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Sample records for autophagic components contribute

  1. Autophagic components contribute to hypersensitive cell death in Arabidopsis

    DEFF Research Database (Denmark)

    Hofius, Daniel; Schultz-Larsen, Torsten; Joensen, Jan;

    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...... expression. Here, we examined receptor-mediated HR PCD responses in autophagy-deficient Arabidopsis knockout mutants (atg), and show that infection-induced lesions are contained in atg mutants. We also provide evidence that HR cell death initiated via Toll/Interleukin-1 (TIR)-type immune receptors through...... the defense regulator EDS1 is suppressed in atg mutants. Furthermore, we demonstrate that PCD triggered by coiled-coil (CC)-type immune receptors via NDR1 is either autophagy-independent or engages autophagic components with cathepsins and other unidentified cell death mediators. Thus, autophagic cell death...

  2. 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

  3. Cotyledon cells of Vigna mungo seedlings use at least two distinct autophagic machineries for degradation of starch granules and cellular components.

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    Toyooka, K; Okamoto, T; Minamikawa, T

    2001-09-01

    alpha-Amylase is expressed in cotyledons of germinated Vigna mungo seeds and is responsible for the degradation of starch that is stored in the starch granule (SG). Immunocytochemical analysis of the cotyledon cells with anti-alpha-amylase antibody showed that alpha-amylase is transported to protein storage vacuole (PSV) and lytic vacuole (LV), which is converted from PSV by hydrolysis of storage proteins. To observe the insertion/degradation processes of SG into/in the inside of vacuoles, ultrastructural analyses of the cotyledon cells were conducted. The results revealed that SG is inserted into LV through autophagic function of LV and subsequently degraded by vacuolar alpha-amylase. The autophagy for SG was structurally similar to micropexophagy detected in yeast cells. In addition to the autophagic process for SG, autophagosome-mediated autophagy for cytoplasm and mitochondria was detected in the cotyledon cells. When the embryo axes were removed from seeds and the detached cotyledons were incubated, the autophagosome-mediated autophagy was observed, but the autophagic process for the degradation of SG was not detected, suggesting that these two autophagic processes were mediated by different cellular mechanisms. The two distinct autophagic processes were thought to be involved in the breakdown of SG and cell components in the cells of germinated cotyledon.

  4. ASSAYING OF AUTOPHAGIC PROTEIN DEGRADATION

    NARCIS (Netherlands)

    C. Bauvy; A.J. Meijer; P. Codogno

    2009-01-01

    Macroautophagy is a three-step process: (1) autophagosomes form and mature, (2) the autophagosomes fuse with lysosomes, and (3) the autophagic cargo is degraded in the lysosomes. It is this lysosomal degradation of the autophagic cargo that constitutes the autophagic flux. As in the case of metaboli

  5. 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...

  6. Autophagic regulation of smooth muscle cell biology

    Science.gov (United States)

    Salabei, Joshua K.; Hill, Bradford G.

    2014-01-01

    Autophagy regulates the metabolism, survival, and function of numerous cell types, including those comprising the cardiovascular system. In the vasculature, changes in autophagy have been documented in atherosclerotic and restenotic lesions and in hypertensive vessels. The biology of vascular smooth muscle cells appears particularly sensitive to changes in the autophagic program. Recent evidence indicates that stimuli or stressors evoked during the course of vascular disease can regulate autophagic activity, resulting in modulation of VSMC phenotype and viability. In particular, certain growth factors and cytokines, oxygen tension, and pharmacological drugs have been shown to trigger autophagy in smooth muscle cells. Importantly, each of these stimuli has a redox component, typically associated with changes in the abundance of reactive oxygen, nitrogen, or lipid species. Collective findings support the hypothesis that autophagy plays a critical role in vascular remodeling by regulating smooth muscle cell phenotype transitions and by influencing the cellular response to stress. In this graphical review, we summarize current knowledge on the role of autophagy in the biology of the smooth muscle cell in (patho)physiology. PMID:25544597

  7. Autophagic regulation of smooth muscle cell biology

    Directory of Open Access Journals (Sweden)

    Joshua K. Salabei

    2015-04-01

    Full Text Available Autophagy regulates the metabolism, survival, and function of numerous cell types, including those comprising the cardiovascular system. In the vasculature, changes in autophagy have been documented in atherosclerotic and restenotic lesions and in hypertensive vessels. The biology of vascular smooth muscle cells appears particularly sensitive to changes in the autophagic program. Recent evidence indicates that stimuli or stressors evoked during the course of vascular disease can regulate autophagic activity, resulting in modulation of VSMC phenotype and viability. In particular, certain growth factors and cytokines, oxygen tension, and pharmacological drugs have been shown to trigger autophagy in smooth muscle cells. Importantly, each of these stimuli has a redox component, typically associated with changes in the abundance of reactive oxygen, nitrogen, or lipid species. Collective findings support the hypothesis that autophagy plays a critical role in vascular remodeling by regulating smooth muscle cell phenotype transitions and by influencing the cellular response to stress. In this graphical review, we summarize current knowledge on the role of autophagy in the biology of the smooth muscle cell in (pathophysiology.

  8. Why should autophagic flux be assessed?

    Institute of Scientific and Technical Information of China (English)

    Xiao-jie ZHANG; Sheng CHEN; Kai-xing HUANG; Wei-dong LE

    2013-01-01

    As autophagy is involved in cell growth,survival,development and death,impaired autophagic flux has been linked to a variety of human pathophysiological processes,including neurodegeneration,cancer,myopathy,cardiovascular and immune-mediated disorders.There is a growing need to identify and quantify the status of autophagic flux in different pathological conditions.Given that autophagy is a highly dynamic and complex process that is regulated at multiple steps,it is often assessed accurately.This perspective review article will focus on the autophagic flux defects in different human disorders and update the current methods of monitoring autophagic flux.This knowledge is essential for developing autophagy-related therapeutics for treating the diseases.

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

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    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.

  10. 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

  11. Targeting autophagic pathways for cancer drug discovery

    Institute of Scientific and Technical Information of China (English)

    Bo Liu; Jin-Ku Bao; Jin-Ming Yang; Yan Cheng

    2013-01-01

    Autophagy,an evolutionarily conserved lysosomal degradation process,has drawn an increasing amount of attention in recent years for its role in a variety of human diseases,such as cancer.Notably,autophagy plays an important role in regulating several survival and death signaling pathways that determine cell fate in cancer.To date,substantial evidence has demonstrated that some key autophagic mediators,such as autophagy-related genes (ATGs),PI3K,mTOR,p53,and Beclin-1,may play crucial roles in modulating autophagic activity in cancer initiation and progression.Because autophagy-modulating agents such as rapamycin and chloroquine have already been used clinically to treat cancer,it is conceivable that targeting autophagic pathways may provide a new opportunity for discovery and development of more novel cancer therapeutics.With a deeper understanding of the regulatory mechanisms governing autophagy,we will have a better opportunity to facilitate the exploitation of autophagy as a target for therapeutic intervention in cancer.This review discusses the current status of targeting autophagic pathways as a potential cancer therapy.

  12. 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...

  13. 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.

  14. 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...

  15. 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.

  16. 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

  17. 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.

  18. 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.

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

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    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.

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

    Science.gov (United States)

    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

  3. Autophagic pathways in Parkinson disease and related disorders.

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    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

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

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    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.

  5. Conditioned place preference for social interaction in rats: contribution of sensory components

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    Kai eKummer

    2011-11-01

    Full Text Available A main challenge in the therapy of drug dependent individuals is to help them reactivate interest in non-drug-associated activities. We previously developed a rat experimental model based on the conditioned place preference (CPP paradigm in which only four 15-min episodes of social interaction with a gender- and weight-matched male Sprague Dawley rat (i reversed CPP from cocaine to social interaction despite continuing cocaine training and (ii prevented the reinstatement of cocaine CPP. In the present study, we investigated which of the sensory modalities of the composite stimulus 'social interaction' contributes most to the rats’ preference for it. If touch was limited by steel bars spaced at a distance of 2 cm and running across the whole length of a partitioning, CPP was still acquired, albeit to a lesser degree. If both rats were placed on the same side of a partitioning, rats did not develop CPP for social interaction. Thus, decreasing the available area for social interaction from 750 to 375 cm² prevented the acquisition of CPP to social interaction despite the fact that animals could touch each other more intensely than through the bars of the partitioning. When touch was fully restricted by a glass screen dividing the conditioning chambers, and the only sensory modalities left were visual and olfactory cues, place preference shifted to place aversion. Overall, our findings indicate that the major rewarding sensory component of the composite stimulus 'social interaction' is touch (tactition.

  6. Left dorsal speech stream components and their contribution to phonological processing.

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    Murakami, Takenobu; Kell, Christian A; Restle, Julia; Ugawa, Yoshikazu; Ziemann, Ulf

    2015-01-28

    Models propose an auditory-motor mapping via a left-hemispheric dorsal speech-processing stream, yet its detailed contributions to speech perception and production are unclear. Using fMRI-navigated repetitive transcranial magnetic stimulation (rTMS), we virtually lesioned left dorsal stream components in healthy human subjects and probed the consequences on speech-related facilitation of articulatory motor cortex (M1) excitability, as indexed by increases in motor-evoked potential (MEP) amplitude of a lip muscle, and on speech processing performance in phonological tests. Speech-related MEP facilitation was disrupted by rTMS of the posterior superior temporal sulcus (pSTS), the sylvian parieto-temporal region (SPT), and by double-knock-out but not individual lesioning of pars opercularis of the inferior frontal gyrus (pIFG) and the dorsal premotor cortex (dPMC), and not by rTMS of the ventral speech-processing stream or an occipital control site. RTMS of the dorsal stream but not of the ventral stream or the occipital control site caused deficits specifically in the processing of fast transients of the acoustic speech signal. Performance of syllable and pseudoword repetition correlated with speech-related MEP facilitation, and this relation was abolished with rTMS of pSTS, SPT, and pIFG. Findings provide direct evidence that auditory-motor mapping in the left dorsal stream causes reliable and specific speech-related MEP facilitation in left articulatory M1. The left dorsal stream targets the articulatory M1 through pSTS and SPT constituting essential posterior input regions and parallel via frontal pathways through pIFG and dPMC. Finally, engagement of the left dorsal stream is necessary for processing of fast transients in the auditory signal.

  7. Can assessing for potential contribution of soil organic and inorganic components for butachlor sorption be improved?

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    He, Yan; Liu, Zhongzhen; Zhang, Jian; Wang, Haizhen; Shi, Jiachun; Xu, Jianming

    2011-01-01

    Sorption of butachlor to various types of common soil components was investigated. Six pure minerals (montmorillonite [Mont], kaolinite [Kaol], Ca homoionic montmorillonite [Ca-Mont] and kaolinite [Ca-Kaol], amorphous hydrated Al and Fe oxides [AHOs-Al, AHOs-Fe]), four soil alkali-extractable pure humic acids (HAs), and the four corresponding HAs originated real unmodified and HO-treated soils were selected as the representative sorbents. Results showed that the HAs played a crucial role, and clay minerals (especially Mont) also showed an important effect in butachlor sorption. The AHOs may likely influence only in a mediator way by enhancing the availability of sorption domains of HAs. By removing 78% (on average) of the total organic carbon (TOC) from the soils with HO, the content ratio of clay to TOC (RCO) increased by an average of 367% and became >60. This change simultaneously decreased the sorption capacity of soils (40%, on average). Considering that the surface sorption domain on clay minerals may be highly exposed and more competitive after the partial removal of soil organic matter (SOM), this reaffirmed the potential contribution from clay minerals. It can thus be inferred that in the real soil where SOM and clay minerals are associated, the coating of clay minerals may have weakened the partition function of SOM or blocked some sorption domain within SOM, resulting in a decreased sorption of butachlor. Therefore, clay minerals, especially 2:1 type expanding minerals, may play a dual function vs. SOM content for the sorption of butachlor in soil.

  8. 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)

  9. The implicit contribution of slab modes to the perpendicular diffusion coefficient of particles interacting with two-component turbulence

    CERN Document Server

    Shalchi, Andreas

    2016-01-01

    We explore the transport of energetic particles in two-component turbulence in which the stochastic magnetic field is assumed to be a superposition of slab and two-dimensional modes. It is known that in magnetostatic slab turbulence, the motion of particles across the mean magnetic field is subdiffusive. If a two-dimensional component is added, diffusion is recovered. It was also shown before that in two-component turbulence, the slab modes do not explicitly contribute to the perpendicular diffusion coefficient. In the current paper the implicit contribution of slab modes is explored and it is shown that this contribution leads to a reduction of the perpendicular diffusion coefficient. This effect improves the agreement between simulations and analytical theory. Furthermore, the obtained results are relevant for investigations of diffusive shock acceleration.

  10. 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.

  11. 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

  12. 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)

  13. 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…

  14. 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.

  15. 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.

  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. 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

  18. Crystalloids in apparent autophagic plastids: remnants of plastids or peroxisomes?

    Science.gov (United States)

    Papini, Alessio; van Doorn, Wouter G

    2015-02-01

    Plant macroautophagy is carried out by autophagosome-type organelles. Recent evidence suggests that plastids also can carry out macroautophagy. The double membrane at the surface of plastids apparently invaginates, forming an intraplastidial space. This space contains a portion of cytoplasm that apparently becomes degraded. Here we report, in Tillandsia sp. and Aechmaea sp., the presence of almost square or diamond-shaped crystalloids inside what seems the intraplastidial space of autophagous plastids. The same type of crystalloids were observed in chloroplasts and other plastids, but were not found in the cytoplasm or the vacuole. Peroxisomes contained smaller and more irregularly shaped crystalloids compared to the ones observed in 'autophagous' plastids. It is hypothesized that plastids are able to sequester chloroplasts and other plastids. PMID:25462964

  19. 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

  20. 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

  1. 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

  2. The Contribution of Cell Surface Components to the Neutrophil Mechanosensitivity to Shear Stresses

    Directory of Open Access Journals (Sweden)

    Michael L. Akenhead

    2015-08-01

    Full Text Available This review discusses the regulation of neutrophils by fluid shear stress in the context of factors that may govern cell mechanosensitivity and its influence on cell functions. There is substantial evidence that mechanoreceptors located on the peripheral membrane contribute to the ability of shear stress to regulate cell activity. In the case of neutrophils, the formyl peptide receptor (FPR and the CD18 integrins on the cell membrane have been shown to provide neutrophils with the ability to sense shear stresses in their local environment and alter their physiological state, accordingly. This configuration is also found for other types of cells, although they involve different cell-specific mechanoreceptors. Moreover, from an examination of the neutrophil mechanotransducing capacity, it is apparent that cellular mechanosensitivity depends on a number of factors that, if altered, contribute to dysregulation and ultimately pathophysiology. To exemplify this, we first describe the neutrophil responses to shear exposure. We then review two neutrophil mechanoreceptors, specifically FPR and CD18 integrins, which participate in controlling cell activity levels under physiological conditions. Next, we discuss the various factors that may alter neutrophil mechanosensitivity to shear stress and how these may underlie the circulatory pathobiology of two cardiovascular disease states: hypertension and hypercholesterolemia. Based on the material presented, it is conceivable that cell mechanosensitivity is a powerful global metric that permits a more efficient approach to understanding the contribution of mechanobiology to physiology and to disease processes.

  3. 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.

  4. 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

  5. Quantification of frequency-components contributions to the discharge of a karst spring

    Science.gov (United States)

    Taver, V.; Johannet, A.; Vinches, M.; Borrell, V.; Pistre, S.; Bertin, D.

    2013-12-01

    Karst aquifers represent important underground resources for water supplies, providing it to 25% of the population. Nevertheless such systems are currently underexploited because of their heterogeneity and complexity, which make work fields and physical measurements expensive, and frequently not representative of the whole aquifer. The systemic paradigm appears thus at a complementary approach to study and model karst aquifers in the framework of non-linear system analysis. Its input and output signals, namely rainfalls and discharge contain information about the function performed by the physical process. Therefore, improvement of knowledge about the karst system can be provided using time series analysis, for example Fourier analysis or orthogonal decomposition [1]. Another level of analysis consists in building non-linear models to identify rainfall/discharge relation, component by component [2]. In this context, this communication proposes to use neural networks to first model the rainfall-runoff relation using frequency components, and second to analyze the models, using the KnoX method [3], in order to quantify the importance of each component. Two different neural models were designed: (i) the recurrent model which implements a non-linear recurrent model fed by rainfalls, ETP and previous estimated discharge, (ii) the feed-forward model which implements a non-linear static model fed by rainfalls, ETP and previous observed discharges. The first model is known to better represent the rainfall-runoff relation; the second one to better predict the discharge based on previous discharge observations. KnoX method is based on a variable selection method, which simply considers values of parameters after the training without taking into account the non-linear behavior of the model during functioning. An amelioration of the KnoX method, is thus proposed in order to overcome this inadequacy. The proposed method, leads thus to both a hierarchization and a quantification

  6. 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.

  7. 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.

  8. 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

  9. Working memory contributions to reading comprehension components in middle childhood children.

    Science.gov (United States)

    Chrysochoou, Elisavet; Bablekou, Zoe; Tsigilis, Nikolaos

    2011-01-01

    This study examined working memory contributions to reading comprehension subskills in Greek children (mean age 9 years, 1 month). The phonological loop of the Baddeley and Hitch working memory model was assessed with 3 recall tasks (words, nonwords, and digits) and a word list matching task. The central executive (CE) was assessed with 3 tasks (listening, counting, and backward digit recall). Participants were also given a receptive vocabulary task, a reading fluency task, and written stories accompanied by comprehension questions. Canonical correlation analyses showed that the comprehension variables were related to the CE rather than the phonological loop measures. CE functions were more strongly associated with elaborative inference generation (involving significant offline processing) and comprehension control (involving metacognitive monitoring). Smaller yet significant associations were observed between the CE and the necessary inference and literal comprehension measures, whereas a moderate relationship was found in the case of the simile comprehension variable. Among the CE variables, listening recall demonstrated the highest loading on the canonical function, followed by moderate yet significant counting and backward digit recall loadings. Vocabulary was found to fully mediate several associations between working memory and comprehension measures; however, the relationship between listening recall and elaborative inferences was partly mediated. Reading fluency and, on several occasions, Greek vocabulary knowledge did not mediate the relationships between CE measures and comprehension skills assessed. This study demonstrates the usefulness of CE measures for identifying young children's possible difficulties in carrying out specific reading comprehension processes.

  10. 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

  11. Do different components of terrestrial sources contribute to the riverine suspended load?

    Science.gov (United States)

    Voss, B. M.; Peucker-Ehrenbrink, B.; Eglinton, T. I.; Galy, V.

    2012-04-01

    Establishing the relationship between source (bedrock, soil, floodplain sediments, vegetation) and mobilized materials (bedload and suspended load) within a river drainage network is critical to understanding the fate of particulate matter exported to the coastal ocean. First, linking material carried in river channels to its terrestrial sources aides in predicting the reactivity of organic matter associated with mineral particles and understanding which portions of a watershed contribute substantially to organic carbon fluxes and transformations in these systems. Second, identifying terrestrial reservoirs of future riverine suspended material can enhance our ability to comprehensively characterize the chemical and physical nature of fluvial sediments. We present a study of sedimentological and bulk organic carbon properties of sediments from across the Fraser River watershed in southwestern British Columbia, Canada. Bulk samples and size fractions from surface soils and riverbank sediments, as well as vegetation, are analyzed for metrics including carbon and nitrogen content, 13C and 14C composition, and specific surface area. These are compared with measurements of riverine suspended sediments and size fractions of sediments deposited in the Fraser estuary. The correspondence of suspended sediment properties with different portions of soil, alluvial, and vegetation pools from different sites suggests a complex link between source materials and exported material. Such variability may stem from the heterogeneous nature of soil types, hillslope morphology, and runoff regimes in different portions of the drainage basin; settling/resuspension processes during river transit; and/or modification of particle structure and organic matter between mobilization of terrestrial material and arrival at distant downstream sites. The preferential loss/preservation of different size fractions within mineral source materials highlights the unequal importance of different mineral

  12. 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.

