somatically well. GWG and skinfold thickness were evaluated in the 1st, 2nd, 3d trimesters, on the 3d day after delivery. Results: fat mass gain in low GWG was similar to recommended GWG and in the high-GWG group was greater one. Women with recommended and low GWG returned to their initial fat level on the 3d day after delivery, in excessive weight gain fat significantly increased (р=0,025. Compared to initial recommended GWG resulted in triceps skinfold thicknesses loss (р=0,001, in abdominal skinfold gained nothing and in thighs skinfold thicknesses increasing (р=0,021. Inadequate GWG leads to fat loss in arms (р=0,017, fat of abdominal area and thighs return to initial level. In excessive GWG fat in the upper trunk and arms not changed, in the lower area (thighs significantly increased compared to initial level (р=0,001 or other groups (р=0,001. Conclusion: excessive GWG was associated with greater adipose tissue cumulation and its deposition preferentially over the thighs. Inadequate GWG was clearly linked to low fat-free mass gain.

  17. Inhibition of G9a induces DUSP4-dependent autophagic cell death in head and neck squamous cell carcinoma

    OpenAIRE

    Li, Kai-Chun; Hua, Kuo-Tai; Lin, Yi-Shen; Su, Chia-Yi; Ko, Jenq-Yuh; Hsiao, Michael; Kuo, Min-Liang; Tan, Ching-Ting

    2014-01-01

    Background Head and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide. Emerging evidence indicates that alteration of epigenetics might be a key event in HNSCC progression. Abnormal expression of histone methyltransferase G9a, which contributes to transcriptional repression of tumor suppressors, has been implicated in promoting cancerous malignancies. However, its role in HNSCC has not been previously characterized. In this study, we elucidate the function of G9a and its downs...

  18. Fumonisin B1 induces autophagic cell death via activation of ERN1-MAPK8/9/10 pathway in monkey kidney MARC-145 cells.

    Science.gov (United States)

    Yin, Shutao; Guo, Xiao; Li, Jinghua; Fan, Linghong; Hu, Hongbo

    2016-04-01

    Mycotoxins are secondary fungal metabolites that are capable of inducing a variety of toxic effects in animals and humans resulting from the consumption of the contaminated food. Understanding the mechanisms of the toxicities behind these mycotoxins is required to develop mechanism-based approach to counteract their toxic potential. Fumonisin B1 (FB1) is the most prevalent member of fumonisins that are a group of mycotoxins produced primarily by Fusarium verticillioides and Fusarium proliferatum. Kidney is one of the primary target organs for FB1 action. Using monkey kidney MARC-145 cells as an intro model, we found that FB1 induced caspase-independent programmed cell death accompanied with autophagy induction. Inhibition of autophagy by either chemical inhibitors or RNAi approach led to a significant reduction in cell death by FB1 exposure, indicating possible involvement of autophagy-mediated cell death in nephrotoxicity of FB1. Further mechanistic investigation revealed that activation of ERN1-MAPK8/9/10 axis played a critical role in autophagy induction and autophagy-mediated cell death by FB1 exposure. In addition, we demonstrated that disruption of sphingolipid metabolism was an apical event in FB1-induced ERN1-MAPK8/9/10-mediated autophagic cell death in MARC-145 cells. Lastly, we identified curcumin, a naturally occurring plant phenolic compound, as a possible anti-FB1 agent that can be used to protect kidney cells from FB1-induced cell death through inhibition of MAPK8/9/10 activation. PMID:25925693

  19. Nucleolin antagonist triggers autophagic cell death in human glioblastoma primary cells and decreased in vivo tumor growth in orthotopic brain tumor model.

    Science.gov (United States)

    Benedetti, Elisabetta; Antonosante, Andrea; d'Angelo, Michele; Cristiano, Loredana; Galzio, Renato; Destouches, Damien; Florio, Tiziana Marilena; Dhez, Anne Chloé; Astarita, Carlo; Cinque, Benedetta; Fidoamore, Alessia; Rosati, Floriana; Cifone, Maria Grazia; Ippoliti, Rodolfo; Giordano, Antonio; Courty, José; Cimini, Annamaria

    2015-12-01

    Nucleolin (NCL) is highly expressed in several types of cancer and represents an interesting therapeutic target. It is expressed at the plasma membrane of tumor cells, a property which is being used as a marker for several human cancer including glioblastoma. In this study we investigated targeting NCL as a new therapeutic strategy for the treatment of this pathology. To explore this possibility, we studied the effect of an antagonist of NCL, the multivalent pseudopeptide N6L using primary culture of human glioblastoma cells. In this system, N6L inhibits cell growth with different sensitivity depending to NCL localization. Cell cycle analysis indicated that N6L-induced growth reduction was due to a block of the G1/S transition with down-regulation of the expression of cyclin D1 and B2. By monitoring autophagy markers such as p62 and LC3II, we demonstrate that autophagy is enhanced after N6L treatment. In addition, N6L-treatment of mice bearing tumor decreased in vivo tumor growth in orthotopic brain tumor model and increase mice survival. The results obtained indicated an anti-proliferative and pro-autophagic effect of N6L and point towards its possible use as adjuvant agent to the standard therapeutic protocols presently utilized for glioblastoma. PMID:26540346

  20. Repairing DNA damage by XRCC6/KU70 reverses TLR4-deficiency-worsened HCC development via restoring senescence and autophagic flux.

    Science.gov (United States)

    Wang, Ziyan; Lin, Heng; Hua, Fang; Hu, Zhuo-wei

    2013-06-01

    Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers in the human population. The initiation and progression of HCC is closely associated with chronic liver inflammation. Recent research indicates that nonhomologous end joining (NHEJ), one of the DNA repair mechanisms, autophagy and senescence are all involved in the pathogenesis of HCC induced by carcinogens or oxidative stress. DNA repair proteins including XRCC6/KU70 and XRCC5/KU80 are the critical NHEJ factors that play pivotal roles in genome-maintenance issues such as DNA replication and repair, telomere maintenance and chromosomal instability. Our studies indicate that a deficiency of toll-like receptor 4 (TLR4)-mediated immune activities results in a decreased expression of XRCC5 and XRCC6 in response to insult by the carcinogen diethylnitrosamine (DEN). This effect causes a failure in DNA repair, and promotes the transformation of precancerous hepatocytes and HCC development. Ectopic expression of XRCC6 protects against HCC initiation and progression by restoring the cellular senescent response and activation of immune networks, which induces an effective autophagic degradation, removes the accumulated reactive oxygen species (ROS), decreases DNA damage, attenuates proliferation, and promotes programmed cell death in TLR4-deficient livers. Our work indicates that repairing DNA damage by XRCC6 reverses TLR4-deficiency-worsened HCC development via restoring immunity to support senescence and autophagy in liver cells. PMID:23518600

  1. The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function

    Science.gov (United States)

    Cai, Weili; Wei, Youheng; Jarnik, Michal; Reich, John; Lilly, Mary A.

    2016-01-01

    TORC1 is a master regulator of metabolism in eukaryotes that responds to multiple upstream signaling pathways. The GATOR complex is a newly defined upstream regulator of TORC1 that contains two sub-complexes, GATOR1, which inhibits TORC1 activity in response to amino acid starvation and GATOR2, which opposes the activity of GATOR1. While the GATOR1 complex has been implicated in a wide array of human pathologies including cancer and hereditary forms of epilepsy, the in vivo relevance of the GATOR2 complex remains poorly understood in metazoans. Here we define the in vivo role of the GATOR2 component Wdr24 in Drosophila. Using a combination of genetic, biochemical, and cell biological techniques we demonstrate that Wdr24 has both TORC1 dependent and independent functions in the regulation of cellular metabolism. Through the characterization of a null allele, we show that Wdr24 is a critical effector of the GATOR2 complex that promotes the robust activation of TORC1 and cellular growth in a broad array of Drosophila tissues. Additionally, epistasis analysis between wdr24 and genes that encode components of the GATOR1 complex revealed that Wdr24 has a second critical function, the TORC1 independent regulation of lysosome dynamics and autophagic flux. Notably, we find that two additional members of the GATOR2 complex, Mio and Seh1, also have a TORC1 independent role in the regulation of lysosome function. These findings represent a surprising and previously unrecognized function of GATOR2 complex components in the regulation of lysosomes. Consistent with our findings in Drosophila, through the characterization of a wdr24-/- knockout HeLa cell line we determined that Wdr24 promotes lysosome acidification and autophagic flux in mammalian cells. Taken together our data support the model that Wdr24 is a key effector of the GATOR2 complex, required for both TORC1 activation and the TORC1 independent regulation of lysosomes. PMID:27166823

  2. Effects of interval and continuous exercise training on CD4 lymphocyte apoptotic and autophagic responses to hypoxic stress in sedentary men.

    Directory of Open Access Journals (Sweden)

    Tzu-Pin Weng

    Full Text Available Exercise is linked with the type/intensity-dependent adaptive immune responses, whereas hypoxic stress facilitates the programmed death of CD4 lymphocytes. This study investigated how high intensity-interval (HIT and moderate intensity-continuous (MCT exercise training influence hypoxia-induced apoptosis and autophagy of CD4 lymphocytes in sedentary men. Thirty healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO2max, n=10 or MCT (sustained 60%VO2max, n=10 for 30 minutes/day, 5 days/week for 5 weeks, or to a control group that did not received exercise intervention (CTL, n=10. CD4 lymphocyte apoptotic and autophagic responses to hypoxic exercise (HE, 100 W under 12%O2 for 30 minutes were determined before and after various regimens. The results demonstrated that HIT exhibited higher enhancements of pulmonary ventilation, cardiac output, and VO2 at ventilatory threshold and peak performance than MCT did. Before the intervention, HE significantly down-regulated autophagy by decreased beclin-1, Atg-1, LC3-II, Atg-12, and LAMP-2 expressions and acridine orange staining, and simultaneously enhanced apoptosis by increased phospho-Bcl-2 and active caspase-9/-3 levels and phosphotidylserine exposure in CD4 lymphocytes. However, five weeks of HIT and MCT, but not CTL, reduced the extents of declined autophagy and potentiated apoptosis in CD4 lymphocytes caused by HE. Furthermore, both HIT and MCT regimens manifestly lowered plasma myeloperoxidase and interleukin-4 levels and elevated the ratio of interleukin-4 to interferon-γ at rest and following HE. Therefore, we conclude that HIT is superior to MCT for enhancing aerobic fitness. Moreover, either HIT or MCT effectively depresses apoptosis and promotes autophagy in CD4 lymphocytes and is accompanied by increased interleukin-4/interferon-γ ratio and decreased peroxide production during HE.

  3. Effects of interval and continuous exercise training on CD4 lymphocyte apoptotic and autophagic responses to hypoxic stress in sedentary men.

    Science.gov (United States)

    Weng, Tzu-Pin; Huang, Shu-Chun; Chuang, Yu-Fen; Wang, Jong-Shyan

    2013-01-01

    Exercise is linked with the type/intensity-dependent adaptive immune responses, whereas hypoxic stress facilitates the programmed death of CD4 lymphocytes. This study investigated how high intensity-interval (HIT) and moderate intensity-continuous (MCT) exercise training influence hypoxia-induced apoptosis and autophagy of CD4 lymphocytes in sedentary men. Thirty healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO2max, n=10) or MCT (sustained 60%VO2max, n=10) for 30 minutes/day, 5 days/week for 5 weeks, or to a control group that did not received exercise intervention (CTL, n=10). CD4 lymphocyte apoptotic and autophagic responses to hypoxic exercise (HE, 100 W under 12%O2 for 30 minutes) were determined before and after various regimens. The results demonstrated that HIT exhibited higher enhancements of pulmonary ventilation, cardiac output, and VO2 at ventilatory threshold and peak performance than MCT did. Before the intervention, HE significantly down-regulated autophagy by decreased beclin-1, Atg-1, LC3-II, Atg-12, and LAMP-2 expressions and acridine orange staining, and simultaneously enhanced apoptosis by increased phospho-Bcl-2 and active caspase-9/-3 levels and phosphotidylserine exposure in CD4 lymphocytes. However, five weeks of HIT and MCT, but not CTL, reduced the extents of declined autophagy and potentiated apoptosis in CD4 lymphocytes caused by HE. Furthermore, both HIT and MCT regimens manifestly lowered plasma myeloperoxidase and interleukin-4 levels and elevated the ratio of interleukin-4 to interferon-γ at rest and following HE. Therefore, we conclude that HIT is superior to MCT for enhancing aerobic fitness. Moreover, either HIT or MCT effectively depresses apoptosis and promotes autophagy in CD4 lymphocytes and is accompanied by increased interleukin-4/interferon-γ ratio and decreased peroxide production during HE. PMID:24236174

  4. 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes induce autophagic cell death in estrogen receptor negative breast cancer

    International Nuclear Information System (INIS)

    A novel series of methylene-substituted DIMs (C-DIMs), namely 1,1-bis(3'-indolyl)-1-(p-substituted phenyl)methanes containing t-butyl (DIM-C-pPhtBu) and phenyl (DIM-C-pPhC6H5) groups inhibit proliferation of invasive estrogen receptor-negative MDA-MB-231 and MDA-MB-453 human breast cancer cell lines with IC50 values between 1-5 uM. The main purpose of this study was to investigate the pathways of C-DIM-induced cell death. The effects of the C-DIMs on apoptotic, necrotic and autophagic cell death were determined using caspase inhibitors, measurement of lactate dehydrogenase release, and several markers of autophagy including Beclin and light chain associated protein 3 expression (LC3). The C-DIM compounds did not induce apoptosis and only DIM-C-pPhCF3 exhibited necrotic effects. However, treatment of MDA-MB-231 and MDA-MB-453 cells with C-DIMs resulted in accumulation of LC3-II compared to LC3-I protein, a characteristic marker of autophagy, and transient transfection of green fluorescent protein-LC3 also revealed that treatment with C-DIMs induced a redistribution of LC3 to autophagosomes after C-DIM treatment. In addition, the autofluorescent drug monodansylcadaverine (MDC), a specific autophagolysosome marker, accumulated in vacuoles after C-DIM treatment, and western blot analysis of lysates from cells treated with C-DIMs showed that the Beclin 1/Bcl-2 protein ratio increased. The results suggest that C-DIM compounds may represent a new mechanism-based agent for treating drug-resistant ER-negative breast tumors through induction of autophagy

  5. A novel strategy inducing autophagic cell death in Burkitt's lymphoma cells with anti-CD19-targeted liposomal rapamycin

    International Nuclear Information System (INIS)

    Relapsed or refractory Burkitt's lymphoma often has a poor prognosis in spite of intensive chemotherapy that induces apoptotic and/or necrotic death of lymphoma cells. Rapamycin (Rap) brings about autophagy, and could be another treatment. Further, anti-CD19-targeted liposomal delivery may enable Rap to kill lymphoma cells specifically. Rap was encapsulated by anionic liposome and conjugated with anti-CD19 antibody (CD19-GL-Rap) or anti-CD2 antibody (CD2-GL-Rap) as a control. A fluorescent probe Cy5.5 was also liposomized in the same way (CD19 or CD2-GL-Cy5.5) to examine the efficacy of anti-CD19-targeted liposomal delivery into CD19-positive Burkitt's lymphoma cell line, SKW6.4. CD19-GL-Cy5.5 was more effectively uptaken into SKW6.4 cells than CD2-GL-Cy5.5 in vitro. When the cells were inoculated subcutaneously into nonobese diabetic/severe combined immunodeficiency mice, intravenously administered CD19-GL-Cy5.5 made the subcutaneous tumor fluorescent, while CD2-GL-Cy5.5 did not. Further, CD19-GL-Rap had a greater cytocidal effect on not only SKW6.4 cells but also Burkitt's lymphoma cells derived from patients than CD2-GL-Rap in vitro. The specific toxicity of CD19-GL-Rap was cancelled by neutralizing anti-CD19 antibody. The survival period of mice treated with intravenous CD19-GL-Rap was significantly longer than that of mice treated with CD2-GL-Rap after intraperitoneal inoculation of SKW6.4 cells. Anti-CD19-targeted liposomal Rap could be a promising lymphoma cell-specific treatment inducing autophagic cell death

  6. Formal Component-Based Semantics

    CERN Document Server

    Madlener, Ken; van Eekelen, Marko; 10.4204/EPTCS.62.2

    2011-01-01

    One of the proposed solutions for improving the scalability of semantics of programming languages is Component-Based Semantics, introduced by Peter D. Mosses. It is expected that this framework can also be used effectively for modular meta theoretic reasoning. This paper presents a formalization of Component-Based Semantics in the theorem prover Coq. It is based on Modular SOS, a variant of SOS, and makes essential use of dependent types, while profiting from type classes. This formalization constitutes a contribution towards modular meta theoretic formalizations in theorem provers. As a small example, a modular proof of determinism of a mini-language is developed.

  7. Resolved Component in Heavy Quark Photoproduction

    International Nuclear Information System (INIS)

    Heavy quarks in γ--N interactions are produced mainly by photon-gluon fusion, nevertheless a tiny contribution to the total cross section comes from processes like those appearing in heavy quarks hadroproduction through the resolved component of the photon. This work present resolved contributions to heavy meson production in terms of kinematic variables, and their dependence of the fragmentation function

  8. Exposure to low-dose X-rays promotes peculiar autophagic cell death in Drosophila melanogaster, an effect that can be regulated by the inducible expression of Hml dsRNA

    International Nuclear Information System (INIS)

    We previously reported that to induce an early emergence effect with low-dose X-irradiation in Drosophila, exposure during the prepupae stage is necessary. The present study examined the mechanism by which low-dose radiation rapidly eliminates larval cells and activates the formation of the imaginal discs during metamorphosis. Upon exposure to 0.5 Gy X-rays at 2 h after puparium formation (APF), the larval salivary glands swelled and were surrounded by remarkably thick structures containing an acid phosphatase (Acph) enzyme, implicating a peculiar autophagic cell death. TUNEL staining revealed the presence of DNA fragmentations compared with cells from sham controls which remained unchanged until 12 h APF. Additionally, the salivary glands of exposed flies were completely destroyed by 10 h APF. Furthermore, exposure to 0.5 Gy X-rays also facilitated the activity of the engulfment function of dendritic cells (DCs); they were generated in the larval salivary glands, engulfed the cell corpses and finally moved to the fat body. Data from an experiment demonstrating the inducible expression of Hml double-stranded RNA (dsRNA) indicate that a slow rate of engulfment of larval cells results in a longer time to emergence. Thus, the animals subjected to low-dose X-rays activated autophagic processes, resulting in significantly faster adult eclosion

  9. Supporting software components production

    OpenAIRE

    Asirelli, Patrizia; Aquilino, Domenico; Inverardi, Paola

    1991-01-01

    In this paper we present an approach to the management of large-scale object-oriented applications based on a sharp distinction between the object-oriented language in which components are described and the way components are assembled into a specific application. In particular, we propose a database component schema which allows for a free development of components and permits to define at the database level all the policies connected to the grouping of components into a specific application...

  10. Multibody model reduction by component mode synthesis and component cost analysis

    Science.gov (United States)

    Spanos, J. T.; Mingori, D. L.

    1990-01-01

    The classical assumed-modes method is widely used in modeling the dynamics of flexible multibody systems. According to the method, the elastic deformation of each component in the system is expanded in a series of spatial and temporal functions known as modes and modal coordinates, respectively. This paper focuses on the selection of component modes used in the assumed-modes expansion. A two-stage component modal reduction method is proposed combining Component Mode Synthesis (CMS) with Component Cost Analysis (CCA). First, each component model is truncated such that the contribution of the high frequency subsystem to the static response is preserved. Second, a new CMS procedure is employed to assemble the system model and CCA is used to further truncate component modes in accordance with their contribution to a quadratic cost function of the system output. The proposed method is demonstrated with a simple example of a flexible two-body system.

  11. 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...

  12. 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.

  13. Gas Quenching Small Components

    Institute of Scientific and Technical Information of China (English)

    Paul Stratton

    2004-01-01

    Gas quenching is an environmentally friendly and effective way of quenching components. However it has not been possible to apply it to small components because of the difficulties of jigging. A method of gas quenching such small components is described in which they are levitated in a confined gas stream. The method is suitable for quenching low alloy steel components that weigh between 1 and 10g.

  14. Social Contributions in Romania

    Directory of Open Access Journals (Sweden)

    Attila Gyorgy

    2012-12-01

    Full Text Available Social contributions have an important impact on payroll policy. Also, social contributions represent a significant budgetary revenue item which can be viewed at the edge between taxation and insurance. Social contributions in Romania experienced many changes which ended in 2008. Nowadays, they are within a long transaction period towards partial externalization of the insurance activity to privately managed funds. The aim of this paper is to analyse the homogeneity of Romanian social security public scheme using annual data extracted from 2002-2009.The main findings reveal that social contributions reached the pinnacle of diversification, being too many, some of them with a small contribution rates; fiscal reforms which reduced contribution rates advantaged employers, and state will be interested to externalize this activity as far private sector will be able to assume this responsibility and the budgetary effects are acceptable for the public finance.

  15. Payroll Taxes and Contributions

    OpenAIRE

    James Alm; Sally Wallace

    2004-01-01

    This staff paper analyzes this “system” of payroll taxes and contributions, focusing mainly on the tax and contribution side rather than on the benefit aspects of the contribution programs. The administration of each of these payroll programs is discussed, and the effects of the entire system are also analyzed. Much of the analyses is based on microsimulation models developed in the course of this tax reform project.

  16. Social Contributions in Romania

    OpenAIRE

    Attila Gyorgy

    2012-01-01

    Social contributions have an important impact on payroll policy. Also, social contributions represent a significant budgetary revenue item which can be viewed at the edge between taxation and insurance. Social contributions in Romania experienced many changes which ended in 2008. Nowadays, they are within a long transaction period towards partial externalization of the insurance activity to privately managed funds. The aim of this paper is to analyse the homogeneity of Romanian social securit...

  17. Bioactivity of Minor Milk Components

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh

    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, and is...... 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...

  18. A abordagem de questões ambientais: contribuições de formadores de professores de componentes curriculares da área de ensino de química Addressing environmental issues: the contribution of teacher-trainers of chemistry teaching curricular components

    OpenAIRE

    Carlos Alberto Marques; Rejane Maria Ghisolfi da Silva; Fábio Peres Gonçalves; Carolina dos Santos Fernandes; Fábio André Sangiogo; Anelise Maria Regiani

    2013-01-01

    This paper presents the results of a study involving current teachers of the chemistry teaching curricular components of twelve Chemistry licentiate courses at state universities in the South and South-east of Brazil. The aim was to analyse how these curricular components can work together to address environmental issues in Chemistry teacher-training. From analysis of the interviews, it can be ascertained for example that environmental themes in the curricular components analysed are treated ...

  19. Major contributions to science

    International Nuclear Information System (INIS)

    It may look difficult to describe the scientific contributions of Léon Van Hove, who started his career as a pure mathematician, and then a mathematical physicist, and ended it as a phenomenologist and an adseveral of Léon's students, in particular N. Hugenholtz. In this domain, his contributions were numerous and fundamental

  20. 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.

  1. 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.

  2. Control component retainer

    International Nuclear Information System (INIS)

    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

  3. SNRS component positioning systems

    International Nuclear Information System (INIS)

    This paper discusses the stationary neutron radiography system (SNRS) with respect to the component positioning systems (CPSs) and the rationale behind their design. As design work is on-going at Science Applications International Corporation, this report gives a current update of progress. The SNRS has four separate radiography bays, Bays 1 through 4. The first three bays have automated positioning systems for real-time and near real-time neutron radiography of aircraft components. Bay 4 has been designed to accommodate components from the solid rocket booster, but will be used first for film radiography of pyrotechnic components

  4. ITER plasma-facing components

    Energy Technology Data Exchange (ETDEWEB)

    Merola, Mario, E-mail: mario.merola@iter.or [ITER Organization, CS 90 046, 13067 St Paul-lez-Durance Cedex (France); Loesser, D. [Blanket Integrated Product Team, Plasma Physics Laboratory, Princeton University, Princeton, NJ 08543 (United States); Martin, A.; Chappuis, P.; Mitteau, R.; Komarov, V.; Pitts, R.A.; Gicquel, S.; Barabash, V.; Giancarli, L.; Palmer, J.; Nakahira, M.; Loarte, A.; Campbell, D.; Eaton, R.; Kukushkin, A.; Sugihara, M.; Zhang, F.; Kim, C.S.; Raffray, R. [ITER Organization, CS 90 046, 13067 St Paul-lez-Durance Cedex (France)

    2010-12-15

    The ITER plasma-facing components directly face the thermonuclear plasma and include the divertor, the blanket and the test blanket modules with their corresponding frames. The divertor is located at the bottom of the plasma chamber and is aimed at exhausting the major part of the plasma thermal power (including alpha power) and at minimising the helium and impurity content in the plasma. The blanket system provides a physical boundary for the plasma transients and contributes to the thermal and nuclear shielding of the vacuum vessel and external machine components. It consists of modular shielding elements known as blanket modules which are attached to the vacuum vessel. Each blanket module consists of two major components: a plasma-facing first wall panel and a shield block. The test blanket modules are mock-ups of DEMO breeding blankets. There are three ITER equatorial ports devoted to test blanket modules, each of them providing for the allocation of two breeding modules inserted in a steel frame and in front of a shield block.

  5. ITER plasma-facing components

    International Nuclear Information System (INIS)

    The ITER plasma-facing components directly face the thermonuclear plasma and include the divertor, the blanket and the test blanket modules with their corresponding frames. The divertor is located at the bottom of the plasma chamber and is aimed at exhausting the major part of the plasma thermal power (including alpha power) and at minimising the helium and impurity content in the plasma. The blanket system provides a physical boundary for the plasma transients and contributes to the thermal and nuclear shielding of the vacuum vessel and external machine components. It consists of modular shielding elements known as blanket modules which are attached to the vacuum vessel. Each blanket module consists of two major components: a plasma-facing first wall panel and a shield block. The test blanket modules are mock-ups of DEMO breeding blankets. There are three ITER equatorial ports devoted to test blanket modules, each of them providing for the allocation of two breeding modules inserted in a steel frame and in front of a shield block.

  6. Discriminant Incoherent Component Analysis.

    Science.gov (United States)

    Georgakis, Christos; Panagakis, Yannis; Pantic, Maja

    2016-05-01

    Face images convey rich information which can be perceived as a superposition of low-complexity components associated with attributes, such as facial identity, expressions, and activation of facial action units (AUs). For instance, low-rank components characterizing neutral facial images are associated with identity, while sparse components capturing non-rigid deformations occurring in certain face regions reveal expressions and AU activations. In this paper, the discriminant incoherent component analysis (DICA) is proposed in order to extract low-complexity components, corresponding to facial attributes, which are mutually incoherent among different classes (e.g., identity, expression, and AU activation) from training data, even in the presence of gross sparse errors. To this end, a suitable optimization problem, involving the minimization of nuclear-and l1 -norm, is solved. Having found an ensemble of class-specific incoherent components by the DICA, an unseen (test) image is expressed as a group-sparse linear combination of these components, where the non-zero coefficients reveal the class(es) of the respective facial attribute(s) that it belongs to. The performance of the DICA is experimentally assessed on both synthetic and real-world data. Emphasis is placed on face analysis tasks, namely, joint face and expression recognition, face recognition under varying percentages of training data corruption, subject-independent expression recognition, and AU detection by conducting experiments on four data sets. The proposed method outperforms all the methods that are compared with all the tasks and experimental settings. PMID:27008268

  7. Scientific Software Component Technology

    Energy Technology Data Exchange (ETDEWEB)

    Kohn, S.; Dykman, N.; Kumfert, G.; Smolinski, B.

    2000-02-16

    We are developing new software component technology for high-performance parallel scientific computing to address issues of complexity, re-use, and interoperability for laboratory software. Component technology enables cross-project code re-use, reduces software development costs, and provides additional simulation capabilities for massively parallel laboratory application codes. The success of our approach will be measured by its impact on DOE mathematical and scientific software efforts. Thus, we are collaborating closely with library developers and application scientists in the Common Component Architecture forum, the Equation Solver Interface forum, and other DOE mathematical software groups to gather requirements, write and adopt a variety of design specifications, and develop demonstration projects to validate our approach. Numerical simulation is essential to the science mission at the laboratory. However, it is becoming increasingly difficult to manage the complexity of modern simulation software. Computational scientists develop complex, three-dimensional, massively parallel, full-physics simulations that require the integration of diverse software packages written by outside development teams. Currently, the integration of a new software package, such as a new linear solver library, can require several months of effort. Current industry component technologies such as CORBA, JavaBeans, and COM have all been used successfully in the business domain to reduce software development costs and increase software quality. However, these existing industry component infrastructures will not scale to support massively parallel applications in science and engineering. In particular, they do not address issues related to high-performance parallel computing on ASCI-class machines, such as fast in-process connections between components, language interoperability for scientific languages such as Fortran, parallel data redistribution between components, and massively

  8. Nonstatistical component of the multifractal spectral function

    International Nuclear Information System (INIS)

    In the multifractal analysis of multiplicity fluctuation in high energy collisions, the statistical contribution to the spectrum function f(α) is calculated using the multinomial distribution. The nonstatistical component can be extracted using a subtraction scheme that is consistent with multifractality. A simple cluster model is considered for illustration. 7 refs., 2 figs

  9. Principal dynamical components

    CERN Document Server

    de la Iglesia, Manuel D

    2010-01-01

    A new procedure is proposed for the dimensional reduction of time series. Similarly to principal components, the procedure seeks a low-dimensional manifold that minimizes information loss. Unlike principal components, however, the new procedure involves dynamical considerations, through the proposal of a predictive dynamical model in the reduced manifold. Hence the minimization of the uncertainty is not only over the choice of a reduced manifold, as in principal components, but also over the parameters of the dynamical model. Further generalizations are provided to non-autonomous and non-Markovian scenarios, which are then applied to historical sea-surface temperature data.

  10. National contributions to observed global warming

    International Nuclear Information System (INIS)

    There is considerable interest in identifying national contributions to global warming as a way of allocating historical responsibility for observed climate change. This task is made difficult by uncertainty associated with national estimates of historical emissions, as well as by difficulty in estimating the climate response to emissions of gases with widely varying atmospheric lifetimes. Here, we present a new estimate of national contributions to observed climate warming, including CO2 emissions from fossil fuels and land-use change, as well as methane, nitrous oxide and sulfate aerosol emissions While some countries’ warming contributions are reasonably well defined by fossil fuel CO2 emissions, many countries have dominant contributions from land-use CO2 and non-CO2 greenhouse gas emissions, emphasizing the importance of both deforestation and agriculture as components of a country’s contribution to climate warming. Furthermore, because of their short atmospheric lifetime, recent sulfate aerosol emissions have a large impact on a country’s current climate contribution We show also that there are vast disparities in both total and per-capita climate contributions among countries, and that across most developed countries, per-capita contributions are not currently consistent with attempts to restrict global temperature change to less than 2 °C above pre-industrial temperatures. (paper)

  11. 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...

  12. Component maintenance system

    International Nuclear Information System (INIS)

    A component maintenance system having a network linked to a data acquisition system, a data analysis system, a historical file of component design and inspection information, and a diagnostic system having the capability to perform structural analysis of discontinuities identified by the data acquisition system. The network nodes may be located apart from each other, for example in the maintenance of a nuclear power plant steam generator, the data acquisition system may be located in a high radiation area while the data analysis system is safely located away from the radiation areas. Furthermore, the diagnostic system and the file of component design and inspection history information may be centrally located and sheared to support component evaluations being conducted in numerous geographic locations. Network communication facilitates the rapid evaluation of discontinuities, thereby permitting the inspection plan to be modified as the inspection results are obtained. (author) figs

  13. Darwin's contributions to genetics.

    Science.gov (United States)

    Liu, Y-S; Zhou, X-M; Zhi, M-X; Li, X-J; Wang, Q-L

    2009-01-01

    Darwin's contributions to evolutionary biology are well known, but his contributions to genetics are much less known. His main contribution was the collection of a tremendous amount of genetic data, and an attempt to provide a theoretical framework for its interpretation. Darwin clearly described almost all genetic phenomena of fundamental importance, such as prepotency (Mendelian inheritance), bud variation (mutation), heterosis, reversion (atavism), graft hybridization (Michurinian inheritance), sex-limited inheritance, the direct action of the male element on the female (xenia and telegony), the effect of use and disuse, the inheritance of acquired characters (Lamarckian inheritance), and many other observations pertaining to variation, heredity and development. To explain all these observations, Darwin formulated a developmental theory of heredity - Pangenesis - which not only greatly influenced many subsequent theories, but also is supported by recent evidence. PMID:19638672

  14. Space laser components reliability

    OpenAIRE

    Riede, Wolfgang; Schroeder, Helmut

    2015-01-01

    Space environment presents unique challenges for operation of optics and optical coatings as part of laser systems. Besides testing components and sub-systems on the component qualification level, the extended testing of complete laser systems like flight modules under acceptance level conditions is an effective way to determine the reliability and long term stability, mitigating the mission risk. Hence, optics as part of high power space laser systems have to be extensively tested in view...

  15. Stochastic component mode synthesis

    OpenAIRE

    Bah, Mamadou T.; Nair, Prasanth B.; Bhaskar, Atul; Keane, Andy J.

    2003-01-01

    In this paper, a stochastic component mode synthesis method is developed for the dynamic analysis of large-scale structures with parameter uncertainties. The main idea is to represent each component displacement using a subspace spanned by a set of stochastic basis vectors in the same fashion as in stochastic reduced basis methods [1, 2]. These vectors represent however stochastic modes in contrast to the deterministic modes used in conventional substructuring methods [3]. The Craig-Bampton r...

  16. Component fragility research program

    International Nuclear Information System (INIS)

    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)

    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. Fusion systems with some sporadic J-components

    OpenAIRE

    Lynd, Justin; Rainbolt, Julianne

    2016-01-01

    Aschbacher's program for the classification of simple fusion systems of "odd" type at the prime 2 has two main stages: the classification of 2-fusion systems of subintrinsic component type and the classification of 2-fusion systems of J-component type. We make a contribution to the latter stage by classifying 2-fusion systems with a J-component isomorphic to the 2-fusion systems of several sporadic groups under the assumption that the centralizer of such a component is cyclic.

  19. Contributing to Functionality

    DEFF Research Database (Denmark)

    Törpel, Bettina

    2006-01-01

    supported joint action space comprises a whole range of appropriate design contributions. The approach is illustrated by the example of the creation of the computer supported joint action space "exchange network of voluntary union educators". As part of the effort a group of participants created and...

  20. NASTRAN component-mode synthesis

    Science.gov (United States)

    Guyan, R. J.

    1976-01-01

    Procedure for dynamic substructuring analysis technique is generally as follows: calculation of component modes; selection of component normal modes, calculation of component generalized matrices, assembly of system matrices, and computation of normal modes; and retrieval of component response.

  1. Contribution to the development of a material-saving mode of operation for a conventional steam generator, characterized by the determination and analysis of transient loads on thick-walled components without external heating. Ein Beitrag zur Entwicklung eines Verfahrens der materialschonenden Fahrweise eines konventionellen Dampferzeugers, gekennzeichnet durch die Erfassung und Bewertung der instationaeren Beanspruchung von aussen unbeheizter, dickwandiger Bauteile

    Energy Technology Data Exchange (ETDEWEB)

    Schlecht, M.

    1986-06-04

    The author proposes to prolong the service life of conventional steam generators by an objectification of the mode of operation. This mode of operation will be microprocesser-controlled; it will be based on the measurement and evaluation of component loads and on a calculation of parameter limitations in real-time operation. The fundamental studies comprised a theoretical analysis of the relationships between fluid parameters and component loads, with particular regard to generally applicable approximations, a discussion of the control requirements for starting a 815 t/h steam generator, and a summarisation of the results for the implementation phase. (orig./HAG).

  2. Multiscale principal component analysis

    International Nuclear Information System (INIS)

    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. Scientific Component Technology Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Kohn, S; Bosl, B; Dahlgren, T; Kumfert, G; Smith, S

    2003-02-07

    The laboratory has invested a significant amount of resources towards the development of high-performance scientific simulation software, including numerical libraries, visualization, steering, software frameworks, and physics packages. Unfortunately, because this software was not designed for interoperability and re-use, it is often difficult to share these sophisticated software packages among applications due to differences in implementation language, programming style, or calling interfaces. This LDRD Strategic Initiative investigated and developed software component technology for high-performance parallel scientific computing to address problems of complexity, re-use, and interoperability for laboratory software. Component technology is an extension of scripting and object-oriented software development techniques that specifically focuses on the needs of software interoperability. Component approaches based on CORBA, COM, and Java technologies are widely used in industry; however, they do not support massively parallel applications in science and engineering. Our research focused on the unique requirements of scientific computing on ASCI-class machines, such as fast in-process connections among components, language interoperability for scientific languages, and data distribution support for massively parallel SPMD components.

  4. Attenuation of Aβ{sub 25–35}-induced parallel autophagic and apoptotic cell death by gypenoside XVII through the estrogen receptor-dependent activation of Nrf2/ARE pathways

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Xiangbao; Wang, Min [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Sun, Guibo, E-mail: sunguibo@126.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Ye, Jingxue [Jilin Agricultural University, Changchun, Jilin 130021 (China); Zhou, Yanhui [Center of Cardiology, People' s Hospital of Jilin Province, Changchun, 130021, Jilin (China); Dong, Xi [Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Wang, Tingting; Lu, Shan [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Sun, Xiaobo, E-mail: sun_xiaobo163@163.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China)

    2014-08-15

    Amyloid-beta (Aβ) has a pivotal function in the pathogenesis of Alzheimer's disease. To investigate Aβ neurotoxicity, we used an in vitro model that involves Aβ{sub 25–35}-induced cell death in the nerve growth factor-induced differentiation of PC12 cells. Aβ{sub 25–35} (20 μM) treatment for 24 h caused apoptotic cell death, as evidenced by significant cell viability reduction, LDH release, phosphatidylserine externalization, mitochondrial membrane potential disruption, cytochrome c release, caspase-3 activation, PARP cleavage, and DNA fragmentation in PC12 cells. Aβ{sub 25–35} treatment led to autophagic cell death, as evidenced by augmented GFP-LC3 puncta, conversion of LC3-I to LC3-II, and increased LC3-II/LC3-I ratio. Aβ{sub 25–35} treatment induced oxidative stress, as evidenced by intracellular ROS accumulation and increased production of mitochondrial superoxide, malondialdehyde, protein carbonyl, and 8-OHdG. Phytoestrogens have been proved to be protective against Aβ-induced neurotoxicity and regarded as relatively safe targets for AD drug development. Gypenoside XVII (GP-17) is a novel phytoestrogen isolated from Gynostemma pentaphyllum or Panax notoginseng. Pretreatment with GP-17 (10 μM) for 12 h increased estrogen response element reporter activity, activated PI3K/Akt pathways, inhibited GSK-3β, induced Nrf2 nuclear translocation, augmented antioxidant responsive element enhancer activity, upregulated heme oxygenase 1 (HO-1) expression and activity, and provided protective effects against Aβ{sub 25–35}-induced neurotoxicity, including oxidative stress, apoptosis, and autophagic cell death. In conclusion, GP-17 conferred protection against Aβ{sub 25–35}-induced neurotoxicity through estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3β and activation of Nrf2/ARE/HO-1 pathways. This finding might provide novel insights into understanding the mechanism for neuroprotective effects of phytoestrogens

  5. Digital Components in Swedish NPP Power Systems

    International Nuclear Information System (INIS)

    Swedish nuclear power plants have over the last 20 years of operation modernised or exchanged several systems and components of the electrical power system. Within these works, new components based on digital technology have been employed in order to realize functionality that was previously achieved by using electro-mechanical or analogue technology. Components and systems such as relay protection, rectifiers, inverters, variable speed drives and diesel-generator sets are today equipped with digital components. Several of the systems and components fulfil functions with a safety-role in the NPP. Recently, however, a number of incidents have occurred which highlight deficiencies in the design or HMI of the equipment, which warrants questions whether there are generic problems with some applications of digital components that needs to be addressed. The use of digital components has presented cost effective solutions, or even the only available solution on the market enabling a modernisation. The vast majority of systems using digital components have been operating without problems and often contribute to improved safety but the challenge of non-detectable, or non-identifiable, failure modes remain. In this paper, the extent to which digital components are used in Swedish NPP power systems will be presented including a description of typical applications. Based on data from maintenance records and fault reports, as well as interviews with designers and maintenance personnel, the main areas where problems have been encountered and where possible risks have been identified will be described. The paper intends to investigate any 'tell-tales' that could give signals of unwanted behaviour. Furthermore, particular benefits experienced by using digital components will be highlighted. The paper will also discuss the safety relevance of these findings and suggest measures to improve safety in the application of digital components in power systems. (authors)

  6. Adaptable component frameworks

    DEFF Research Database (Denmark)

    Katajainen, Jyrki; Simonsen, Bo

    of balanced search tree. Also, we do provide safe and compact versions of each container. To ease the maintenance of this large collection of implementations, we have developed component frameworks for the STL containers. In this paper, we describe the design and implementation of a component...... framework 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....

  7. 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...

  8. Blood Component Therapy

    OpenAIRE

    Kelton, J. G.

    1984-01-01

    Human blood has been transfused for about 60-70 years. Over this time, the practice of blood transfusion has changed dramatically. One major change is the separation of blood into its various components. As a result, the patient can receive only the blood component in which he is deficient. In this way, the risk of side effects—particularly hepatitis—is lessened. This article briefly reviews the various blood products, the indications for their use, and some associated risks. These products i...

  9. 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...... semantics, not only in text, but also in dynamic text (chat), images, and combinations of text and images. Here we further expand on the relevance of the ICA model for representing context, including two new analyzes of abstract data: social networks and musical features....

  10. 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

  11. Cognitive Component Analysis

    DEFF Research Database (Denmark)

    Feng, Ling

    2008-01-01

    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...... unsupervised learning discovers statistical regularities. However human cognition is too complicated and not yet fully understood. Nevertheless, in our approach we represent human cognitive processes as a classification rule in supervised learning. Thus we have devised a testable protocol to test the...

  12. IVS contribution to ITRF2014

    Science.gov (United States)

    Bachmann, Sabine; Thaller, Daniela; Roggenbuck, Ole; Lösler, Michael; Messerschmitt, Linda

    2016-07-01

    Every few years the International Terrestrial Reference System (ITRS) Center of the International Earth Rotation and Reference Systems Service (IERS) decides to generate a new version of the International Terrestrial Reference Frame (ITRF). For the upcoming ITRF2014 the official contribution of the International VLBI Service for Geodesy and Astrometry (IVS) comprises 5796 combined sessions in SINEX file format from 1979.6 to 2015.0 containing 158 stations, overall. Nine AC contributions were included in the combination process, using five different software packages. Station coordinate time series of the combined solution show an overall repeatability of 3.3 mm for the north, 4.3 mm for the east and 7.5 mm for the height component over all stations. The minimum repeatabilities are 1.5 mm for north, 2.1 mm for east and 2.9 mm for height. One of the important differences between the IVS contribution to the ITRF2014 and the routine IVS combination is the omission of the correction for non-tidal atmospheric pressure loading (NTAL). Comparisons between the amplitudes of the annual signals derived by the VLBI observations and the annual signals from an NTAL model show that for some stations, NTAL has a high impact on station height variation. For other stations, the effect of NTAL is low. Occasionally other loading effects have a higher influence (e.g. continental water storage loading). External comparisons of the scale parameter between the VTRF2014 (a TRF based on combined VLBI solutions), DTRF2008 (DGFI-TUM realization of ITRS) and ITRF2008 revealed a significant difference in the scale. A scale difference of 0.11 ppb (i.e. 0.7 mm on the Earth's surface) has been detected between the VTRF2014 and the DTRF2008, and a scale difference of 0.44 ppb (i.e. 2.8 mm on the Earth's surface) between the VTRF2014 and ITRF2008. Internal comparisons between the EOP of the combined solution and the individual solutions from the AC contributions show a WRMS in X- and Y-Pole between

  13. IVS contribution to ITRF2014

    Science.gov (United States)

    Bachmann, Sabine; Thaller, Daniela; Roggenbuck, Ole; Lösler, Michael; Messerschmitt, Linda

    2016-04-01

    Every few years the International Terrestrial Reference System (ITRS) Center of the International Earth Rotation and Reference Systems Service (IERS) decides to generate a new version of the International Terrestrial Reference Frame (ITRF). For the upcoming ITRF2014 the official contribution of the International VLBI Service for Geodesy and Astrometry (IVS) comprises 5796 combined sessions in SINEX file format from 1979.6 to 2015.0 containing 158 stations, overall. Nine AC contributions were included in the combination process, using five different software packages. Station coordinate time series of the combined solution show an overall repeatability of 3.3 mm for the north, 4.3 mm for the east and 7.5 mm for the height component over all stations. The minimum repeatabilities are 1.5 mm for north, 2.1 mm for east and 2.9 mm for height. One of the important differences between the IVS contribution to the ITRF2014 and the routine IVS combination is the omission of the correction for non-tidal atmospheric pressure loading (NTAL). Comparisons between the amplitudes of the annual signals derived by the VLBI observations and the annual signals from an NTAL model show that for some stations, NTAL has a high impact on station height variation. For other stations, the effect of NTAL is low. Occasionally other loading effects have a higher influence (e.g. continental water storage loading). External comparisons of the scale parameter between the VTRF2014 (a TRF based on combined VLBI solutions), DTRF2008 (DGFI-TUM realization of ITRS) and ITRF2008 revealed a significant difference in the scale. A scale difference of 0.11 ppb (i.e. 0.7 mm on the Earth's surface) has been detected between the VTRF2014 and the DTRF2008, and a scale difference of 0.44 ppb (i.e. 2.8 mm on the Earth's surface) between the VTRF2014 and ITRF2008. Internal comparisons between the EOP of the combined solution and the individual solutions from the AC contributions show a WRMS in X- and Y-Pole between

  14. Authors: who contributes what?

    Science.gov (United States)

    Squires, B P

    1996-10-01

    In this issue (see pages 877 to 882) Dr. H. Dele Davies and associates examine how a sample of pediatric department chairs and faculty deans' offices perceive the involvement of faculty members in medical research. Their findings point to the confusion that surrounds the question of authorship in collaborative research. Dr. Drummond Rennie, deputy editor of the Journal of the American Medical Association, has proposed that a complete and descriptive list of "contributors" replace author lists and acknowledgements. Slight modifications to the International Committee of Medical Journal Editors guidelines on authorship retain the designation "author" and the use of acknowledgements but encourage the explicit description of each investigator's contribution. Researchers and editors should continue to explore ways to ensure that contributions to published research are clearly and honestly identified. PMID:8837537

  15. Contributions to statistics

    CERN Document Server

    Mahalanobis, P C

    1965-01-01

    Contributions to Statistics focuses on the processes, methodologies, and approaches involved in statistics. The book is presented to Professor P. C. Mahalanobis on the occasion of his 70th birthday. The selection first offers information on the recovery of ancillary information and combinatorial properties of partially balanced designs and association schemes. Discussions focus on combinatorial applications of the algebra of association matrices, sample size analogy, association matrices and the algebra of association schemes, and conceptual statistical experiments. The book then examines latt

  16. Abstracts of contributed papers

    Energy Technology Data Exchange (ETDEWEB)

    1994-08-01

    This volume contains 571 abstracts of contributed papers to be presented during the Twelfth US National Congress of Applied Mechanics. Abstracts are arranged in the order in which they fall in the program -- the main sessions are listed chronologically in the Table of Contents. The Author Index is in alphabetical order and lists each paper number (matching the schedule in the Final Program) with its corresponding page number in the book.

  17. Contributions to sampling statistics

    CERN Document Server

    Conti, Pier; Ranalli, Maria

    2014-01-01

    This book contains a selection of the papers presented at the ITACOSM 2013 Conference, held in Milan in June 2013. ITACOSM is the bi-annual meeting of the Survey Sampling Group S2G of the Italian Statistical Society, intended as an international  forum of scientific discussion on the developments of theory and application of survey sampling methodologies and applications in human and natural sciences. The book gathers research papers carefully selected from both invited and contributed sessions of the conference. The whole book appears to be a relevant contribution to various key aspects of sampling methodology and techniques; it deals with some hot topics in sampling theory, such as calibration, quantile-regression and multiple frame surveys, and with innovative methodologies in important topics of both sampling theory and applications. Contributions cut across current sampling methodologies such as interval estimation for complex samples, randomized responses, bootstrap, weighting, modeling, imputati...

  18. Variation in Hsp70-1A Expression Contributes to Skin Color Diversity.

    Science.gov (United States)

    Murase, Daiki; Hachiya, Akira; Fullenkamp, Rachel; Beck, Anita; Moriwaki, Shigeru; Hase, Tadashi; Takema, Yoshinori; Manga, Prashiela

    2016-08-01

    The wide range in human skin color results from varying levels of the pigment melanin. Genetic mechanisms underlying coloration differences have been explored, but identified genes do not account for all variation seen in the skin color spectrum. Post-transcriptional and post-translational regulation of factors that determine skin color, including melanin synthesis in epidermal melanocytes, melanosome transfer to keratinocytes, and melanosome degradation, is also critical for pigmentation. We therefore investigated proteins that are differentially expressed in melanocytes derived from either white or African American skin. Two-dimensional gel electrophoresis and mass spectrometry demonstrated that heat shock protein 70-1A (Hsp70-1A) protein levels were significantly higher in African American melanocytes compared with white melanocytes. Hsp70-1A expression significantly correlated with levels of tyrosinase, the rate-limiting melanogenic enzyme, consistent with a proposed role for Hsp70 family members in tyrosinase post-translational modification. In addition, pharmacologic inhibition and small interfering RNA-mediated downregulation of Hsp70-1A correlated with pigmentation changes in cultured melanocytes, modified human skin substitutes, and ex vivo skin. Furthermore, Hsp70-1A inhibition led to increased autophagy-mediated melanosome degradation in keratinocytes. Our data thus reveal that epidermal Hsp70-1A contributes to the diversity of skin color by regulating the amount of melanin synthesized in melanocytes and modulating autophagic melanosome degradation in keratinocytes. PMID:27094592

  19. 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...

  20. Component Reengineering Workshops

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius; Christensen, Henrik Bærbak

    2004-01-01

    reengineering workshops, for assessing reengineering costs of reusing components between different product lines. The approach works on the level of software architectures, and relies critically on input from various (technical) stakeholders. It has been validated through case studies that are also presented...

  1. ITER plasma facing components

    International Nuclear Information System (INIS)

    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

  2. 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....

  3. Ubiquitous Fractal Components

    OpenAIRE

    Hoareau, Didier; Mahéo, Yves

    2006-01-01

    In this article we present a distribution scheme for Fractal-based applications that is namely based on a user-transparent extension to the Fractal component model. This scheme allows any Fractal application to expose it provided services in an ubiquitous way on several machines. The mechanisms implemented support network disconnections and let the application run in a degraded mode if necessary.