  13. OMIP contribution to CMIP6: experimental and diagnostic protocol for the physical component of the Ocean Model Intercomparison Project

    Science.gov (United States)

    Griffies, Stephen M.; Danabasoglu, Gokhan; Durack, Paul J.; Adcroft, Alistair J.; Balaji, V.; Böning, Claus W.; Chassignet, Eric P.; Curchitser, Enrique; Deshayes, Julie; Drange, Helge; Fox-Kemper, Baylor; Gleckler, Peter J.; Gregory, Jonathan M.; Haak, Helmuth; Hallberg, Robert W.; Heimbach, Patrick; Hewitt, Helene T.; Holland, David M.; Ilyina, Tatiana; Jungclaus, Johann H.; Komuro, Yoshiki; Krasting, John P.; Large, William G.; Marsland, Simon J.; Masina, Simona; McDougall, Trevor J.; Nurser, A. J. George; Orr, James C.; Pirani, Anna; Qiao, Fangli; Stouffer, Ronald J.; Taylor, Karl E.; Treguier, Anne Marie; Tsujino, Hiroyuki; Uotila, Petteri; Valdivieso, Maria; Wang, Qiang; Winton, Michael; Yeager, Stephen G.

    2016-09-01

    The Ocean Model Intercomparison Project (OMIP) is an endorsed project in the Coupled Model Intercomparison Project Phase 6 (CMIP6). OMIP addresses CMIP6 science questions, investigating the origins and consequences of systematic model biases. It does so by providing a framework for evaluating (including assessment of systematic biases), understanding, and improving ocean, sea-ice, tracer, and biogeochemical components of climate and earth system models contributing to CMIP6. Among the WCRP Grand Challenges in climate science (GCs), OMIP primarily contributes to the regional sea level change and near-term (climate/decadal) prediction GCs.OMIP provides (a) an experimental protocol for global ocean/sea-ice models run with a prescribed atmospheric forcing; and (b) a protocol for ocean diagnostics to be saved as part of CMIP6. We focus here on the physical component of OMIP, with a companion paper (Orr et al., 2016) detailing methods for the inert chemistry and interactive biogeochemistry. The physical portion of the OMIP experimental protocol follows the interannual Coordinated Ocean-ice Reference Experiments (CORE-II). Since 2009, CORE-I (Normal Year Forcing) and CORE-II (Interannual Forcing) have become the standard methods to evaluate global ocean/sea-ice simulations and to examine mechanisms for forced ocean climate variability. The OMIP diagnostic protocol is relevant for any ocean model component of CMIP6, including the DECK (Diagnostic, Evaluation and Characterization of Klima experiments), historical simulations, FAFMIP (Flux Anomaly Forced MIP), C4MIP (Coupled Carbon Cycle Climate MIP), DAMIP (Detection and Attribution MIP), DCPP (Decadal Climate Prediction Project), ScenarioMIP, HighResMIP (High Resolution MIP), as well as the ocean/sea-ice OMIP simulations.

  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. 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;

    2011-01-01

    quantitative contributions of IA and liver fat to components of the syndrome, fasting serum (fS) insulin, and liver enzymes and measures of hepatic insulin sensitivity in 356 subjects (mean age 42 years, mean BMI 29.7 kg/m²) in whom liver fat and abdominal fat volumes were measured. IA and liver fat contents...... were correlated (r = 0.65, P liver or IA fat, liver fat or IA fat explained variation in fS-triglyceride (TG) and high-density lipoprotein (HDL) cholesterol, plasma glucose, insulin and liver enzyme concentrations, and hepatic....... Liver fat independently predicted glucose and liver enzymes. SC fat and age explained variation in blood pressure. In conclusion, both IA and liver fat independently of each other explain variation in serum TG, HDL cholesterol, insulin concentrations and hepatic insulin sensitivity, thus supporting...

  16. HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.

    Science.gov (United States)

    Aits, Sonja; Gustafsson, Lotta; Hallgren, Oskar; Brest, Patrick; Gustafsson, Mattias; Trulsson, Maria; Mossberg, Ann-Kristin; Simon, Hans-Uwe; Mograbi, Baharia; Svanborg, Catharina

    2009-03-01

    HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

  17. Cellular metabolic and autophagic pathways: traffic control by redox signaling.

    Science.gov (United States)

    Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua

    2013-10-01

    It has been established that the key metabolic pathways of glycolysis and oxidative phosphorylation are intimately related to redox biology through control of cell signaling. Under physiological conditions glucose metabolism is linked to control of the NADH/NAD redox couple, as well as providing the major reductant, NADPH, for thiol-dependent antioxidant defenses. Retrograde signaling from the mitochondrion to the nucleus or cytosol controls cell growth and differentiation. Under pathological conditions mitochondria are targets for reactive oxygen and nitrogen species and are critical in controlling apoptotic cell death. At the interface of these metabolic pathways, the autophagy-lysosomal pathway functions to maintain mitochondrial quality and generally serves an important cytoprotective function. In this review we will discuss the autophagic response to reactive oxygen and nitrogen species that are generated from perturbations of cellular glucose metabolism and bioenergetic function.

  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. Clozapine Induces Autophagic Cell Death in Non-Small Cell Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yu-Chun Yin

    2015-02-01

    Full Text Available Background/Aims: Previous studies have shown that patients with schizophrenia have a lower incidence of cancer than the general population, and several antipsychotics have been demonstrated to have cytotoxic effects on cancer cells. However, the mechanisms underlying these results remain unclear. The present study aimed to investigate the effect of clozapine, which is often used to treat patients with refractory schizophrenia, on the growth of non-small cell lung carcinoma cell lines and to examine whether autophagy contributes to its effects. Methods: A549 and H1299 cells were treated with clozapine, and cell cytotoxicity, cell cycle and autophagy were then assessed. The autophagy inhibitor bafilomycin A1 and siRNA-targeted Atg7 were used to determine the role of autophagy in the effect of clozapine. Results: Clozapine inhibited A549 and H1299 proliferation and increased p21 and p27 expression levels, leading to cell cycle arrest. Clozapine also induced a high level of autophagy, but not apoptosis, in both cell lines, and the growth inhibitory effect of clozapine was blunted by treatment with the autophagy inhibitor bafilomycin A1 or with an siRNA targeting atg7. Conclusions: Clozapine inhibits cell proliferation by inducing autophagic cell death in two non-small cell lung carcinoma cell lines. These findings may provide insights into the relationship between clozapine use and the lower incidence of lung cancer among patients with schizophrenia.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Aggressive human neuroblastomas show a massive increase in the numbers of autophagic vacuoles and damaged mitochondria.

    Science.gov (United States)

    Samardzija, Gordana; Stevovic, Tamara Kravic; Djuricic, Slavisa; Djokic, Dragomir; Djurisic, Marina; Ciric, Darko; Martinovic, Tamara; Bumbasirevic, Vladimir; Vujic, Dragana

    2016-01-01

    Autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance in neuroblastoma (NB). This study was conducted to analyze the ultrastructural features of peripheral neuroblastic tumors (pNTs) and identify the relation of the types of NTs, the proliferation rate, and MYCN gene amplification with a number of autophagic vacuoles. Our results indicate that aggressive human NBs show a massive increase in the number of autophagic vacuoles associated with proliferation rate and that alteration of the mitochondria might be an important factor for the induction of autophagy in NTs. PMID:27669398

  11. HDAC1 inactivation induces mitotic defect and caspase-independent autophagic cell death in liver cancer.

    Directory of Open Access Journals (Sweden)

    Hong Jian Xie

    Full Text Available Histone deacetylases (HDACs are known to play a central role in the regulation of several cellular properties interlinked with the development and progression of cancer. Recently, HDAC1 has been reported to be overexpressed in hepatocellular carcinoma (HCC, but its biological roles in hepatocarcinogenesis remain to be elucidated. In this study, we demonstrated overexpression of HDAC1 in a subset of human HCCs and liver cancer cell lines. HDAC1 inactivation resulted in regression of tumor cell growth and activation of caspase-independent autophagic cell death, via LC3B-II activation pathway in Hep3B cells. In cell cycle regulation, HDAC1 inactivation selectively induced both p21(WAF1/Cip1 and p27(Kip1 expressions, and simultaneously suppressed the expression of cyclin D1 and CDK2. Consequently, HDAC1 inactivation led to the hypophosphorylation of pRb in G1/S transition, and thereby inactivated E2F/DP1 transcription activity. In addition, we demonstrated that HDAC1 suppresses p21(WAF1/Cip1 transcriptional activity through Sp1-binding sites in the p21(WAF1/Cip1 promoter. Furthermore, sustained suppression of HDAC1 attenuated in vitro colony formation and in vivo tumor growth in a mouse xenograft model. Taken together, we suggest the aberrant regulation of HDAC1 in HCC and its epigenetic regulation of gene transcription of autophagy and cell cycle components. Overexpression of HDAC1 may play a pivotal role through the systemic regulation of mitotic effectors in the development of HCC, providing a particularly relevant potential target in cancer therapy.

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

    Directory of Open Access Journals (Sweden)

    Jinglan Zhang

    2016-04-01

    Full Text Available 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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...

  19. The diffuse galactic gamma radiation - The Compton contribution and component separation by energy interval and galactic coordinates

    Science.gov (United States)

    Kniffen, D. A.; Fichtel, C. E.

    1981-01-01

    The diffuse high-energy galactic gamma radiation to be expected from cosmic ray interactions with matter and photons is considered with particular emphasis on the contribution of Compton radiation from cosmic ray electrons. The intensity, spectrum and spatial distribution of the expected galactic gamma radiation are estimated based on models of the matter, cosmic ray and photon distributions to take into account the contributions of bremsstrahlung, high-energy cosmic-ray nucleon and interstellar matter interactions as well as Compton interactions between cosmic ray electrons and background photons. Results suggest that the Compton gamma ray contribution from cosmic ray electron interactions with galactic visible and infrared photons is substantially larger than previously believed. Analysis of the energy spectra and latitude dependence of the various sources reveals that the Compton radiation, bremsstrahlung and nuclear cosmic ray-matter interaction radiation should be separable, with Compton radiation dominating at energies from 10 to 100 MeV at galactic latitudes greater than several degrees. Results demonstrate the potential of gamma ray observations in studies of galactic structure, cosmic ray electrons and galactic photon density.

  20. 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

  1. 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.

  2. 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.

  3. 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.

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

    DEFF Research Database (Denmark)

    Hukkerikar, Amol; Sarup, Bent; Abildskov, Jens;

    and uncertainty analysis, in general, is developed and used. In total 21 properties of pure components, which include normal boiling point, critical constants, normal melting point among others have been analysed. The statistical analysis of the model performance for these properties is highlighted through...... several illustrative examples. Important issues related to property modeling such as thermodynamic consistency of the predicted properties (relation of normal boiling point versus critical temperature etc.) are analysed. The developed methodology is simple, yet sound and effective and provides not only...

  5. 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...

  6. 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

  7. 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

  8. Autophagic induction of amyotrophic lateral sclerosis-linked Cu/Zn superoxide dismutase 1 G93A mutant in NSC34 cells

    Institute of Scientific and Technical Information of China (English)

    Yanming Wei

    2014-01-01

    Previous studies have conifrmed that the beclin 1 complex plays a key role in the initial stage of autophagy and deregulated autophagy might involve in amyotrophic lateral sclerosis. However, the mechanism underlying altered autophagy associated with the beclin 1 complex remains un-clear. In this study, we transfected the Cu/Zn superoxide dismutase 1 G93A mutant protein into the motor neuron-like cell line NSC34 cultured in vitro. Western blotting and co-immunopre-cipitation showed that the Cu/Zn superoxide dismutase 1 G93A mutant enhanced the turnover of autophagic marker microtubule-associated protein light chain 3II (LC3II) and stimulated the conversion of EGFP-LC3I to EGFP-LC3II, but had little inlfuence on the binding capacity of the autophagy modulators ATG14L, rubicon, UVRAG, and hVps34 to beclin 1 during auto-phagosome formation. These results suggest that the amyotrophic lateral sclerosis-linked Cu/Zn superoxide dismutase 1 G93A mutant can upregulate autophagic activity in NSC34 cells, but that this does not markedly affect beclin 1 complex components.

  9. 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

  10. 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.

  11. 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

  12. 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...

  13. 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...

  14. Exaggerated arsenic nephrotoxicity in female mice through estrogen-dependent impairments in the autophagic flux.

    Science.gov (United States)

    Kimura, Akihiko; Ishida, Yuko; Nosaka, Mizuho; Kuninaka, Yumi; Hama, Mizuki; Kawaguchi, Takashi; Sakamoto, Shoichi; Shinozaki, Kohei; Iwahashi, Yumi; Takayasu, Tatsunori; Kondo, Toshikazu

    2016-01-01

    Gender is one of the essential factors in the development of various diseases and poisoning. Therefore, we herein examined gender differences in sodium arsenite (NaAsO2)-induced acute renal dysfunction. When male and female BALB/c mice were subcutaneously injected with NaAsO2 (12.5mg/kg), serum and urinary markers for proximal tubular injury were significantly higher in female mice than in male ones. NaAsO2-induced histopathological alterations were consistently more evident in females than in males. Ovariectomy, but not orchiectomy significantly attenuated NaAsO2-induced renal injury. These results imply that the hypersusceptibility of female mice is attributed to estrogen signals. NaAsO2 suppressed the autophagic flux in tubular cells through the activation of ERK. Enhancements in the activation of ERK were significantly greater in females than in males, with the eventual accumulation of LC3-II and P62 in the kidneys, implying that the autophagic flux is impaired in females. The IL-6/STAT3 signaling pathway had protective roles in NaAsO2-induced nephrotoxicity through the suppression of ERK activation. Despite the absence of differences in intrarenal IL-6 expression between male and female mice, STAT3 was less activated with enhanced SOCS3 expression in females than in males. An in vitro study using mProx24 cells revealed that the estrogen treatment induced SOCS3 expression, and eventually suppressed the autophagic flux, as evidenced by greater increases in the accumulation of LC3-II and p62 with ERK activation, which was canceled by the knockdown of Socs3. Collectively, these results indicate that estrogen has a negative impact on the development of NaAsO2 nephrotoxicity through its suppression of the autophagic flux.

  15. 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...

  16. 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...

  17. MP Resulting in Autophagic Cell Death of Microglia through Zinc Changes against Spinal Cord Injury

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    Dingding Li

    2016-01-01

    Full Text Available Methylprednisolone pulse therapy (MPPT, as a public recognized therapy of spinal cord injury (SCI, is doubted recently, and the exact mechanism of MP on SCI is unclear. This study sought to investigate the exact effect of MP on SCI. We examined the effect of MP in a model of SCI in vivo and an LPS induced model in vitro. We found that administration of MP produced an increase in the Basso, Beattie, and Bresnahan scores and motor neurons counts of injured rats. Besides the number of activated microglia was apparently reduced by MP in vivo, and Beclin-1 dependent autophagic cell death of microglia was induced by MP in LPS induced model. At the same time, MP increases cellular zinc concentration and level of ZIP8, and TPEN could revert effect of MP on autophagic cell death of microglia. Finally, we have found that MP could inhibit NF-κβ in LPS induced model. These results show that the MP could result in autophagic cell death of microglia, which mainly depends on increasing cellular labile zinc, and may be associated with inhibition of NF-κβ, and that MP can produce neuroprotective effect in SCI.

  18. MP Resulting in Autophagic Cell Death of Microglia through Zinc Changes against Spinal Cord Injury.

    Science.gov (United States)

    Li, Dingding; Wang, Guannan; Han, Donghe; Bi, Jing; Li, Chenyuan; Wang, Hongyu; Liu, Zhiyuan; Gao, Wei; Gao, Kai; Yao, Tianchen; Wan, Zhanghui; Li, Haihong; Mei, Xifan

    2016-01-01

    Methylprednisolone pulse therapy (MPPT), as a public recognized therapy of spinal cord injury (SCI), is doubted recently, and the exact mechanism of MP on SCI is unclear. This study sought to investigate the exact effect of MP on SCI. We examined the effect of MP in a model of SCI in vivo and an LPS induced model in vitro. We found that administration of MP produced an increase in the Basso, Beattie, and Bresnahan scores and motor neurons counts of injured rats. Besides the number of activated microglia was apparently reduced by MP in vivo, and Beclin-1 dependent autophagic cell death of microglia was induced by MP in LPS induced model. At the same time, MP increases cellular zinc concentration and level of ZIP8, and TPEN could revert effect of MP on autophagic cell death of microglia. Finally, we have found that MP could inhibit NF-κβ in LPS induced model. These results show that the MP could result in autophagic cell death of microglia, which mainly depends on increasing cellular labile zinc, and may be associated with inhibition of NF-κβ, and that MP can produce neuroprotective effect in SCI. PMID:27057544

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

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    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.

  20. Differential autophagic responses to nano-sized materials.

    Science.gov (United States)

    Popp, Lauren; Segatori, Laura

    2015-12-01

    Autophagy is a complex catabolic pathway that mediates degradation of excess or unwanted cytoplasmic components through the lysosome. Activated by environmental factors, such as nutrient depletion, and intracellular stimuli, such as proteotoxic stress, it provides a highly dynamic quality control mechanism to recycle cellular components, eliminate aberrant materials, and, ultimately, maintain cellular homeostasis. A growing body of evidence suggests that autophagy is also activated upon internalization of engineered nanomaterials, most likely as a protective response to what is perceived as foreign or toxic. This review describes the mechanisms of autophagy activation in response to naturally occurring and engineered nanomaterials. We provide a comprehensive analysis of the impact of nanomaterials on the lysosome-autophagy system, with particular emphasis on cellular markers associated with biocompatible and bioadverse outcomes of autophagy activation, such as clearance of toxic material and autophagy-associated cell death. Potential applications of the next-generation nanomaterials designed to interface with cellular clearance mechanisms with precisely tunable properties are also discussed.

  1. 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

  2. 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

  3. 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

  4. CORRELATION AND PATH ANALYSIS OF SEED YIELD AND YIELD CONTRIBUTING COMPONENTS OF BLACKGRAM ( VIGNA MUNGO L. HEPPER UNDER RAINFED CONDITION FROM ANDHRA PRADESH, INDIA

    Directory of Open Access Journals (Sweden)

    G. Vijay Kumar

    2014-09-01

    Full Text Available Correlation coefficient and path analysis studies werecarried out with seventeen parents (fourteen lines and three testers resulting 42 F1crosses for fifteen yield contributing component characters. The phenotypic and genotypic correlation analysis revealed that seed yield was highly significantly and positively correlated with number of branches, number of clusters, number of pods per plant, number of seeds per plant pod weight, total biomass and also highly significantly and positively correlated among themselves. Path coefficient analysis for seed yield revealed that significant phenotypic and genotypic direct effect with seeds per plant, 100 seed weight, harvest index, pod weight and number of clusters per plant. Hence selection for these characters may be carried out in the field and lab for overall yield improvement in blackgram.

  5. Contributions of Two-Component Regulatory Systems, Alternative σ Factors, and Negative Regulators to Listeria monocytogenes Cold Adaptation and Cold Growth

    Science.gov (United States)

    Chan, Yvonne C.; Hu, Yuewei; Chaturongakul, Soraya; Files, Kali D.; Bowen, Barbara M.; Boor, Kathryn J.; Wiedmann, Martin

    2011-01-01

    The ability of Listeria monocytogenes to grow at refrigeration temperatures is critical for transmission of this foodborne pathogen. We evaluated the contributions of different transcriptional regulators and two-component regulatory systems to L. monocytogenes cold adaptation and cold growth. L. monocytogenes parent strain 10403S and selected isogenic null mutants in genes encoding four alternative σ factors (sigB, sigH, sigC, and sigL), two regulators of σB (rsbT and rsbV), two negative regulators (ctsR and hrcA), and 15 two-component response regulators were grown in brain heart infusion broth at 4°C with (i) a high-concentration starting inoculum (108 CFU/ml), (ii) a low-concentration starting inoculum (102 CFU/ml), and (iii) a high-concentration starting inoculum of cold-adapted cells. With a starting inoculum of 108 CFU/ml, null mutants in genes encoding selected alternative σ factors (ΔsigH, ΔsigC, and ΔsigL), a negative regulator (ΔctsR), regulators of σB (ΔrsbT and ΔrsbV), and selected two-component response regulators (ΔlisR, Δlmo1172, and Δlmo1060) had significantly reduced growth (P < 0.05) compared with the parent strain after 12 days at 4°C. The growth defect for ΔsigL was limited and was not confirmed by optical density (OD600) measurement data. With a starting inoculum of 102 CFU/ml and after monitoring growth at 4°C over 84 days, only the ΔctsR strain had a consistent but limited growth defect; the other mutant strains had either no growth defects or limited growth defects apparent at only one or two of the nine sampling points evaluated during the 84-day growth period (ΔsigB, ΔsigC, and Δlmo1172). With a 108 CFU/ml starting inoculum of cold-adapted cells, none of the mutant strains that had a growth defect when inoculation was performed with cells pregrown at 37°C had reduced growth as compared with the parent strain after 12 days at 4°C, suggesting a specific defect in the ability of these mutant strains to adapt to 4

  6. Is principal component analysis an effective tool to predict face attractiveness? A contribution based on real 3D faces of highly selected attractive women, scanned with stereophotogrammetry.

    Science.gov (United States)

    Galantucci, Luigi Maria; Di Gioia, Eliana; Lavecchia, Fulvio; Percoco, Gianluca

    2014-05-01

    In the literature, several papers report studies on mathematical models used to describe facial features and to predict female facial beauty based on 3D human face data. Many authors have proposed the principal component analysis (PCA) method that permits modeling of the entire human face using a limited number of parameters. In some cases, these models have been correlated with beauty classifications, obtaining good attractiveness predictability using wrapped 2D or 3D models. To verify these results, in this paper, the authors conducted a three-dimensional digitization study of 66 very attractive female subjects using a computerized noninvasive tool known as 3D digital photogrammetry. The sample consisted of the 64 contestants of the final phase of the Miss Italy 2010 beauty contest, plus the two highest ranked contestants in the 2009 competition. PCA was conducted on this real faces sample to verify if there is a correlation between ranking and the principal components of the face models. There was no correlation and therefore, this hypothesis is not confirmed for our sample. Considering that the results of the contest are not only solely a function of facial attractiveness, but undoubtedly are significantly impacted by it, the authors based on their experience and real faces conclude that PCA analysis is not a valid prediction tool for attractiveness. The database of the features belonging to the sample analyzed are downloadable online and further contributions are welcome. PMID:24728666

  7. 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

  8. 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

  9. 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 (consumption and production, and carbon assimilation associated with photolithotrophic and chemolithoautotrophic (nitrification) metabolisms in the water column were performed. Despite low water column concentrations of ammonium in wintertime, intense ammonium transformations were registered. Prokaryotes (or bacterioplankton) contributed most to ammonium generation rates over the entire water column; these rates increased with depth (0.4-3.1 μM d -1). In surface waters (10 m depth), aerobic ammonium oxidation (potentially by Bacteria and Archaea) was the dominant consumption process (average 0.7 μM d -1) whereas in the subsurface layer (20 and 50 m depth), unexpectedly, eukaryotes accounted for most of its consumption (average 2.1 μM d -1). Nitrification oxidized an important proportion of the ammonium in both layers (from 25% to 100%) and provided regenerated nitrate. The integrated water column rates of 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.

  10. 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.

  11. Developmental changes in polyamines and autophagic marker levels in normal and growth-restricted fetal pigs.

    Science.gov (United States)

    Zhu, Y H; Lin, G; Dai, Z L; Zhou, T J; Yuan, T L; Feng, C P; Chen, F; Wu, G Y; Wang, J J

    2015-07-01

    Polyamines are essential for embryonic and fetal survival, growth, and development. Additionally, polyamines may induce autophagy in mammalian cells. However, little is known about the availability of polyamines or autophagy in the porcine conceptus with intrauterine growth restriction (IUGR). The present study was performed to evaluate the developmental changes of polyamine concentrations in IUGR and normal porcine fetuses as well as autophagic marker levels in the fetal intestinal mucosa during the second half of gestation when most fetal growth occurs. Allantoic fluid (ALF), amniotic fluid (AMF), umbilical vein, and the small-intestinal mucosa were obtained from both IUGR and normal fetal pigs at d 60, 90, and 110 of gestation. Concentrations of polyamines in fetal fluids as well as protein abundances of microtubule-associated protein light chain 3B (LC3B), an autophagic marker, in the fetal small-intestinal mucosa were determined. Concentrations of polyamines varied greatly in different fetal compartments and changed substantially with advancing gestation. Concentrations of polyamines in IUGR fetal fluids and the small-intestinal mucosa were markedly different from those in their normal counterparts at d 60 and 90 of gestation, whereas most of the differences were not detected by late (d 110) gestation. Specifically, polyamine levels were lower in the umbilical vein plasma but higher in ALF and AMF from IUGR fetuses. Furthermore, enhanced levels of an autophagic marker were observed in the small-intestinal mucosa of IUGR fetuses throughout mid and late gestation in association with abnormal spermidine levels in fetal plasma. These findings support the notion that enhanced autophagy may be an important survival mechanism in IUGR fetuses. Collectively, our findings provide a new framework for future studies to define the roles for polyamines in the prevention and treatment of IUGR in both human medicine and animal production.

  12. 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.

  13. Blocking autophagic flux enhances matrine-induced apoptosis in human hepatoma cells.

    Science.gov (United States)

    Wang, Li; Gao, Chun; Yao, Shukun; Xie, Bushan

    2013-11-25

    Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC). Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V-FITC/PI double-staining assay), the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1) both autophagy and apoptosis could be induced by treatment with matrine; (2) using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3) autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.

  14. Blocking Autophagic Flux Enhances Matrine-Induced Apoptosis in Human Hepatoma Cells

    Directory of Open Access Journals (Sweden)

    Li Wang

    2013-11-01

    Full Text Available Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC. Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V–FITC/PI double-staining assay, the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1 both autophagy and apoptosis could be induced by treatment with matrine; (2 using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3 autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.

  15. 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.

  16. Precise temporal regulation of roughest is required for correct salivary gland autophagic cell death in Drosophila.

    Science.gov (United States)

    Simon, Claudio R; Moda, Livia M R; Octacilio-Silva, Shirlei; Anhezini, Lucas; Machado-Gitai, Luciana C H; Ramos, Ricardo Guelerman P

    2009-07-01

    The Drosophila roughest (rst) locus encodes an immunoglobulin superfamily transmembrane glycoprotein implicated in a variety of embryonic and postembryonic developmental processes. Here we demonstrate a previously unnoticed role for this gene in the autophagic elimination of larval salivary glands during early pupal stages by showing that overexpression of the Rst protein ectodomain in early pupa leads to persistence of salivary glands up to at least 12 hours after head eversion, although with variable penetrance. The same phenotype is observed in individuals carrying the dominant regulatory allele rst(D), but not in loss of function alleles. Analysis of persistent glands at the ultrastructural level showed that programmed cell death starts at the right time but is arrested at an early stage of the process. Finally we describe the expression pattern and intracellular distribution of Rst in wild type and rst(D) mutants, showing that its downregulation in salivary glands at the beginning of pupal stage is an important factor in the correct implementation of the autophagic program of this tissue in space and time.

  17. 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.

  18. Monitoring autophagic flux using Ref(2)P, the Drosophila p62 ortholog.

    Science.gov (United States)

    DeVorkin, Lindsay; Gorski, Sharon M

    2014-09-02

    Human p62, also known as Sequestome-1 (SQSTM1), is a multifunctional scaffold protein that contains many domains, including a Phox/Bem1P (PB1) multimerization domain, an ubiquitin-associated (UBA) domain, and a light chain 3 (LC3) recognition sequence. p62 binds ubiquitinated proteins and targets them for degradation by the proteasome. In addition, p62 directly binds LC3; this may serve as a mechanism to deliver ubiquitinated proteins for degradation by autophagy. During this process, p62 itself is degraded. The inhibition of autophagy leads to the accumulation of p62, indicating that it can be used as a marker of autophagic flux. Ref(2)P (refractory to sigma P), the Drosophila ortholog of p62, is also required for the formation of ubiquitinated protein aggregates. Ref(2)P contains a putative LC3-interacting region, and genetic inhibition of autophagy in Drosophila leads to the accumulation of Ref(2)P protein levels. Thus, like p62, Ref(2)P may serve as a marker of autophagic flux. Here we provide two procedures to examine Ref(2)P protein levels in Drosophila ovaries.

  19. 5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase

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    Lin Yu-Hsin

    2010-04-01

    Full Text Available Abstract Photodynamic therapy (PDT has been developed as an anticancer treatment, which is based on the tumor-specific accumulation of a photosensitizer that induces cell death after irradiation of light with a specific wavelength. Depending on the subcellular localization of the photosensitizer, PDT could trigger various signal transduction cascades and induce cell death such as apoptosis, autophagy, and necrosis. In this study, we report that both AMP-activated protein kinase (AMPK and mitogen-activated protein kinase (MAPK signaling cascades are activated following 5-aminolevulinic acid (ALA-mediated PDT in both PC12 and CL1-0 cells. Although the activities of caspase-9 and -3 are elevated, the caspase inhibitor zVAD-fmk did not protect cells against ALA-PDT-induced cell death. Instead, autophagic cell death was found in PC12 and CL1-0 cells treated with ALA-PDT. Most importantly, we report here for the first time that it is the activation of AMPK, but not MAPKs that plays a crucial role in mediating autophagic cell death induced by ALA-PDT. This novel observation indicates that the AMPK pathway play an important role in ALA-PDT-induced autophagy.

  20. Isogambogenic acid induces apoptosis-independent autophagic cell death in human non-small-cell lung carcinoma cells.

    Science.gov (United States)

    Yang, Jianhong; Zhou, Yongzhao; Cheng, Xia; Fan, Yi; He, Shichao; Li, Shucai; Ye, Haoyu; Xie, Caifeng; Wu, Wenshuang; Li, Chunyan; Pei, Heying; Li, Luyuan; Wei, Zhe; Peng, Aihua; Wei, Yuquan; Li, Weimin; Chen, Lijuan

    2015-01-09

    To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second, iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3 conversion, caused the appearance of autophagosomes and increased the expression of autophagy-related proteins. These findings provide evidence that iso-GNA induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes. Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Finally, a xenograft model provided additional evidence that iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell death in NSCLC cells. Taken together, our results demonstrated that iso-GNA exhibited an anticancer effect by inducing autophagy-dependent cell death in NSCLC cells, which may be an effective chemotherapeutic agent that can be used against NSCLC in a clinical setting.

  1. 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 ePukaß

    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

  2. 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.

  3. 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.

  4. Carbonaceous components, levoglucosan and inorganic ions in tropical aerosols from Tanzania, East Africa: implication for biomass burning contribution to organic aerosols

    Directory of Open Access Journals (Sweden)

    S. L. Mkoma

    2012-11-01

    Full Text Available Atmospheric aerosol samples of PM2.5 and PM10 were collected at a rural site in Tanzania in 2011 during wet and dry seasons and they were analysed for carbonaceous components, levoglucosan and water-soluble inorganic ions. The mean mass concentrations of PM2.5 and PM10 were 28.2±6.4 μg m−3 and 47±8.2 μg m−3 in wet season, and 39.1±9.8 μg m−3 and 61.4±19.2 μg m−3 in dry season, respectively. Total carbon (TC accounted for 16–19% of the PM2.5 mass and 13–15% of the PM10 mass. On average, 85.9 to 88.7% of TC in PM2.5 and 87.2 to 90.1% in PM10 was organic carbon (OC, of which 67–72% and 63% was found to be water-soluble organic carbon (WSOC in PM2.5 and PM10, respectively. Water-soluble potassium (K+ and sulphate (SO42− in PM2.5 and, sodium (Na+ and SO42− in PM10 were the dominant ionic species. We found, that concentrations of biomass burning tracers (levoglucosan and mannosan well correlated with non-sea-salt-K+, WSOC and OC in the aerosols from Tanzania, East Africa. Mean contributions of levoglucosan to OC ranged between 3.9–4.2% for PM2.5 and 3.5–3.8% for PM10. This study demonstrates that emissions from biomass- and biofuel-burning activities followed by atmospheric photochemical processes mainly control the air quality in Tanzania.

  5. 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

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

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    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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Mediation of autophagic cell death by type 3 ryanodine receptor (RyR3 in adult hippocampal neural stem cells

    Directory of Open Access Journals (Sweden)

    Kyung Min eChung

    2016-05-01

    Full Text Available Cytoplasmic Ca2+ actively engages in diverse intracellular processes from protein synthesis, folding and trafficking to cell survival and death. Dysregulation of intracellular Ca2+ levels is observed in various neuropathological states including Alzheimer’s and Parkinson’s diseases. Ryanodine receptors (RyRs and IP3 receptors (IP3Rs, the main Ca2+ release channels located in endoplasmic reticulum (ER membranes, are known to direct various cellular events such as autophagy and apoptosis. Here we investigated the intracellular Ca2+-mediated regulation of survival and death of adult hippocampal neural stem (HCN cells utilizing an insulin withdrawal model of autophagic cell death. Despite comparable expression levels of RyR and IP3R transcripts in HCN cells at normal state, the expression levels of RyRs — especially RyR3 — were markedly upregulated upon insulin withdrawal. While treatment with the RyR agonist caffeine significantly promoted the autophagic death of insulin-deficient HCN cells, treatment with its inhibitor dantrolene prevented the induction of autophagy following insulin withdrawal. Furthermore, CRISPR/Cas9-mediated knockout of the RyR3 gene abolished autophagic cell death of HCN cells. This study delineates a distinct, RyR3-mediated ER Ca2+ regulation of autophagy and programmed cell death in neural stem cells. Our findings provide novel insights into the critical, yet understudied mechanisms underlying the regulatory function of ER Ca2+ in neural stem cell biology.

  14. 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

  15. 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...

  16. 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

  17. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Involvement of Autophagic Pathway in the Progression of Retinal Degeneration in a Mouse Model of Diabetes.

    Science.gov (United States)

    Piano, Ilaria; Novelli, Elena; Della Santina, Luca; Strettoi, Enrica; Cervetto, Luigi; Gargini, Claudia

    2016-01-01

    The notion that diabetic retinopathy (DR) is essentially a micro-vascular disease has been recently challenged by studies reporting that vascular changes are preceded by signs of damage and loss of retinal neurons. As to the mode by which neuronal death occurs, the evidence that apoptosis is the main cause of neuronal loss is far from compelling. The objective of this study was to investigate these controversies in a mouse model of streptozotocin (STZ) induced diabetes. Starting from 8 weeks after diabetes induction there was loss of rod but not of cone photoreceptors, together with reduced thickness of the outer and inner synaptic layers. Correspondingly, rhodopsin expression was downregulated and the scotopic electroretinogram (ERG) is suppressed. In contrast, cone opsin expression and photopic ERG response were not affected. Suppression of the scotopic ERG preceded morphological changes as well as any detectable sign of vascular alteration. Only sparse apoptotic figures were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and glia was not activated. The physiological autophagy flow was altered instead, as seen by increased LC3 immunostaining at the level of outer plexiform layer (OPL) and upregulation of the autophagic proteins Beclin-1 and Atg5. Collectively, our results show that the streptozotocin induced DR in mouse initiates with a functional loss of the rod visual pathway. The pathogenic pathways leading to cell death develop with the initial dysregulation of autophagy well before the appearance of signs of vascular damage and without strong involvement of apoptosis.

  20. Endothelial cells are damaged by autophagic induction before hepatocytes in Con A-induced acute hepatitis.

    Science.gov (United States)

    Yang, Ming-Chen; Chang, Chih-Peng; Lei, Huan-Yao

    2010-08-01

    We have reported both T-cell-dependent and -independent hepatitis in immunocompetent and immunodeficiency mice, respectively, after intravenous injection of Con A in mice. The mode of hepatocyte cell death is different: autophagy for T-cell-independent hepatitis in contrast to apoptosis for T-cell-dependent one. In this study, we further demonstrate that liver blood vessels are the first target in both modes. The infused Con A bond to the hepatic vascular endothelial cells and cause its damage with autophagy. Before the elevation of the serum alanine aminotransferase at 6 h post-injection, the plasma leakage and hemorrhage occur at 1-3 h without inflammation. Con A induces autophagy of endothelial cells and hemorrhage that is enhanced by IFN-gamma. Using the endothelial cell line HMEC-1, a dose- and time-dependent cell death with autophagic LC3-II (microtubule-associated protein light chain 3) conversion was induced by Con A and was enhanced by IFN-gamma. In conclusion, Con A induced autophagy on hepatic endothelial cells; the damage of liver blood vessel occurs before the induction of T-cell-dependent hepatitis via apoptosis or T-cell-independent hepatitis via autophagy.

  1. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus.

    Science.gov (United States)

    Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D; Saeed, Fahad; Michael Payne, D; Chen, Shu-Hui; Fenton, Robert A; Pisitkun, Trairak

    2015-12-17

    Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.

  2. 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

  3. 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.

  4. 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/...

  5. Synthesis, stereochemical analysis, and derivatization of myricanol provide new probes that promote autophagic tau clearance.