  4. Complement component 4

    Science.gov (United States)

    ... may have lower-than-normal levels of the complement proteins C3 and C4 . Complement activity varies throughout the body. ... Saunders; 2013:chap 6. Read More Cirrhosis Complement Complement component 3 (C3) Glomerulonephritis Hepatitis Hereditary angioedema Kidney transplant Lupus nephritis ...

  5. LABVirt – basic components

    Directory of Open Access Journals (Sweden)

    Codrin NISIOIU

    2006-01-01

    Full Text Available This article presents some aspects about a project integrated in a national research and development project "Information society" (INFOSOC financed by Romanian Government. A iLab called LABVirt is available for use by Universities, college, high-school.The goal of this paper is to present the main components of LABVirt, Romanian solution for remote lab access.

  6. 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

  7. 大鼠坐骨神经再生过程中许旺氏细胞的自噬作用%The autophagic role of Schwann cell on regeneration of rat sciatic nerves

    Institute of Scientific and Technical Information of China (English)

    王万山; 朴仲贤; 王启伟; Han Ming-Hu; 朴英杰

    2004-01-01

    背景 :Wallerian变性时髓鞘溃变碎片的清除对于神经的再生至关重要 ,但溃变碎片的清除机制一直没有彻底阐明 ,关于参与清除的细胞成分类型仍有很大争议. 目的 :探讨大鼠坐骨神经再生过程中许旺氏细胞的自噬作用. 设计 :完全随机自身对照研究. 地点和对象 :本实验由第一军医大学解剖教研室、汕头大学医学院中心实验室和西南大学达拉斯医学中心精神病学部共同完成 ,研究对象为成年 Wistar大鼠 30只 ,雌雄各半 ,体质量 180- 250 g. 干预 :横切大鼠坐骨神经制作 Wallerian变性模型 ,分别于造模后 0,0.5,1,1.5,2,3,4,5,7,10,15 d取远断端组织行电镜观察. 主要观察指标 :电镜观察轴突和髓鞘的超微结构 ,Gomori染色后检查酸性磷酸酶活性. 结果 :轴突在第 0.5天时从髓鞘脱离,溃变呈空泡状.第 2天开始髓鞘皱褶、断裂形成碎片,许旺氏细胞内见大的膜结合髓鞘碎片和许多散在小碎片,并与溶酶体融合形成自噬泡,呈酸性磷酸酶 (AcPase)阳性.第 4天时内膜区偶见幼稚细胞 ,1周后见大量幼稚细胞.第 7天后许旺氏细胞内自噬泡数量开始减少.实验全程偶见巨噬细胞 ,内有吞噬泡. 结论 :大鼠坐骨神经再生过程中溃变髓鞘主要经许旺氏细胞自噬清除,许旺氏细胞脱分化为许旺氏细胞祖细胞后大量增殖分化参与神经再生过程.%BACKGROUND:The removal of degenerated debris of myelin sheath during wallerian degeneration is very important for nerve regeneration,but the mechanism by which the debris is removed has not been completely clarified and there is still considerable controversies on the types of cells involved in the clearance process.OBJECTIVE:To investigate the autophagic role of Schwann cell on regeneration of rat sciatic nerves.DESIGN: Completely randomized animal experiment conducted in March 2003. SETTING AND PARTICIPANTS:Rats were bought from the Laboratory Animal

  8. T-stresses for internally cracked components

    International Nuclear Information System (INIS)

    The failure of cracked components is governed by the stresses in the vicinity of the crack tip. The singular stress contribution is characterised by the stress intensity factor K, the first regular stress term is represented by the so-called T-stress. T-stress solutions for components containing an internal crack were computed by application of the Bundary Collocation Method (BCM). The results are compiled in form of tables or approximative relations. In addition a Green's function of T-stresses is proposed for internal cracks which enables to compute T-stress terms for any given stress distribution in the uncracked body. (orig.)

  9. Durability of building materials and components

    CERN Document Server

    Delgado, JMPQ

    2013-01-01

    Durability of Building Materials and Components provides a collection of recent research works to contribute to the systematization and dissemination of knowledge related to the long-term performance and durability of construction and, simultaneously, to show the most recent advances in this domain. It includes a set of new developments in the field of durability, service life prediction methodologies, the durability approach for historical and old buildings, asset and maintenance management and on the durability of materials, systems and components. The book is divided in several chapters that intend to be a resume of the current state of knowledge for benefit of professional colleagues.

  10. Tank waste isotope contributions

    International Nuclear Information System (INIS)

    This document presents the results of a calculation to determine the relative contribution of selected isotopes to the inhalation and ingestion doses for a postulated release of Hanford tank waste. The fraction of the dose due to 90Sr, 90Y, 137Cs and the alpha emitters for single shell solids and liquids, double shell solids and liquids, aging waste solids and liquids and all solids and liquids. An effective dose conversion factor was also calculated for the alpha emitters for each composite of the tank waste

  11. Compressive Principal Component Pursuit

    CERN Document Server

    Wright, John; Min, Kerui; Ma, Yi

    2012-01-01

    We consider the problem of recovering a target matrix that is a superposition of low-rank and sparse components, from a small set of linear measurements. This problem arises in compressed sensing of structured high-dimensional signals such as videos and hyperspectral images, as well as in the analysis of transformation invariant low-rank recovery. We analyze the performance of the natural convex heuristic for solving this problem, under the assumption that measurements are chosen uniformly at random. We prove that this heuristic exactly recovers low-rank and sparse terms, provided the number of observations exceeds the number of intrinsic degrees of freedom of the component signals by a polylogarithmic factor. Our analysis introduces several ideas that may be of independent interest for the more general problem of compressed sensing and decomposing superpositions of multiple structured signals.

  12. Defining talent management components

    OpenAIRE

    Golchin Shafieian

    2014-01-01

    In today's world of global trade, it can guarantee success and excellence of organizations against competitors is talented human resources in an organization, especially at the managerial level. But the challenges that organizations face include: attracting, evaluating, exploring, and developing and keeping talent. The main objective of this study is to define the components of talent management in the University of Chaloos, in order to provide a way to reduce the challenges and short comings...

  13. Functional Components of Foods.

    OpenAIRE

    Guiné, Raquel; Lima, Maria João; Barroca, Maria João

    2010-01-01

    The primary role of diet is to provide sufficient nutrients to meet the nutritional requirements of an individual. However, many professionals recognise that health promoting foods have a major role in health enhancement, which justifies the focus on research on the identification of biologically active components in foods that have the potential to optimise physical and mental well being and which may also reduce the risk of disease. Recent increases on research also aimed the identification...

  14. Components of aging

    OpenAIRE

    Wiegand, Iris

    2013-01-01

    Age-related cognitive decline has been linked to a reduction in attentional resources that are assumed to result from alterations in the aging brain. A core ability that is subject to age-related decline is visual attention, which enables individuals to select the most important information for conscious processing and action. However, visual attention is considered a conglomerate of various functions and the specific components underlying age differences in performance remain little understo...

  15. Enterprise Architecture Evaluation Components

    OpenAIRE

    Niemi, Eetu; Ylimäki, Tanja

    2008-01-01

    Enterprise Architecture (EA) is a holistic view of an organization, including the viewpoints of business, information, systems and technology. It is stated to provide significant benefits to organizations, and is therefore of interest for both academics and practitioners. However, evaluating EA, or its benefits, is difficult. Moreover, the studies on EA evaluation are mostly inconsistent, and almost omit the planning aspect of evaluation. This study suggests the evaluation components that nee...

  16. Components of the environment

    International Nuclear Information System (INIS)

    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

  17. Defining talent management components

    Directory of Open Access Journals (Sweden)

    Golchin Shafieian

    2014-07-01

    Full Text Available In today's world of global trade, it can guarantee success and excellence of organizations against competitors is talented human resources in an organization, especially at the managerial level. But the challenges that organizations face include: attracting, evaluating, exploring, and developing and keeping talent. The main objective of this study is to define the components of talent management in the University of Chaloos, in order to provide a way to reduce the challenges and short comings and also to look for ways to improve employee performance is discussed. This study is based on data collected from all employees of the University of Chaloos in August 2013; through two questionnaires have been developed. The statistical population has been considered 407 persons in these universities and according the Morgan Table, 198 persons were selected as sample of among research society. More over, 28 questions are used for determining components of talent management. Finally, we concluded that the component of talent management have been properly defined in the Universities of Chaloos.

  18. Japanese contributions to CERN-LHC

    International Nuclear Information System (INIS)

    The Large Hadron Collider (LHC) is now under construction at CERN, Geveva, to study frontier researches of particle physics. The LHC is the biggest superconducting accelerator using the most advanced cryogenics and applied superconductivities. The accelerator and large scale detectors for particle physics experiments are being constructed by collaboration with European countries and also by participation with non-CERN countries worldwide. In 1995, the Japanese government decided to take on a share in the LHC project with funding and technological contributions. KEK contributes to the development of low beta insertion superconducting quadrupole magnets and of components of the ATLAS detector by collaboration with university groups. Some Japanese companies have received contracts for technically key elements such as superconducting cable, cold compressor, nonmagnetic steel, polyimide film, and so on. An outline of the LHC project and Japanese contributions are described. (author)

  19. Nanochemoprevention by Bioactive Food Components: A Perspective

    OpenAIRE

    Siddiqui, Imtiaz A.; Mukhtar, Hasan

    2010-01-01

    Chemoprevention through the use of bioactive food components is a practical approach for cancer control. Despite abundant efficacy data under preclinical settings, this strategy has resulted in limited success for human cancer control. Amongst many reasons, inefficient systemic delivery and bioavailability of promising chemopreventive agents are considered to significantly contribute to such a disconnect. We recently introduced a novel concept in which we utilized nanotechnology for enhancing...

  20. Modeling accelerator structures and RF components

    International Nuclear Information System (INIS)

    Computer modeling has become an integral part of the design and analysis of accelerator structures RF components. Sophisticated 3D codes, powerful workstations and timely theory support all contributed to this development. We will describe our modeling experience with these resources and discuss their impact on ongoing work at SLAC. Specific examples from R ampersand D on a future linear collide and a proposed e+e- storage ring will be included

  1. Modeling accelerator structures and RF components

    Energy Technology Data Exchange (ETDEWEB)

    Ko, K., Ng, C.K.; Herrmannsfeldt, W.B.

    1993-03-01

    Computer modeling has become an integral part of the design and analysis of accelerator structures RF components. Sophisticated 3D codes, powerful workstations and timely theory support all contributed to this development. We will describe our modeling experience with these resources and discuss their impact on ongoing work at SLAC. Specific examples from R&D on a future linear collide and a proposed e{sup +}e{sup {minus}} storage ring will be included.

  2. Ageing management for systems, structures and components

    International Nuclear Information System (INIS)

    During operation, ageing will influence the quality of systems, structures and components (SSC). Experts make a distinction between the phenomena of conceptional ageing, technological ageing and physical ageing. The quality of SSC may be influenced by conceptional ageing, quality, technological or physical ageing. The contribution outlines the preconditions for a comprehensive, standardized ageing management of nuclear power stations in the Federal Republic of Germany. (orig.)

  3. An Introductory Idea for Teaching Two-Component Phase Diagrams

    Science.gov (United States)

    Peckham, Gavin D.; McNaught, Ian J.

    2011-01-01

    The teaching of two-component phase diagrams has attracted little attention in this "Journal," and it is hoped that this article will make a useful contribution. Current physical chemistry textbooks describe two-component phase diagrams adequately, but do so in a piecemeal fashion one section at a time; first solid-liquid equilibria, then…

  4. IDS contribution to ITRF2008

    Science.gov (United States)

    Valette, Jean-Jacques; Lemoine, Frank G.; Ferrage, Pascale; Yaya, Philippe; Altamimi, Zuheir; Willis, Pascal; Soudarin, Laurent

    2010-12-01

    scale and geocenter of the IDS-3 combination. The final IDS-3 combination has an internal position consistency (WRMS) that is 15 to 20 mm before 2002 and 8 to 10 mm after 2002, when 4 or 5 satellites contribute to the weekly solutions. The final IDS-3 combination includes solutions for 130 DORIS stations on 67 different sites of which 35 have occupations over 16 years (1993.0-2009.0). The EOPs from the IDS-3 combination were compared with the IERS 05 C04 time series and the RMS agreement was 0.24 mas and 0.35 mas for the X and Y components of polar motion. The comparison to ITRF2005 in station position shows an agreement of 6 to 8 mm RMS in horizontal and 10.3 mm in height. The RMS comparison to ITRF2005 in station velocity is at 1.8 mm/year on the East component, to 1.2 mm/year in North component and 1.6 mm/year in height.

  5. Resilience-based network component importance measures

    International Nuclear Information System (INIS)

    Disruptive events, whether malevolent attacks, natural disasters, manmade accidents, or common failures, can have significant widespread impacts when they lead to the failure of network components and ultimately the larger network itself. An important consideration in the behavior of a network following disruptive events is its resilience, or the ability of the network to “bounce back” to a desired performance state. Building on the extensive reliability engineering literature on measuring component importance, or the extent to which individual network components contribute to network reliability, this paper provides two resilience-based component importance measures. The two measures quantify the (i) potential adverse impact on system resilience from a disruption affecting link i, and (ii) potential positive impact on system resilience when link i cannot be disrupted, respectively. The resilience-based component importance measures, and an algorithm to perform stochastic ordering of network components due to the uncertain nature of network disruptions, are illustrated with a 20 node, 30 link network example

  6. 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

  7. Making Components Fit: SPINing

    Czech Academy of Sciences Publication Activity Database

    Kofroň, Jan; Poch, T.; Šerý, O.

    Los Alamitos : IEEE Computer Society, 2009, s. 65-74. ISBN 978-0-7695-3617-0. [SEW 2008. Annual IEEE/NASA Software Engineering Workshop /32./. Kassandra (GR), 15.10.2008-16.10.2008] R&D Projects: GA ČR(CZ) GD201/05/H014 Grant ostatní: GA ČR(CZ) GA201/06/0770 Institutional research plan: CEZ:AV0Z10300504 Keywords : software components * behavior specification * model-checking Subject RIV: JC - Computer Hardware ; Software

  8. Autonomous component carrier selection

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...... 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...

  9. Aging effects in PWR power plants components

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Diogo da S.; Guimaraes, Antonio C.F.; Moreira, Maria de Lourdes, E-mail: diogosb@outlook.com, E-mail: tony@ien.gov.br, E-mail: malu@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2013-07-01

    This paper presents a contribution to the study of aging process of components in commercial plants of Pressurized Water Reactors (PWRs). The analysis is made through application of the Fault Trees Method, Monte Carlo Method and Fussell-Vesely Importance Measure. The approach of the study of aging in nuclear power plants, besides giving attention to the economic factors involved directly with the extent of their operational life, also provide significant data on security issues. The latest case involving process of life extension of a PWR could be seen in Angra 1 Nuclear Power Plant through investing of $27 million for the installation of a new reactor lid. The corrective action has generated an estimated operating life extension of Angra I in twenty years, offering great economy compared with building cost of a new plant and anterior decommissioning, if it had reached the time operating limit of forty years. The Extension of the operating life of a nuclear power plant must be accompanied by a special attention to the components of the systems and their aging process. After the application of the methodology (aging analysis of the injection system of the containment spray) proposed in this work, it can be seen that 'the increase in the rate of component failure, due the aging process, generates the increase in the general unavailability of the system that containing these basic components'. The final results obtained were as expected and may contribute to the maintenance policy, preventing premature aging process in Nuclear Plant Systems. (author)

  10. Aging effects in PWR power plants components

    International Nuclear Information System (INIS)

    This paper presents a contribution to the study of aging process of components in commercial plants of Pressurized Water Reactors (PWRs). The analysis is made through application of the Fault Trees Method, Monte Carlo Method and Fussell-Vesely Importance Measure. The approach of the study of aging in nuclear power plants, besides giving attention to the economic factors involved directly with the extent of their operational life, also provide significant data on security issues. The latest case involving process of life extension of a PWR could be seen in Angra 1 Nuclear Power Plant through investing of $27 million for the installation of a new reactor lid. The corrective action has generated an estimated operating life extension of Angra I in twenty years, offering great economy compared with building cost of a new plant and anterior decommissioning, if it had reached the time operating limit of forty years. The Extension of the operating life of a nuclear power plant must be accompanied by a special attention to the components of the systems and their aging process. After the application of the methodology (aging analysis of the injection system of the containment spray) proposed in this work, it can be seen that 'the increase in the rate of component failure, due the aging process, generates the increase in the general unavailability of the system that containing these basic components'. The final results obtained were as expected and may contribute to the maintenance policy, preventing premature aging process in Nuclear Plant Systems. (author)

  11. Advanced Power Electronics Components

    Science.gov (United States)

    Schwarze, Gene E.

    2004-01-01

    This paper will give a description and status of the Advanced Power Electronics Materials and Components Technology program being conducted by the NASA Glenn Research Center for future aerospace power applications. The focus of this research program is on the following: 1) New and/or significantly improved dielectric materials for the development of power capacitors with increased volumetric efficiency, energy density, and operating temperature. Materials being investigated include nanocrystalline and composite ceramic dielectrics and diamond-like carbon films; 2) New and/or significantly improved high frequency, high temperature, low loss soft magnetic materials for the development of transformers/inductors with increased power/energy density, electrical efficiency, and operating temperature. Materials being investigated include nanocrystalline and nanocomposite soft magnetic materials; 3) Packaged high temperature, high power density, high voltage, and low loss SiC diodes and switches. Development of high quality 4H- and 6H- SiC atomically smooth substrates to significantly improve device performance is a major emphasis of the SiC materials program; 4) Demonstration of high temperature (> 200 C) circuits using the components developed above.

  12. 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.

  13. Laser generating metallic components

    Science.gov (United States)

    McLean, Marc A.; Shannon, G. J.; Steen, William M.

    1997-04-01

    Recent developments in rapid prototyping have led to the concept of laser generating, the first additive manufacturing technology. This paper presents an innovative process of depositing multi-layer tracks, by fusing successive powder tracks, to generate three dimensional components, thereby offering an alternative to casting for small metal component manufacture. A coaxial nozzle assembly has been designed and manufactured enabling consistent omni-directional multi-layer deposition. In conjunction with this the software route from a CAD drawing to machine code generation has been established. The part is manufactured on a six axes machining center incorporating a 1.8 kW carbon-dioxide laser, providing an integrated opto-mechanical workstation. The part build-up program is controlled by a P150 host computer, linked directly to the DNC machining center. The direct manufacturing route is shown, including initial examples of simple objects (primitives -- cube, cylinder, cone) leading to more complex turbine blade generation, incorporating build-up techniques and the associated mechanical properties.

  14. Contribution to postnonclassical psychopathology.

    Directory of Open Access Journals (Sweden)

    Quintino-Aires J.

    2014-09-01

    Full Text Available Any psychological paradigm needs a psychopathological system that helps professionals to describe and explain the behavioral expressions that deviate from “normal” (whether this term is used with the semantic property of statistical or ideal adaptations. In this work, I seek to present the system that I have been developing since 1998 among the psychologists at the Instituto Vegotsky de Lisboa (Vygotsky Institute of Lisbon, Portugal, to understand psychopathology with regard to the vygotskian approach. It was conceived and designed according to the work of Rita Mendes Leal and her contribution to socioemotional development theory, AR Luria’s systemic and dynamic theory of the human brain, the theory of Activity (dyatel’nost of AN Leont’ev, and the psychopathological German school of E Kraepelin, presented and disseminated in Portugal in the early twentieth century by Professor Sobral Cid. It is intended to be a proposal to colleagues who are interested in postnonclassical psychology and a request for arguments.

  15. Mechanism for Clofarabine Inducing Autophagic Death of Acute Myelocytic Leukemia Cell U937%氯法拉滨诱导U937细胞自噬性死亡的机制

    Institute of Scientific and Technical Information of China (English)

    李程亮; 刘海波; 张梅; 贺鹏程

    2013-01-01

    本研究旨在探讨氯法拉滨诱导急性髓系白血病(AML)细胞U937自噬性死亡的机制.不同浓度氯法拉滨作用U937细胞24、48 h后,用MTT法计算细胞生长抑制率及氯法拉滨半数抑制浓度(IC50),流式细胞术检测细胞自噬率的变化;Western blot方法检测细胞自噬相关蛋白Beclin1的表达变化.结果表明,0.01和0.15 μmol/L氯法拉滨作用U937细胞48 h,增殖抑制率分别为(46.92±4.24)%和(86.10±1.16)%,IC50为0.022 μmol/L,与对照组比较差异有统计学意义(P<0.05).0.01和0.1μmol/L氯法拉滨作用U937细胞48 h,自噬率分别为(11.0033±1.4387)%和(59.4133±3.5409)%,且呈剂量依赖性增强(r=0.99);随药物浓度的增加,Beclin 1表达逐渐上调,与对照组比较差异有统计学意义(P<0.05).结论:氯法拉滨对U937细胞有明显的增殖抑制作用,且存在剂量依赖性,其作用机制可能是通过上调Beclin 1的蛋白表达诱导U937细胞自噬性死亡.%To explore the mechanism of autophagic death of acute myelocytic leukemia cell U937 induced by clofarabine, the MTT bioassay was used to analyze the growth inhibitory effect and half inhibition concentration on U937 incubated in vitro with different concentrations of clofarabine for 24 and 48 hours, and the flow cytometry was used to detect the autophagy rate of U937. The expression of Beclin 1 in U937 treated by clofarabine for 48h was meaused by Western blot. The results indicated that when U937 cells were treated with 0. 01 μmol/L and 0.15 μmol/L clofarabine for 48 hours, the proliferation inhibition rate was 46. 92% ±4. 24% and 86. 10% ± 1. 16% , and the half inhibition concentration of clofarabine was 0.022 μmol/L. With 0.01 μmol/L and 0.1μmol/L clofarabine on U937 for 48 hours, the autophagy rate was 11.0033% ±1.4387% and 59.4133% ±3.5409% ,and increased in dose-dependent manner(r = 0.99). Meanwhile the Beclin 1 was upregulated along with increase of clofarabine concentration, as

  16. Component failure data handbook

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Hyaluronan: A Matrix Component

    Science.gov (United States)

    Rügheimer, Louise

    2008-09-01

    The glucosaminoglycan hyaluronan is a key component of the extracellular matrix. It is a large, negatively charged molecule that can act as an ion exchange reservoir for positive ions. Hyaluronan is involved in renomedullary water handling through its water-binding capacity. In the renal medulla, the main source for hyaluronan production is the renomedullary interstitial cells. Hyaluronan synthases are found in the inner part of the plasma membrane and polymerize hyaluronan chains which are extruded into the extracellular space. Hyaluronidases are a family of enzymes involved in the degradation of hyaluronan. They have a wide range of properties, including differences in size, inhibitor sensitivities, catalytic mechanisms, substrate specificities and pH optima.

  18. 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.

  19. 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...... 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...

  20. Solar bowl component efficiencies

    Energy Technology Data Exchange (ETDEWEB)

    O' Hair, E.A.; Green, B.L. (College of Engineering, Texas Tech. Univ., Lubbock, TX (United States))

    1992-11-01

    Battelle Pacific Northwest Laboratory has published two volumes on the economic evaluation of various proposed configurations and plant sizes for the four solar thermal technologies. These are the latest in a series of publications sponsored by the Department of Energy (DOE) on plant and operational costs and are more complete in that they include calculations of electrical output. These latest Battelle volumes use the 1976 solar data from Barstow, Calif., and by calculating or estimating the energy conversion efficiency of each element in the process from sun to electricity predict the output and cost of electricity from different plant sizes for each of the four technologies. In this paper a comparison is presented of the component efficiencies developed by Battelle and those of the solar bowl at Crosbyton, Tex.

  1. The mechanical components market

    International Nuclear Information System (INIS)

    Evolution of CANDU power station design is described and installed nuclear power in Canada to 2000 is forecast. The predicted value of various mechanical components is depicted. Improvements are being made in reliability and speed of repair, which reduce man-rem expenditure in concert with radiation field reduction. Actual reactor operating performance is very good; a significant portion of power plant downtime is associated with steam turbine and generator unreliability. Heavy water upkeep has been reduced by improved equipment layout, live loading of valve stem packing, improved flange seals, and improved leak detection techniques. Steam generator tube reliability is 1000 times better than that of light water reactors. Pump seal reliability has progressed to the point that current station design eliminates pump redundancy. Fuel bundle defect rates are now less than 0.03%. (E.C.B.)

  2. Optical communication components

    Science.gov (United States)

    Eldada, Louay

    2004-03-01

    We review and contrast key technologies developed to address the optical components market for communication applications. We first review the component requirements from a network perspective. We then look at different material systems, compare their properties, and describe the functions achieved to date in each of them. The material systems reviewed include silica fiber, silica on silicon, silicon on insulator, silicon oxynitride, sol-gels, polymers, thin-film dielectrics, lithium niobate, indium phosphide, gallium arsenide, magneto-optic materials, and birefringent crystals. We then describe the most commonly used classes of optical device technology and present their pros and cons as well as the functions achieved to date in each of them. The technologies reviewed include passive, actuation, and active technologies. The passive technologies described include fused fibers, dispersion-compensating fiber, beam steering, Bragg gratings, diffraction gratings, holographic elements, thin-film filters, photonic crystals, microrings, and birefringent elements. The actuation technologies include thermo-optics, electro-optics, acousto-optics, magneto-optics, electroabsorption, liquid crystals, total internal reflection technologies, and mechanical actuation. The active technologies include heterostructures, quantum wells, rare-earth doping, dye doping, Raman amplification, and semiconductor amplification. We also investigate the use of different material systems and device technologies to achieve building-block functions, including lasers, amplifiers, detectors, modulators, polarization controllers, couplers, filters, switches, attenuators, isolators, circulators, wavelength converters, chromatic dispersion compensators, and polarization mode dispersion compensators. Some of the technologies presented are well established in the industry and in some cases have reached the commodity stage, others have recently become ready for commercial introduction, while some others

  3. Distributed and Parallel Component Library

    Institute of Scientific and Technical Information of China (English)

    XU Zheng-quan; XU Yang; YAN Ai-ping

    2005-01-01

    Software component library is the essential part of reuse-based software development. It is shown that making use of a single component library to store all kinds of components and from which components are searched is very inefficient. We construct multi-libraries to support software reuse and use PVM as development environments to imitate largescale computer, which is expected to fulfill distributed storage and parallel search of components efficiently and improve software reuse.