    Science.gov (United States)

    Martin, Mackenzie D; Calcul, Laurent; Smith, Courtney; Jinwal, Umesh K; Fontaine, Sarah N; Darling, April; Seeley, Kent; Wojtas, Lukasz; Narayan, Malathi; Gestwicki, Jason E; Smith, Garry R; Reitz, Allen B; Baker, Bill J; Dickey, Chad A

    2015-04-17

    We previously discovered that one specific scalemic preparation of myricanol (1), a constituent of Myrica cerifera (bayberry/southern wax myrtle) root bark, could lower the levels of the microtubule-associated protein tau (MAPT). The significance is that tau accumulates in a number of neurodegenerative diseases, the most common being Alzheimer's disease (AD). Herein, a new synthetic route to prepare myricanol using a suitable boronic acid pinacol ester intermediate is reported. An X-ray crystal structure of the isolated myricanol (1) was obtained and showed a co-crystal consisting of (+)-aR,11S-myricanol (2) and (-)-aS,11R-myricanol (3) coformers. Surprisingly, 3, obtained from chiral separation from 1, reduced tau levels in both cultured cells and ex vivo brain slices from a mouse model of tauopathy at reasonable mid-to-low micromolar potency, whereas 2 did not. SILAC proteomics and cell assays revealed that 3 promoted tau degradation through an autophagic mechanism, which was in contrast to that of other tau-lowering compounds previously identified by our group. During the course of structure-activity relationship (SAR) development, we prepared compound 13 by acid-catalyzed dehydration of 1. 13 had undergone an unexpected structural rearrangement through the isomyricanol substitution pattern (e.g., 16), as verified by X-ray structural analysis. Compound 13 displayed robust tau-lowering activity, and, importantly, its enantiomers reduced tau levels similarly. Therefore, the semisynthetic analogue 13 provides a foundation for further development as a tau-lowering agent without its SAR being based on chirality.

  6. 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

  7. 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)

  8. New insights into the interactions between cork chemical components and pesticides. The contribution of π-π interactions, hydrogen bonding and hydrophobic effect.

    Science.gov (United States)

    Olivella, M À; Bazzicalupi, C; Bianchi, A; Fiol, N; Villaescusa, I

    2015-01-01

    The role of chemical components of cork in the sorption of several pesticides has been investigated. For this purpose raw cork and three cork extracted fractions (i.e. cork free of aliphatic extractives, cork free of all extractives and cork free of all extractives and suberin) were used as sorbent of three ionic pesticides (propazine, 2,4-dichlorophenoxy acetic acid (2,4-D) and alachlor) and five non-ionic pesticides (chlorpyrifos, isoproturon, metamitron, methomyl and oxamyl) with a logKow within the range -0.47 to 4.92. The effect of cations on the ionic pesticides, propazine and 2,4-D sorption was also analyzed. Results indicated that the highest yields were obtained for chlorpyrifos and alachlor sorption onto raw cork (>55%). After removal of aliphatic extractives sorption of all pesticides increased that ranged from 3% for propazine to 31% for alachlor. In contrast, removal of phenolic extractives caused a sorption decrease. Low sorption yields were obtained for hydrophobic pesticides such as metamitron, oxamyl and methomyl (cork fractions and extremely low when using raw cork (cork toward aromatic pesticides. Results presented in this paper gain insights into the cork affinities for pesticides and the interactions involved in the sorption process and also enables to envisage sorption affinity of cork for other organic pollutants.

  9. Thymoquinone induces caspase-independent, autophagic cell death in CPT-11-resistant lovo colon cancer via mitochondrial dysfunction and activation of JNK and p38.

    Science.gov (United States)

    Chen, Ming-Cheng; Lee, Nien-Hung; Hsu, Hsi-Hsien; Ho, Tsung-Jung; Tu, Chuan-Chou; Hsieh, Dennis Jine-Yuan; Lin, Yueh-Min; Chen, Li-Mien; Kuo, Wei-Wen; Huang, Chih-Yang

    2015-02-11

    Chemotherapy causes unwanted side effects and chemoresistance, limiting its effectiveness. Therefore, phytochemicals are now used as alternative treatments. Thymoquinone (TQ) is used to treat different cancers, including colon cancer. The irinotecan-resistant (CPT-11-R) LoVo colon cancer cell line was previously constructed by stepwise CPT-11 challenges to untreated parental LoVo cells. TQ dose-dependently increased the total cell death index and activated apoptosis at 2 μM, which then diminished at increasing doses. The possibility of autophagic cell death was then investigated. TQ caused mitochondrial outer membrane permeability (MOMP) and activated autophagic cell death. JNK and p38 inhibitors (SP600125 and SB203580, respectively) reversed TQ autophagic cell death. TQ was also found to activate apoptosis before autophagy, and the direction of cell death was switched toward autophagic cell death at initiation of autophagosome formation. Therefore, TQ resulted in caspase-independent, autophagic cell death via MOMP and activation of JNK and p38 in CPT-11-R LoVo colon cancer cells.

  10. Lysosomotropic cationic drugs induce cytostatic and cytotoxic effects: Role of liposolubility and autophagic flux and antagonism by cholesterol ablation.

    Science.gov (United States)

    Parks, Alexandre; Marceau, François

    2016-08-15

    Cation trapping in acidic cell compartments determines an antiproliferative effect that has a potential interest in oncology, as shown by clinical data and trials involving chloroquine and hydroxychloroquine. To further characterize the mechanism of this effect, we studied a series of 6 substituted triethylamine (s-Et3N) drugs that encompasses a wide range of liposolubility (amiodarone, quinacrine, chloroquine, hydroxychloroquine, lidocaine, and procainamide). Three tumor cell lines and primary human endothelial cells were exploited in proliferation assays (48h, cell counts). Accumulation of the autophagic effector LC3 II and the apoptotic marker cleaved PARP1 (immunoblots), cytotoxicity, cell cycle analysis and endocytic function were further tested in the p53-null histiocytic lymphoma U937 line. A profound and desynchronized antiproliferative effect was observed in response to all s-Et3Ns with essentially no cell type specificity. Predictors of s-Et3N potency were liposolubility and the acute accumulation of the autophagic effector LC3 II (6h-treatments). For each s-Et3N, there was an antiproliferative concentration range where cytotoxicity and apoptosis were not triggered in U937 cells (24-48h-treatments). Quinacrine was the most potent cytostatic drug (1-5μM). Co-treatment of cells with inhibitors of cholesterol, β-cyclodextrin or lovastatin, partially reversed the antiproliferative effect of each s-Et3N. The cytopathology induced by cationic drug accumulation includes a cytostatic effect. Its intensity is cell type- and p53-independent, but predicted by the inhibition of autophagic flux and by the liposolubility of individual drugs and alleviated by cholesterol ablation. The superiority of quinacrine, biomarker value of LC3 II and antagonism by a statin may be clinically relevant. PMID:27288732

  11. Polycyclic aromatic hydrocarbon components contribute to the mitochondria-antiapoptotic effect of fine particulate matter on human bronchial epithelial cells via the aryl hydrocarbon receptor

    Directory of Open Access Journals (Sweden)

    Baeza-Squiban Armelle

    2010-07-01

    Full Text Available Abstract Background Nowadays, effects of fine particulate matter (PM2.5 are well-documented and related to oxidative stress and pro-inflammatory response. Nevertheless, epidemiological studies show that PM2.5 exposure is correlated with an increase of pulmonary cancers and the remodeling of the airway epithelium involving the regulation of cell death processes. Here, we investigated the components of Parisian PM2.5 involved in either the induction or the inhibition of cell death quantified by different parameters of apoptosis and delineated the mechanism underlying this effect. Results In this study, we showed that low levels of Parisian PM2.5 are not cytotoxic for three different cell lines and primary cultures of human bronchial epithelial cells. Conversely, a 4 hour-pretreatment with PM2.5 prevent mitochondria-driven apoptosis triggered by broad spectrum inducers (A23187, staurosporine and oligomycin by reducing the mitochondrial transmembrane potential loss, the subsequent ROS production, phosphatidylserine externalization, plasma membrane permeabilization and typical morphological outcomes (cell size decrease, massive chromatin and nuclear condensation, formation of apoptotic bodies. The use of recombinant EGF and specific inhibitor led us to rule out the involvement of the classical EGFR signaling pathway as well as the proinflammatory cytokines secretion. Experiments performed with different compounds of PM2.5 suggest that endotoxins as well as carbon black do not participate to the antiapoptotic effect of PM2.5. Instead, the water-soluble fraction, washed particles and organic compounds such as polycyclic aromatic hydrocarbons (PAH could mimic this antiapoptotic activity. Finally, the activation or silencing of the aryl hydrocarbon receptor (AhR showed that it is involved into the molecular mechanism of the antiapoptotic effect of PM2.5 at the mitochondrial checkpoint of apoptosis. Conclusions The PM2.5-antiapoptotic effect in addition

  12. 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

  13. 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

  14. 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.

  15. 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.

    Science.gov (United States)

    Pukaß, Katharina; Richter-Landsberg, Christiane

    2015-01-01

    α-Synuclein (α-syn) positive glial cytoplasmic inclusions (GCI) originating in oligodendrocytes (ODC) are a characteristic hallmark in multiple system atrophy (MSA). 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 (DUBs) before proteolytic degradation is performed. The DUB ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a component of the UPS, it is abundantly expressed in neuronal brain cells and has been connected to Parkinson's disease (PD). It interacts with α-syn and tubulin. The present study was undertaken to investigate whether UCH-L1 is a constituent of ODC, 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 (MT) 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 UCH-L1 is expressed in ODC 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 MT network by affecting tubulin posttranslational modifications, i.e., acetylation and tyrosination. An increase in α-tubulin detyrosination was observed and detyrosinated MT 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

  16. 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...

  17. UCP2 inhibition triggers ROS-dependent nuclear translocation of GAPDH and autophagic cell death in pancreatic adenocarcinoma cells.

    Science.gov (United States)

    Dando, Ilaria; Fiorini, Claudia; Pozza, Elisa Dalla; Padroni, Chiara; Costanzo, Chiara; Palmieri, Marta; Donadelli, Massimo

    2013-03-01

    Mitochondrial uncoupling protein 2 (UCP2) can moderate oxidative stress by favoring the influx of protons into the mitochondrial matrix, thus reducing electron leakage from respiratory chain and mitochondrial superoxide production. Here, we demonstrate that UCP2 inhibition by genipin or UCP2 siRNA strongly increases reactive oxygen species (ROS) production inhibiting pancreatic adenocarcinoma cell growth. We also show that UCP2 inhibition triggers ROS-dependent nuclear translocation of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH), formation of autophagosomes, and the expression of the autophagy marker LC3-II. Consistently, UCP2 over-expression significantly reduces basal autophagy confirming the anti-autophagic role of UCP2. Furthermore, we demonstrate that autophagy induced by UCP2 inhibition determines a ROS-dependent cell death, as indicated by the apoptosis decrease in the presence of the autophagy inhibitors chloroquine (CQ) or 3-methyladenine (3-MA), or the radical scavenger NAC. Intriguingly, the autophagy induced by genipin is able to potentiate the autophagic cell death triggered by gemcitabine, the standard chemotherapeutic drug for pancreatic adenocarcinoma, supporting the development of an anti-cancer therapy based on UCP2 inhibition associated to standard chemotherapy. Our results demonstrate for the first time that UCP2 plays a role in autophagy regulation bringing new insights into mitochondrial uncoupling protein field.

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

    Science.gov (United States)

    Almeida, Luciana O; Goto, Renata N; Neto, Marinaldo P C; Sousa, Lucas O; Curti, Carlos; Leopoldino, Andréia M

    2015-03-01

    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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Effect of the pituitary adenylate cyclase-activating polypeptide on the autophagic activation observed in in vitro and in vivo models of Parkinson's disease.

    Science.gov (United States)

    Lamine-Ajili, Asma; Fahmy, Ahmed M; Létourneau, Myriam; Chatenet, David; Labonté, Patrick; Vaudry, David; Fournier, Alain

    2016-04-01

    Parkinson's disease (PD) is a neurodegenerative disorder that leads to destruction of the midbrain dopaminergic (DA) neurons. This phenomenon is related to apoptosis and its activation can be blocked by the pituitary adenylate cyclase-activating polypeptide (PACAP). Growing evidence indicates that autophagy, a self-degradation activity that cleans up the cell, is induced during the course of neurodegenerative diseases. However, the role of autophagy in the pathogenesis of neuronal disorders is yet poorly understood and the potential ability of PACAP to modulate the related autophagic activation has never been significantly investigated. Hence, we explored the putative autophagy-modulating properties of PACAP in in vitro and in vivo models of PD, using the neurotoxic agents 1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), respectively, to trigger alterations of DA neurons. In both models, following the toxin exposure, PACAP reduced the autophagic activity as evaluated by the production of LC3 II, the modulation of the p62 protein levels, and the formation of autophagic vacuoles. The ability of PACAP to inhibit autophagy was also observed in an in vitro cell assay by the blocking of the p62-sequestration activity produced with the autophagy inducer rapamycin. Thus, the results demonstrated that autophagy is induced in PD experimental models and that PACAP exhibits not only anti-apoptotic but also anti-autophagic properties.

  4. 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

  5. Clinical utility of LC3 and p62 immunohistochemistry in diagnosis of drug-induced autophagic vacuolar myopathies: a case-control study.

    Directory of Open Access Journals (Sweden)

    Han S Lee

    Full Text Available BACKGROUND: Some patients treated with chloroquine, hydroxychloroquine, or colchicine develop autophagic vacuolar myopathy, the diagnosis of which currently requires electron microscopy. The goal of the current study was to develop an immunohistochemical diagnostic marker for this pathologic entity. METHODOLOGY: Microtubule-associated protein light chain 3 (LC3 has emerged as a robust marker of autophagosomes. LC3 binds p62/SQSTM1, an adapter protein that is selectively degraded via autophagy. In this study, we evaluated the utility of immunohistochemical stains for LC3 and p62 as diagnostic markers of drug-induced autophagic vacuolar myopathy. The staining was performed on archival muscle biopsy material, with subject assignment to normal control, drug-treated control, and autophagic myopathy groups based on history of drug use and morphologic criteria. PRINCIPAL FINDINGS: In all drug-treated subjects, but not in normal controls, LC3 and p62 showed punctate staining characteristic of autophagosome buildup. In the autophagic myopathy subjects, puncta were coarser and tended to coalesce into linear structures aligned with the longitudinal axis of the fiber, often in the vicinity of vacuoles. The percentage of LC3- and p62-positive fibers was significantly higher in the autophagic myopathy group compared to either the normal control (p<0.001 or the drug-treated control group (p<0.05. With the diagnostic threshold set between 8% and 15% positive fibers (depending on the desired level of sensitivity and specificity, immunohistochemical staining for either LC3 or p62 could be used to identify subjects with autophagic vacuolar myopathy within the drug-treated subject group (p ≤ 0.001. SIGNIFICANCE: Immunohistochemistry for LC3 and p62 can facilitate tissue-based diagnosis of drug-induced autophagic vacuolar myopathies. By limiting the need for electron microscopy (a time consuming and costly technique with high specificity, but low sensitivity

  6. The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox.

    Science.gov (United States)

    Martinez-Outschoorn, Ubaldo E; Whitaker-Menezes, Diana; Pavlides, Stephanos; Chiavarina, Barbara; Bonuccelli, Gloria; Casey, Trimmer; Tsirigos, Aristotelis; Migneco, Gemma; Witkiewicz, Agnieszka; Balliet, Renee; Mercier, Isabelle; Wang, Chengwang; Flomenberg, Neal; Howell, Anthony; Lin, Zhao; Caro, Jaime; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P

    2010-11-01

    The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the "Autophagy Paradox". We have recently reported a simple solution to this paradox. We demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. We have termed this new paradigm "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism" or "Battery-Operated Tumor Growth". In this sense, autophagy in the tumor stroma serves as a "battery" to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients-both effectively "starving" cancer cells. We discuss the idea that tumor cells could become resistant to the systemic induction of autophagy, by the upregulation of natural endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy, by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. If autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor stroma. As such, an

  7. 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;

    1998-01-01

    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......Staurosporine blocks signal transduction associated with cell survival, proliferation and chemosensory behaviour in the ciliated protozoan, Tetrahymena thermophila. Staurosporine inhibits cell proliferation and in vivo protein phosphorylation induced by phorbol ester. It also reduces the in vitro...... by 8-bromo-cyclic GMP, protoporphyrin IX, hemin or actinomycin D, although phorbol ester and insulin were ineffective. The results support the notion that staurosporine-induced cell death is an active process, associated with and/or requiring de novo RNA synthesis....

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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...

  16. 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.

  17. 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

  18. 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...

  19. Reduced cathepsins B and D cause impaired autophagic degradation that can be almost completely restored by overexpression of these two proteases in Sap C-deficient fibroblasts.

    Science.gov (United States)

    Tatti, Massimo; Motta, Marialetizia; Di Bartolomeo, Sabrina; Scarpa, Susanna; Cianfanelli, Valentina; Cecconi, Francesco; Salvioli, Rosa

    2012-12-01

    Saposin (Sap) C deficiency, a rare variant form of Gaucher disease, is due to mutations in the Sap C coding region of the prosaposin (PSAP) gene. Sap C is required as an activator of the lysosomal enzyme glucosylceramidase (GCase), which catalyzes glucosylceramide (GC) degradation. Deficit of either GCase or Sap C leads to the accumulation of undegraded GC and other lipids in lysosomes of monocyte/macrophage lineage. Recently, we reported that Sap C mutations affecting a cysteine residue result in increased autophagy. Here, we characterized the basis for the autophagic dysfunction. We analyzed Sap C-deficient and GCase-deficient fibroblasts and observed that autophagic disturbance was only associated with lack of Sap C. By a combined fluorescence microscopy and biochemical studies, we demonstrated that the accumulation of autophagosomes in Sap C-deficient fibroblasts is not due to enhanced autophagosome formation but to delayed degradation of autolysosomes caused, in part, to decreased amount and reduced enzymatic activity of cathepsins B and D. On the contrary, in GCase-deficient fibroblasts, the protein level and enzymatic activity of cathepsin D were comparable with control fibroblasts, whereas those of cathepsin B were almost doubled. Moreover, the enhanced expression of both these lysosomal proteases in Sap C-deficient fibroblasts resulted in close to functional autophagic degradation. Our data provide a novel example of altered autophagy as secondary event resulting from insufficient lysosomal function.

  20. Graveoline isolated from ethanolic extract of Ruta graveolens triggers apoptosis and autophagy in skin melanoma cells: a novel apoptosis-independent autophagic signaling pathway.

    Science.gov (United States)

    Ghosh, Samrat; Bishayee, Kausik; Khuda-Bukhsh, Anisur Rahman

    2014-08-01

    Anti-cancer drugs generally kill cancer cells by apoptosis but fail to do so when they become resistant and escape apoptosis signals. But these resistant cells can still be killed by autophagy. Therefore, drugs having both apoptotic and autophagic abilities are solicited in effective cancer management. In search of such a drug, we examined the efficacy of graveoline, a bioactive compound isolated from Ruta graveolens on skin melanoma A375 cells through the use of specific signaling cascades and their inhibitors. Cytotoxicity of graveoline was tested by conducting MTT assay. Induction of autophagy and apoptosis was checked. Expression of related proteins and their localization were studied by conducting immunoblot assay and through confocal microscopy, respectively. We found graveoline-induced Beclin-1 associated autophagy in A375 cells and 3-methyladenine, an inhibitor of autophagy did not affect apoptosis. Conversely, caspase inhibitor that blocked apoptosis did not affect autophagic cell death, suggesting thereby that these two were independent events. Use of reactive oxygen species (ROS) scavengers inhibited cell death, but blocking autophagy did not affect graveoline-induced ROS generation, suggesting that ROS generation ensued autophagy. Thus, graveoline-induced both apoptotic and autophagic cell death in skin melanoma cells, a desirable quality in effective anti-cancer drug design.