  4. EMSL Contribution Plan

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, Allison A.

    2008-12-01

    This Contribution Plan is EMSL’s template for achieving our vision of simultaneous excellence in all aspects of our mission as a national scientific user facility. It reflects our understanding of the long-term stewardship we must work toward to meet the scientific challenges faced by the Department of Energy (DOE) and the nation. During the next decade, we will implement the strategies contained in this Plan, working closely with the scientific community, our advisory committees, DOE’s Office of Biological and Environmental Research, and other key stakeholders. This Plan is fully aligned with the strategic plans of DOE, its Office of Science, and the Pacific Northwest National Laboratory (PNNL). We recognize that shifts in science and technology, national priorities, and resources made available through the Federal budget process create planning uncertainties and, ultimately, a highly dynamic planning environment. Accordingly, this Plan should be viewed as a living document and we continually evaluate the changing needs and opportunities posed by our stakeholders (i.e., DOE, users, staff, advisory committees), work closely with them to understand and respond to those changes, and align our strategy accordingly. This Plan is organized around two sections. Section 1 describes our vision and four strategic outcomes: 1) Scientific Innovation, 2) Capabilities that Transform Science, 3) Outstanding Management and Operations, and Engaged and Proactive Users. These outcomes provide the framework for seven critical actions we must take during the next 3 to 5 years: 1) Establishing leadership in EMSL science themes, 2) building and deploying transformational capabilities, 3) integrating computation with experiment, 4) ensuring EMSL’s workforce meets the scientific challenges of the future, 5) creating partnerships, 6) attracting and engaging users in EMSL’s long-term strategy, and 7) building a research infrastructure that meets emerging scientific needs. Section 2

  5. Improved Principal Component Analysis and its Application in the Evaluation of the Industrial Structure

    OpenAIRE

    LI Fen-Hong

    2013-01-01

    In this study, improved principal component analysis method is put forward to avoid the shortage of comprehensive evaluation dealt with principal component analysis method. When the contribution rate of the first principal components is short of asks, we can choose to rotate factor loading matrix and select multiple main components and synthesize and weigh the variation coefficient and variance contribution as weight coefficient, to set up a comprehensive evaluation model. As an example of th...

  6. Specific distribution of the autophagic protein GABARAPL1/GEC1 in the developing and adult mouse brain and identification of neuronal populations expressing GABARAPL1/GEC1.

    Directory of Open Access Journals (Sweden)

    Jaclyn Nicole Le Grand

    Full Text Available Macroautophagy is a highly conserved cellular degradation process, regulated by autophagy-related (atg factors, in which a double membrane autophagosome engulfs cytoplasmic components to target them for degradation. In yeast, the Atg8 protein is indispensable for autophagosome formation. In mammals, this is complicated by the presence of six Atg8 homologues grouped into the GABARAP and MAP1LC3 subfamilies. Although these proteins share a high similarity, their transcript expression, regulation and protein interactions differ, suggesting they may display individual properties and specific functions. GABARAPL1/GEC1 is a member of the GABARAP subfamily and its mRNA is the most highly expressed Atg8 homologue in the central nervous system. Consequently, we performed an in depth study of GABARAPL1 distribution in the developing and adult murine brain. Our results show that GABARAPL1 brain expression is visible as early as embryonic day 11 and progressively increases to a maximum level in the adult. Immunohistochemical staining was detected in both fibers and immature neurons in embryos but was restrained to neurons in adult tissue. By E17, intense punctate-like structures were visible and these accumulated in cortical primary neurons treated with the autophagosome/lysosome fusion inhibitor Bafilomycin A1 (Baf A1, suggesting that they represent autophagosomes. Finally, GABARAPL1 expression was particularly intense in motoneurons in the embryo and in neurons involved in somatomotor and neuroendocrine functions in the adult, particularly in the substantia nigra pars compacta, a region affected in Parkinson's disease. Our study of cerebral GABARAPL1 protein expression provides insight into its role in the development and homeostasis of the mouse brain.

  7. Surface Active Components: Review

    Directory of Open Access Journals (Sweden)

    Z. Shafiei

    2014-03-01

    Full Text Available Biosurfactant or surface active components are produced by many different microorganisms. Biosurfactants are amphiphilic molecules with both hydrophilic and hydrophobic (generally hydrocarbon moieties that partition preferentially a within the interface between fluid phases with some other degrees of polarity and hydrogen bonding including oil/water or air/water interfaces. These properties render surfactants able to reducing surface and interfacial tension and forming microemulsion where hydrocarbons can solubilize in water or where water can solubilize in hydrocarbons, the majority of surfactants have gained importance in the fields of enhanced oil recovery, environmental bioremediation, food processing and pharmaceuticals. However, large-scale production of these molecules has not been realized as a result of low yields in production processes and high recovery and purification costs. This review article represents a classification of biosurfactant in addition to their microbial origin and effect of some nutrition and environmental factor for high production of biosurfactant. The nitrogen, carbon sources and environmental factors can make a difference key to the regulating biosurfactants synthesis Fascination with microbial surfactants have been steadily increasing recently because of advantages over the chemical surfactants for example environmentally friendly nature, lower toxicity, higher biodegradability, higher selectivity and specific gravity at extreme temperature, pH and salinity. For this reason the demand of biosurfactant are increasing day by day.

  8. RTD Component 6

    International Nuclear Information System (INIS)

    Within the Integrated Project FUNMIG RTD Component 6 plays the role of the coordinator for linking the scientific work with the application of its results in Performance Assessment. The linking itself is in the custody of RTDCs 1-5. To play its role as coordinator an information exchange forum was furnished: On one hand all the Waste Management Organisations (WMOs) involved in FUNMIG participate in RTDC 6; on the other hand an Integration Monitoring Group (IMG) representing RTDCs 1-5 was established. RTDC 6 is divided into three work packages (WPs): WP 6.1 deals with the boundary conditions to the near field and will consider the outcome of NF-PRO, a sister project within the sixth Framework Programme. WP 6.2 is the core task of RDTC 6. It monitors the scientific results of the project with respect to their application in PA and will give feedback to researchers. Within WP 6.3 Sorption data bases currently used by participating WMOs were compiled and a frame to compile sorption data acquired within FUNMIG will be established

  9. Security Components of Globalization

    Directory of Open Access Journals (Sweden)

    Florin Iftode

    2015-05-01

    Full Text Available The objective of this paper is our intention to present what are the main connections between globalization and international security. In terms of global security we can perceive the globalization as a process by which global state is represented by the UN, with a single world system, represented by major security organizations and with global effects. We will present from the beginning the main theoretical aspects that define the phenomenon of globalization, and then our contribution in assessing the implications of this phenomenon on the regional and global security. The results of our research are materialized in the last part of the paper. They emphasize the personal assessments on how the phenomenon of globalization has direct effect on global security. When talking about government, we think of norms, rules and decisionmaking procedures in the management of international life. The value that we add to the new scientific interpretation of the definition of globalization is represented, primarily, by the valuable bibliographic used resources and the original approach on the concept that refers to the links between globalization and security. This article may be, at any time, a starting point in an interesting research direction in the field of global security.

  10. A model for semantic integration of business components

    CERN Document Server

    Kzaz, Larbi; Sekkaki, Abderrahim; 10.1016/S0550-3213(01)00405-9

    2010-01-01

    Today, reusable components are available in several repositories. These last are certainly conceived for the reusing However, this re-use is not immediate; it requires, in the fact, to pass through some essential conceptual operations, among them in particular, research, integration, adaptation, and composition. We are interested in the present work to the problem of semantic integration of heterogeneous Business Components. This problem is often put in syntactical terms, while the real stake is of semantic order. Our contribution concerns a model proposal for Business components integration as well as resolution method of semantic naming conflicts, met during the integration of Business Components.

  11. Towards an architecture for semantic integration of business components

    CERN Document Server

    Elasri, Hicham; Sekkaki, Abderrahim; 10.1016/S0550-3213(01)00405-8

    2010-01-01

    Today, reusable components are available in several repositorys. These are certainly conceived for re-use. However, this re-use is not immediate, it requires, in effect, to pass by some essential conceptual operations, among which in particular, research, integration, adaptation, and composition. We are interested in the present work to the problem of semantic integration of heterogeneous Business Components. This problem is often put in syntactical terms, while the real stake is of semantic order. Our contribution concerns an architecture proposal for Business components integration and a resolution method of semantic naming conflicts, met during the integration of Business Components

  12. Application of fuzzy-MOORA method: Ranking of components for reliability estimation of component-based software systems

    Directory of Open Access Journals (Sweden)

    Zeeshan Ali Siddiqui

    2016-01-01

    Full Text Available Component-based software system (CBSS development technique is an emerging discipline that promises to take software development into a new era. As hardware systems are presently being constructed from kits of parts, software systems may also be assembled from components. It is more reliable to reuse software than to create. It is the glue code and individual components reliability that contribute to the reliability of the overall system. Every component contributes to overall system reliability according to the number of times it is being used, some components are of critical usage, known as usage frequency of component. The usage frequency decides the weight of each component. According to their weights, each component contributes to the overall reliability of the system. Therefore, ranking of components may be obtained by analyzing their reliability impacts on overall application. In this paper, we propose the application of fuzzy multi-objective optimization on the basis of ratio analysis, Fuzzy-MOORA. The method helps us find the best suitable alternative, software component, from a set of available feasible alternatives named software components. It is an accurate and easy to understand tool for solving multi-criteria decision making problems that have imprecise and vague evaluation data. By the use of ratio analysis, the proposed method determines the most suitable alternative among all possible alternatives, and dimensionless measurement will realize the job of ranking of components for estimating CBSS reliability in a non-subjective way. Finally, three case studies are shown to illustrate the use of the proposed technique.

  13. Performance Engineering Technology for Scientific Component Software

    Energy Technology Data Exchange (ETDEWEB)

    Malony, Allen D.

    2007-05-08

    Large-scale, complex scientific applications are beginning to benefit from the use of component software design methodology and technology for software development. Integral to the success of component-based applications is the ability to achieve high-performing code solutions through the use of performance engineering tools for both intra-component and inter-component analysis and optimization. Our work on this project aimed to develop performance engineering technology for scientific component software in association with the DOE CCTTSS SciDAC project (active during the contract period) and the broader Common Component Architecture (CCA) community. Our specific implementation objectives were to extend the TAU performance system and Program Database Toolkit (PDT) to support performance instrumentation, measurement, and analysis of CCA components and frameworks, and to develop performance measurement and monitoring infrastructure that could be integrated in CCA applications. These objectives have been met in the completion of all project milestones and in the transfer of the technology into the continuing CCA activities as part of the DOE TASCS SciDAC2 effort. In addition to these achievements, over the past three years, we have been an active member of the CCA Forum, attending all meetings and serving in several working groups, such as the CCA Toolkit working group, the CQoS working group, and the Tutorial working group. We have contributed significantly to CCA tutorials since SC'04, hosted two CCA meetings, participated in the annual ACTS workshops, and were co-authors on the recent CCA journal paper [24]. There are four main areas where our project has delivered results: component performance instrumentation and measurement, component performance modeling and optimization, performance database and data mining, and online performance monitoring. This final report outlines the achievements in these areas for the entire project period. The submitted progress

  14. 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...

  15. Cooling system for electronic components

    Energy Technology Data Exchange (ETDEWEB)

    Anderl, William James; Colgan, Evan George; Gerken, James Dorance; Marroquin, Christopher Michael; Tian, Shurong

    2016-05-17

    Embodiments of the present invention provide for non interruptive fluid cooling of an electronic enclosure. One or more electronic component packages may be removable from a circuit card having a fluid flow system. When installed, the electronic component packages are coincident to and in a thermal relationship with the fluid flow system. If a particular electronic component package becomes non-functional, it may be removed from the electronic enclosure without affecting either the fluid flow system or other neighboring electronic component packages.

  16. Cooling system for electronic components

    Science.gov (United States)

    Anderl, William James; Colgan, Evan George; Gerken, James Dorance; Marroquin, Christopher Michael; Tian, Shurong

    2015-12-15

    Embodiments of the present invention provide for non interruptive fluid cooling of an electronic enclosure. One or more electronic component packages may be removable from a circuit card having a fluid flow system. When installed, the electronic component packages are coincident to and in a thermal relationship with the fluid flow system. If a particular electronic component package becomes non-functional, it may be removed from the electronic enclosure without affecting either the fluid flow system or other neighboring electronic component packages.

  17. 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 aspe...

  18. Component reliability data collection in HANARO

    International Nuclear Information System (INIS)

    In this paper, the reliability data used in PSA performed at HANARO design stage are compared with the generic data compiled by IAEA. In order to produce specific-site data, reliability data collection has been initiated. Appropriate database format has been developed and coded database until the year, 2001 has been analyzed for some selected components. These are also compared with the generic data. This study will be continued for more components and PSA application that can contribute for the safe and effective operation of HANARO will be proposed from the result of this study. The specific-site reliability data produced will be a source to review HANARO PSA and to perform PSA of similar reactors

  19. A novel contribution of spvB to pathogenesis of Salmonella Typhimurium by inhibiting autophagy in host cells

    Science.gov (United States)

    Chu, Yuanyuan; Gao, Song; Wang, Ting; Yan, Jing; Xu, Guangmei; Li, Yuanyuan; Niu, Hua; Huang, Rui; Wu, Shuyan

    2016-01-01

    Salmonella plasmid virulence genes (spv) are highly conserved in strains of clinically important Salmonella serovars. It is essential for Salmonella plasmid-correlated virulence, although the exact mechanism remains to be elucidated. Autophagy has been reported to play an important role in host immune responses limiting Salmonella infection. Our previous studies demonstrated that Salmonella conjugative plasmid harboring spv genes could enhance bacterial cytotoxicity by inhibiting autophagy. In the present study, we investigated whether spvB, which is one of the most important constituents of spv ORF could intervene in autophagy pathway. Murine macrophage-like cells J774A.1, human epithelial HeLa cells, and BALB/c mice infected with Salmonella Typhimurium wild type, mutant and complementary strains (carrying or free spvB or complemented only with ADP-ribosyltransferase activity of SpvB) were used in vitro and in vivo assay, respectively. To further explore the molecular mechanisms, both SpvB ectopic eukaryotic expression system and cells deficient in essential autophagy components by siRNA were generated. Results indicated that spvB could suppress autophagosome formation through its function in depolymerizing actin, and aggravate inflammatory injury of the host in response to S. Typhimurium infection. Our studies demonstrated virulence of spvB involving in inhibition of autophagic flux for the first time, which could provide novel insights into Salmonella pathogenesis, and have potential application to develop new antibacterial strategies for Salmonellosis. PMID:26811498

  20. A novel contribution of spvB to pathogenesis of Salmonella Typhimurium by inhibiting autophagy in host cells.

    Science.gov (United States)

    Chu, Yuanyuan; Gao, Song; Wang, Ting; Yan, Jing; Xu, Guangmei; Li, Yuanyuan; Niu, Hua; Huang, Rui; Wu, Shuyan

    2016-02-16

    Salmonella plasmid virulence genes (spv) are highly conserved in strains of clinically important Salmonella serovars. It is essential for Salmonella plasmid-correlated virulence, although the exact mechanism remains to be elucidated. Autophagy has been reported to play an important role in host immune responses limiting Salmonella infection. Our previous studies demonstrated that Salmonella conjugative plasmid harboring spv genes could enhance bacterial cytotoxicity by inhibiting autophagy. In the present study, we investigated whether spvB, which is one of the most important constituents of spv ORF could intervene in autophagy pathway. Murine macrophage-like cells J774A.1, human epithelial HeLa cells, and BALB/c mice infected with Salmonella Typhimurium wild type, mutant and complementary strains (carrying or free spvB or complemented only with ADP-ribosyltransferase activity of SpvB) were used in vitro and in vivo assay, respectively. To further explore the molecular mechanisms, both SpvB ectopic eukaryotic expression system and cells deficient in essential autophagy components by siRNA were generated. Results indicated that spvB could suppress autophagosome formation through its function in depolymerizing actin, and aggravate inflammatory injury of the host in response to S. Typhimurium infection. Our studies demonstrated virulence of spvB involving in inhibition of autophagic flux for the first time, which could provide novel insights into Salmonella pathogenesis, and have potential application to develop new antibacterial strategies for Salmonellosis. PMID:26811498

  1. 75 FR 43799 - Employee Contribution Elections and Contribution Allocations

    Science.gov (United States)

    2010-07-27

    ..., the Agency published a proposed rule with request for comments in the Federal Register (75 FR 34388... ``Automatic Contribution Arrangements'' 74 FR 8200, 8206 (February 24, 2009). The TSP must follow applicable... the default employee contributions will be invested in the G Fund unless the employee makes...

  2. Gamma dose effects valuation on micro computing components

    International Nuclear Information System (INIS)

    Robotics in hostile environment raises the problem of micro computing components resistance with gamma radiation cumulated dose. The current aim is to reach a dose of 3000 grays with industrial components. A methodology and an instrumentation adapted to test this type of components have been developed. The aim of this work is to present the advantages and disadvantages bound to the use of industrial components in the presence of gamma radiation. After an analysis of the criteria allowing to justify the technological choices, the different steps which characterize the selection and the assessment methodology used are explained. The irradiation and measures means now operational are mentioned. Moreover, the supply aspects of the chosen components for the design of an industrialized system is taken into account. These selection and assessment components contribute to the development and design of computers for civil nuclear robotics. (O.M.)

  3. Evaluation of gamma dose effects on micro-computer components

    International Nuclear Information System (INIS)

    The use of robots in hostile environments is confronted to the problem of cumulative gamma radiation dose resistance of micro-computer components. The present-day objective is to reach a 3000 grays dose with CMOS technology industrial components. To reach this objective, a testing methodology and instrumentation adapted to this kind of component has been developed at the CEA Department for Nuclear Instrumentation and Electronics. The aim of this paper is to present the advantages and drawbacks of industrial components used in presence of gamma radiations. After an analysis of criteria for the justification of technological choices, the different steps which characterize the selection and evaluation methodology used are presented. Today's operational irradiation and measurement methods are mentioned. The supplying aspect for selected components used in industrialized systems is also considered. This components selection and evaluation work contributes directly to the development and realization of robot calculators for civil nuclear use. (J.S.). 7 refs., 1 tab

  4. A Component Based Heuristic Search Method with Evolutionary Eliminations

    CERN Document Server

    Li, Jingpeng; Burke, Edmund

    2009-01-01

    Nurse rostering is a complex scheduling problem that affects hospital personnel on a daily basis all over the world. This paper presents a new component-based approach with evolutionary eliminations, for a nurse scheduling problem arising at a major UK hospital. The main idea behind this technique is to decompose a schedule into its components (i.e. the allocated shift pattern of each nurse), and then to implement two evolutionary elimination strategies mimicking natural selection and natural mutation process on these components respectively to iteratively deliver better schedules. The worthiness of all components in the schedule has to be continuously demonstrated in order for them to remain there. This demonstration employs an evaluation function which evaluates how well each component contributes towards the final objective. Two elimination steps are then applied: the first elimination eliminates a number of components that are deemed not worthy to stay in the current schedule; the second elimination may a...

  5. Component-specific modeling. [jet engine hot section components

    Science.gov (United States)

    Mcknight, R. L.; Maffeo, R. J.; Tipton, M. T.; Weber, G.

    1992-01-01

    Accomplishments are described for a 3 year program to develop methodology for component-specific modeling of aircraft hot section components (turbine blades, turbine vanes, and burner liners). These accomplishments include: (1) engine thermodynamic and mission models, (2) geometry model generators, (3) remeshing, (4) specialty three-dimensional inelastic structural analysis, (5) computationally efficient solvers, (6) adaptive solution strategies, (7) engine performance parameters/component response variables decomposition and synthesis, (8) integrated software architecture and development, and (9) validation cases for software developed.

  6. Components of multifractality in the Central England Temperature anomaly series

    CERN Document Server

    de Souza, Jeferson; Grimm, Alice M

    2013-01-01

    We study the multifractal nature of the Central England Temperature (CET) anomaly, a time series that spans more than 200 years. The series is analyzed as a complete data set and considering a sliding window of 11 years. In both cases, we quantify the broadness of the multifractal spectrum as well as its components defined by the deviations from the Gaussian distribution and the influence of the dependence between measurements. The results show that the chief contribution to the multifractal structure comes from the dynamical dependencies, mainly the weak ones, followed by a residual contribution of the deviations from Gaussianity. However, using the sliding window, we verify that the spikes in the non-Gaussian contribution occur at very close dates associated with climate changes determined in previous works by component analysis methods. Moreover, the strong non-Gaussian contribution found in the multifractal measures from the 1960s onwards is in agreement with global results very recently proposed in the l...

  7. Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Zabel Claus

    2011-09-01

    Full Text Available Abstract Parkinson's disease (PD is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO, in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia

  8. Using Independent Component Analysis to Separate Signals in Climate Data

    Energy Technology Data Exchange (ETDEWEB)

    Fodor, I K; Kamath, C

    2003-01-28

    Global temperature series have contributions from different sources, such as volcanic eruptions and El Nino Southern Oscillation variations. We investigate independent component analysis as a technique to separate unrelated sources present in such series. We first use artificial data, with known independent components, to study the conditions under which ICA can separate the individual sources. We then illustrate the method with climate data from the National Centers for Environmental Prediction.

  9. Computational Support for the Selection of Energy Saving Building Components

    OpenAIRE

    De Wilde, P.J.C.J.

    2004-01-01

    Buildings use energy for heating, cooling and lighting, contributing to the problems of exhaustion of fossil fuel supplies and environmental pollution. In order to make buildings more energy-efficient an extensive set of âenergy saving building componentsâ has been developed that contributes to minimizing the energy need of buildings, that helps buildings to access renewable energy sources, and that helps buildings to utilize fossil fuels as efficiently as possible. Examples of such energy sa...

  10. Multi-component assembly casting

    Energy Technology Data Exchange (ETDEWEB)

    James, Allister W.

    2015-10-13

    Multi-component vane segment and method for forming the same. Assembly includes: positioning a pre-formed airfoil component (12) and a preformed shroud heat resistant material (18) in a mold, wherein the airfoil component (12) and the shroud heat resistant material (18) each comprises an interlocking feature (24); preheating the mold; introducing molten structural material (46) into the mold; and solidifying the molten structural material such that it interlocks the pre-formed airfoil component (12) with respect to the preformed shroud heat resistant material (18) and is effective to provide structural support for the shroud heat resistant material (18). Surfaces between the airfoil component (12) and the structural material (46), between the airfoil component (12) and the shroud heat resistant material (18), and between the shroud heat resistant material (18) and the structural material (46) are free of metallurgical bonds.

  11. Frameworks Between Components And Objects

    Directory of Open Access Journals (Sweden)

    Mohamed Belal

    2012-10-01

    Full Text Available Before the emergence of Component-Based Frameworks, similar issues have been addressed by othersoftware development paradigms including e.g. Object-Oriented Programming (OOP, Component-Based Development (CBD, and Object-Oriented Framework. In this study, these approaches especiallyobject-oriented Frameworks are compared to Component-Based Frameworks and their relationship arediscussed. Different software reuse methods impacts on architectural patterns and support forapplication extensions and versioning. It is concluded that many of the mechanisms provided byComponent-Based Framework can be enabled by software elements at the lower level. The maincontribution of Component-Based Framework is the focus on Component development. All of them can bebuilt on each other in layered manner by adopting suitable design patterns. Still some things such aswhich method to develop and upgrade existing application to other approach.

  12. Tree-dependent Component Analysis

    OpenAIRE

    Bach, Francis R.; Jordan, Michael I.

    2012-01-01

    We present a generalization of independent component analysis (ICA), where instead of looking for a linear transform that makes the data components independent, we look for a transform that makes the data components well fit by a tree-structured graphical model. Treating the problem as a semiparametric statistical problem, we show that the optimal transform is found by minimizing a contrast function based on mutual information, a function that directly extends the contrast function used for c...

  13. On verification of software components

    OpenAIRE

    Basem Y. Alkazem

    2012-01-01

    Utilizing third party software components in the development of new systems became somewhat unfavourable approach among many organizations nowadays. This reluctance is primarily built due to the lack of support to verify the quality attributes of software components in order to avoid potential mismatches with systems requirements. This paper presents an approach to overcome this problem by providing a tool support to check component compatibility to a specification provided by developers. So,...

  14. Component separation in abdominal trauma

    OpenAIRE

    Rawstorne, Edward; Smart, Christopher J.; Fallis, Simon A.; Suggett, Nigel

    2014-01-01

    Component separation is established for complex hernia repairs. This case presents early component separation and release of the anterior and posterior sheath to facilitate closure of the abdominal wall following emergency laparotomy, reinforcing the repair with a biological mesh. On Day 11 following an emergency laparotomy for penetrating trauma, this patient underwent component separation and release of the anterior and posterior sheath. An intra-abdominal biological mesh was secured, and t...