  1. Paeoniflorin protects HUVECs from AGE-BSA-induced injury via an autophagic pathway by acting on the RAGE.

    Science.gov (United States)

    Chen, Yufang; Du, Xing; Zhou, Yande; Zhang, Yanlin; Yang, Yaping; Liu, Zhihua; Liu, Chunfeng; Xie, Ying

    2015-01-01

    The aim of our study was to investigate the protective effects of Paeoniflorin (PF) against injury induced by AGE-modified bovine serum albumin (AGE-BSA) in human umbilical vein endothelial cells (HUVECs), and to examine the underlying mechanisms of these effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine cell viability. Protein expression levels were determined by western blotting. For function-blocking experiments, we used small interfering RNA molecules (siRNA) for function-blocking experiments. At 6 h, we found that 100 μg/mL AGE-BSA reduced the viability of HUVECs. However, pretreatment with PF restored cell viability in a dose-dependent manner. AGE-BSA increased the levels of microtubule-associated protein light chain 3-II (LC3-II) and the receptor for advanced glycation end products (RAGE). Expression of p62 protein was also increased, but not at a statistically significant level. Pretreatment with PF further increased levels of LC3-II and RAGE, but reduced the expression of p62. In cells transfected with Atg5 and RAGE siRNA, cell viability and expression of LC3-II decreased in both the AGE-BSA and PF + AGE-BSA treatments. PF can protect HUVECs from AGE-BSA-induced injury by upregulating autophagy and promoting the completion of autophagy flux. RAGE plays an important role in this autophagic protection effect.

  2. 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

  3. 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

  4. 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.

  5. Toll-like receptor 8 ligands activate a vitamin D mediated autophagic response that inhibits human immunodeficiency virus type 1.

    Directory of Open Access Journals (Sweden)

    Grant R Campbell

    Full Text Available Toll-like receptors (TLR are important in recognizing microbial pathogens and triggering host innate immune responses, including autophagy, and in the mediation of immune activation during human immunodeficiency virus type-1 (HIV infection. We report here that TLR8 activation in human macrophages induces the expression of the human cathelicidin microbial peptide (CAMP, the vitamin D receptor (VDR and cytochrome P450, family 27, subfamily B, polypeptide 1 (CYP27B1, which 1α-hydroxylates the inactive form of vitamin D, 25-hydroxycholecalciferol, into its biologically active metabolite. Moreover, we demonstrate using RNA interference, chemical inhibitors and vitamin D deficient media that TLR8 agonists inhibit HIV through a vitamin D and CAMP dependent autophagic mechanism. These data support an important role for vitamin D in the control of HIV infection, and provide a biological explanation for the benefits of vitamin D. These findings also provide new insights into potential novel targets to prevent and treat HIV infection.

  6. 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

  7. 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

  8. The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells.

    Science.gov (United States)

    Hsieh, Min-Tsang; Chen, Hao-Ping; Lu, Chi-Cheng; Chiang, Jo-Hua; Wu, Tian-Shung; Kuo, Daih-Huang; Huang, Li-Jiau; Kuo, Sheng-Chu; Yang, Jai-Sing

    2014-08-01

    Pterostilbene is an effective chemopreventive agent against multiple types of cancer cells. A novel pterostilbene derivative, ANK-199, was designed and synthesized by our group. Its antitumor activity and mechanism in cisplatin-resistant CAR human oral cancer cells were investigated in this study. Our results show that ANK-199 has an extremely low toxicity in normal oral cell lines. The formation of autophagic vacuoles and acidic vesicular organelles (AVOs) was observed in the ANK-199-treated CAR cells by monodansylcadaverine (MDC) and acridine orange (AO) staining, suggesting that ANK-199 is able to induce autophagic cell death in CAR cells. Neither DNA fragmentation nor DNA condensation was observed, which means that ANK-199-induced cell death is not triggered by apoptosis. In accordance with morphological observation, 3-MA, a specific inhibitor of PI3K kinase class III, can inhibit the autophagic vesicle formation induced by ANK-199. In addition, ANK-199 is also able to enhance the protein levels of autophagic proteins, Atg complex, beclin 1, PI3K class III and LC3-II, and mRNA expression of autophagic genes Atg7, Atg12, beclin 1 and LC3-II in the ANK-199-treated CAR cells. A molecular signaling pathway induced by ANK-199 was therefore summarized. Results presented in this study show that ANK-199 may become a novel therapeutic reagent for the treatment of oral cancer in the near future (patent pending).

  9. FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation.

    Science.gov (United States)

    Dunlop, Elaine A; Seifan, Sara; Claessens, Tijs; Behrends, Christian; Kamps, Miriam Af; Rozycka, Ewelina; Kemp, Alain J; Nookala, Ravi K; Blenis, John; Coull, Barry J; Murray, James T; van Steensel, Maurice Am; Wilkinson, Simon; Tee, Andrew R

    2014-10-01

    Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant condition caused by mutations in the FLCN gene and characterized by benign hair follicle tumors, pneumothorax, and renal cancer. Folliculin (FLCN), the protein product of the FLCN gene, is a poorly characterized tumor suppressor protein, currently linked to multiple cellular pathways. Autophagy maintains cellular homeostasis by removing damaged organelles and macromolecules. Although the autophagy kinase ULK1 drives autophagy, the underlying mechanisms are still being unraveled and few ULK1 substrates have been identified to date. Here, we identify that loss of FLCN moderately impairs basal autophagic flux, while re-expression of FLCN rescues autophagy. We reveal that the FLCN complex is regulated by ULK1 and elucidate 3 novel phosphorylation sites (Ser406, Ser537, and Ser542) within FLCN, which are induced by ULK1 overexpression. In addition, our findings demonstrate that FLCN interacts with a second integral component of the autophagy machinery, GABA(A) receptor-associated protein (GABARAP). The FLCN-GABARAP association is modulated by the presence of either folliculin-interacting protein (FNIP)-1 or FNIP2 and further regulated by ULK1. As observed by elevation of GABARAP, sequestome 1 (SQSTM1) and microtubule-associated protein 1 light chain 3 (MAP1LC3B) in chromophobe and clear cell tumors from a BHD patient, we found that autophagy is impaired in BHD-associated renal tumors. Consequently, this work reveals a novel facet of autophagy regulation by ULK1 and substantially contributes to our understanding of FLCN function by linking it directly to autophagy through GABARAP and ULK1.

  10. 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.)

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. Multilevel Contracts for Trusted Components

    CERN Document Server

    Messabihi, Mohamed; Attiogbé, Christian; 10.4204/EPTCS.37.6

    2010-01-01

    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. Aqueous Extract of Solanum nigrum Leaf Activates Autophagic Cell Death and Enhances Docetaxel-Induced Cytotoxicity in Human Endometrial Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Cheng-Jeng Tai

    2012-01-01

    Full Text Available Chemotherapy is the main approach in dealing with advanced and recurrent endometrial cancer. An effective complementary ingredient can be helpful in improving the clinical outcome. Aqueous extract of Solanum nigrum leaf (AE-SN is a principal ingredient for treating cancer patients in traditional Chinese medicinal practice but lacks sufficient evidence to verify its tumor suppression efficacy. This study evaluated the antitumor effects of AE-SN and also assessed the synergistic effects of AE-SN with docetaxel On the human endometrial cancer cell lines, HEC1A, HEC1B, and KLE. The activation of apoptotic markers, caspase-3 and poly-ADP-ribose polymerase, and autophagic marker, microtubule-associated protein 1 light chain 3 A/B, wAS determined to clarify the cell death pathways responsible for AE-SN induced tumor cell death. Results indicated that AE-SN-treatment has significant cytotoxicity on the tested endometrial cancer cells with accumulation of LC3 A/B II and demonstrated a synergistic effect of AE-SN and docetaxel in HEC1A and HEC1B cells, but not KLE cells. In conclusion, AE-SN treatment was effective in suppressing endometrial cancer cells via the autophagic pathway and was also capable of enhancing the cytotoxicity of docetaxel in human endometrial cancer cells. Our results provide meaningful evidence for integrative cancer therapy in the future.

  17. 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.

  18. 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.

  19. Bioinert Anodic Alumina Nanotubes for Targeting of Endoplasmic Reticulum Stress and Autophagic Signaling: A Combinatorial Nanotube-Based Drug Delivery System for Enhancing Cancer Therapy.

    Science.gov (United States)

    Wang, Ye; Kaur, Gagandeep; Chen, Yuting; Santos, Abel; Losic, Dusan; Evdokiou, Andreas

    2015-12-16

    Although nanoparticle-based targeted delivery systems have gained promising achievements for cancer therapy, the development of sophisticated strategies with effective combinatorial therapies remains an enduring challenge. Herein, we report the fabrication of a novel nanomaterial, so-called anodic alumina nanotubes (AANTs) for proof-of-concept cancer therapy by targeting cell signaling networks. This strategy is to target autophagic and endoplasmic reticulum (ER) stress signaling by using thapsigargin (TG)-loaded AANTs cotreated with an autophagy inhibitor 3-methyladenine (3-MA). We first show that AANTs are nontoxic and can activate autophagy in different cell types including human fibroblast cells (HFF), human monocyte cells (THP-1), and human breast cancer cells (MDA-MB 231-TXSA). Treatment with 3-MA at a nontoxic dose reduced the level of autophagy induced by AANTs, and consequently sensitized breast cancer cells to AANTs-induced cellular stresses. To target autophagic and ER stress signaling networking, breast cancer cells were treated with 3-MA together with AANTs loaded with the prototype ER stress inducer TG. We demonstrated that 3-MA enhanced the cancer cell killing effect of AANTs loaded with TG. This effect was associated with enhanced ER stress signaling due to the combination effect of TG and 3-MA. These findings not only demonstrate the excellent biocompatibility of AANTs as novel biomaterials but also provide new opportunities for developing ER- and autophagy-targeted delivery systems for future clinical cancer therapy.

  20. The Ketone Body, β-Hydroxybutyrate Stimulates the Autophagic Flux and Prevents Neuronal Death Induced by Glucose Deprivation in Cortical Cultured Neurons.

    Science.gov (United States)

    Camberos-Luna, Lucy; Gerónimo-Olvera, Cristian; Montiel, Teresa; Rincon-Heredia, Ruth; Massieu, Lourdes

    2016-03-01

    Glucose is the major energy substrate in brain, however, during ketogenesis induced by starvation or prolonged hypoglycemia, the ketone bodies (KB), acetoacetate and β-hydroxybutyrate (BHB) can substitute for glucose. KB improve neuronal survival in diverse injury models, but the mechanisms by which KB prevent neuronal damage are still not well understood. In the present study we have investigated whether protection by the D isomer of BHB (D-BHB) against neuronal death induced by glucose deprivation (GD), is related to autophagy. Autophagy is a lysosomal-dependent degradation process activated during nutritional stress, which leads to the digestion of damaged proteins and organelles providing energy for cell survival. Results show that autophagy is activated in cortical cultured neurons during GD, as indicated by the increase in the levels of the lipidated form of the microtubule associated protein light chain 3 (LC3-II), and the number of autophagic vesicles. At early phases of glucose reintroduction (GR), the levels of p62 declined suggesting that the degradation of the autophagolysosomal content takes place at this time. In cultures exposed to GD and GR in the presence of D-BHB, the levels of LC3-II and p62 rapidly declined and remained low during GR, suggesting that the KB stimulates the autophagic flux preventing autophagosome accumulation and improving neuronal survival.

  1. 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

    2016-01-01

    Summary 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

  2. Study of the contribution of the different components of atmospheric cosmic radiation in dose received by the aircraft crew; Avaliacao da contribuicao dos diferentes componentes da radiacao cosmica atmosferica na dose em tripulacoes de aeronaves

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Marlon A.; Prado, Adriane C.M., E-mail: adriane.acm@hotmail.com, E-mail: marlon@ieav.cta.br [Instituto Tecnologico de Aeronautica (ITA/DCTA), Sao Jose dos Campos, SP (Brazil); Federico, Claudio A.; Goncalez, Odair L., E-mail: claudiofederico@ieav.cta.br, E-mail: odairl@ieav.cta.br [Instituto de Estudos Avancados (IEAv/DCTA), Sao Jose dos Campos, SP (Brazil)

    2014-07-01

    The crews and aircraft passengers are exposed to atmospheric cosmic radiation. The flow of this radiation is modulated by the solar cycle and space weather, varying with the geomagnetic latitude and altitude. This paper presents a study of the contributions of radiation in total ambient dose equivalent of the crews depending on flight altitude up to 20 km, during maximum and minimum solar and in equatorial and polar regions. The results of calculations of the particle flows generated by the EXPACS and QARM codes are used. The particles evaluated that contributing significantly in the ambient dose equivalent are neutrons, protons, electrons, positrons, alphas, photons, muons and charged pions. This review allows us to characterize the origin of the dose received by crews and also support a project of a dosimetric system suitable for this ionizing radiation field in aircraft and on the ground.

  3. Multi-component modelling of human brain tissue: a contribution to the constitutive and computational description of deformation, flow and diffusion processes with application to the invasive drug-delivery problem.

    Science.gov (United States)

    Ehlers, Wolfgang; Wagner, Arndt

    2015-01-01

    Human brain tissue is complex and multi-component in nature. It consists of an anisotropic hyperelastic solid material composed of tissue cells and blood vessel walls. Brain tissue is permeated by two viscous pore liquids, the interstitial fluid and the blood. Both liquids are mobile within the tissue and exhibit a significant anisotropic perfusion behaviour. To model this complex aggregate, the well-founded Theory of Porous Media, a continuum-mechanical approach for the description of multi-component aggregates, is used. To include microscopic information, the model is enhanced by tissue characteristics obtained from medical imaging techniques. Moreover, the model is applied to invasive drug-delivery strategies, i.e. the direct extra-vascular infusion of therapeutic agents. For this purpose, the overall interstitial fluid is treated as a real two-component mixture of a liquid solvent and a dissolved therapeutic solute. Finally, the continuum-mechanical model results in a set of strongly coupled partial differential equations which are spatially discretised using mixed finite elements and solved in a monolithic manner with an implicit Euler time-integration scheme. Numerical examples demonstrate the applicability of the presented model.

  4. 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-...

  5. 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

  6. 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

  7. 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.

  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. 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

  11. Poster contributions; Contributions par affiches

    Energy Technology Data Exchange (ETDEWEB)

    Allegraud, K.; Gatilova, I.; Guaitella, O.; Ionikh, Y.; Roepcke, J.; Rousseau, A.; Aranchuk, L.E.; Larour, J.; Asad, S.; Tendero, C.; Tixier, C.; Jaoul, C.; Tristant, P.; Boisse-Laporte, C.; Leprince, P.; Leniniven, C.; Assouar, M.B.; Jimenez Rioboo, R.J.; Aubert, X.; Rousseau, A.; Sadeghi, N.; Bekstein, A.; Benhenni, M.; Yousfi, M.; Bousquet, A.; Granier, A.; Cartry, G.; Calafat, M.; Escaich, D.; Raynaud, P.; Clergereaux, R.; Cardoso, R.P.; Belmonte, T.; Henrion, G.; Sadeghi, N.; Cavarroc, M.; Mikikian, M.; Tessier, Y.; Boufendi, I.; Celestin, S.; Guaitella, O.; Bourdon, A.; Rousseau, A.; Cernogora, G.; Szopa, C.; Cavarroc, M.; Boufendi, I.; Commaux, N.; Geraud, A.; Pegourie, B.; Clairet, F.; Gil, C.; Gros, G.; Gunn, J.; Joffrin, E.; Hertout, P.; Costin, C.; Choimet, J.B.; Minea, T.; Couedel, L.; Mikikian, M.; Tessier, Y.; Boufendi, I.; Samarian, A.A.; Cousin, R.; Larour, J.; Gouard, P.; Raymond, P.; Curley, G.A.; Booth, J.P.; Corr, C.S.; Foldes, T.; Guillon, J.; Czarny, O.; Huysmans, G.; Daniel, A.; Belmonte, T.; Poucques, L. de; Imbert, J.C.; Teule-Gay, L.; Boisse-Laporte, C.; Devaux, S.; Manfredi, G.; Dif-Pradalier, G.; Grandgirard, V.; Sarazin, Y.; Garbet, X.; Ghendrih, Ph.; Dong, B.; Bauchire, J.M.; Pouvesle, J.M.; Magnier, P.; Hong, D.; Duluard, C.; Tillocher, T.; Mekkakia Maaza, N.; Dussart, R.; Mellhaoui, X.; Lefaucheux, P.; Puech, M.; Ranson, P.; Faudot, E.; Heuraux, S.; Colas, L.; Fubiani, G.; Boilson, D.; Hemsworth, R.S.; Gatilova, L.; Allegraud, K.; Ionikh, Y.; Roepcke, J.; Cartry, G.; Rousseau, A.; Gauthier, J.C.; Fourment, C.; Schurtz, G.; Nicolai, Ph.; Peyrusse, O.; Feugeas, J.L

    2006-07-01

    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.)

  12. 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...

  13. 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。

  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. 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.

  16. 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

  17. 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.

  18. 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

  19. Bioactivity of Minor Milk Components

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh

    of infant formula. Thereafter, bioactive milk components which were preserved in gently-processed infant formula were selected for further investigation of their immunomodulatory activity in cell and preterm pig models. We hope this project will contribute to the research on the development of new...

  20. Inflammasome, mTORC1 activation, and metabolic derangement contribute to the susceptibility of diabetics to infections.

    Science.gov (United States)

    Krakauer, Teresa

    2015-12-01

    and stress signals. However, in diabetics, hyperactivation of mTORC1 disrupts the host autophagic degradation of microbes and damaged mitochondria which in turn exacerbates inflammasome activation and alters cell resistance to infection. Recognition of viral lipids and bacterial components by host cell pattern recognition receptors including TLR activates NFκB and stress kinase c-jun N-terminal kinase (JNK) signaling. The transcription factor NFκB and JNK independently induce inflammatory cytokines, chemokines, and further activate inflammasome. The convergence of inflammasome and mTORC1 activation with metabolic stress and vascular dysfunction in diabetics prevents pathogen clearance and contributes to an increased risk of infection. PMID:26384528

  1. 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

  2. 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

  3. 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.

  4. NAC1 modulates sensitivity of ovarian cancer cells to cisplatin by altering the HMGB1-mediated autophagic response.

    Science.gov (United States)

    Zhang, Y; Cheng, Y; Ren, X; Zhang, L; Yap, K L; Wu, H; Patel, R; Liu, D; Qin, Z-H; Shih, I-M; Yang, J-M

    2012-02-23

    Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, is known to have important roles in proliferation and growth of tumor cells and in chemotherapy resistance. Yet, the mechanisms underlying how NAC1 contributes to drug resistance remain largely unclear. We report here that autophagy was involved in NAC1-mediated resistance to cisplatin, a commonly used chemotherapeutic drug in the treatment of ovarian cancer. We found that treatment with cisplatin caused an activation of autophagy in ovarian cancer cell lines, A2780, OVCAR3 and SKOV3. We further demonstrated that knockdown of NAC1 by RNA interference or inactivation of NAC1 by inducing the expression of a NAC1 deletion mutant that contains only the BTB/POZ domain significantly inhibited the cisplatin-induced autophagy, resulting in increased cisplatin cytotoxicity. Moreover, inhibition of autophagy and sensitization to cisplatin by NAC1 knockdown or inactivation were accompanied by induction of apoptosis. To confirm that the sensitizing effect of NAC1 inhibition on the cytotoxicity of cisplatin was attributed to suppression of autophagy, we assessed the effects of the autophagy inhibitors 3-methyladenosine and chloroquine, and small interfering RNAs (siRNAs) targeting beclin 1 or Atg5 on the cytotoxicity of cisplatin. Treatment with 3-methyladenosine, chloroquine or beclin 1 and Atg5-targeted siRNA also enhanced the sensitivity of SKOV3, A2780 and OVCAR3 cells to cisplatin, indicating that suppression of autophagy indeed renders tumor cells more sensitive to cisplatin. Regulation of autophagy by NAC1 was mediated by the high-mobility group box 1 (HMGB1), as the functional status of NAC1 was associated with the expression, translocation and release of HMGB1. The results of our study not only revealed a new mechanism determining cisplatin sensitivity but also identified NAC1 as a novel regulator of autophagy. Thus, the NAC1-mediated autophagy may be exploited as a new target for

  5. 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.