  15. Application of Anisotropic Texture Components

    OpenAIRE

    Eschner, Th.; Fundenberger, J.-J.

    1997-01-01

    The description of textures in terms of texture components is an established conception in quantitative texture analysis. Recent developments lead to the representation of orientation distribution functions as a weighted sum of model functions, each corresponding to one anisotropic texture component. As was shown previously, an adequate texture description is possible with only a very small number of anisotropic texture components. As a result, textures and texture changes can be described by...

  16. Facets of Software Component Repository

    OpenAIRE

    Vaneet Kaur; Shivani Goel

    2011-01-01

    The software repository is used for storing, managing, and retrieving large numbers of software components. Repositories should be designed to meet the growing and changing needs of the software development organizations. Storage and representation of reusable software components in software repositories to assist retrieval is a key concern area. In this paper we have discussed various assets of thecomponent repository like component searching mechanisms and classifications such as Free Text,...

  17. Methods of component mode synthesis

    Science.gov (United States)

    Craig, R. R., Jr.

    1977-01-01

    A generalized substructure coupling, or component mode synthesis, procedure is described. Specific methods, applications, and such special topics as damping and experimental verification are surveyed.

  18. Component separation in abdominal trauma.

    Science.gov (United States)

    Rawstorne, Edward; Smart, Christopher J; Fallis, Simon A; Suggett, Nigel

    2014-01-01

    Component separation is established for complex hernia repairs. This case presents early component separation and release of the anterior and posterior sheath to facilitate closure of the abdominal wall following emergency laparotomy, reinforcing the repair with a biological mesh. On Day 11 following an emergency laparotomy for penetrating trauma, this patient underwent component separation and release of the anterior and posterior sheath. An intra-abdominal biological mesh was secured, and the fascia and skin closed successfully. Primary abdominal closure can be achieved in patients with penetrating abdominal trauma with the use of component separation and insertion of intra-abdominal biological mesh, where standard closure is not possible. PMID:24876334

  19. Connected Component Labeling Using Components Neighbors-Scan Labeling Approach

    Directory of Open Access Journals (Sweden)

    Akmal Rakhmadi

    2010-01-01

    Full Text Available Problem statement: Many approaches have been proposed in previous such as the classic sequential connected components labeling algorithm which is relies on two subsequent raster-scans of a binary image. This method produced good performance in terms of accuracy, but because of the implementation of the image processing systems now requires faster process of the computer, the speed of this technique’s process has become an important issue. Approach: A computational approach, called components neighbors-scan labeling algorithm for connected component labeling was presented in this study. This algorithm required scanning through an image only once to label connected components. The algorithm started by scanning from the head of the component’s group, before tracing all the components neighbors by using the main component’s information. This algorithm had desirable characteristics, it is simple while promoted accuracy and low time consuming. By using a table of components, this approach also gave other advantages as the information for the next higher process. Results: The approach had been tested with a collection of binary images. In practically all cases, the technique had successfully given the desired result. Averagely, from the results the algorithm increased the speed around 67.4% from the two times scanning method. Conclusion: Conclusion from the comparison with the previous method, the approach of components neighbors-scan for connected component labeling promoted speed, accuracy and simplicity. The results showed that the approach has a good performance in terms of accuracy, the time consumed and the simplicity of the algorithm.

  20. Components selection for ageing management

    International Nuclear Information System (INIS)

    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

  1. Handbook - Component modelling in analysis of external events

    International Nuclear Information System (INIS)

    contribution due to the area dependence of the component is reduced considerably

  2. APS beamline standard components handbook

    International Nuclear Information System (INIS)

    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

  3. Protection against neurotoxicity by an autophagic mechanism

    Directory of Open Access Journals (Sweden)

    Kangyong Liu

    2012-05-01

    Full Text Available The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP on a 1-methyl-4-phenylpyridinium (MPP+-induced cellular model of Parkinson’s disease (PD and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM for 24 h following pretreatment with NBP (0.1 mM. Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3 were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1 NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2 NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3 Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.

  4. Autophagic degradation of peroxisomes in mammals

    Science.gov (United States)

    Katarzyna, Zientara-Rytter; Suresh, Subramani

    2016-01-01

    Peroxisomes are essential organelles required for proper cell function in all eukaryotic organisms. They participate in a wide range of cellular processes including the metabolism of lipids and generation, as well as detoxification, of hydrogen peroxide. Therefore, peroxisome homeostasis, manifested by the precise and efficient control of peroxisome number and functionality, must be tightly regulated in response to environmental changes. Due to the existence of many physiological disorders and diseases associated with peroxisome homeostasis imbalance, the dynamics of peroxisomes have been widely examined. The increasing volume of reports demonstrating significant involvement of the autophagy machinery in peroxisome removal leads us to summarize current knowledge of peroxisome degradation in mammalian cells. In this review we present current models of peroxisome degradation. We particularly focus on pexophagy - the selective clearance of peroxisomes through autophagy. We also critically discuss concepts of peroxisome recognition for pexophagy, including signaling and selectivity factors. Finally, we present examples of the pathological effects of pexophagy dysfunction and suggest promising future directions. PMID:27068951

  5. The autophagic paradox in cancer therapy.

    Science.gov (United States)

    Wu, W K K; Coffelt, S B; Cho, C H; Wang, X J; Lee, C W; Chan, F K L; Yu, J; Sung, J J Y

    2012-02-23

    Autophagy, hallmarked by the formation of double-membrane bound organelles known as autophagosomes, is a lysosome-dependent pathway for protein degradation. The role of autophagy in carcinogenesis is context dependent. As a tumor-suppressing mechanism in early-stage carcinogenesis, autophagy inhibits inflammation and promotes genomic stability. Moreover, disruption of autophagy-related genes accelerates tumorigenesis in animals. However, autophagy may also act as a pro-survival mechanism to protect cancer cells from various forms of cellular stress. In cancer therapy, adaptive autophagy in cancer cells sustains tumor growth and survival in face of the toxicity of cancer therapy. To this end, inhibition of autophagy may sensitize cancer cells to chemotherapeutic agents and ionizing radiation. Nevertheless, in certain circumstances, autophagy mediates the therapeutic effects of some anticancer agents. Data from recent studies are beginning to unveil the apparently paradoxical nature of autophagy as a cell-fate decision machinery. Taken together, modulation of autophagy is a novel approach for enhancing the efficacy of existing cancer therapy, but its Janus-faced nature may complicate the clinical development of autophagy modulators as anticancer therapeutics. PMID:21765470

  6. Protection against neurotoxicity by an autophagic mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Kangyong; Huang, Jiankang; Chen, Rongfu; Zhang, Ting [Department of Neurology, Affiliated Sixth People' s Hospital, Shanghai Jiaotong University, Shanghai (China); Shen, Liwei [Department of Neurology, Fifth People' s Hospital, Fudan University, Shanghai (China); Yang, Jiajun; Sun, Xiaojiang [Department of Neurology, Affiliated Sixth People' s Hospital, Shanghai Jiaotong University, Shanghai (China)

    2012-03-23

    The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP{sup +})-induced cellular model of Parkinson's disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP{sup +} (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP{sup +}-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP{sup +}-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP{sup +}-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.

  7. Protection against neurotoxicity by an autophagic mechanism

    International Nuclear Information System (INIS)

    The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of Parkinson's disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD

  8. Diesel fuel component contribution to engine emissions and performance. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Erwin, J.; Ryan, T.W. III; Moulton, D.S. [Southwest Research Institute, San Antonio, TX (United States)

    1994-11-01

    Contemporary diesel fuel is a blend of several refinery streams chosen to meet specifications. The need to increase yield of transportation fuel from crude oil has resulted in converting increased proportions of residual oil to lighter products. This conversion is accomplished by thermal, catalytic, and hydrocracking of high molecular weight materials rich in aromatic compounds. The current efforts to reformulate California diesel fuel for reduced emissions from existing engines is an example of another driving force affecting refining practice: regulations designed to reduce exhaust emissions. Although derived from petroleum crude oil, reformulated diesel fuel is an alternative to current specification-grade diesel fuel, and this alternative presents opportunities and questions to be resolved by fuel and engine research. Various concerned parties have argued that regulations for fuel reformulation have not been based on an adequate data base. Despite numerous studies, much ambiguity remains about the relationship of exhaust parameters to fuel composition, particularly for diesel fuel. In an effort to gather pertinent data, the automobile industry and the oil refiners have joined forces in the Air Quality Improvement Research Program (AUTO/OIL) to address this question for gasoline. The objective of that work is to define the relationship between gasoline composition and the magnitude and composition of the exhaust emissions. The results of the AUTO/OEL program will also be used, along with other data bases, to define the EPA {open_quotes}complex model{close_quotes} for reformulated gasolines. Valuable insights have been gained for compression ignition engines in the Coordinating Research Council`s VE-1 program, but no program similar to AUTO/OIL has been started for diesel fuel reformulation. A more detailed understanding of the fuel/performance relationship is a readily apparent need.

  9. Diverse Multilingual Researchers Contribute Language Acquisition Components to an Integrated Model of Education

    Science.gov (United States)

    Hobbs, Robert Dean

    2012-01-01

    Evidence-based outcomes in the literature have caused adjustments in neuro-psycholinguistic and sociolinguistic perspectives that indicate a need for a current model of education. Implications from research suggest the new model of education should use a multilingual framework: L3 enhances and reinforces L2 and L1, if L2 and L1 are supported. The…

  10. DataTAG Contributing to LCG-0 Pilot Startup

    CERN Document Server

    Donno, Flavia; Ciaschini, Vincenzo; Fantinel, Sergio; Rebatto, David; Ronchieri, Elisabetta; Tortone, Gennaro; Vaccarossa, Luca; Verlato, Marco; Vistoli, Cristina; CERN. Geneva. IT Department

    2003-01-01

    The DataTAG project has contributed to the creation of the middleware distribution constituting the base of the LCG-0 pilot. This distribution has demonstrated the possibility of building an EDG release based on iVDGL/VDT, integrating the GLUE schema and early components of the EDG middleware.

  11. Japanese contributions to IAEA INTOR workshop, phase IIA

    International Nuclear Information System (INIS)

    This report corresponds to Chapter X of Japanese contribution report to IAEA INTOR workshop, Phase IIA. Transitional analysis of electromagnetic phenomenon which includes joule heat depositions in supper conducting coil system, electromagnetic force acting on torus components and shell effects for stabilizing plasma positional instability, is carried out. (author)

  12. The Contribution of Visualization to Learning Computer Architecture

    Science.gov (United States)

    Yehezkel, Cecile; Ben-Ari, Mordechai; Dreyfus, Tommy

    2007-01-01

    This paper describes a visualization environment and associated learning activities designed to improve learning of computer architecture. The environment, EasyCPU, displays a model of the components of a computer and the dynamic processes involved in program execution. We present the results of a research program that analysed the contribution of…

  13. Complement component 3 (C3)

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003539.htm Complement component 3 (C3) To use the sharing features on this page, ... be some throbbing. Why the Test is Performed C3 and C4 are the most commonly measured complement components. A complement test may be used to monitor ...

  14. Secure coupling of hardware components

    NARCIS (Netherlands)

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

    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, f

  15. 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 her

  16. Unblockable Compositions of Software Components

    DEFF Research Database (Denmark)

    Dong, Ruzhen; Faber, Johannes; Liu, Zhiming;

    2012-01-01

    end, we develop an algorithm to compute the unblockable interaction behavior, called the interface model of a component, from its execution model. Based on this model, we introduce composition operators for the components and prove important compositionality results, showing the conditions under which...... composition of interface models preserves unblockable sequences of provided services....

  17. A Model for Semantic Integration of Business Components

    Directory of Open Access Journals (Sweden)

    Larbi KZAZ

    2010-02-01

    Full Text Available Reusable components are available in several repositories; they are certainly conceived for reusing indeveloping information system, however, their re-use is not immediate; it requires, in fact, to passthrough some essential conceptual operations, among them in particular, research, integration,adaptation, and composition. We are interested in the present work to the problem of semanticintegration of heterogeneous Business Components. This problem is often put in syntactical terms,while the real stake is of semantic order. Our contribution concerns a model proposal for Businesscomponents integration as well as resolution method of semantic naming conflicts, met during theintegration of Business Components.

  18. 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.

  19. ECN contributions to GLOBAL '95

    International Nuclear Information System (INIS)

    This report contains the 9 contributions of the Netherlands Energy Research Foundation ECN to the international conference on evaluation of emerging nuclear fuel cycle systems, GLOBAL '95, held in Versailles, France, on September 11-14, 1995. (orig./GL)

  20. Uncapacitated facility location problems: contributions

    Directory of Open Access Journals (Sweden)

    Galvão Roberto Diéguez

    2004-01-01

    Full Text Available The objective of the present paper is to review my personal contributions in the field of uncapacitated facility location problems. These contributions took place throughout my academic career, from the time I was a Ph.D. student at Imperial College to the present day. They cover approximately 30 years, from 1973 to 2003; they address: algorithms developed for the p-median problem and for a general formulation of uncapacitated location problems; the study of dynamic location models; covering and hierarchical location problems; queuing-based probabilistic location models. The contributions encompass theoretical developments, computational algorithms and practical applications. All work took place in an academic environment, with the invaluable collaboration of colleagues (both in Brazil and abroad and research students at COPPE. Each section in the paper is dedicated to a topic that involves a personal contribution. Every one of them is placed within the context of the existing literature.

  1. ECN contributions to GLOBAL `95

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-06-01

    This report contains the 9 contributions of the Netherlands Energy Research Foundation ECN to the international conference on evaluation of emerging nuclear fuel cycle systems, GLOBAL `95, held in Versailles, France, on September 11-14, 1995. (orig./GL).

  2. DFB component production at IHEP complete

    CERN Multimedia

    2007-01-01

    The last of the components for the 42 DFBs (electrical distribution boxes feeding the strings of superconducting magnets in the LHC) produced for CERN by IHEP Protvino (Russia) were delivered to CERN in January 2007. The DFBs will provide the electrical supply for the superconducting magnets for the LHC, making possible the transition from room temperature down to -268ºC (4.5 K) (see Bulletin No. 37/2006). This important achievement was celebrated on the 14th February 2007 at the IHEP House of Scientists in Protvino in the presence of all the IHEP personnel who contributed to the DFB components production, and with the participation of eight delegates from CERN Management and CERN engineers involved in DFB production. Lyn Evans handed over a present symbolizing the IHEP-CERN collaboration to Nikolaj Tyurin, who offered to Lyn Evans a model of a DFB. Since August 2005, when the components for the first two boxes arrived at CERN, a total of 360 tonnes of raw materials were transported to IHEP on 19 lorries...

  3. Stuart Hall’ Contributions to CCCS

    Institute of Scientific and Technical Information of China (English)

    涂艳

    2014-01-01

    Hall is the most prominent master of Birmingham school. To some extent, Hall just represents CCCS and makes outstanding contributions to establishment of this school. Hall’s cultural theory is characterized by the interdisciplinary ideology, cultural gaze of race diaspora, collective creation, academic openness, cultural politics, civilization of the talent and so on, so that displays his value and significance as a cultural theorists and critic, in addition demonstrates his contribution to the whole world.

  4. Individual focus and knowledge contribution

    OpenAIRE

    Adamic, Lada A.; Wei, Xiao; Yang, Jiang; Gerrish, Sean; Nam, Kevin K.; Clarkson, Gavin S.

    2010-01-01

    Before contributing new knowledge, individuals must attain requisite background knowledge or skills through schooling, training, practice, and experience. Given limited time, individuals often choose either to focus on few areas, where they build deep expertise, or to delve less deeply and distribute their attention and efforts across several areas. In this paper we measure the relationship between the narrowness of focus and the quality of contribution across a range of both traditional and ...

  5. Contribution of Groundwater Depletion to Global Mean Sea Level Rise

    Science.gov (United States)

    Lambinicio, A.; An, K.; Reager, J. T.; Druffel-Rodriguez, R. E.; Richey, A. S.; Famiglietti, J. S.; Rodell, M.

    2012-12-01

    The contribution of groundwater depletion to Global Mean Sea Level Rise (GMSLR) is an important topic and source of great uncertainty in the GMSLR budget. This research uses gridded GRACE Tellus satellite data to quantify changes in total land water storage, including those of groundwater. Global Land Data Assimilation System land components such as soil moisture, canopy moisture, and snow, are subtracted from the GRACE data to isolate the groundwater component. The resulting trends show that most continents are gaining in groundwater storage, which is consistent with GRACE-based estimates of zero-to-increasing changes in total land water. Results indicate a negative contribution to GMSLR for the GRACE time period, which is in contrast to the positive contribution identified in recent studies.

  6. Apparatus for remotely handling components

    Science.gov (United States)

    Szkrybalo, Gregory A.; Griffin, Donald L.

    1994-01-01

    The inventive apparatus for remotely handling bar-like components which define a longitudinal direction includes a gripper mechanism for gripping the component including first and second gripper members longitudinally fixedly spaced from each other and oriented parallel to each other in planes transverse to the longitudinal direction. Each gripper member includes a jaw having at least one V-groove with opposing surfaces intersecting at a base and extending radially relative to the longitudinal direction for receiving the component in an open end between the opposing surfaces. The V-grooves on the jaw plate of the first and second gripper members are aligned in the longitudinal direction to support the component in the first and second gripper members. A jaw is rotatably mounted on and a part of each of the first and second gripper members for selectively assuming a retracted mode in which the open end of the V-groove is unobstructed and active mode in which the jaw spans the open end of the V-groove in the first and second gripper members. The jaw has a locking surface for contacting the component in the active mode to secure the component between the locking surface of the jaw and the opposing surfaces of the V-groove. The locking surface has a plurality of stepped portions, each defining a progressively decreasing radial distance between the base of the V-groove and the stepped portion opposing the base to accommodate varying sizes of components.

  7. Vacuum Brazing of Accelerator Components

    Science.gov (United States)

    Singh, Rajvir; Pant, K. K.; Lal, Shankar; Yadav, D. P.; Garg, S. R.; Raghuvanshi, V. K.; Mundra, G.

    2012-11-01

    Commonly used materials for accelerator components are those which are vacuum compatible and thermally conductive. Stainless steel, aluminum and copper are common among them. Stainless steel is a poor heat conductor and not very common in use where good thermal conductivity is required. Aluminum and copper and their alloys meet the above requirements and are frequently used for the above purpose. The accelerator components made of aluminum and its alloys using welding process have become a common practice now a days. It is mandatory to use copper and its other grades in RF devices required for accelerators. Beam line and Front End components of the accelerators are fabricated from stainless steel and OFHC copper. Fabrication of components made of copper using welding process is very difficult and in most of the cases it is impossible. Fabrication and joining in such cases is possible using brazing process especially under vacuum and inert gas atmosphere. Several accelerator components have been vacuum brazed for Indus projects at Raja Ramanna Centre for Advanced Technology (RRCAT), Indore using vacuum brazing facility available at RRCAT, Indore. This paper presents details regarding development of the above mentioned high value and strategic components/assemblies. It will include basics required for vacuum brazing, details of vacuum brazing facility, joint design, fixturing of the jobs, selection of filler alloys, optimization of brazing parameters so as to obtain high quality brazed joints, brief description of vacuum brazed accelerator components etc.

  8. Vacuum Brazing of Accelerator Components

    International Nuclear Information System (INIS)

    Commonly used materials for accelerator components are those which are vacuum compatible and thermally conductive. Stainless steel, aluminum and copper are common among them. Stainless steel is a poor heat conductor and not very common in use where good thermal conductivity is required. Aluminum and copper and their alloys meet the above requirements and are frequently used for the above purpose. The accelerator components made of aluminum and its alloys using welding process have become a common practice now a days. It is mandatory to use copper and its other grades in RF devices required for accelerators. Beam line and Front End components of the accelerators are fabricated from stainless steel and OFHC copper. Fabrication of components made of copper using welding process is very difficult and in most of the cases it is impossible. Fabrication and joining in such cases is possible using brazing process especially under vacuum and inert gas atmosphere. Several accelerator components have been vacuum brazed for Indus projects at Raja Ramanna Centre for Advanced Technology (RRCAT), Indore using vacuum brazing facility available at RRCAT, Indore. This paper presents details regarding development of the above mentioned high value and strategic components/assemblies. It will include basics required for vacuum brazing, details of vacuum brazing facility, joint design, fixturing of the jobs, selection of filler alloys, optimization of brazing parameters so as to obtain high quality brazed joints, brief description of vacuum brazed accelerator components etc.

  9. Ultrasonic testing of complex materials, components and joints. Seminar

    International Nuclear Information System (INIS)

    This seminar proceedings contains 17 contributions on the topic ultrasonic testing of complex materials and material combinations that are increasingly being used in lightweight components in the application fields of aerospace, automotive sector and renewable energies. These demand increased requirement profile to already established NDT methods, which are discussed in this seminar.

  10. Evaluation of cutting force uncertainty components in turning

    DEFF Research Database (Denmark)

    Axinte, Dragos Aurelian; Belluco, Walter; De Chiffre, Leonardo

    2000-01-01

    A procedure is proposed for the evaluation of those uncertainty components of a single cutting force measurement in turning that are related to the contributions of the dynamometer calibration and the cutting process itself. Based on an empirical model including errors form both sources, the unce...

  11. A Critical Analysis of Football Bowl Subdivision Coaching Contract Components

    Science.gov (United States)

    Nichols, Justin Keith

    2012-01-01

    This exploratory study is designed to inventory and analyze contract components used by Football Bowl Subdivision (FBS) institutions in the National Collegiate Athletic Association (NCAA) to further contribute to the body research. The FBS is comprised of 120 institutions and 94 of those institutions submitted contracts to "USA Today"…

  12. Bacterial contamination of blood components.

    Science.gov (United States)

    Seghatchian, J

    2001-10-01

    Despite considerable advances in the safety of blood components, transfusion associated bacterial infection (TABI) remains an unresolved problem. As yet there are no perfect preventative, screening and/or detection methodologies for eliminating contaminated units. Until a practical, rapid, cost-effective and logistically acceptable test becomes available, we should be satisfied with the choice of various limited solutions that at least partially improve the bacterial safety of blood components. It is also necessary to establish standardised guidelines and agreed upon systematic procedures for the recognition and reporting of the laboratory and clinical evaluation of adverse reactions in recipients of contaminated blood components. PMID:11761277

  13. Electronic components, tubes and transistors

    CERN Document Server

    Dummer, G W A

    1965-01-01

    Electronic Components, Tubes and Transistors aims to bridge the gap between the basic measurement theory of resistance, capacitance, and inductance and the practical application of electronic components in equipments. The more practical or usage aspect of electron tubes and semiconductors is given emphasis over theory. The essential characteristics of each main type of component, tube, and transistor are summarized. This book is comprised of six chapters and begins with a discussion on the essential characteristics in terms of the parameters usually required in choosing a resistor, including s

  14. Composite components on commercial aircraft

    Science.gov (United States)

    Dexter, H. B.

    1980-01-01

    The paper considers the use of composite components in commercial aircraft. NASA has been active in sponsoring flight service programs with advanced composites for the last 10 years, with 2.5 million total composite component hours accumulated since 1970 on commercial transports and helicopters with no significant degradation in residual strength of composite components. Design, inspection, and maintenance procedures have been developed; a major NASA/US industry technology program has been developed to reduce fuel consumption of commercial transport aircraft through the use of advanced composites.

  15. Ceramic components for MHD electrode

    Science.gov (United States)

    Marchant, D.D.

    A ceramic component which exhibits electrical conductivity down to near room temperatures has the formula: Hf/sub x/In/sub y/A/sub z/O/sub 2/ where x = 0.1 to 0.4, y = 0.3 to 0.6, z = 0.1 to 0.4 and A is a lanthanide rare earth or yttrium. The component is suitable for use in the fabrication of MHD electrodes or as the current leadout portion of a composite electrode with other ceramic components.

  16. Biophotons Contribute to Retinal Dark Noise.

    Science.gov (United States)

    Li, Zehua; Dai, Jiapei

    2016-06-01

    The discovery of dark noise in retinal photoreceptors resulted in a long-lasting controversy over its origin and the underlying mechanisms. Here, we used a novel ultra-weak biophoton imaging system (UBIS) to detect biophotonic activity (emission) under dark conditions in rat and bullfrog (Rana catesbeiana) retinas in vitro. We found a significant temperature-dependent increase in biophotonic activity that was completely blocked either by removing intracellular and extracellular Ca(2+) together or inhibiting phosphodiesterase 6. These findings suggest that the photon-like component of discrete dark noise may not be caused by a direct contribution of the thermal activation of rhodopsin, but rather by an indirect thermal induction of biophotonic activity, which then activates the retinal chromophore of rhodopsin. Therefore, this study suggests a possible solution regarding the thermal activation energy barrier for discrete dark noise, which has been debated for almost half a century. PMID:27059222

  17. Decontamination of CAGR gas circulator components

    International Nuclear Information System (INIS)

    This paper describes the development and full-scale trial of two methods for removal of radioactive contamination on the surfaces of CAGR gas circulator components. The two methods described are a particle impact cleaning (PIC) decontamination technique and an electrochemical technique, 'electro-swabbing', which is based on the principle of decontamination by electro-polishing. In developing these techniques it was necessary to take account of the physical and chemical nature of the surface deposits on the gas circulator components; these were shown to consist of magnetite-type oxide and carbonaceous material. In order to follow the progress of the decontamination it was also necessary to develop a surface sampling technique which was effective and precise under these conditions; an electrochemical technique, employing similar principles to the electro-swabbing process, was developed for this purpose. The full-scale trial of the PIC decontamination technique was carried out on an inlet guide vane (IGV) assembly, this having been identified as the component from the gas circulator which contributes most to the radiation dose accumulated during routine circulator maintenance. The technique was shown to be practically viable and some 99% of the radioactive contamination was readily removed from the treated surfaces with only negligible surface damage being caused. The full-scale trial of the electro-swabbing decontamination technique was carried out on a gas circulator impeller. High decontamination factors were again achieved with ≥ 99% of the radioactive contamination being removed from the treated surfaces. The technique has practical limitations in terms of handling and treatment of waste-arisings. However, the use of specially-designed swabbing electrodes may allow the treatment of constricted geometries inaccessible to techniques such as PIC. The technique is also highly suitable for the treatment of soft-finish materials and of components fabricated from a

  18. 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,...