  6. Variability and component composition

    NARCIS (Netherlands)

    Storm, T. van der

    2004-01-01

    In component-based product populations, feature models have to be described at the component level to be able to benefit from a product family approach. As a consequence, composition of components becomes very complex. We describe how component-level variability can be managed in the face of compone

  7. A novel herbal medicine, KIOM-C, induces autophagic and apoptotic cell death mediated by activation of JNK and reactive oxygen species in HT1080 human fibrosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Aeyung Kim

    Full Text Available KIOM-C was recently demonstrated to have anti-metastatic activity in highly malignant cancer cells via suppression of NF-κB-mediated MMP-9 activity. In addition, it was reported to be effective for clearance of the influenza virus by increasing production of anti-viral cytokines, such as TNF-α and IFN-γ, and efficacious in the treatment of pigs suffering from porcine circovirus-associated disease (PCVAD. In this study, we investigated whether KIOM-C induces cancer cell death and elucidated the underlying anti-cancer mechanisms. In addition, we examined whether KIOM-C oral administration suppresses in vivo tumor growth of HT1080 cells in athymic nude mice. We initially found that KIOM-C at concentrations of 500 and 1000 µg/ml caused dose- and time-dependent cell death in cancer cells, but not normal hepatocytes, to approximately 50% of control levels. At the early stage of KIOM-C treatment (12 h, cells were arrested in G1 phase, which was accompanied by up-regulation of p21 and p27, down-regulation of cyclin D1, and subsequent increases in apoptotic and autophagic cells. Following KIOM-C treatment, the extent of caspase-3 activation, PARP cleavage, Beclin-1 expression, and LC3-II conversion was remarkably up-regulated, but p62 expression was down-regulated. Phosphorylation of AMPK, ULK, JNK, c-jun, and p53 was increased significantly in response to KIOM-C treatment. The levels of intracellular ROS and CHOP expression were also increased. In particular, the JNK-specific inhibitor SP600125 blocked KIOM-C-induced ROS generation and CHOP expression almost completely, which consequently almost completely rescued cell death, indicating that JNK activation plays a critical role in KIOM-C-induced cell death. Furthermore, daily oral administration of 85 and 170 mg/kg KIOM-C efficiently suppressed the tumorigenic growth of HT1080 cells, without systemic toxicity. These results collectively suggest that KIOM-C efficiently induces cancer cell death by

  8. 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.

  9. 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...

  10. 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.

  11. 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.

  12. Dynamic Component Composition

    Directory of Open Access Journals (Sweden)

    Efim Grinkrug

    2014-07-01

    Full Text Available This paper presents an approach to dynamic component composition that facilitates creating new composed components using existing ones at runtime and without any code generation. The dynamic abilities are supported by extended type notion and implementation based on additional superstructure provided with its Java API and corresponding JavaBeans components. The new component composition is performed by building the composed prototype object that can be dynamically transformed into the new instantiable type (component. That approach demonstrates interrelations between prototype-based and class-based component-oriented programming. The component model proposed can be used when implementing user-defined types in declarative languages for event-driven applications programming.

  13. 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...

  14. Sparse Principal Component Analysis with missing observations

    CERN Document Server

    Lounici, Karim

    2012-01-01

    In this paper, we study the problem of sparse Principal Component Analysis (PCA) in the high-dimensional setting with missing observations. Our goal is to estimate the first principal component when we only have access to partial observations. Existing estimation techniques are usually derived for fully observed data sets and require a prior knowledge of the sparsity of the first principal component in order to achieve good statistical guarantees. Our contributions is threefold. First, we establish the first information-theoretic lower bound for the sparse PCA problem with missing observations. Second, we propose a simple procedure that does not require any prior knowledge on the sparsity of the unknown first principal component or any imputation of the missing observations, adapts to the unknown sparsity of the first principal component and achieves the optimal rate of estimation up to a logarithmic factor. Third, if the covariance matrix of interest admits a sparse first principal component and is in additi...

  15. The Significance of Common Molecular Biomarkers of Autophay Pathway in Reflecting Autophagic Activity%自噬途径常用分子生物学指标在反映自噬活性上的意义

    Institute of Scientific and Technical Information of China (English)

    潘明娇; 王小丹(综述); 喻陆(审校)

    2015-01-01

    As a self-degradative cell pathway in eukaryotic cells,autophagy is evolutionarily conserved and mainly responsible for the degradation of long-lived proteins and damaged organelles.Autophagy is alsoconducive to maintaining the normal cellular homeostasis.The past decades have witnessed a remarkable progressof research on autophagy.A great number of studies obtain their conclusions through observing thechange of autophagic activity,therefore it is important to correctly explain the results from the autophagy activity test.Among the test methods,the molecular biological methods are widely used,and through clarifying the molecular mechanisms of autophagy and the relationship between autophagy and ubiquitin proteasome system,we could make better use of the common molecular biomarkers to reflect the change of autophagic activity.%自噬是一种真核细胞自我降解、维持自稳态的细胞途径,在进化过程中高度保守,主要负责降解长寿蛋白和损伤细胞器。近年来,关于自噬的研究较多,其中许多研究需要通过观察自噬活性的变化来得出结论,因此准确解释自噬活性检测结果十分重要。在众多自噬活性检测方法中,分子生物学检测技术应用较为广泛,通过了解自噬的分子机制及其与泛素蛋白酶体系的关系,可以更好地利用自噬途径常用分子生物学指标来反映自噬活性变化。

  16. 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

  17. Supply chain components

    Directory of Open Access Journals (Sweden)

    Vieraşu, T.

    2011-01-01

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

  18. 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.

  19. Multilevel component analysis

    NARCIS (Netherlands)

    Timmerman, M.E.

    2006-01-01

    A general framework for the exploratory component analysis of multilevel data (MLCA) is proposed. In this framework, a separate component model is specified for each group of objects at a certain level. The similarities between the groups of objects at a given level can be expressed by imposing cons

  20. 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.

  1. 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

  2. GCS component development cycle

    Science.gov (United States)

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

    2012-09-01

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

  3. Robust Principal Component Analysis?

    CERN Document Server

    Candes, Emmanuel J; Ma, Yi; Wright, John

    2009-01-01

    This paper is about a curious phenomenon. Suppose we have a data matrix, which is the superposition of a low-rank component and a sparse component. Can we recover each component individually? We prove that under some suitable assumptions, it is possible to recover both the low-rank and the sparse components exactly by solving a very convenient convex program called Principal Component Pursuit; among all feasible decompositions, simply minimize a weighted combination of the nuclear norm and of the L1 norm. This suggests the possibility of a principled approach to robust principal component analysis since our methodology and results assert that one can recover the principal components of a data matrix even though a positive fraction of its entries are arbitrarily corrupted. This extends to the situation where a fraction of the entries are missing as well. We discuss an algorithm for solving this optimization problem, and present applications in the area of video surveillance, where our methodology allows for th...

  4. 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...

  5. 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...

  6. 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

  7. Component fragility research program

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, N.C.; Mochizuki, G.L.; Holman, G.S. (NCT Engineering, Inc., Lafayette, CA (USA); Lawrence Livermore National Lab., CA (USA))

    1989-11-01

    To demonstrate how high-level'' qualification test data can be used to estimate the ultimate seismic capacity of nuclear power plant equipment, we assessed in detail various electrical components tested by the Pacific Gas 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.

  8. 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...

  9. 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

  10. National contributions to observed global warming

    Science.gov (United States)

    Damon Matthews, H.; Graham, Tanya L.; Keverian, Serge; Lamontagne, Cassandra; Seto, Donny; Smith, Trevor J.

    2014-01-01

    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.

  11. 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)

  12. 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.

  13. 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.

  14. 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).

  15. 硫链丝菌素诱导非小细胞肺癌细胞自噬性死亡%Thiostrepton induces autophagic cell death in non-small-cell lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    邹争志; 聂培培; 倪艺榕; 周小明

    2014-01-01

    Autophagy is a fundamental cellular process that controls cells in a normal homeostatic state by recycling nu-trients to maintain cellular energy levels for cell survival through the turnover of proteins and damaged organelles.Where-as,persistent activation of autophagy can cause excessive depletion of cellular organelles and essential proteins,leading to caspase-independent autophagic cell death.Therefore,inducing cell death via this autophagic pathway might be an al-ternative approach for cancer therapy.Here,we show that the thiazole antibiotic thiostrepton decreased cell viability and induced cell apoptosis in non-small-cell lung cancer (NSCLC)PC-9 cells.Additionally,we found thiostrepton induced cell autophagy in PC-9 cells.Moreover,the cell apoptosis induced by thiostrepton could be blocked by 3-Methyladenine (3-MA),a autophagy inhibitor.These findings suggested that thiostrepton can promote the autophagic death of human NSCLC cells.Moreover,this study provided evidence that administration of thiostrepton combined with autophagy induc-er may be an effective therapeutic strategy for targeting human non-small-cell lung cancers.%自噬在细胞的生命过程中起了非常重要的作用,它能通过清除受损的细胞器和过多的蛋白质以维持细胞内环境稳定基本能量代谢的稳定。然而,自噬的持续激活可导致细胞器以及必需的蛋白质的过度消耗,导致不依赖caspase的自噬性细胞死亡。因此,通过这种自噬途径诱导细胞死亡可能是癌症治疗的一种新方法。在本研究我们发现,硫链丝菌素能够减少非小细胞肺癌PC-9细胞的细胞活力和诱导细胞凋亡。另外,我们发现硫链丝菌素诱导了PC-9细胞自噬。此外,我们也发现硫链丝菌素诱导的细胞凋亡可以被自噬抑制剂3-甲基腺嘌呤(3-MA)阻止。这些结果表明,硫链丝菌素促进人体非小细胞肺癌细胞的自噬性死亡。在本研究我们的发现也提示硫

  16. 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.

  17. 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...

  18. Residual Component Analysis

    CERN Document Server

    Kalaitzis, Alfredo A

    2011-01-01

    Probabilistic principal component analysis (PPCA) seeks a low dimensional representation of a data set in the presence of independent spherical Gaussian noise, Sigma = (sigma^2)*I. The maximum likelihood solution for the model is an eigenvalue problem on the sample covariance matrix. In this paper we consider the situation where the data variance is already partially explained by other factors, e.g. covariates of interest, or temporal correlations leaving some residual variance. We decompose the residual variance into its components through a generalized eigenvalue problem, which we call residual component analysis (RCA). We show that canonical covariates analysis (CCA) is a special case of our algorithm and explore a range of new algorithms that arise from the framework. We illustrate the ideas on a gene expression time series data set and the recovery of human pose from silhouette.

  19. Cognitive Component Analysis

    DEFF Research Database (Denmark)

    Feng, Ling

    2008-01-01

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

  20. 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

  1. Component Reengineering Workshops

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius; Christensen, Henrik Bærbak

    2004-01-01

    In mature domains, a number of competing product lines may emerge, and from the point of view of customers of such product lines, reengineering and reuse of assets across product lines from different vendors becomes important. To address this issue we present a low-cost approach, component...... 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...

  2. 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....

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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...

  8. 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.

  9. Grey component analysis

    NARCIS (Netherlands)

    Westerhuis, J.A.; Derks, E.P.P.A.; Hoefsloot, H.C.J.; Smilde, A.K.

    2007-01-01

    The interpretation of principal component analysis (PCA) models of complex biological or chemical data can be cumbersome because in PCA the decomposition is performed without any knowledge of the system at hand. Prior information of the system is not used to improve the interpretation. In this paper

  10. 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....

  11. 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 ...

  12. 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...

  13. 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.

  14. Multimode geodesic branching components

    Science.gov (United States)

    Schulz, D.; Voges, E.

    1983-01-01

    Geodesic branching components are investigated for multimode guided wave optics. Geodesic structures with particular properties, e.g. focussing star couplers, are derived by a synthesis technique based on a theorem of Toraldo di Francia. Experimentally, the geodesic surfaces are printed on acrylic glass and are spin-coated with organic film waveguides.

  15. 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

  16. 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.

  17. 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

  18. Autophagy Contributes to the Death/Survival Balance in Cancer PhotoDynamic Therapy

    Directory of Open Access Journals (Sweden)

    Luciana Dini

    2012-08-01

    Full Text Available Autophagy is an important cellular program with a “double face” role, since it promotes either cell survival or cell death, also in cancer therapies. Its survival role occurs by recycling cell components during starvation or removing stressed organelles; when damage becomes extensive, autophagy provides another programmed cell death pathway, known as Autophagic Cell Death (ACD. The induction of autophagy is a common outcome in PhotoDynamic Therapy (PDT, a two-step process involving the irradiation of photosensitizer (PS-loaded cancer cells. Upon tissue oxygen interaction, PS provokes immediate and direct Reactive Oxygen Species (ROS-induced damage to Endoplasmic Reticulum (ER, mitochondria, plasma membrane, and/or lysosomes. The main biological effects carried out in cancer PDT are direct cytotoxicity to tumor cells, vasculature damage and induction of inflammatory reactions stimulating immunological responses. The question about the role of autophagy in PDT and its putative immunological impact is hotly controversial and largely studied in recent times. This review deals with the induction of autophagy in PDT protocols and its dual role, also considering its interrelationship with apoptosis, the preferential cell death program triggered in the photodynamic process.

  19. Towards Software Component Procurement Automation

    NARCIS (Netherlands)

    Gross, H-G.; Lormans, M.; Zhou, J.

    2007-01-01

    One of the first steps of component procurement is the identification of required component features in large repositories of existing components. On the highest level of abstraction, component requirements as well as component descriptions are usually written in natural language. Therefore, we can

  20. 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

  1. 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

  2. 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.

  3. Food Components and Supplements

    DEFF Research Database (Denmark)

    Parlesak, Alexandr

    2012-01-01

    .g., secondary plant metabolites such as flavonoids), or as contaminants that enter the food chain at different stages or during the food production process. For these components, a wide spectrum of biological effects was observed that ranges from health-threatening impacts (e.g., polycyclic aromatic amines...... the growth of these bacteria (prebiotics) are added to food to achieve health effects exceeding its pure nutritional function. Several of these effects are mediated by enzyme systems involved in xenobiotic and drug metabolism, and in some cases this might lead to undesired interactions with medication...... cases, nutrients, food contaminants, and secondary plant metabolites can themselves become substrates for xenobiotic-metabolizing enzymes, resulting in health-promoting or health-threatening products. This chapter focuses on how important components of our daily nutrition and supplements can interfere...

  4. 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.......g., secondary plant metabolites such as flavonoids), or as contaminants that enter the food chain at different stages or during the food production process. For these components, a wide spectrum of biological effects was observed that ranges from health-threatening impacts (e.g., polycyclic aromatic amines......, 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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

  9. 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...

  10. 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.

  11. Stable Principal Component Pursuit

    CERN Document Server

    Zhou, Zihan; Wright, John; Candes, Emmanuel; Ma, Yi

    2010-01-01

    In this paper, we study the problem of recovering a low-rank matrix (the principal components) from a high-dimensional data matrix despite both small entry-wise noise and gross sparse errors. Recently, it has been shown that a convex program, named Principal Component Pursuit (PCP), can recover the low-rank matrix when the data matrix is corrupted by gross sparse errors. We further prove that the solution to a related convex program (a relaxed PCP) gives an estimate of the low-rank matrix that is simultaneously stable to small entrywise noise and robust to gross sparse errors. More precisely, our result shows that the proposed convex program recovers the low-rank matrix even though a positive fraction of its entries are arbitrarily corrupted, with an error bound proportional to the noise level. We present simulation results to support our result and demonstrate that the new convex program accurately recovers the principal components (the low-rank matrix) under quite broad conditions. To our knowledge, this is...

  12. Fundamental plane: dark matter and dissipation contributions

    CERN Document Server

    Ribeiro, Andre L B

    2010-01-01

    Stellar and galactic systems are objects in dynamical equilibrium that are composed of ordinary baryonic matter hypothetically embedded in extended dominant dark matter halos. Our aim is to investigate the scaling relations and dissipational features of these objects over a wide range of their properties, taking the dynamical influence of the dark matter component into account. We study the physical properties of these self-gravitating systems using the two-component virial theorem in conjunction with data that embrace a wide range of astrophysical systems. We find that the scaling relations defined by the properties of these objects admit a dark-to-luminous density ratio parameter as a natural requirement in this framework. We also probe dissipational effects on the fundamental surface defined by the two-component virial theorem and discuss their relations with respect to the region devoid of objects in the data distribution. Our results indicate complementary contributions of dissipation and dark matter to ...

  13. Composing simulations using persistent software components

    Energy Technology Data Exchange (ETDEWEB)

    Holland, J.V.; Michelsen, R.E.; Powell, D.R.; Upton, S.C.; Thompson, D.R.

    1999-03-01

    The traditional process for developing large-scale simulations is cumbersome, time consuming, costly, and in some cases, inadequate. The topics of software components and component-based software engineering are being explored by software professionals in academic and industrial settings. A component is a well-delineated, relatively independent, and replaceable part of a software system that performs a specific function. Many researchers have addressed the potential to derive a component-based approach to simulations in general, and a few have focused on military simulations in particular. In a component-based approach, functional or logical blocks of the simulation entities are represented as coherent collections of components satisfying explicitly defined interface requirements. A simulation is a top-level aggregate comprised of a collection of components that interact with each other in the context of a simulated environment. A component may represent a simulation artifact, an agent, or any entity that can generated events affecting itself, other simulated entities, or the state of the system. The component-based approach promotes code reuse, contributes to reducing time spent validating or verifying models, and promises to reduce the cost of development while still delivering tailored simulations specific to analysis questions. The Integrated Virtual Environment for Simulation (IVES) is a composition-centered framework to achieve this potential. IVES is a Java implementation of simulation composition concepts developed at Los Alamos National Laboratory for use in several application domains. In this paper, its use in the military domain is demonstrated via the simulation of dismounted infantry in an urban environment.

  14. 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.)

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

    NARCIS (Netherlands)

    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 mini

  16. Electronic components and technology

    CERN Document Server

    Sangwine, Stephen

    2007-01-01

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

  17. Similar component analysis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong; WANG Xin; LI Junwei; CAO Xianguang

    2006-01-01

    A new unsupervised feature extraction method called similar component analysis (SCA) is proposed in this paper. SCA method has a self-aggregation property that the data objects will move towards each other to form clusters through SCA theoretically,which can reveal the inherent pattern of similarity hidden in the dataset. The inputs of SCA are just the pairwise similarities of the dataset,which makes it easier for time series analysis due to the variable length of the time series. Our experimental results on many problems have verified the effectiveness of SCA on some engineering application.

  18. The solvent component of macromolecular crystals

    Energy Technology Data Exchange (ETDEWEB)

    Weichenberger, Christian X. [European Academy of Bozen/Bolzano (EURAC), Viale Druso 1, Bozen/Bolzano, I-39100 Südtirol/Alto Adige (Italy); Afonine, Pavel V. [Lawrence Berkeley National Laboratory (LBNL), 1 Cyclotron Road, Mail Stop 64R0121, Berkeley, CA 94720 (United States); Kantardjieff, Katherine [California State University, San Marcos, CA 92078 (United States); Rupp, Bernhard, E-mail: br@hofkristallamt.org [k.-k. Hofkristallamt, 991 Audrey Place, Vista, CA 92084 (United States); Medical University of Innsbruck, Schöpfstrasse 41, A-6020 Innsbruck (Austria)

    2015-04-30

    On average, the mother liquor or solvent and its constituents occupy about 50% of a macromolecular crystal. Ordered as well as disordered solvent components need to be accurately accounted for in modelling and refinement, often with considerable complexity. The mother liquor from which a biomolecular crystal is grown will contain water, buffer molecules, native ligands and cofactors, crystallization precipitants and additives, various metal ions, and often small-molecule ligands or inhibitors. On average, about half the volume of a biomolecular crystal consists of this mother liquor, whose components form the disordered bulk solvent. Its scattering contributions can be exploited in initial phasing and must be included in crystal structure refinement as a bulk-solvent model. Concomitantly, distinct electron density originating from ordered solvent components must be correctly identified and represented as part of the atomic crystal structure model. Herein, are reviewed (i) probabilistic bulk-solvent content estimates, (ii) the use of bulk-solvent density modification in phase improvement, (iii) bulk-solvent models and refinement of bulk-solvent contributions and (iv) modelling and validation of ordered solvent constituents. A brief summary is provided of current tools for bulk-solvent analysis and refinement, as well as of modelling, refinement and analysis of ordered solvent components, including small-molecule ligands.

  19. 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.

  20. 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.

  1. One-component nanomedicine.

    Science.gov (United States)

    Su, Hao; Koo, Jin Mo; Cui, Honggang

    2015-12-10

    One-component nanomedicine (OCN) represents an emerging class of therapeutic nanostructures that contain only one type of chemical substance. This one-component feature allows for fine-tuning and optimization of the drug loading and physicochemical properties of nanomedicine in a precise manner through molecular engineering of the underlying building blocks. Using a precipitation procedure or effective molecular assembly strategies, molecularly crafted therapeutic agents (e.g. polymer-drug conjugates, small molecule prodrugs, or drug amphiphiles) could involuntarily aggregate, or self-assemble into nanoscale objects of well-defined sizes and shapes. Unlike traditional carrier-based nanomedicines that are inherently multicomponent systems, an OCN does not require the use of additional carriers and could itself possess desired physicochemical features for preferential accumulation at target sites. We review here recent progress in the molecular design, conjugation methods, and fabrication strategies of OCN, and analyze the opportunities that this emerging platform could open for the new and improved treatment of devastating diseases such as cancer.

  2. 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.

  3. 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.

  4. Turmeric toxicity in A431 epidermoid cancer cells associates with autophagy degradation of anti-apoptotic and anti-autophagic p53 mutant.

    Science.gov (United States)

    Thongrakard, Visa; Titone, Rossella; Follo, Carlo; Morani, Federica; Suksamrarn, Apichart; Tencomnao, Tewin; Isidoro, Ciro

    2014-12-01

    The keratinocyte-derived A431 Squamous Cell Carcinoma cells express the p53R273H mutant, which has been reported to inhibit apoptosis and autophagy. Here, we show that the crude extract of turmeric (Curcuma longa), similarly to its bioactive component Curcumin, could induce both apoptosis and autophagy in A431 cells, and these effects were concomitant with degradation of p53. Turmeric and curcumin also stimulated the activity of mTOR, which notoriously promotes cell growth and acts negatively on basal autophagy. Rapamycin-mediated inhibition of mTOR synergized with turmeric and curcumin in causing p53 degradation, increased the production of autophagosomes and exacerbated cell toxicity leading to cell necrosis. Small-interference mediated silencing of the autophagy proteins BECLIN 1 or ATG7 abrogated the induction of autophagy and largely rescued p53 stability in Turmeric-treated or Curcumin-treated cells, indicating that macroautophagy was mainly responsible for mutant p53 degradation. These data uncover a novel mechanism of turmeric and curcumin toxicity in chemoresistant cancer cells bearing mutant p53.

  5. 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.

  6. 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......Low-power base stations such as e.g. Femto-cells are one of the candidates for high data rate provisioning in local areas, such as residences, apartment complexes, business offices and outdoor hotspot scenarios. Unfortunately, the benefits are not without new challenges in terms of interference...... 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...

  7. 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.

  8. 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.

  9. Sprayed skin turbine component

    Science.gov (United States)

    Allen, David B

    2013-06-04

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

  10. 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

  11. Sensitivity Analysis of Component Reliability

    Institute of Scientific and Technical Information of China (English)

    ZhenhuaGe

    2004-01-01

    In a system, Every component has its unique position within system and its unique failure characteristics. When a component's reliability is changed, its effect on system reliability is not equal. Component reliability sensitivity is a measure of effect on system reliability while a component's reliability is changed. In this paper, the definition and relative matrix of component reliability sensitivity is proposed, and some of their characteristics are analyzed. All these will help us to analyse or improve the system reliability.

  12. 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.

  13. 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

  14. Crystalline Nickel Sulfide Induced Malignant Transformation of 16HBE Cells through Autophagic Pathway%结晶型硫化镍通过自噬途径诱导16HBE细胞恶性转化癌变

    Institute of Scientific and Technical Information of China (English)

    张岚; 杨磊; 吕嘉春

    2012-01-01

    Nickel compounds, which widely exist in the environment of human occupation, are the major risk factor for human lung cancer. Our previous studies had confirmed that exposure to toxic,metallic crystalline nickel sulfide (NiS) was an important cause of lung cancer, but the concrete carcinogenic mechanism is still unclear. In this study, we used the previouslyestablished human bronchial epithelial (16HBE-T) cells malignant transformation model, which was induced by crystalline NiS. For the first time, fluorescence intensity and position of the GFP-LC3 protein in malignant transformed (16HBE-T) cells and normal cell (16HBE-N), were real-time monitored with the technique of confocal laser scanning microscopy imaging without damaging the condition. Moreover, we used Western Blotting to detect the intracellular autophagic signal which is expressed by key effective molecule pathway. Confocal experimental results showed that: Compared with that of 16HBE-N-cells, the GFP-LC3 protein punctate aggregation of 16HBE-T cells significantly reduced to the merely 1/3 amount of 16HBE-N-cells, suggesting that autophagy levels declined. At the same time, it was found that the mTOR kinase activity increased, and that Beclin 1 expression decreased. The above research result demonstrated that the mechanism of crystalline NiS induced 16HBE cell malignant transformation was through multiple autophagic pathway and it will provide an important message in the prevention and treatment of lung cancer.%镍化合物广泛存在于人类职业环境中,是人类发生肺癌的主要危险因素.我们前期研究已证实金属毒物结晶型硫化镍(NiS)的暴露是发生肺癌的重要病因,但具体的致癌机制仍未明了.本研究利用前期建立的结晶型NiS恶性转化人支气管上皮细胞的细胞模型,首次采用激光共聚焦扫描显微镜成像技术,在无损伤状态下,实时观测恶性转化细胞(16HBE-T)和正常细胞(16HBE-N)中自噬体标记蛋白GFP-LC3

  15. 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

  16. 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.

  17. Effects of Different Irrigation Methods and Fertilization Measures on Soil Respiration and Its Component Contributions in Cotton Field in Arid Region%干旱区不同灌溉方式及施肥措施对棉田土壤呼吸及各组分贡献的影响

    Institute of Scientific and Technical Information of China (English)

    张前兵; 杨玲; 王进; 罗宏海; 张亚黎; 张旺锋

    2012-01-01

    [Objective] It is of great significance to explore the effects of different irrigation methods and fertilization measures on soil carbon balance in cotton field during cotton growth season in arid region, and to compare the effects of different management practices on soil carbon sequestration intensity in cotton field.! MethodiTwo-factor experiments with two irrigation methods and four fertilizer treatments were conducted during cotton growth period. Drip irrigation and flood irrigation were arranged as two different irrigation methods and organic manure (OM), N P K fertilizer (NPK), combined application of NPK fertilizer and organic manure (NPK.+OM) and no fertilization (CK) were arranged as four fertilizer treatments. Soil respiration rate in cotton field was measured by LI-8100 automated soil CO2 efflux system and root contribution of soil respiration was detected by root exclusion method. Soil carbon sequestration intensity in cotton field under different irrigation methods and fertilization measures was analyzed by calculating net ecosystem productivity (NEP). [Result] Under the conditions of different irrigation methods and fertilization measures, seasonal variation of cropland soil respiration rate showed an increase at first, then followed a declining trend with air temperature change. Soil respiration rate reached a peak in mid-July and then reduced to the minimum in mid-October after cotton harvest. Soil carbon emission under drip irrigation was larger than that under flood irrigation, and under the same irrigation condition, the soil carbon emission with NPK+OM treatment was the highest, then with OM, CK, NPK in turn. The ratio of root respiration contribution to soil respiration was fluctuated between 36.38% and 58.74% under drip irrigation method, whereas between 33.73% and 52.03% under flood irrigation method. Root respiration contribution was the highest at the boiling stage. During the whole growth period, the root respiration contribution under

  18. 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

  19. 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.

  20. Introducing and Modeling Inefficiency Contributions

    DEFF Research Database (Denmark)

    Asmild, Mette; Kronborg, Dorte; Matthews, Kent

    2016-01-01

    -called inefficiency contributions, which are defined as the relative contributions from specific variables to the overall levels of inefficiencies. A statistical model for distinguishing the inefficiency contributions between subgroups is proposed and the method is illustrated on a data set on Chinese banks....

  1. 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.

  2. 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.

  3. 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

  4. 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...

  5. 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...... by small examples, using UML as concrete syntax for various aspects, and is illustrated by one larger case study based on an industrial prototype of a complex component based system....

  6. 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.

  7. 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.

  8. Biometric relationships of ocular components in esotropic amblyopia

    Directory of Open Access Journals (Sweden)

    Iara Debert

    2012-02-01

    Full Text Available PURPOSE: To investigate the contribution of the individual ocular components, i.e. anterior chamber depth, lens thickness and vitreous chamber depth, to total axial length in patients with esotropic amblyopia. METHODS: The study population consisted of 74 children, aged between 5 and 8 years: thirty-seven patients with esotropic amblyopia and 37 healthy volunteers (control group. The participants underwent a comprehensive ophthalmological examination, including cycloplegic refraction and A-scan ultrasonography. Anterior chamber depth, lens thickness, vitreous chamber depth and total axial length were recorded. Paired Student's t-tests were used to compare biometric measurements between amblyopic eyes and their fellow eyes and between right and left eyes in the control group. To evaluate the contribution of the ocular components to the total axial length, we report the individual components as a percentage of total axial length. RESULTS: The comparison between amblyopic and fellow eyes regarding the individual contribution from ocular components to the total axial length revealed greater contribution from lens thickness (P=0.001 and smaller contribution from vitreous chamber depth (P=0.001 in amblyopic eyes, despite similar contribution from anterior chamber depth (P=0.434. The comparison between right and left eyes in the control group showed similar contributions from anterior chamber depth (P=0.620, lens thickness (P=0.721, and vitreous chamber depth (P=0.483. CONCLUSIONS: This study shows differences between amblyopic and non-amblyopic eyes when the total axial length is broken down into the individual contribution from the ocular components.

  9. Actual service life prediction of building components

    DEFF Research Database (Denmark)

    Aagaard, Niels-Jørgen; Brandt, Erik; Hansen, Ernst Jan de Place

    2014-01-01

    , the paper presents an analysis of service life of buildings as such with respect to the use of the building partially based on analysis of data from the nationwide Danish register of buildings and housing as well as turnover in the Danish construction industry from refurbishment and demolition activities...... a condensed method for assessment of life cycle costs for buildings. Estimation of life cycle costs has traditionally been based on predicted service life for building components in terms of technical performance. This paper suggests a method for taking into account other contributing factors...... such as economics, aesthetics and use of the building. Each of these factors is regarded as a stochastic variable and can be seen as competing causes of bringing service life to an end. A model is proposed for combining such variables resulting in the actual service life of building components. Furthermore...

  10. Campaign Contributions and Agricultural Subsidies

    OpenAIRE

    Rigoberto A. Lopez

    2001-01-01

    This article examines the influence of campaign contributions on agricultural subsidies. Empirical results revealed that rent seeking works, i.e., campaign contributions of agricultural-related industries influence agricultural subsidies in the manner they best serve contributors' economic interests. Eliminating campaign contributions would significantly decrease agricultural subsidies, hurt farm groups, benefit consumers and taxpayers, and increase social welfare by approximately $5.5 billio...

  11. 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.)

  12. 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.

  13. 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.

  14. 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.

  15. Autophagic effect on tumor and its potential applicationsin non-small cell lung cancer molecular targeted therapy%肿瘤自噬效应及其在非小细胞肺癌分子靶向治疗中的潜在应用

    Institute of Scientific and Technical Information of China (English)

    陈美娟; 詹瑧; 张旭

    2012-01-01

    目前针对非小细胞肺癌(NSCLC)的手术、放化疗等治疗手段临床疗效仍很不足,相应的分子靶向治疗药物随着临床抗药性的产生疗效也明显下降.自噬对肿瘤进展具有双重影响作用.在NSCLC临床治疗的各个阶段都应充分考虑自噬效应所起的作用,对其进行合理调节和利用,从而提高各种治疗手段的临床疗效.%Now clinical treatments for non-small cell lung cancer ( NSCLC ) such as surgery, radiotherapy, and chemotherapy are still insufficient, and the efficacy of some molecular targeted therapy is also limited because of natural and acquired resistance in clinics. Autophagy exhibited the effects of a double-blade sword on tumor progression. On the one hand, autophagic can induce the death of tumor cells, and on the other hand, it alsoprotects the tumor in stress such as nutritional deficiency. Clinical treatment of NSCLC at various stages should take full account of autophagic effect on its progression, which can improve the clinical efficacy of various treatments by reasonable combination.

  16. 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.

  17. 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,...

  18. 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...

  19. 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...

  20. Component Reification in Systems Modelling

    DEFF Research Database (Denmark)

    Bendisposto, Jens; Hallerstede, Stefan

    When modelling concurrent or distributed systems in Event-B, we often obtain models where the structure of the connected components is specified by constants. Their behaviour is specified by the non-deterministic choice of event parameters for events that operate on shared variables. From a certain...... point on in a development we would rather develop components separately. The other -behaviourally identical- components should not concern us when we are focusing on one of them. We have to ask the following question: How can we systematically extract "real" components from such a model...

  1. 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.

  2. 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

  3. Active and passive contributions to spatial learning.

    Science.gov (United States)

    Chrastil, Elizabeth R; Warren, William H

    2012-02-01

    It seems intuitively obvious that active exploration of a new environment will lead to better spatial learning than will passive exposure. However, the literature on this issue is decidedly mixed-in part, because the concept itself is not well defined. We identify five potential components of active spatial learning and review the evidence regarding their role in the acquisition of landmark, route, and survey knowledge. We find that (1) idiothetic information in walking contributes to metric survey knowledge, (2) there is little evidence as yet that decision making during exploration contributes to route or survey knowledge, (3) attention to place-action associations and relevant spatial relations contributes to route and survey knowledge, although landmarks and boundaries appear to be learned without effort, (4) route and survey information are differentially encoded in subunits of working memory, and (5) there is preliminary evidence that mental manipulation of such properties facilitates spatial learning. Idiothetic information appears to be necessary to reveal the influence of attention and, possibly, decision making in survey learning, which may explain the mixed results in desktop virtual reality. Thus, there is indeed an active advantage in spatial learning, which manifests itself in the task-dependent acquisition of route and survey knowledge.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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’ type...

  13. Novel Structural Components Contribute to the High Thermal Stability of Acyl Carrier Protein from Enterococcus faecalis.

    Science.gov (United States)

    Park, Young-Guen; Jung, Min-Cheol; Song, Heesang; Jeong, Ki-Woong; Bang, Eunjung; Hwang, Geum-Sook; Kim, Yangmee

    2016-01-22

    Enterococcus faecalis is a Gram-positive, commensal bacterium that lives in the gastrointestinal tracts of humans and other mammals. It causes severe infections because of high antibiotic resistance. E. faecalis can endure extremes of temperature and pH. Acyl carrier protein (ACP) is a key element in the biosynthesis of fatty acids responsible for acyl group shuttling and delivery. In this study, to understand the origin of high thermal stabilities of E. faecalis ACP (Ef-ACP), its solution structure was investigated for the first time. CD experiments showed that the melting temperature of Ef-ACP is 78.8 °C, which is much higher than that of Escherichia coli ACP (67.2 °C). The overall structure of Ef-ACP shows the common ACP folding pattern consisting of four α-helices (helix I (residues 3-17), helix II (residues 39-53), helix III (residues 60-64), and helix IV (residues 68-78)) connected by three loops. Unique Ef-ACP structural features include a hydrophobic interaction between Phe(45) in helix II and Phe(18) in the α1α2 loop and a hydrogen bonding between Ser(15) in helix I and Ile(20) in the α1α2 loop, resulting in its high thermal stability. Phe(45)-mediated hydrophobic packing may block acyl chain binding subpocket II entry. Furthermore, Ser(58) in the α2α3 loop in Ef-ACP, which usually constitutes a proline in other ACPs, exhibited slow conformational exchanges, resulting in the movement of the helix III outside the structure to accommodate a longer acyl chain in the acyl binding cavity. These results might provide insights into the development of antibiotics against pathogenic drug-resistant E. faecalis strains.

  14. 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.

  15. 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…

  16. 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 ...

  17. 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

  18. 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

  19. 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....

  20. 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.

  1. 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)

  2. Contribution analysis of a Bolivian innovation grant fund

    NARCIS (Netherlands)

    Ton, Giel

    2016-01-01

    We used contribution analysis to verify the key assumption in the intervention logic of an innovation fund in Bolivia directed to economic farmer organisations to develop value-added activities. We focussed the research on three sub-components of the intervention logic: relevance of the farmer gr

  3. 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...

  4. 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.

  5. 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).

  6. 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 ...

  7. 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.

  8. 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.

  9. 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.

  10. Component Fragility Research Program: Phase 1 component prioritization

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-06-01

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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Sparse principal component analysis in hyperspectral change detection

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Larsen, Rasmus; Vestergaard, Jacob Schack

    2011-01-01

    This contribution deals with change detection by means of sparse principal component analysis (PCA) of simple differences of calibrated, bi-temporal HyMap data. Results show that if we retain only 15 nonzero loadings (out of 126) in the sparse PCA the resulting change scores appear visually very ...