  19. Ageing of zirconium alloy components

    International Nuclear Information System (INIS)

    India has two types (pressurized heavy water reactors (PHWRs) and boiling water reactors (BWRs)) of commercial nuclear reactors in operation, in addition to research reactors. Many of the life limiting critical components in these reactors are fabricated from zirconium alloys. The progressive degradation of these components caused by the cumulative exposure of high energy neutron irradiation with increasing period of reactor operation was monitored to assess the degree of ageing. The components/specimens examined included fuel element claddings removed from BWRs, pressure tubes and garter springs removed from PHWRs and calandria tube specimens used in PHWRs. The tests included tension test (for cladding, garter spring), fracture toughness test (for pressure tube), crush test (for garter spring), and measurement of irradiation induced growth (for calandria tube). Results of various tests conducted are presented and applications of the test results are elaborated for residual life estimation/life extension of the components

  20. US LMFBR coolant system components

    International Nuclear Information System (INIS)

    Development and use of LMFBR coolant system components in the United States has progressed through more than two decades, with both the government and private sectors participating significantly in the support and conduct of the work. The purpose of this paper is to present the major functional requirements that these components are expected to meet, their current status and future direction of development, and recent test results. The components to be discussed are: (1) primary and intermediate system large sodium piping; (2) primary and intermediate system large sodium valves; (3) primary and intermediate main sodium pumps; (4) intermediate heat exchanger (IHX); and (5) sodium-heated steam generators. The major near-term activities associated with the above components are focused primarily on the Fast Flux Test Facility (FFTF), the Clinch River Breeder Reactor Plant (CRBRP), and the anticipated commercial LMFBR's

  1. Principles of Principal Component Analysis

    OpenAIRE

    Durham, Catherine A.; King, Robert P.

    2010-01-01

    With increasing frequency consumer studies are supplementing demographic and price variables with responses to an extended set of Likert-scale questions to elicit information on consumer motivations and attitudes. Principal compo­nent analysis (PCA) is a statistical tool that reduces a large number of variables to a smaller set of "components" that describe as much as possible of the variation in the original variables. Attitudinal responses can then be represented by component scores in sta...

  2. Plasmonic components fabrication via nanoimprint

    DEFF Research Database (Denmark)

    Boltasseva, Alexandra

    2009-01-01

    A review report on nanoimprinted plasmonic components is given. The fabrication of different metal–dielectric geometries and nanostructured surfaces that support either propagating or localized surface plasmon modes is discussed. The main characteristics and advantages of the nanoimprint technolo...... surfaces for enhanced transmission studies and sensor applications is also discussed. Throughout the report, the main fabrication schemes are described, as well as the challenges facing future manufacturing of plasmonic components for device applications....

  3. Formal aspects of component software

    OpenAIRE

    Sun, Meng; Schatz, B.

    2014-01-01

    This issue includes extended versions of selected best papers from the 7th International Workshop on Formal Aspects of Component Software (FACS 2010) held in Guimarães, Portugal on October 14–16, 2010. The component-based software development approach has emerged as a promising paradigm to cope with an ever increasing complexity of present-day software solutions by bringing sound production and engineering principles into software engineering. However, many conceptual and technological iss...

  4. Components in models of learning: Different operationalisations and relations between components

    Directory of Open Access Journals (Sweden)

    Mirkov Snežana

    2013-01-01

    Full Text Available This paper provides the presentation of different operationalisations of components in different models of learning. Special emphasis is on the empirical verifications of relations between components. Starting from the research of congruence between learning motives and strategies, underlying the general model of school learning that comprises different approaches to learning, we have analyzed the empirical verifications of factor structure of instruments containing the scales of motives and learning strategies corresponding to these motives. Considering the problems in the conceptualization of the achievement approach to learning, we have discussed the ways of operational sing the goal orientations and exploring their role in using learning strategies, especially within the model of the regulation of constructive learning processes. This model has served as the basis for researching learning styles that are the combination of a large number of components. Complex relations between the components point to the need for further investigation of the constructs involved in various models. We have discussed the findings and implications of the studies of relations between the components involved in different models, especially between learning motives/goals and learning strategies. We have analyzed the role of regulation in the learning process, whose elaboration, as indicated by empirical findings, can contribute to a more precise operationalisation of certain learning components. [Projekat Ministarstva nauke Republike Srbije, br. 47008: Unapređivanje kvaliteta i dostupnosti obrazovanja u procesima modernizacije Srbije i br. 179034: Od podsticanja inicijative, saradnje i stvaralaštva u obrazovanju do novih uloga i identiteta u društvu

  5. Stuart Hall’ Contributions to CCCS

    Institute of Scientific and Technical Information of China (English)

    涂艳

    2014-01-01

    Hall is the most prominent master of Birmingham school.To some extent,Hall just represents CCCS and makes outstanding contributions to establishment of this school.Hall’s cultural theory is characterized by the interdisciplinary ideology,cultural gaze of race diaspora,collective creation,academic openness,cultural politics,civilization of the talent and so on,so that displays his value and significance as a cultural theorists and critic,in addition demonstrates his contribution to the whole world.

  6. Individual focus and knowledge contribution

    CERN Document Server

    Adamic, Lada A; Yang, Jiang; Gerrish, Sean; Nam, Kevin K; Clarkson, Gavin S

    2010-01-01

    Before contributing new knowledge, individuals must attain requisite background knowledge or skills through schooling, training, practice, and experience. Given limited time, individuals often choose either to focus on few areas, where they build deep expertise, or to delve less deeply and distribute their attention and efforts across several areas. In this paper we measure the relationship between the narrowness of focus and the quality of contribution across a range of both traditional and recent knowledge sharing media, including scholarly articles, patents, Wikipedia, and online question and answer forums. Across all systems, we observe a small but significant positive correlation between focus and quality.

  7. The contributions of Marcel Proust to psychoanalysis.

    Science.gov (United States)

    Bernstein, Anne Elayne

    2005-01-01

    This article is about the major contribution of Marcel Proust to psychoanalysis in his seven-part novel, A La Rècherche Du Temps Perdu (translated as Rembrance of Things Past, 1934). This work spans two decades, from 1988, when Proust writing to 1927, when the last part was published 5 years after his death. Proust, a literary scholar whose knowledge dated to the early Greeks, knew nothing of Freud or psychoanalysis. His major contributions were to the emergence of memory, specifically the exquisite details of the descriptive unconscious, which we can now explain in cognitive neuroscientific terms. Freud wanted to do this for all mental processes in 'The Project'. Proust contributed to the projective aspects of passionate love. Kernberg has pointed out that although psychoanalysts knew about transference love, idealization, and sex, love has only been a subject for us in the 1900s. Proust also wrote of jealousy as a necessary concomitant of love. He proposed that all humans had pluripotential sexuality and recognized the psychodynamics of the perversions in a way that is closer to modern psychoanalysts like Chassuguet-Smirgel. Proust was himself psychologically disabled, with an illness his father called neurasthenia, adding somatic components and abulia, inability to make decisions. We would probably recognize him today as having a borderline personality disorder, with superior cognition, depression, somatization, obsessions, compulsions, phobias, and severe anxiety, which he understood was the result of his inability to separate from his mother. Proust's findings in all these areas are compared with the psychoanalytic literature--Freud, to the present. PMID:15953781

  8. Autophagy contributes to resistance of tumor cells to ionizing radiation

    International Nuclear Information System (INIS)

    Background and purpose: Autophagy signaling is a novel important target to improve anticancer therapy. To study the role of autophagy on resistance of tumor cells to ionizing radiation (IR), breast cancer cell lines differing in their intrinsic radiosensitivity were used. Materials and methods: Breast cancer cell lines MDA-MB-231 and HBL-100 were examined with respect to clonogenic cell survival and induction of autophagy after radiation exposure and pharmacological interference of the autophagic process. As marker for autophagy the appearance of LC3-I and LC3-II proteins was analyzed by SDS-PAGE and Western blotting. Formation of autophagic vacuoles was monitored by immunofluorescence staining of LC3. Results: LC3-I and LC3-II formation differs markedly in radioresistant MDA-MB-231 versus radiosensitive HBL-100 cells. Western blot analyses of LC3-II/LC3-I ratio indicated marked induction of autophagy by IR in radioresistant MDA-MB-231 cells, but not in radiosensitive HBL-100 cells. Indirect immunofluorescence analysis of LC3-II positive vacuoles confirmed this differential effect. Pre-treatment with 3-methyladenine (3-MA) antagonized IR-induced autophagy. Likewise, pretreatment of radioresistant MDA-231 cells with autophagy inhibitors 3-MA or chloroquine (CQ) significantly reduced clonogenic survival of irradiated cells. Conclusion: Our data clearly indicate that radioresistant breast tumor cells show a strong post-irradiation induction of autophagy, which thus serves as a protective and pro-survival mechanism in radioresistance.

  9. RELATIVE PRINCIPLE COMPONENT AND RELATIVE PRINCIPLE COMPONENT ANALYSIS ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    Wen Chenglin; Wang Tianzhen; Hu Jing

    2007-01-01

    In this letter, the new concept of Relative Principle Component (RPC) and method of RPC Analysis (RPCA) are put forward. Meanwhile, the concepts such as Relative Transform (RT), Rotundity Scatter (RS) and so on are introduced. This new method can overcome some disadvantages of the classical Principle Component Analysis (PCA) when data are rotundity scatter. The RPC selected by RPCA are more representative, and their significance of geometry is more notable, so that the application of the new algorithm will be very extensive. The performance and effectiveness are simply demonstrated by the geometrical interpretation proposed.

  10. RF current drive components in a tokamak

    International Nuclear Information System (INIS)

    Theoretical analysis of low frequency current drive in a tokamak is presented. The global model discussed includes kinetic hot plasma effects and collisions. It is found that all kinds of wave-plasma interactions (resonant wave-electron interaction, resonant wave-ion interaction and collisions) can contribute to the current drive. The analysis presented stresses the two new current drive components, the resonant helicity current and the nonresonant collisionless current. Helicity current drive is proportional to the parallel helicity flux and to the wave damping strength, which is defined by the wave-plasma interaction process. The collisionless part of the nonresonant current is proportional to wave damping on ions. However, this is an electron current, and wave-ion interaction just creates necessary polarization of the wave to drive a current. The resistive MHD limit is considered as well, and the correct expression for the RF driven current including the Alfven resonance effect, is given. (author) 17 refs

  11. Incorporating global components into ethics education.

    Science.gov (United States)

    Wang, George; Thompson, Russell G

    2013-03-01

    Ethics is central to science and engineering. Young engineers need to be grounded in how corporate social responsibility principles can be applied to engineering organizations to better serve the broader community. This is crucial in times of climate change and ecological challenges where the vulnerable can be impacted by engineering activities. Taking a global perspective in ethics education will help ensure that scientists and engineers can make a more substantial contribution to development throughout the world. This paper presents the importance of incorporating the global and cross culture components in the ethic education. The authors bring up a question to educators on ethics education in science and engineering in the globalized world, and its importance, necessity, and impendency. The paper presents several methods for discussion that can be used to identify the differences in ethics standards and practices in different countries; enhance the student's knowledge of ethics in a global arena. PMID:21769592

  12. Diesel engine management systems and components

    CERN Document Server

    2014-01-01

    This reference book provides a comprehensive insight into todays diesel injection systems and electronic control. It focusses on minimizing emissions and exhaust-gas treatment. Innovations by Bosch in the field of diesel-injection technology have made a significant contribution to the diesel boom. Calls for lower fuel consumption, reduced exhaust-gas emissions and quiet engines are making greater demands on the engine and fuel-injection systems. Contents History of the diesel engine.- Areas of use for diesel engines.- Basic principles of the diesel engine.- Fuels: Diesel fuel.- Fuels: Alternative fuels.- Cylinder-charge control systems.- Basic principles of diesel fuel-injection.- Overview of diesel fuel-injection systems.- Fuel supply to the low pressure stage.- Overview of discrete cylinder systems.- Unit injector system.- Unit pump system.- Overview of common-rail systems.- High pressure components of the common-rail system.- Injection nozzles.- Nozzle holders.- High pressure lines.- Start assist systems.-...

  13. Nuclear Apoptosis Contributes to Sarcopenia

    OpenAIRE

    Alway, Stephen E.; Parco M. Siu

    2008-01-01

    Apoptosis results in DNA fragmentation and, subsequently, destruction of cells containing a single nucleus. Our hypothesis is that multinucleated cells such as muscle fibers can experience apoptotic-induced loss of single nuclei (nuclear apoptosis) without destruction of the entire fiber. The loss of nuclei likely contributes to atrophy and sarcopenia. Furthermore, increased chronic activity attenuates apoptotic signaling, which may reduce sarcopenia.

  14. The component compensation of geomagnetic field vector measurement system

    International Nuclear Information System (INIS)

    Magnetic field distortion of INS is the major factor influencing the accuracy of geomagnetic field information measurement system. Simulation and experiment results show that traditional scalar compensation methods are disabled for component compensation. A component compensation method is proposed, in which parallelepiped frame and perpendicular platform are used with designed operation process. Comparing with traditional methods, the component compensation method is effective for distortion parameter estimation, and it shows better component compensation performance. Experimental test result demonstrates that distortion field components of INS are suppressed approximately two orders after compensation, and the North, Vertical and East component measurement error of the geomagnetic field are reduced to 2.3%, 3.3% and 4.5% of the former values respectively. Declination error is reduced from 7.074° to 0.331° (4.6% of the former value). This compensation method contributes to the accuracy improvement of geomagnetic field vector measurement system. - Highlights: • A component compensation method is proposed. • All parameters of soft-iron matrix and hard-iron matrix are calculated accurately. • The proposed method shows better component compensation performance. • It can overcome the problem of TMI measurement. • The compensation method has a wide application in geoscience

  15. 纤维蛋白凝胶承载内皮祖细胞在移植梗死心肌后的细胞自噬变化%Autophagic changes of the endothelial progenitor cells carried with fibrin glue after transplantation into the infracted myocardium

    Institute of Scientific and Technical Information of China (English)

    张丹; 王海杰; 谭玉珍; 王强利; 伍金红; 李志华; 权哲

    2013-01-01

    Objective To investigate autophagic changes endothelial progenitor cells (EPCs) carried with fibrin glue after transplantation into the infarcted myocardial and to explore effects of autophagy on maintaining the implanted cells to survive and fibrin on protecting the cells. Methods The model of myocardial infarction was established with ligating the anterior descending branch of the left coronary artery of rats. The EPCs sorted from human umbilical cord blood were injected into the myocardium at the normal region, periphery of the infarcted region and infarcted region. After transplantation for two hours, the tissues at injection sites were removed, the semithin sections were prepared. Distribution of the EPCs carried with fibrin glue were examined. After positioning the implanted cells, the ultrathin sections were prepared. The changes of the autophagic structures in EPCs and compatibility of fibrin with EPCs and myocardium were evaluated. Results Compared with the normal region, the autophagic EPCs in the periphery of the infarcted region increased, and the autophagic structures in the cells increased. In the infarcted region, EPC autophagy enhanced significantly, and necrosis or apoptosis occurred in some cells. Compatibility of fibrin with EPCs and myocardium was good. The implanted cells in fibrin glue extended well, some EPCs adhered to cardiaomyocytes. Conclusion When EPCs are transplanted into the periphery of the infarcted region, mild ischemia induces autophagy of the cells, which is beneficial for maintaining survival of the transplanted cells. Carrying EPCs with fibrin glue may avoid of cell lose and promote cell survival.%目的 观察心肌梗死后移植内皮祖细胞(EPCs)时的细胞自噬变化,探讨自噬维持移植细胞存活和纤维蛋白凝胶保护细胞的作用.方法 通过结扎左冠状动脉的前降支建立大鼠心肌梗死模型后,在正常区、梗死边缘区和梗死区分别注射从人脐带血中分选的EPCs.2h后取

  16. Hemodynamic response based mixture model to estimate micro- and macro-vasculature contributions in functional MRI

    CERN Document Server

    Singh, Manbir; Sungkarat, Witaya; Zhou, Yongxia

    2003-01-01

    A multi-componet model reflecting the temporal characteristics of micro- and macro-vasculature hemodynamic responses was used to fit the time-course of voxels in functional MRI (fMRI). The number of relevant components, the latency of the first component, the time- separation among the components, their relative amplitude and possible interpretation in terms of partial volume contributions of micro- and macro-components to the time-course data were investigated. Analysis of a reversing checkerboard experiment revealed that there was no improvement in the filing beyond two components. Using a two-component model, the fractional abundances of the micro- and macro-vasculature were estimated in individual voxels. These results suggest the potential of a mixture-model approach to mitigate partial volume effects and separate contributions of vascular components within a voxel in fMRI.

  17. Component protection based automatic control

    International Nuclear Information System (INIS)

    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

  18. Automated cleaning of electronic components

    International Nuclear Information System (INIS)

    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

  19. 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.

  20. Intelligent Component Monitoring for Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Lefteri Tsoukalas

    2010-07-30

    Reliability and economy are two major concerns for a nuclear power generation system. Next generation nuclear power reactors are being developed to be more reliable and economic. An effective and efficient surveillance system can generously contribute toward this goal. Recent progress in computer systems and computational tools has made it necessary and possible to upgrade current surveillance/monitoring strategy for better performance. For example, intelligent computing techniques can be applied to develop algorithm that help people better understand the information collected from sensors and thus reduce human error to a new low level. Incidents incurred from human error in nuclear industry are not rare and have been proven costly. The goal of this project is to develop and test an intelligent prognostics methodology for predicting aging effects impacting long-term performance of nuclear components and systems. The approach is particularly suitable for predicting the performance of nuclear reactor systems which have low failure probabilities (e.g., less than 10-6 year-). Such components and systems are often perceived as peripheral to the reactor and are left somewhat unattended. That is, even when inspected, if they are not perceived to be causing some immediate problem, they may not be paid due attention. Attention to such systems normally involves long term monitoring and possibly reasoning with multiple features and evidence, requirements that are not best suited for humans.

  1. Principal Component Analysis In Radar Polarimetry

    Directory of Open Access Journals (Sweden)

    A. Danklmayer

    2005-01-01

    Full Text Available Second order moments of multivariate (often Gaussian joint probability density functions can be described by the covariance or normalised correlation matrices or by the Kennaugh matrix (Kronecker matrix. In Radar Polarimetry the application of the covariance matrix is known as target decomposition theory, which is a special application of the extremely versatile Principle Component Analysis (PCA. The basic idea of PCA is to convert a data set, consisting of correlated random variables into a new set of uncorrelated variables and order the new variables according to the value of their variances. It is important to stress that uncorrelatedness does not necessarily mean independent which is used in the much stronger concept of Independent Component Analysis (ICA. Both concepts agree for multivariate Gaussian distribution functions, representing the most random and least structured distribution. In this contribution, we propose a new approach in applying the concept of PCA to Radar Polarimetry. Therefore, new uncorrelated random variables will be introduced by means of linear transformations with well determined loading coefficients. This in turn, will allow the decomposition of the original random backscattering target variables into three point targets with new random uncorrelated variables whose variances agree with the eigenvalues of the covariance matrix. This allows a new interpretation of existing decomposition theorems.

  2. Intelligent Component Monitoring for Nuclear Power Plants

    International Nuclear Information System (INIS)

    Reliability and economy are two major concerns for a nuclear power generation system. Next generation nuclear power reactors are being developed to be more reliable and economic. An effective and efficient surveillance system can generously contribute toward this goal. Recent progress in computer systems and computational tools has made it necessary and possible to upgrade current surveillance/monitoring strategy for better performance. For example, intelligent computing techniques can be applied to develop algorithm that help people better understand the information collected from sensors and thus reduce human error to a new low level. Incidents incurred from human error in nuclear industry are not rare and have been proven costly. The goal of this project is to develop and test an intelligent prognostics methodology for predicting aging effects impacting long-term performance of nuclear components and systems. The approach is particularly suitable for predicting the performance of nuclear reactor systems which have low failure probabilities (e.g., less than 10-6 year-1). Such components and systems are often perceived as peripheral to the reactor and are left somewhat unattended. That is, even when inspected, if they are not perceived to be causing some immediate problem, they may not be paid due attention. Attention to such systems normally involves long term monitoring and possibly reasoning with multiple features and evidence, requirements that are not best suited for humans.

  3. Basic Components of Connective Tissues and Extracellular Matrix

    DEFF Research Database (Denmark)

    Halper, Jaroslava; Kjær, Michael

    2014-01-01

    Collagens are the most abundant components of the extracellular matrix and many types of soft tissues. Elastin is another major component of certain soft tissues, such as arterial walls and ligaments. Many other molecules, though lower in quantity, function as essential components...... network. Laminins contribute to the structure of the extracellular matrix (ECM) and modulate cellular functions such as adhesion, differentiation, migration, stability of phenotype, and resistance towards apoptosis. Though the primary role of fibrinogen is in clot formation, after conversion to fibrin...... by thrombin, it also binds to a variety of compounds, particularly to various growth factors, and as such fibrinogen is a player in cardiovascular and extracellular matrix physiology. Elastin, an insoluble polymer of the monomeric soluble precursor tropoelastin, is the main component of elastic fibers...

  4. Modelling of power system components

    CERN Document Server

    Murty, PSR

    2008-01-01

    Relationsof Power System Components is a prerequisite course for the Study of Power System Analysis, Operation and control. Models for several electric power network components are not readily available for dynamic studies. In this book these models are presented in a lucid way. In chapter 1 per Unit Relations and primitive network models are reviewed. Chapter 2 deals with graph theory that is relevant to various incidence Matrices required in network modeling and these different incidence matrices are presented in Chapter 3. In chapter 4 the various methods of obtaining network matrices in bo

  5. Radioactive resistance of EEPROM components

    International Nuclear Information System (INIS)

    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)

  6. 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.

  7. Does Impaired Gallbladder Function Contribute to the Development of Barrett's Esophagus and Esophageal Adenocarcinoma?

    LENUS (Irish Health Repository)

    Nassr, Ayman O

    2011-06-01

    Esophageal adenocarcinoma is aetiologically associated with gastro-esophageal reflux, but the mechanisms responsible for the metaplasia-dysplasia sequence are unknown. Bile components are implicated. Impaired gallbladder function may contribute to duodenogastric reflux (DGR) and harmful GERD.

  8. Mead's contributions to learner's identities

    OpenAIRE

    Gatt, Suzanne; Puigdellívol, Ignasi; Molina Roldán, Silvia

    2010-01-01

    Mead’s approach of symbolic interactionism is useful for explaining both how students learn and how learning environments can be improved. This article reviews Mead’s theoretical contributions, which serve as a base for successful educational actions in several countries. The interactionist view of learning is examined in depth, as well as the dialogical nature of the self, and the way that verbal language and gestures mediate interaction. These concepts are illustrated with examples from cas...

  9. Abstracts of the scientific contributions

    International Nuclear Information System (INIS)

    The abstracts are reproduced of the 66 scientific contributions to the 39th annual meeting of the following three German associations or societies for medical radiology: Vereinigung Suedwestdeutscher Radiologen und Mediziner, Hessische Gesellschaft fuer Medizinische Strahlenkunde, and Thueringische Gesellschaft fuer Radiologie. The topics discussed include: intracerebral hemorrage, image quality and dose, lesions of the space of the disk, diagnostics and therapy of liver tumors, lesions of the knee joint, and free subjects. The 39 posters are reproduced in full. (MG)

  10. Contributions to Simplifying Bidomain Simulations

    OpenAIRE

    2009-01-01

    The theme of this thesis is the use of the bidomain equations for modeling the electrical activity in the human heart, and the pursuit of ways to use these equations for medical applications. The first paper investigates a simplification of the actual equations themselves which may contribute to speed up the necessary computing. The second looks at their use in inverse methods to identify ischemic heart disease from electrocardiograms (ECGs) recorded at the body surface. In Paper III they are...

  11. Employee contributions to brand equity

    OpenAIRE

    Gelb, BD; Rangarajan, Deva

    2014-01-01

    Viewing employees as elements of a brand or as "brand ambassadors" means that almost any policy can affect brand equity. Resource allocation for brand-building requires understanding what differentiates "our brand" in order to focus resources on the employees who provide that difference. Employees' commitment to the brand increases when they know how they can contribute. Management actions matter from small issues like free coffee to large issues like mass layoffs.

  12. Ergonomics Contributions to Company Strategies

    OpenAIRE

    Dul, Jan; Neumann, Patrick

    2008-01-01

    textabstractManagers usually associate ergonomics with occupational health and safety and related legislation, not with business performance. In many companies, these decision makers seem not to be positively motivated to apply ergonomics for reasons of improving health and safety. In order to strengthen the position of ergonomics and ergonomists in the business and management world, we discuss company strategies and business goals to which ergonomics could contribute. Conceptual models are p...

  13. CLEO contributions to tau physics

    Energy Technology Data Exchange (ETDEWEB)

    Weinstein, Alan J

    2003-07-01

    We review many of the contributions of the CLEO experiment to tau physics. Topics discussed are: branching fractions for major decay modes and tests of lepton universality; rare decays; forbidden decays; Michel parameters and spin physics; hadronic sub-structure and resonance parameters; the tau mass, tau lifetime, and tau neutrino mass; searches for CP violation in tau decay; tau pair production, dipole moments, and CP violating EDM; and tau physics at CLEO-III and at OLEO-c.

  14. Public relations: contributions from Ljubljana:

    OpenAIRE

    Verčič, Dejan

    2011-01-01

    Public relations emerged as an academic discipline in the 1980s in the US, and in 1990s it institutionalised itself in European academia as well. Work at the Marketing Communication and Public Relations department, Faculty of Social Sciences, University of Ljubljana, has been instrumental in the Europeanisation and globalisation of the predominantly US public relations theory and contributed to the development of the reflective model of public relations. Odnosi z javnostmi so se kot akadem...

  15. Feller's Contributions to Mathematical Biology

    OpenAIRE

    Baake, Ellen; Wakolbinger, Anton

    2015-01-01

    This is a review of William Feller's important contributions to mathematical biology. The seminal paper [Feller1951] "Diffusion processes in genetics" was particularly influential on the development of stochastic processes at the interface to evolutionary biology, and interesting ideas in this direction (including a first characterization of what is nowadays known as "Feller's branching diffusion") already shaped up in the paper [Feller 1939] (written in German) "The foundations of a probabis...

  16. Nobel Prizes: Contributions to Cardiology

    OpenAIRE

    Evandro Tinoco Mesquita; Luana de Decco Marchese; Danielle Warol Dias; Andressa Brasil Barbeito; Jonathan Costa Gomes; Maria Clara Soares Muradas; Pedro Gemal Lanzieri; Ronaldo Altenburg Gismondi

    2015-01-01

    The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901 and Emil Adolf von Behring was the first laureate in medicine due to his research in diphtheria serum. Regarding cardiology, Nobel Prize’s history permits a global comprehension of progress in pathophysiology, diagnosis and therapeutics of various cardiac diseases in last 120 years. The objective of this study was to review the major scientific discoveries contemplated by Nobel Prizes that contributed to cardiolo...

  17. 5 CFR 1600.12 - Contribution elections.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Contribution elections. 1600.12 Section... ELECTIONS AND CONTRIBUTION ALLOCATIONS Elections § 1600.12 Contribution elections. (a) An employee may make a contribution election at any time. (b) A participant must submit a contribution election to his...

  18. 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 certa...

  19. Opinions about Component Energetic Security

    OpenAIRE

    Elena GOLUMBEANU (GEORGESCU)

    2012-01-01

    Collective security (international) represent the morphological expression of individual security components. According to the Report presented at the United Nations Development Programme, collective security (international) as well as national security, is the expression of seven synergistic dimensions as follows: economic security, food security, environmental security, personal security, community security, political security and individual security. As part of economic security, energy an...

  20. Fractionalization of graphitic reactor components

    International Nuclear Information System (INIS)

    Within the scope of this project, a stock taking took place that comprised graphic components in German research and prototype reactors. From a long set of experiments mechanical breaking was determined to represent the optimal solution for the problem of fractionalizing graphitic components with a reasonable tritium content. Be sides the very low dust emission and the total lack of secondary waste emission, the small and mobile tool are outstanding advantages of this technique. Graphitic dust which was emitted throughout the different experiments was characterized and analyzed with respect to its explosion properties. Choosing the right conditions, a graphite dust explosion can safety be expelled during the trials on activated graphite. Successful fractionalization experiments performed on activated graphite clearly show that a planar mechanical breaking of graphite as well as a yawing of graphitic components is possible. The performance of the filter installation is evidenced by the fact that all tools and components - with exception of the filters themselves - applied during the experiments could be decontaminated and measured for free release. (orig.)

  1. Fabrication of plastic microfluidic components

    Science.gov (United States)

    Martin, Peter M.; Matson, Dean W.; Bennett, Wendy D.; Hammerstrom, D. J.

    1998-09-01

    Plastic components have many advantages, including ease of fabrication, low cost, chemical inertness, lightweight, and disposability. We report on the fabrication of three plastics-based microfluidic components: a motherboard, a dialysis unit, and a metal sensor. Microchannels, headers, and interconnects were produced in thin sheets (>=50 microns) of polyimide, PMMA, polyethylene, and polycarbonate using a direct-write excimer laser micromachining system. Machined sheets were laminated by thermal and adhesive bonding to form leak-tight microfluidic components. The microfluidic motherboard borrowed the `functionality on a chip' concept from the electronics industry and was the heart of a complex microfluidic analytical device. The motherboard platform was designed to be tightly integrated and self-contained (i.e., liquid flows are all confined within machined microchannels), reducing the need for tubing with fluid distribution and connectivity. This concept greatly facilitated system integration and miniaturization. As fabricated, the motherboard consisted of three fluid reservoirs connected to micropumps by microchannels. The fluids could either be pumped independently or mixed in microchannels prior to being directed to exterior analytical components via outlet ports. The microdialysis device was intended to separate electrolytic solutes from low volume samples prior to mass spectrometric analysis. The device consisted of a dialysis membrane laminated between opposed serpentine microchannels containing the sample fluid and a buffer solution. The laminated metal sensor consisted of fluid reservoirs, micro-flow channels, micropumps, mixing channels, reaction channels, and detector circuitry.

  2. Nitrogen laser with additional components

    International Nuclear Information System (INIS)

    The development and construction of a Nitrogen laser with low cost domestic components is described. The model built is operated at 50 pulses per second with a 50 kW power per pulse at the ultraviolet 337.1 nm wavelength. (Author)

  3. Placement of the acetabular component.

    Science.gov (United States)

    Beverland, D E; O'Neill, C K J; Rutherford, M; Molloy, D; Hill, J C

    2016-01-01

    Ideal placement of the acetabular component remains elusive both in terms of defining and achieving a target. Our aim is to help restore original anatomy by using the transverse acetabular ligament (TAL) to control the height, depth and version of the component. In the normal hip the TAL and labrum extend beyond the equator of the femoral head and therefore, if the definitive acetabular component is positioned such that it is cradled by and just deep to the plane of the TAL and labrum and is no more than 4mm larger than the original femoral head, the centre of the hip should be restored. If the face of the component is positioned parallel to the TAL and psoas groove the patient specific version should be restored. We still use the TAL for controlling version in the dysplastic hip because we believe that the TAL and labrum compensate for any underlying bony abnormality. The TAL should not be used as an aid to inclination. Worldwide, > 75% of surgeons operate with the patient in the lateral decubitus position and we have shown that errors in post-operative radiographic inclination (RI) of > 50° are generally caused by errors in patient positioning. Consequently, great care needs to be taken when positioning the patient. We also recommend 35° of apparent operative inclination (AOI) during surgery, as opposed to the traditional 45°. PMID:26733639

  4. Factor Analysis via Components Analysis

    Science.gov (United States)

    Bentler, Peter M.; de Leeuw, Jan

    2011-01-01

    When the factor analysis model holds, component loadings are linear combinations of factor loadings, and vice versa. This interrelation permits us to define new optimization criteria and estimation methods for exploratory factor analysis. Although this article is primarily conceptual in nature, an illustrative example and a small simulation show…

  5. Factor Analysis via Components Analysis

    OpenAIRE

    Bentler, Peter M.; Jan de Leeuw

    2011-01-01

    Under the null hypothesis, component loadings are linear combinations of factor loadings, and vice versa. This interrelation permits defining new optimization criteria and estimation methods for exploratory factor analysis. Although this note is primarily conceptual in nature, an illustrative example shows the methodology to be promising.

  6. Inspection of disposal canisters components

    International Nuclear Information System (INIS)

    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

  7. Black Component of Dark Matter

    Directory of Open Access Journals (Sweden)

    A. V. Grobov

    2014-01-01

    Full Text Available A mechanism of primordial black hole formation with specific mass spectrum is discussed. It is shown that these black holes could contribute to the energy density of dark matter. Our approach is elaborated in the framework of universal extra dimensions.

  8. Possible solar noble-gas component in Hawaiian basalts

    Science.gov (United States)

    Honda, M.; McDougall, I.; Patterson, D.B.; Doulgeris, A.; Clague, D.A.

    1991-01-01

    THE noble-gas elemental and isotopic composition in the Earth is significantly different from that of the present atmosphere, and provides an important clue to the origin and history of the Earth and its atmosphere. Possible candidates for the noble-gas composition of the primordial Earth include a solar-like component, a planetary-like component (as observed in primitive meteorites) and a component similar in composition to the present atmosphere. In an attempt to identify the contributions of such components, we have measured isotope ratios of helium and neon in fresh basaltic glasses dredged from Loihi seamount and the East Rift Zone of Kilauea1-3. We find a systematic enrichment in 20Ne and 21Ne relative to 22Ne, compared with atmospheric neon. The helium and neon isotope signatures observed in our samples can be explained by mixing of solar, present atmospheric, radiogenic and nucleogenic components. These data suggest that the noble-gas isotopic composition of the mantle source of the Hawaiian plume is different from that of the present atmosphere, and that it includes a significant solar-like component. We infer that this component was acquired during the formation of the Earth.

  9. Possible solar noble-gas component in Hawaiian basalts

    International Nuclear Information System (INIS)

    The noble-gas elemental and isotopic composition in the Earth is significantly different from that of the present atmosphere, and provides an important clue to the origin and history of the Earth and its atmosphere. Possible candidates for the noble-gas composition of the primordial Earth include a solar-like component, a planetary-like component (as observed in primitive meteorites) and a component similar in composition to the present atmosphere. In an attempt to identify the contributions of such components, we have measured isotope ratios of helium and neon in fresh basaltic glasses dredged from Loihi seamount and the East Rift Zone of Kilauea. We find a systematic enrichment in 20Ne and 21Ne relative to 22Ne, compared with atmospheric neon. The helium and neon isotope signatures observed in our samples can be explained by mixing of solar, present atmospheric, radiogenic and nucleogenic components. These data suggest that the noble-gas isotopic composition of the mantle source of the Hawaiian plume is different from that of the present atmosphere, and that it includes a significant solar-like component. We infer that this component was acquired during the formation of the Earth. (author)

  10. Galactic and extragalactic contributions to the astrophysical muon neutrino signal

    CERN Document Server

    Neronov, A

    2016-01-01

    Spectral and anisotropy properties of IceCube astrophysical neutrino signal reveal an evidence for a significant Galactic contribution to the neutrino flux in Southern hemisphere. We check if the Galactic contribution is detectable in the astrophysical muon neutrino flux observed from a low positive declinations region of the Northern sky. Estimating the Galactic neutrino flux in this part of the sky from gamma-ray and Southern sky neutrino data, we find that the Northern sky astrophysical muon neutrino signal shows an excess over the Galactic flux. This points to the presence of an additional hard spectrum (extragalactic or large scale Galactic halo) component of astrophysical neutrino flux. We show that the Galactic flux component should still be detectable in the muon neutrino data in a decade long IceCube exposure.

  11. The ILRS Contribution to ITRF2013

    Science.gov (United States)

    Pavlis, Erricos C.; Luceri, Cinzia; Sciarretta, Cecilia; Evans, Keith

    2014-05-01

    Satellite Laser Ranging (SLR) data have contributed to the definition of the International Terrestrial Reference Frame (ITRF) over the past three decades. The development of ITRF2005 ushered a new era with the use of weekly or session contributions, allowing greater flexibility in the editing, relative weighting and the combination of information from the four contributing techniques. The new approach allows each Service to generate a solution based on the rigorous combination of the individual Analysis Centers' contributions that provides an opportunity to verify the intra-technique consistency and a comparison of internal procedures and adopted models. The intra- and inter-technique comparisons that the time series approach facilitates are an extremely powerful diagnostic that highlights differences and inconsistencies at the single station level. Over the past year the ILRS Analysis Working Group (AWG) worked on designing an improved ILRS contribution for the development of ITRF2013. The ILRS approach is based on the current IERS Conventions 2010 and our internal ILRS standards, with a few deviations that are documented. Since the Global Geodetic Observing System - GGOS identified the ITRF as its key project, the ILRS has taken a two-pronged approach in order to meet its stringent goals: modernizing the engineering components (ground and space segments), and revising the modeling standards taking advantage of recent improvements in system Earth modeling. The main concern in the case of SLR is monitoring systematic errors at individual stations, accounting for undocumented discontinuities, and improving the target signature models. The latter has been addressed with the adoption of mm-level models for all of our targets. As far as the station systematics, the AWG had already embarked on a major effort to improve the handling of such errors prior to the development of ITRF2008. The results of that effort formed the foundation for the re-examination of the

  12. Parallel components for PDEs and optimization: some issues and experiences

    International Nuclear Information System (INIS)

    High-performance simulations in computational science often involve the combined software contributions of multidisciplinary teams of scientists, engineers, mathematicians, and computer scientists. One goal of component-based software engineering in large-scale scientific simulations is to help manage such complexity by enabling better interoperability among codes developed by different groups. This paper discusses recent work on building component interfaces and implementations in parallel numerical toolkits for mesh manipulations, discretization, linear algebra, and optimization. We consider several motivating applications involving partial differential equations and unconstrained minimization to demonstrate this approach and evaluate performance.

  13. The domestic garden: its contribution to urban green infrastructure

    OpenAIRE

    Cameron, Ross; Blanusa, Tijana; Taylor, Jane; Salisbury, Andrew; Halstead, Andrew; Henricot, Beatrice; Thompson, Ken

    2012-01-01

    Domestic gardens provide a significant component of urban green infrastructure but their relative contribution to eco-system service provision remains largely un-quantified. ‘Green infrastructure’ itself is often ill-defined, posing problems for planners to ascertain what types of green infrastructure provide greatest benefit and under what circumstances. Within this context the relative merits of gardens are unclear; however, at a time of greater urbanization where private gardens are increa...

  14. Contributions to the financial mathematics of energy markets

    OpenAIRE

    Permana, F.J.

    2008-01-01

    This thesis provides several contributions to quantitative finance for energy markets: electricity price modelling, implying oil price volatilities, pricing and hedging of exotic commodity options. Electricity spot prices are characterized by spikes (jumps) because electricity is non-storable. A widely used model for stochastic component of electricity spot prices, a mean-reversion jump-diffusion model, is only partially successful to capture spikes. We propose the so-called potential L&eacut...

  15. Tank waste isotope contributions; FINAL

    International Nuclear Information System (INIS)

    This document presents the results of a calculation to determine the relative contribution of selected isotopes to the inhalation and ingestion doses for a postulated release of Hanford tank waste. The fraction of the dose due to(sup 90)Sr,(sup 90)Y,(sup 137)Cs and the alpha emitters for single shell solids and liquids, double shell solids and liquids, aging waste solids and liquids and all solids and liquids. An effective dose conversion factor was also calculated for the alpha emitters for each composite of the tank waste

  16. Adam Smith's contribution to secularisation

    OpenAIRE

    Petrus Simons

    2013-01-01

    This article examined several crucial themes in Adam Smith’s philosophy with the purpose of highlighting and assessing his contribution to the secularisation of Western society. The article, written from the perspective of reformational philosophy, begins with a brief biography and sketch of Adam Smith’s influence on modern society, followed by a summary of Ponti Venter’s view on Smith. This sets the scene for a discussion of Adam Smith’s project, his method of tackling it, and his views on s...

  17. Contributions to the EPAC Conference

    International Nuclear Information System (INIS)

    Seven contributions to the EPAC Conference are presented in this work whose titles are : review of electron guns, first operation of a femtosecond laser driven photo-injector, Priam/Antigone : a 2 D/3 D package for accelerator design, the Tesla test facility linac injector, on some RF three-dimensional simulation of magnetically coupled cells, dark current under low and high electric field, a versatile TBA lattice for a Tau-Charm factory with and without beam monochromatization. (O.L.). 78 refs., 19 figs., 9 tabs

  18. Contributions to the EPAC Conference

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-07-01

    Seven contributions to the EPAC Conference are presented in this work whose titles are : review of electron guns, first operation of a femtosecond laser driven photo-injector, Priam/Antigone : a 2 D/3 D package for accelerator design, the Tesla test facility linac injector, on some RF three-dimensional simulation of magnetically coupled cells, dark current under low and high electric field, a versatile TBA lattice for a Tau-Charm factory with and without beam monochromatization. (O.L.). 78 refs., 19 figs., 9 tabs.

  19. Genes contributing to prion pathogenesis

    DEFF Research Database (Denmark)

    Tamgüney, Gültekin; Giles, Kurt; Glidden, David V;

    2008-01-01

    incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes...... show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1), and...

  20. Traits contributing to the autistic spectrum.

    Directory of Open Access Journals (Sweden)

    Colin D Steer

    Full Text Available BACKGROUND: It is increasingly recognised that traits associated with autism reflect a spectrum with no clear boundary between typical and atypical behaviour. Dimensional traits are needed to investigate the broader autism phenotype. METHODS AND PRINCIPAL FINDINGS: Ninety-three individual measures reflecting components of social, communication and repetitive behaviours characterising autistic spectrum disorder (ASD were identified between the ages of 6 months and 9 years from the ALSPAC database. Using missing value imputation, data for 13,138 children were analysed. Factor analysis suggested the existence of 7 factors explaining 85% of the variance. The factors were labelled: verbal ability, language acquisition, social understanding, semantic-pragmatic skills, repetitive-stereotyped behaviour, articulation and social inhibition. Four factors (1, 3, 5 and 7 were specific to ASD being more strongly associated with this phenotype than other co-morbid conditions while other factors were more associated with learning difficulties and specific language impairment. Nevertheless, all 7 factors contributed independently to the explanation of ASD (p<0.001. Exploration of putative genetic causal factors such as variants in the CNTNAP2 gene showed a varying pattern of associations with these traits. An alternative predictive model of ASD was derived using four individual measures: the coherence subscale of the Children's Communication Checklist (9y, the Social and Communication Disorders Checklist (91 m, repetitive behaviour (69 m and the sociability subscale of the Emotionality Activity and Sociability measure (38 m. Although univarably these traits performed better than some factors, their combined explanations of ASD were similar (R(2 =  0.48. CONCLUSIONS AND SIGNIFICANCE: These results support the fractional nature of ASD with different aetiological origins for these components despite pleiotropic genetic effects being observed. These traits are

  1. Components of Co-creation

    DEFF Research Database (Denmark)

    Tanev, Stoyan

    2009-01-01

    . However, these typically focus on the study, discussion and analysis of a small number of cases using deep, ethnographic description of their practices aiming at conceptualization and categorization of the different types of interactions between end users, the firm and the value network. Although useful...... the benefits of both qualitative and quantitative research approaches for studying the nature of value co-creation. The article provides a first attempt to identify the main research steps of such a methodology. It provides some preliminary results on the key components of value co-creation between firms...... and end customers based on the application of web search and Principal Component Analysis (PCA) techniques. The analysis of these preliminary results is then used as an opportunity to identify a number of research questions to be addressed in future research. The emerging research questions follow...

  2. 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...

  3. Tritium in fusion reactor components

    International Nuclear Information System (INIS)

    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

  4. Centrifugal slip casting of components

    International Nuclear Information System (INIS)

    Research in layered and functionally gradient materials has emerged because of the increasing demand for high-performance engineering materials. Many techniques have been used to produce layered and functionally gradient components. Common examples include thermal spray processing, powder processing, chemical and physical vapor deposition, high-temperature or combustion synthesis, diffusion treatments, microwave processing and infiltration. Of these techniques, powder processing routes offer excellent microstructural control and product quality, and they are capable of producing large components. Centrifugal slip casting is a powder-processing technique combining the effects of slip casting and centrifugation. In slip casting, consolidation takes place as fluid is removed by the porous mold. Particles within the slip move with the suspending fluid until reaching the mold wall, at which point they are consolidated. In centrifugation, particles within the slip move through the fluid at a rate dependent upon the gravitational force and particle drag

  5. Statistical Significance of the Contribution of Variables to the PCA Solution: An Alternative Permutation Strategy

    Science.gov (United States)

    Linting, Marielle; van Os, Bart Jan; Meulman, Jacqueline J.

    2011-01-01

    In this paper, the statistical significance of the contribution of variables to the principal components in principal components analysis (PCA) is assessed nonparametrically by the use of permutation tests. We compare a new strategy to a strategy used in previous research consisting of permuting the columns (variables) of a data matrix…

  6. Modelling Livestock Component in FSSIM

    OpenAIRE

    Thorne, P.J.; Hengsdijk, H.; Janssen, S.J.C.; Louhichi, K.; Keulen, van, M.; 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 parameters for FSSIM. The treatments are derived principally from the “French” feed evaluation and rationing system for protein and energy. Currently, we have constructed routines that are capable o...

  7. Substructuring and Component Mode Synthesis

    Directory of Open Access Journals (Sweden)

    P. Seshu

    1997-01-01

    Full Text Available Substructuring and component mode synthesis (CMS, is a very popular method of model reduction for large structural dynamics problems. Starting from the pioneering works on this technique in the early 1960s, many researchers have studied and used this technique in a variety of applications. Besides model reduction, CMS offers several other crucial advantages. The present work aims to provide a review of the available literature on this important technique.

  8. Substructuring and Component Mode Synthesis

    OpenAIRE

    Seshu, P.

    1997-01-01

    Substructuring and component mode synthesis (CMS), is a very popular method of model reduction for large structural dynamics problems. Starting from the pioneering works on this technique in the early 1960s, many researchers have studied and used this technique in a variety of applications. Besides model reduction, CMS offers several other crucial advantages. The present work aims to provide a review of the available literature on this important technique.

  9. Two-component Dirac equation

    OpenAIRE

    Luo, Da-Wei; Pyshkin, P. V.; Yu, Ting; Lin, Hai-Qing; You, J. Q.; Wu, Lian-Ao

    2016-01-01

    We provide an alternative approach to relativistic dynamics based on the Feshbach projection technique. Instead of directly studying the Dirac equation, we derive a two-component equation for the upper spinor. This approach allows one to investigate the underlying physics in a different perspective. For particles with small mass such as the neutrino, the leading order equation has a Hermitian effective Hamiltonian, implying there is no leakage between the upper and lower spinors. In the weak ...

  10. NAT: perspectives for cellular components.

    Science.gov (United States)

    Barbara, J A

    1999-12-01

    The introduction of routine testing to detect viral genomes in donated blood was originally driven by requirements for plasma fractionation in relation to exclusion of hepatitis C virus (HCV) RNA. Nevertheless, it was obvious from the outset that a dual standard for fractionated products and individual blood components would be untenable. In many countries therefore, planning for introduction of nucleic acid testing (NAT) of blood incorporated progression to release of HCV RNA tested components. HCV was singled out because of its long seronegative 'window period', relatively high prevalence and incidence in blood donors, rapid burst time and high genome copy number during seroconversion. The latter properties made HCV particularly suitable for detection in pools of samples. If HCV RNA testing is required for release of labile components such as platelets, rapid provision of NAT results is vital because of short shelf life of platelets and the problems of delays when resolving the infectious unit in a reactive pool. For NAT release of labile components smaller sample pool sizes allow faster resolution of RNA positive units. Smaller pools involve high test throughput, the likely need for more testing laboratories and ensuing increased costs. Single sample testing is the ultimate extrapolation of reducing sample pool size. With reduced pool sizes or single sample testing, the option of testing for other viruses (e.g. HIV or HBV) singly or in multiplex also arises. The cost-benefit and incremental yield of such strategies in the light of 'combo' assays for HIV Ag/Ab and the recently described HCV Ag assay will require careful and objective assessment, together with re-appraisal of anti-HBc screening for detection of HBV infected donors at the "tail-end" of carriage. PMID:10686060

  11. Bounding Component Behavior via Protocols

    Czech Academy of Sciences Publication Activity Database

    Plášil, František; Višňovský, Stanislav; Besta, Miloslav

    Los Alamitos : IEEE Computer Society, 1999 - (Firesmith, D.; Riehle, R.; Pour, G.; Meyer, B.), s. 387-398 ISBN 0-7695-0278-4. [TOOLS /30./. Santa Barbara (US), 01.08.1999-05.08.1999] R&D Projects: GA AV ČR IAA2030902; GA ČR GA201/99/0244 Institutional research plan: AV0Z1030915 Keywords : software components * behavior protocols * software architecture Subject RIV: JC - Computer Hardware ; Software

  12. Optimization of structures and components

    CERN Document Server

    Muñoz-Rojas, Pablo Andrés

    2013-01-01

    Written by an international group of active researchers in the field, this volume presents innovative formulations and applied procedures for sensitivity analysis and structural design optimization. Eight chapters discuss subjects ranging from recent developments in the determination and application of topological gradients, to the use of evolutionary algorithms and meta-models to solve practical engineering problems. With such a comprehensive set of contributions, the book is a valuable source of information for graduate students and researchers entering or working in the matter.

  13. Aging risk of passive components

    International Nuclear Information System (INIS)

    This paper presents an approach for determining the increasing failure probability of an aging passive component and for calculating its resulting effect on plant risk by modifying an existing commercial nuclear reactor probabilistic risk assessment (PRA). A technique was developed for introducing aging into failure probability calculations using probabilistic structural analysis (PSA) techniques. Various probabilistic structural analysis methods were reviewed, and the PRAISE computer code was selected to perform the PSA. A component was selected that could fail and have a significant effect on the risk of core damage frequency. This component is a weld in the auxiliary feedwater system (AFW) of a pressurized water reactor (PWR). The stress on the AFW weld, for input in PRAISE, was determined for piping design loads, plant transient loads, and a thermal cyclic load that could cause crack growth and ultimate pipe failure. One PRAISE calculation might be made with the possibility of water hammer introduced to determine the effect on core damage frequency. An existing PRA (for a NUREG 1150 plant) was modified to include the failure of the AFW weld. Because this work is not complete, only preliminary conclusions and recommendations are presented

  14. Fusion-component lifetime analysis

    International Nuclear Information System (INIS)

    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

  15. Heritage contribution in sustainable city

    International Nuclear Information System (INIS)

    The concept of sustainability has been an integral part of development work since the late 1970s. Sustainability is no longer a buzzword but a reality that must be addressed by cities all over the world. Increasing empirical evidence indicates that city sustainability is not just related to technical issues, such as carbon emissions, energy consumption and waste management, or on the economic aspects of urban regeneration and growth, but also it covers social well-being of different groups living within increasingly cosmopolitan towns and cities. Heritage is seen as a major component of quality of life, features that give a city its unique character and provide the sense of belonging that lies at the core of cultural identity. In other words, heritage by providing important social and psychological benefits enrich human life with meanings and emotions, and raise quality of life as a key component of sustainability. The purpose of this paper, therefore, is to examine the role that built cultural heritage can play within sustainable urban development

  16. Nobel Prizes: Contributions to Cardiology

    International Nuclear Information System (INIS)

    The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901 and Emil Adolf von Behring was the first laureate in medicine due to his research in diphtheria serum. Regarding cardiology, Nobel Prize’s history permits a global comprehension of progress in pathophysiology, diagnosis and therapeutics of various cardiac diseases in last 120 years. The objective of this study was to review the major scientific discoveries contemplated by Nobel Prizes that contributed to cardiology. In addition, we also hypothesized why Carlos Chagas, one of our most important scientists, did not win the prize in two occasions. We carried out a non-systematic review of Nobel Prize winners, selecting the main studies relevant to heart diseaseamong the laureates. In the period between 1901 and 2013, 204 researches and 104 prizes were awarded in Nobel Prize, of which 16 (15%) studies were important for cardiovascular area. There were 33 (16%) laureates, and two (6%) were women. Fourteen (42%) were American, 15 (45%) Europeans and four (13%) were from other countries. There was only one winner born in Brazil, Peter Medawar, whose career was all in England. Reviewing the history of the Nobel Prize in physiology or medicine area made possible to identify which researchers and studies had contributed to advances in the diagnosis, prevention and treatment of cardiovascular diseases. Most winners were North Americans and Europeans, and male

  17. Nobel Prizes: Contributions to Cardiology

    Directory of Open Access Journals (Sweden)

    Evandro Tinoco Mesquita

    2015-01-01

    Full Text Available The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901 and Emil Adolf von Behring was the first laureate in medicine due to his research in diphtheria serum. Regarding cardiology, Nobel Prize’s history permits a global comprehension of progress in pathophysiology, diagnosis and therapeutics of various cardiac diseases in last 120 years. The objective of this study was to review the major scientific discoveries contemplated by Nobel Prizes that contributed to cardiology. In addition, we also hypothesized why Carlos Chagas, one of our most important scientists, did not win the prize in two occasions. We carried out a non-systematic review of Nobel Prize winners, selecting the main studies relevant to heart diseaseamong the laureates. In the period between 1901 and 2013, 204 researches and 104 prizes were awarded in Nobel Prize, of which 16 (15% studies were important for cardiovascular area. There were 33 (16% laureates, and two (6% were women. Fourteen (42% were American, 15 (45% Europeans and four (13% were from other countries. There was only one winner born in Brazil, Peter Medawar, whose career was all in England. Reviewing the history of the Nobel Prize in physiology or medicine area made possible to identify which researchers and studies had contributed to advances in the diagnosis, prevention and treatment of cardiovascular diseases. Most winners were North Americans and Europeans, and male.

  18. Nobel Prizes: Contributions to Cardiology

    Directory of Open Access Journals (Sweden)

    Evandro Tinoco Mesquita

    2015-08-01

    Full Text Available The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901 and Emil Adolf von Behring was the first laureate in medicine due to his research in diphtheria serum. Regarding cardiology, Nobel Prize’s history permits a global comprehension of progress in pathophysiology, diagnosis and therapeutics of various cardiac diseases in last 120 years. The objective of this study was to review the major scientific discoveries contemplated by Nobel Prizes that contributed to cardiology. In addition, we also hypothesized why Carlos Chagas, one of our most important scientists, did not win the prize in two occasions. We carried out a non-systematic review of Nobel Prize winners, selecting the main studies relevant to heart diseaseamong the laureates. In the period between 1901 and 2013, 204 researches and 104 prizes were awarded in Nobel Prize, of which 16 (15% studies were important for cardiovascular area. There were 33 (16% laureates, and two (6% were women. Fourteen (42% were American, 15 (45% Europeans and four (13% were from other countries. There was only one winner born in Brazil, Peter Medawar, whose career was all in England. Reviewing the history of the Nobel Prize in physiology or medicine area made possible to identify which researchers and studies had contributed to advances in the diagnosis, prevention and treatment of cardiovascular diseases. Most winners were North Americans and Europeans, and male.

  19. Nobel Prizes: Contributions to Cardiology

    Energy Technology Data Exchange (ETDEWEB)

    Mesquita, Evandro Tinoco; Marchese, Luana de Decco; Dias, Danielle Warol; Barbeito, Andressa Brasil; Gomes, Jonathan Costa; Muradas, Maria Clara Soares; Lanzieri, Pedro Gemal; Gismondi, Ronaldo Altenburg, E-mail: ronaldo@floralia.com.br [Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2015-08-15

    The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901 and Emil Adolf von Behring was the first laureate in medicine due to his research in diphtheria serum. Regarding cardiology, Nobel Prize’s history permits a global comprehension of progress in pathophysiology, diagnosis and therapeutics of various cardiac diseases in last 120 years. The objective of this study was to review the major scientific discoveries contemplated by Nobel Prizes that contributed to cardiology. In addition, we also hypothesized why Carlos Chagas, one of our most important scientists, did not win the prize in two occasions. We carried out a non-systematic review of Nobel Prize winners, selecting the main studies relevant to heart diseaseamong the laureates. In the period between 1901 and 2013, 204 researches and 104 prizes were awarded in Nobel Prize, of which 16 (15%) studies were important for cardiovascular area. There were 33 (16%) laureates, and two (6%) were women. Fourteen (42%) were American, 15 (45%) Europeans and four (13%) were from other countries. There was only one winner born in Brazil, Peter Medawar, whose career was all in England. Reviewing the history of the Nobel Prize in physiology or medicine area made possible to identify which researchers and studies had contributed to advances in the diagnosis, prevention and treatment of cardiovascular diseases. Most winners were North Americans and Europeans, and male.

  20. Nobel prizes: contributions to cardiology.

    Science.gov (United States)

    Mesquita, Evandro Tinoco; Marchese, Luana de Decco; Dias, Danielle Warol; Barbeito, Andressa Brasil; Gomes, Jonathan Costa; Muradas, Maria Clara Soares; Lanzieri, Pedro Gemal; Gismondi, Ronaldo Altenburg

    2015-08-01

    The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901 and Emil Adolf von Behring was the first laureate in medicine due to his research in diphtheria serum. Regarding cardiology, Nobel Prize's history permits a global comprehension of progress in pathophysiology, diagnosis and therapeutics of various cardiac diseases in last 120 years. The objective of this study was to review the major scientific discoveries contemplated by Nobel Prizes that contributed to cardiology. In addition, we also hypothesized why Carlos Chagas, one of our most important scientists, did not win the prize in two occasions. We carried out a non-systematic review of Nobel Prize winners, selecting the main studies relevant to heart diseaseamong the laureates. In the period between 1901 and 2013, 204 researches and 104 prizes were awarded in Nobel Prize, of which 16 (15%) studies were important for cardiovascular area. There were 33 (16%) laureates, and two (6%) were women. Fourteen (42%) were American, 15 (45%) Europeans and four (13%) were from other countries. There was only one winner born in Brazil, Peter Medawar, whose career was all in England. Reviewing the history of the Nobel Prize in physiology or medicine area made possible to identify which researchers and studies had contributed to advances in the diagnosis, prevention and treatment of cardiovascular diseases. Most winners were North Americans and Europeans, and male. PMID:25945466

  1. Nobel Prizes: Contributions to Cardiology

    Science.gov (United States)

    Mesquita, Evandro Tinoco; Marchese, Luana de Decco; Dias, Danielle Warol; Barbeito, Andressa Brasil; Gomes, Jonathan Costa; Muradas, Maria Clara Soares; Lanzieri, Pedro Gemal; Gismondi, Ronaldo Altenburg

    2015-01-01

    The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901 and Emil Adolf von Behring was the first laureate in medicine due to his research in diphtheria serum. Regarding cardiology, Nobel Prize’s history permits a global comprehension of progress in pathophysiology, diagnosis and therapeutics of various cardiac diseases in last 120 years. The objective of this study was to review the major scientific discoveries contemplated by Nobel Prizes that contributed to cardiology. In addition, we also hypothesized why Carlos Chagas, one of our most important scientists, did not win the prize in two occasions. We carried out a non-systematic review of Nobel Prize winners, selecting the main studies relevant to heart diseaseamong the laureates. In the period between 1901 and 2013, 204 researches and 104 prizes were awarded in Nobel Prize, of which 16 (15%) studies were important for cardiovascular area. There were 33 (16%) laureates, and two (6%) were women. Fourteen (42%) were American, 15 (45%) Europeans and four (13%) were from other countries. There was only one winner born in Brazil, Peter Medawar, whose career was all in England. Reviewing the history of the Nobel Prize in physiology or medicine area made possible to identify which researchers and studies had contributed to advances in the diagnosis, prevention and treatment of cardiovascular diseases. Most winners were North Americans and Europeans, and male. PMID:25945466

  2. Instantons contributions to nonleptonic decays

    International Nuclear Information System (INIS)

    Instantons contributions to nonleptonic decays in chiral-bag model are the subject of this study. The instanton induced-term was introduced in chiral-bag model based analysis of K→π decays. Almost perfect fit of the experimental data was possible with the induced-term coefficient C1≅1.4. However, this conclusion, which is appreciably larger than the rough theoretical estimate (which was C1=0.15) depends on the approximation used in the theoretical approach. Also, the μ-dependence of the operator matrix elements were studied. Although the μ-dependence must in principle cancel as was illustrated by using a simple model, in practice the choice of μ markledy influences the theoretical predictions for K→2π decays, with and without instantons. Nonleptonic strangeness-changing hyperon decays were also considered together with instanton induced term. The same type of analysis has led previously to a reasonable qualitytive, and to some extent quantitative, description of the decay amplitudes. The instanton contributions do not improve old results. Data favor a very small instanton influence. (author)

  3. Towards Dependable Emergent Ensembles of Components: The DEECo Component Model

    Czech Academy of Sciences Publication Activity Database

    Keznikl, J.; Bureš, T.; Plášil, František; Kit, M.

    Los Alamitos: IEEE CS, 2012 - (Babar, M.; Cuesta, C.; Savolainen, J.; Männistö, T.), s. 249-252 ISBN 978-0-7695-4827-2. [WICSA / ECSA 2012. Joint Working Conference on Software Architecture /10./ & European Conference on Software Architecture /6./. Helsinki (FI), 20.08.2012-24.08.2012] EU Projects: European Commission(XE) ASCENS 257414 Grant ostatní: GA AV ČR(CZ) GAP202/11/0312; MFF UK(CZ) SVV-2012-265312 Institutional support: RVO:67985807 Keywords : component * ensemble * adaptation * dynamic architecture * implicit communication * implicit bindings Subject RIV: JC - Computer Hardware ; Software

  4. The pion-cloud contribution to the electromagnetic nucleon structure

    CERN Document Server

    Kupelwieser, D

    2015-01-01

    The present contribution continues and extends foregoing work on the calculation of electroweak form factors of hadrons using the point-form of relativistic quantum mechanics. Here we are particularly interested in studying pionic effects on the electromagnetic structure of the nucleon. To this aim we employ a hybrid constituent-quark model that comprises, in addition to the $3q$ valence component, also a $3q$+$\\pi$ non-valence component. With a simple wave function for the $3q$ component we get reasonable results for the nucleon form factors. In accordance with other authors we find that the pionic effect is significant only below $Q^2\\lesssim 0.5$~GeV$^2$.

  5. Soil Organic Nitrogen and Its Contribution to Crop Production

    Institute of Scientific and Technical Information of China (English)

    LI Sheng-xiu; WANG Zhao-hui; MIAO Yan-fang; LI Shi-qing

    2014-01-01

    Plant growth and crop production depend to a large extent on soil N supplying capacity (SNSC):The higher the SNSC, the higher the dependence of crops on soil and the lower the N fertilizer recovery. Of the SNSC, soil organic N (ON) played a key role in supplying N nutrient to crop production and still does in many subsistence and low-input farming systems. In this paper, soil ON contents, types, chemical components and its contribution to plant production are reviewed up to date in details, the characteristics of ON in dryland soils discussed together with its chemical components, and the mineralization and availability to plants of some important chemical components are emphasized at the last part for practical considerations.

  6. Review of contributed papers. Session IIc: The safety case and confidence building

    International Nuclear Information System (INIS)

    The paper presents an overview of the contributed papers submitted to Session IIc on The Safety Case and Confidence Building; 11 papers were contributed on a wide range of topics including: (a) key components for safety, (b) regulatory compliance, (c) discussion of relevant scenarios, (d) treatment of uncertainty, and (e) use of the volunteer process to develop confidence in selection of repositories. The paper presents some conclusions and recommendations based on a review of these contributed papers. (author)

  7. Contributions to thermal and fluid dynamic problems in nuclear technology

    International Nuclear Information System (INIS)

    The majority of contributions compiled in this report deals with thermal and fluid dynamic problems in nuclear engineering. Especially problems of heat transfer and cooling are represented which may arise during and afer a loss-of-coolant accident both in light water reactors and in liquid metal cooled fast breeder reactors. Papers on the mass transfer in pressurized water, tribological problems in sodium cooled reactors, the fluid dynamics of pulsed column, and fundamental investigations of convective flows supplement these contributions on problems connected with accidents. Furthermore, a keynote paper presents the individual activities relating to the reliability of reactor components, a field recently included in our research program. Technical solutions to special problems are closely connected to the investigations based on experiments. Therefore, several contributions deal with new developments in technology and measuring techniques. (orig.)

  8. The contribution of instrumentation and control software to system reliability

    International Nuclear Information System (INIS)

    Advanced instrumentation and control systems are usually implemented using computers that monitor the instrumentation and issue commands to control elements. The control commands are based on instrument readings and software control logic. The reliability of the total system will be affected by the software design. When comparing software designs, an evaluation of how each design can contribute to the reliability of the system is desirable. Unfortunately, the science of reliability assessment of combined hardware and software systems is in its infancy. Reliability assessment of combined hardware/software systems is often based on over-simplified assumptions about software behavior. A new method of reliability assessment of combined software/hardware systems is presented. The method is based on a procedure called fault tree analysis which determines how component failures can contribute to system failure. Fault tree analysis is a well developed method for reliability assessment of hardware systems and produces quantitative estimates of failure probability based on component failure rates. It is shown how software control logic can be mapped into a fault tree that depicts both software and hardware contributions to system failure. The new method is important because it provides a way for quantitatively evaluating the reliability contribution of software designs. In many applications, this can help guide designers in producing safer and more reliable systems. An application to the nuclear power research industry is discussed

  9. Compositional data-driven alternatives to single geochemical component maps

    OpenAIRE

    van den Boogaart, K. G.; McKinley, J.; de Caritat, P.; Filzmoser, P; Grunsky, E.; Hron, K.; Reimann, C.; Tolosana-Delgado, R.

    2015-01-01

    Conventional practice in Regional Geochemistry includes as a final step of any geochemical campaign the generation of a series of maps, to show the spatial distribution of each of the components considered. Such maps, though necessary, do not comply with the compositional, relative nature of the data, which unfortunately make any conclusion based on them sensitiveto spurious correlation problems. This is one of the reasons why these maps are never interpreted isolated. This contribution aims ...

  10. Adsorption component of the disjoining pressure in thin liquid films

    OpenAIRE

    Tsekov, R.

    2011-01-01

    The disjoining pressure isotherm in foam films is theoretically studied and an important contribution of adsorption is discovered. On the basis of the interfacial thermodynamics an adsorption disjoining pressure component is derived, which is repulsive and exponentially decaying by the film thickness. Expressions for its magnitude and decay length are derived in terms of well-known thermodynamic characteristics such as the partial Gibbs elasticity and adsorption length. Several adsorption iso...

  11. SCAM – Software Component Assessment Model

    OpenAIRE

    Hasan Tahir; Aasia Khannum; Ruhma Tahir

    2011-01-01

    It is widely understood that component based development is different from conventional development because components offer accelerated growth. In the absence of an effective component assessment strategy the developers of a software project have no way of assessing the quality of the software component they are about to incorporate into the project. We present two laws that link software components, software projects and their quality. We further propose a simple software component assessme...

  12. 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...

  13. The contribution of China's emissions to global climate forcing.

    Science.gov (United States)

    Li, Bengang; Gasser, Thomas; Ciais, Philippe; Piao, Shilong; Tao, Shu; Balkanski, Yves; Hauglustaine, Didier; Boisier, Juan-Pablo; Chen, Zhuo; Huang, Mengtian; Li, Laurent Zhaoxin; Li, Yue; Liu, Hongyan; Liu, Junfeng; Peng, Shushi; Shen, Zehao; Sun, Zhenzhong; Wang, Rong; Wang, Tao; Yin, Guodong; Yin, Yi; Zeng, Hui; Zeng, Zhenzhong; Zhou, Feng

    2016-03-17

    Knowledge of the contribution that individual countries have made to global radiative forcing is important to the implementation of the agreement on "common but differentiated responsibilities" reached by the United Nations Framework Convention on Climate Change. Over the past three decades, China has experienced rapid economic development, accompanied by increased emission of greenhouse gases, ozone precursors and aerosols, but the magnitude of the associated radiative forcing has remained unclear. Here we use a global coupled biogeochemistry-climate model and a chemistry and transport model to quantify China's present-day contribution to global radiative forcing due to well-mixed greenhouse gases, short-lived atmospheric climate forcers and land-use-induced regional surface albedo changes. We find that China contributes 10% ± 4% of the current global radiative forcing. China's relative contribution to the positive (warming) component of global radiative forcing, mainly induced by well-mixed greenhouse gases and black carbon aerosols, is 12% ± 2%. Its relative contribution to the negative (cooling) component is 15% ± 6%, dominated by the effect of sulfate and nitrate aerosols. China's strongest contributions are 0.16 ± 0.02 watts per square metre for CO2 from fossil fuel burning, 0.13 ± 0.05 watts per square metre for CH4, -0.11 ± 0.05 watts per square metre for sulfate aerosols, and 0.09 ± 0.06 watts per square metre for black carbon aerosols. China's eventual goal of improving air quality will result in changes in radiative forcing in the coming years: a reduction of sulfur dioxide emissions would drive a faster future warming, unless offset by larger reductions of radiative forcing from well-mixed greenhouse gases and black carbon. PMID:26983540

  14. 5 CFR 1604.3 - Contribution elections.

    Science.gov (United States)

    2010-01-01

    ... § 1604.3 Contribution elections. A service member may make contribution elections as described in 5 CFR... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Contribution elections. 1604.3 Section... incentive pay when the contribution election is made); those elections will take effect when the...

  15. TRW Contributes $10,000

    Science.gov (United States)

    The Solar-Planetary Relationships Section proposed in fall 1988 that a fund be established to honor Fred Scarf, who died July 17, 1988, while in the Soviet Union for launch of the missions to Phobos (see "Frederick L. Scarf, 1930-1988," Eos, 69, 1601, 1988). TRW of Redondo Beach, Calif., Fred's employer, agreed to match the money contributed when the amount reached 10,000.The fund has now grown to just over 8000 and TRW, in good faith that the fund will reach 10,000, has sent AGU a check for 10,000. TRW and AGU both believe that this fund is an especially fitting way for Fred to be remembered.

  16. Minisuperspace models as infrared contributions

    CERN Document Server

    Bojowald, Martin

    2015-01-01

    A direct correspondence of quantum mechanics as a minisuperspace model for a self-interacting scalar quantum-field theory is established by computing, in several models, the infrared contributions to 1-loop effective potentials of Coleman--Weinberg type. A minisuperspace approximation rather than truncation is thereby obtained. By this approximation, the spatial averaging scale of minisuperspace models is identified with an infrared scale (but not a regulator or cut-off) delimiting the modes included in the minisuperspace model. Some versions of the models studied here have discrete space or modifications of the Hamiltonian expected from proposals of loop quantum gravity. They shed light on the question of how minisuperspace models of quantum cosmology can capture features of full quantum gravity. While it is shown that modifications of the Hamiltonian can well be described by minisuperspace truncations, some related phenomena such as signature change, confirmed and clarified here for modified scalar field th...

  17. Ergonomics contributions to company strategies.

    Science.gov (United States)

    Dul, Jan; Neumann, W Patrick

    2009-07-01

    Managers usually associate ergonomics with occupational health and safety and related legislation, not with business performance. In many companies, these decision makers seem not to be positively motivated to apply ergonomics for reasons of improving health and safety. In order to strengthen the position of ergonomics and ergonomists in the business and management world, we discuss company strategies and business goals to which ergonomics could contribute. Conceptual models are presented and examples are given to illustrate: (1) the present situation in which ergonomics is not part of regular planning and control cycles in organizations to ensure business performance; and (2) the desired situation in which ergonomics is an integrated part of strategy formulation and implementation. In order to realize the desired situation, considerable changes must take place within the ergonomics research, education and practice community by moving from a health ergonomics paradigm to a business ergonomics paradigm, without losing the health and safety goals. PMID:18775532

  18. Ethnographic Contributions to Method Development

    DEFF Research Database (Denmark)

    Leander, Anna

    2015-01-01

    Contrary to common assumptions, there is much to be learned about methods from constructivist/post-structuralist approaches to International Relations (IR) broadly speaking. This article develops this point by unpacking the contributions of one specific method—ethnography—as used in one subfield of...... IR—Critical Security Studies. Ethnographic research works with what has been termed a “strong” understanding of objectivity. When this understanding is taken seriously, it must lead to a refashioning of the processes of gathering, analyzing, and presenting data in ways that reverse many standard...... assumptions and instructions pertaining to “sound methods.” Both in the context of observation and in that of justification, working with “strong objectivity” requires a flexibility and willingness to shift research strategies that is at odds with the usual emphasis on stringency, consistency, and carefully...

  19. Making High-Tensile-Strength Amalgam Components

    Science.gov (United States)

    Grugel, Richard

    2008-01-01

    Structural components made of amalgams can be made to have tensile strengths much greater than previously known to be possible. Amalgams, perhaps best known for their use in dental fillings, have several useful attributes, including room-temperature fabrication, corrosion resistance, dimensional stability, and high compressive strength. However, the range of applications of amalgams has been limited by their very small tensile strengths. Now, it has been discovered that the tensile strength of an amalgam depends critically on the sizes and shapes of the particles from which it is made and, consequently, the tensile strength can be greatly increased through suitable choice of the particles. Heretofore, the powder particles used to make amalgams have been, variously, in the form of micron-sized spheroids or flakes. The tensile reinforcement contributed by the spheroids and flakes is minimal because fracture paths simply go around these particles. However, if spheroids or flakes are replaced by strands having greater lengths, then tensile reinforcement can be increased significantly. The feasibility of this concept was shown in an experiment in which electrical copper wires, serving as demonstration substitutes for copper powder particles, were triturated with gallium by use of a mortar and pestle and the resulting amalgam was compressed into a mold. The tensile strength of the amalgam specimen was then measured and found to be greater than 10(exp 4) psi (greater than about 69 MPa). Much remains to be done to optimize the properties of amalgams for various applications through suitable choice of starting constituents and modification of the trituration and molding processes. The choice of wire size and composition are expected to be especially important. Perusal of phase diagrams of metal mixtures could give insight that would enable choices of solid and liquid metal constituents. Finally, whereas heretofore, only binary alloys have been considered for amalgams

  20. On the extension of Importance Measures to complex components

    International Nuclear Information System (INIS)

    Importance Measures are indicators of the risk significance of the components of a system. They are widely used in various applications of Probabilistic Safety Analyses, off-line and on-line, in decision making for preventive and corrective purposes, as well as to rank components according to their contribution to the global risk. They are primarily defined for the case the support model is a coherent fault tree and failures of components are described by basic events of this fault tree. In this article, we study their extension to complex components, i.e. components whose failures are modeled by a gate rather than just a basic event. Although quite natural, such an extension has not received much attention in the literature. We show that it raises a number of problems. The Birnbaum Importance Measure and the notion of Critical States concentrate these difficulties. We present alternative solutions for the extension of these notions. We discuss their respective advantages and drawbacks. This article gives a new point of view on the mathematical foundations of Importance Measures and helps us to clarify their physical meaning. - Highlights: • We propose an extension of Importance Measures to complex components. • We define our extension in term minterms, i.e. states of the system. • We discuss the physical interpretation of Importance Measures in light of this interpretation