  16. 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

  17. 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

  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. Multiview Bayesian Correlated Component Analysis

    DEFF Research Database (Denmark)

    Kamronn, Simon Due; Poulsen, Andreas Trier; Hansen, Lars Kai

    2015-01-01

    Correlated component analysis as proposed by Dmochowski, Sajda, Dias, and Parra (2012) is a tool for investigating brain process similarity in the responses to multiple views of a given stimulus. Correlated components are identified under the assumption that the involved spatial networks...... are identical. Here we propose a hierarchical probabilistic model that can infer the level of universality in such multiview data, from completely unrelated representations, corresponding to canonical correlation analysis, to identical representations as in correlated component analysis. This new model, which...... we denote Bayesian correlated component analysis, evaluates favorably against three relevant algorithms in simulated data. A well-established benchmark EEG data set is used to further validate the new model and infer the variability of spatial representations across multiple subjects....

  20. 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

  1. Passive Microwave Components and Antennas

    DEFF Research Database (Denmark)

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

  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. 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

  4. BRAF associated autophagy exploitation: BRAF and autophagy inhibitors synergise to efficiently overcome resistance of BRAF mutant colorectal cancer cells.

    Science.gov (United States)

    Goulielmaki, Maria; Koustas, Evangelos; Moysidou, Eirini; Vlassi, Margarita; Sasazuki, Takehiko; Shirasawa, Senji; Zografos, George; Oikonomou, Eftychia; Pintzas, Alexander

    2016-02-23

    Autophagy is the basic catabolic mechanism that involves cell degradation of unnecessary or dysfunctional cellular components. Autophagy has a controversial role in cancer--both in protecting against tumor progression by isolation of damaged organelles, or by potentially contributing to cancer growth. The impact of autophagy in RAS induced transformation still remains to be further analyzed based on the differential effect of RAS isoforms and tumor cell context. In the present study, the effect of KRAS/BRAF/PIK3CA oncogenic pathways on the autophagic cell properties and on main components of the autophagic machinery like p62 (SQSTM1), Beclin-1 (BECN1) and MAP1LC3 (LC3) in colon cancer cells was investigated. This study provides evidence that BRAF oncogene induces the expression of key autophagic markers, like LC3 and BECN1 in colorectal tumor cells. Herein, PI3K/AKT/MTOR inhibitors induce autophagic tumor properties, whereas RAF/MEK/ERK signalling inhibitors reduce expression of autophagic markers. Based on the ineffectiveness of BRAFV600E inhibitors in BRAFV600E bearing colorectal tumors, the BRAF related autophagic properties in colorectal cancer cells are further exploited, by novel combinatorial anti-cancer protocols. Strong evidence is provided here that pre-treatment of autophagy inhibitor 3-MA followed by its combination with BRAFV600E targeting drug PLX4720 can synergistically sensitize resistant colorectal tumors. Notably, colorectal cancer cells are very sensitive to mono-treatments of another autophagy inhibitor, Bafilomycin A1. The findings of this study are expected to provide novel efficient protocols for treatment of otherwise resistant colorectal tumors bearing BRAFV600E, by exploiting the autophagic properties induced by BRAF oncogene.

  5. BRAF associated autophagy exploitation: BRAF and autophagy inhibitors synergise to efficiently overcome resistance of BRAF mutant colorectal cancer cells

    Science.gov (United States)

    Goulielmaki, Maria; Koustas, Evangelos; Moysidou, Eirini; Vlassi, Margarita; Sasazuki, Takehiko; Shirasawa, Senji; Zografos, George; Oikonomou, Eftychia; Pintzas, Alexander

    2016-01-01

    Autophagy is the basic catabolic mechanism that involves cell degradation of unnecessary or dysfunctional cellular components. Autophagy has a controversial role in cancer – both in protecting against tumor progression by isolation of damaged organelles, or by potentially contributing to cancer growth. The impact of autophagy in RAS induced transformation still remains to be further analyzed based on the differential effect of RAS isoforms and tumor cell context. In the present study, the effect of KRAS/BRAF/PIK3CA oncogenic pathways on the autophagic cell properties and on main components of the autophagic machinery like p62 (SQSTM1), Beclin-1 (BECN1) and MAP1LC3 (LC3) in colon cancer cells was investigated. This study provides evidence that BRAF oncogene induces the expression of key autophagic markers, like LC3 and BECN1 in colorectal tumor cells. Herein, PI3K/AKT/MTOR inhibitors induce autophagic tumor properties, whereas RAF/MEK/ERK signalling inhibitors reduce expression of autophagic markers. Based on the ineffectiveness of BRAFV600E inhibitors in BRAFV600E bearing colorectal tumors, the BRAF related autophagic properties in colorectal cancer cells are further exploited, by novel combinatorial anti-cancer protocols. Strong evidence is provided here that pre-treatment of autophagy inhibitor 3-MA followed by its combination with BRAFV600E targeting drug PLX4720 can synergistically sensitize resistant colorectal tumors. Notably, colorectal cancer cells are very sensitive to mono-treatments of another autophagy inhibitor, Bafilomycin A1. The findings of this study are expected to provide novel efficient protocols for treatment of otherwise resistant colorectal tumors bearing BRAFV600E, by exploiting the autophagic properties induced by BRAF oncogene. PMID:26802026

  6. 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.

  7. 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.

  8. 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

  9. 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.-...

  10. 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

  11. 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.

  12. 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.

  13. Processed foods: contributions to nutrition.

    Science.gov (United States)

    Weaver, Connie M; Dwyer, Johanna; Fulgoni, Victor L; King, Janet C; Leveille, Gilbert A; MacDonald, Ruth S; Ordovas, Jose; Schnakenberg, David

    2014-06-01

    Both fresh and processed foods make up vital parts of the food supply. Processed food contributes to both food security (ensuring that sufficient food is available) and nutrition security (ensuring that food quality meets human nutrient needs). This ASN scientific statement focuses on one aspect of processed foods: their nutritional impacts. Specifically, this scientific statement 1) provides an introduction to how processed foods contribute to the health of populations, 2) analyzes the contribution of processed foods to "nutrients to encourage" and "constituents to limit" in the American diet as recommended by the Dietary Guidelines for Americans, 3) identifies the responsibilities of various stakeholders in improving the American diet, and 4) reviews emerging technologies and the research needed for a better understanding of the role of processed foods in a healthy diet. Analyses of the NHANES 2003-2008 show that processed foods provide both nutrients to encourage and constituents to limit as specified in the 2010 Dietary Guidelines for Americans. Of the nutrients to encourage, processed foods contributed 55% of dietary fiber, 48% of calcium, 43% of potassium, 34% of vitamin D, 64% of iron, 65% of folate, and 46% of vitamin B-12. Of the constituents to limit, processed foods contributed 57% of energy, 52% of saturated fat, 75% of added sugars, and 57% of sodium. Diets are more likely to meet food guidance recommendations if nutrient-dense foods, either processed or not, are selected. Nutrition and food science professionals, the food industry, and other stakeholders can help to improve the diets of Americans by providing a nutritious food supply that is safe, enjoyable, affordable, and sustainable by communicating effectively and accurately with each other and by working together to improve the overall knowledge of consumers.

  14. 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

  15. 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.

  16. Additive manufacturing of optical components

    Science.gov (United States)

    Heinrich, Andreas; Rank, Manuel; Maillard, Philippe; Suckow, Anne; Bauckhage, Yannick; Rößler, Patrick; Lang, Johannes; Shariff, Fatin; Pekrul, Sven

    2016-08-01

    The development of additive manufacturing methods has enlarged rapidly in recent years. Thereby, the work mainly focuses on the realization of mechanical components, but the additive manufacturing technology offers a high potential in the field of optics as well. Owing to new design possibilities, completely new solutions are possible. This article briefly reviews and compares the most important additive manufacturing methods for polymer optics. Additionally, it points out the characteristics of additive manufactured polymer optics. Thereby, surface quality is of crucial importance. In order to improve it, appropriate post-processing steps are necessary (e.g. robot polishing or coating), which will be discussed. An essential part of this paper deals with various additive manufactured optical components and their use, especially in optical systems for shape metrology (e.g. borehole sensor, tilt sensor, freeform surface sensor, fisheye lens). The examples should demonstrate the potentials and limitations of optical components produced by additive manufacturing.

  17. Two component systems: physiological effect of a third component.

    Directory of Open Access Journals (Sweden)

    Baldiri Salvado

    Full Text Available Signal transduction systems mediate the response and adaptation of organisms to environmental changes. In prokaryotes, this signal transduction is often done through Two Component Systems (TCS. These TCS are phosphotransfer protein cascades, and in their prototypical form they are composed by a kinase that senses the environmental signals (SK and by a response regulator (RR that regulates the cellular response. This basic motif can be modified by the addition of a third protein that interacts either with the SK or the RR in a way that could change the dynamic response of the TCS module. In this work we aim at understanding the effect of such an additional protein (which we call "third component" on the functional properties of a prototypical TCS. To do so we build mathematical models of TCS with alternative designs for their interaction with that third component. These mathematical models are analyzed in order to identify the differences in dynamic behavior inherent to each design, with respect to functionally relevant properties such as sensitivity to changes in either the parameter values or the molecular concentrations, temporal responsiveness, possibility of multiple steady states, or stochastic fluctuations in the system. The differences are then correlated to the physiological requirements that impinge on the functioning of the TCS. This analysis sheds light on both, the dynamic behavior of synthetically designed TCS, and the conditions under which natural selection might favor each of the designs. We find that a third component that modulates SK activity increases the parameter space where a bistable response of the TCS module to signals is possible, if SK is monofunctional, but decreases it when the SK is bifunctional. The presence of a third component that modulates RR activity decreases the parameter space where a bistable response of the TCS module to signals is possible.

  18. Space storable propulsion components development

    Science.gov (United States)

    Hagler, R., Jr.

    1982-01-01

    The current development status of components to control the flow of propellants (liquid fluorine and hydrazine) in a demonstration space storable propulsion system is discussed. The criteria which determined the designs for the pressure regulator, explosive-actuated valves, propellant shutoff valve, latching solenoid-actuated valve and propellant filter are presented. The test philosophy that was followed during component development is outlined. The results from compatibility demonstrations for reusable connectors, flange seals, and CRES/Ti-6Al4V transition tubes and the evaluations of processes for welding (hand-held TIG, automated TIG, and EB), cleaning for fluorine service, and decontamination after fluorine exposure are described.

  19. 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

  20. 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.

  1. 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.

  2. Contribution of Oceanic Circulation to the Poleward Heat Flux

    Institute of Scientific and Technical Information of China (English)

    HUANG Ruixin

    2005-01-01

    Oceanic contribution to the poleward heat flux in the climate system includes two components: the sensible heat flux and the latent heat flux. Although the latent heat flux has been classified as atmospheric heat flux exclusively, it is argued that oceanic control over this component of poleward heat flux should play a critically important role. The so-called swamp ocean model practice is analyzed in detail, and the critical role of oceanic circulation in the establishment of the meridional moisture transport is emphasized.

  3. 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...

  4. Carcinogenicity of hair dye components.

    Science.gov (United States)

    Van Duuren, B L

    1980-03-01

    The available animal carcinogenicity data on hair dye components was reviewed. From this review it became clear that certain hair dye components, some of which are still in hair dye formulations now on the market, are animal carcinogens. The compounds of concern that are still in use are: 3-amino-4-methoxyaniline, 2-nitro-4-aminoaniline and 3-nitro-4-hydroxyaniline. Certain azo dyes formerly used, and related compounds still in use, contain the benzidine moiety. Two of these compounds, Direct Blue 6 and Direct Black 38, have been shown to be metabolized in animals to the human carcinogen benzidine. Furthermore, skin absorption studies carried out with radiolabeled hair dye components applied to animal or human skin have conclusively shown that these compounds are systemically absorbed and excreted. Known cocarcinogens such as catechol and pyrogallol, which enhance benzo(a)pyrene carcinogenicity on mouse skin, are used as hair dye components. It is not known whether such compounds will enhance the carcinogenicity of substituted aniline hair dye chemicals. The available epidemiologic data are not sufficient to link hair dye use with an increased incidence in human cancer.

  5. 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.

  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. 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)

  8. 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...

  9. 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...

  10. 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...

  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. Changes in accounting for contributions.

    Science.gov (United States)

    Pelfrey, S

    1992-03-01

    A proposed accounting change in the timing of income recognition for restricted contributions and pledges can greatly impact a hospital's excess of revenue over expenses (net income). The author addresses steps that administrators can take to lessen its impact. With this knowledge, nurse administrators and other hospital executives can plan alternatives to reduce the income recognition and prepare themselves to answer questions posed by patients and members of the community regarding increased hospital profits.

  13. 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...

  14. 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.

  15. 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...

  16. Possible solar noble-gas component in Hawaiian basalts

    Energy Technology Data Exchange (ETDEWEB)

    Honda, Masahiko; McDougall, I.; Patterson, D.B.; Doulgeris, A. (Australian National Univ., Canberra (Australia). Research School of Earth Sciences); Clague, D.A. (Geological Survey, Menlo Park, CA (USA))

    1991-01-10

    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 {sup 20}Ne and {sup 21}Ne relative to {sup 22}Ne, 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).

  17. 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.

  18. 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 uncertainty for a single measurement of cutting force is presented, and expressions for the expected uncertainty vs. cutting parameters are proposed. This approach gives the possibility of evaluating cutting force uncertainty components in turning, for a defined range of cutting parameters, based on few...

  19. 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

  20. 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...

  1. 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

  2. Components of Attention in Synesthesia

    DEFF Research Database (Denmark)

    Sørensen, Thomas Alrik; Nordfang, Maria; Pedersen, Michael Nygaard;

    2013-01-01

    One of the most common forms of synesthesia is between colors and graphemes (Colizoli, Murre, & Rouw, 2012). Numerous studies have investigated different aspects of attention and synesthesia, e.g. effects of Stroop-like interference by colors that are incongruent with the synesthetic experience....... Here we attempt to isolate how specific components of attention are affected by grapheme-color synesthesia. Eight carefully screened healthy participants with synesthesia reported the letters in briefly presented, post-masked arrays of letters and digits. On half the trials, the letters and digits were...... presented in colors congruent with the synesthetic experience. On the other half of the trials, the letters and digits were presented in colors that were incongruent with the synesthetic experience. Components of attention were estimated separately for congruent and incongruent trials by fitting the data...

  3. 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...

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. Quasar redshifts: the intrinsic component

    Science.gov (United States)

    Hansen, Peter M.

    2016-09-01

    The large observed redshift of quasars has suggested large cosmological distances and a corresponding enormous energy output to explain the brightness or luminosity as seen at earth. Alternative or complementary sources of redshift have not been identified by the astronomical community. This study examines one possible source of additional redshift: an intrinsic component based on the plasma characteristics of high temperature and high electron density which are believed to be present.

  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. 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...

  11. 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...

  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. 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

  14. Heritage contribution in sustainable city

    Science.gov (United States)

    Rostami, R.; Khoshnava, S. M.; Lamit, H.

    2014-02-01

    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.

  15. 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.

  16. 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.

  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

    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

  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

    2015-01-01

    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

  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

    2015-08-01

    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

  2. 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.

  3. 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...

  4. 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.)

  5. 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...

  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. Component Control System for a Vehicle

    Science.gov (United States)

    Fraser-Chanpong, Nathan (Inventor); Spain, Ivan (Inventor); Dawson, Andrew D. (Inventor); Bluethmann, William J. (Inventor); Lee, Chunhao J. (Inventor); Vitale, Robert L. (Inventor); Guo, Raymond (Inventor); Waligora, Thomas M. (Inventor); Akinyode, Akinjide Akinniyi (Inventor); Reed, Ryan M. (Inventor)

    2016-01-01

    A vehicle includes a chassis, a modular component, and a central operating system. The modular component is supported by the chassis. The central operating system includes a component control system, a primary master controller, and a secondary master controller. The component control system is configured for controlling the modular component. The primary and secondary master controllers are in operative communication with the component control system. The primary and secondary master controllers are configured to simultaneously transmit commands to the component control system. The component control system is configured to accept commands from the secondary master controller only when a fault occurs in the primary master controller.

  8. Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death

    Science.gov (United States)

    Huo, Ruichao; Wang, Lili; Liu, Peijuan; Zhao, Yong; Zhang, Caiqin; Bai, Bing; Liu, Xueying; Shi, Changhong; Wei, Sanhua; Zhang, Hai

    2016-01-01

    Cabazitaxel has been used to treat castration-resistant prostate cancer since its approval by the US Food and Drug Administration in 2010. However, whether cabazitaxel may inhibit the proliferation of other tissue-derived cancer cells, and its underlying mechanism, remains unknown. In the present study, the A549 lung adenocarcinoma cancer cell line was exposed to cabazitaxel, in order to investigate its cytotoxic effect and determine the underlying mechanism. The results demonstrated that cabazitaxel was able to induce autophagy in A549 cells, as evidenced by the formation of autophagosomes, upregulated LC3-II expression and increased LC3 puncta. Cabazitaxel-induced autophagy had a cytotoxic effect on A549 cells, as evidenced by the induction of cell death and cell cycle arrest at G2/M phase, which was independent of the apoptotic pathway. Furthermore, transfection with Beclin1 small interfering RNA and treatment with the autophagy inhibitor 3-methyladenine protected cells from cabazitaxel-induced cell death, thus confirming that cabazitaxel-induced autophagy contributed to A549 cell death. In addition, cabazitaxel targeted the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway to induce autophagy, as indicated by reduced phosphorylation of Akt and mTOR. In conclusion, the present study demonstrated that cabazitaxel exerts a cytotoxic effect on A549 cells by acting on the PI3K/Akt/mTOR pathway to promote autophagic cell death. This result supports the potential use of cabazitaxel as a chemotherapeutic agent for the treatment of lung cancer. PMID:27572899

  9. Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death.

    Science.gov (United States)

    Huo, Ruichao; Wang, Lili; Liu, Peijuan; Zhao, Yong; Zhang, Caiqin; Bai, Bing; Liu, Xueying; Shi, Changhong; Wei, Sanhua; Zhang, Hai

    2016-10-01

    Cabazitaxel has been used to treat castration-resistant prostate cancer since its approval by the US Food and Drug Administration in 2010. However, whether cabazitaxel may inhibit the proliferation of other tissue‑derived cancer cells, and its underlying mechanism, remains unknown. In the present study, the A549 lung adenocarcinoma cancer cell line was exposed to cabazitaxel, in order to investigate its cytotoxic effect and determine the underlying mechanism. The results demonstrated that cabazitaxel was able to induce autophagy in A549 cells, as evidenced by the formation of autophagosomes, upregulated LC3‑II expression and increased LC3 puncta. Cabazitaxel‑induced autophagy had a cytotoxic effect on A549 cells, as evidenced by the induction of cell death and cell cycle arrest at G2/M phase, which was independent of the apoptotic pathway. Furthermore, transfection with Beclin1 small interfering RNA and treatment with the autophagy inhibitor 3‑methyladenine protected cells from cabazitaxel‑induced cell death, thus confirming that cabazitaxel‑induced autophagy contributed to A549 cell death. In addition, cabazitaxel targeted the phosphoinositide 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway to induce autophagy, as indicated by reduced phosphorylation of Akt and mTOR. In conclusion, the present study demonstrated that cabazitaxel exerts a cytotoxic effect on A549 cells by acting on the PI3K/Akt/mTOR pathway to promote autophagic cell death. This result supports the potential use of cabazitaxel as a chemotherapeutic agent for the treatment of lung cancer.

  10. 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

  11. 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

  12. Hydrocarbon components in carbonaceous meteorites

    Science.gov (United States)

    Kissin, Y. V.

    2003-05-01

    Currently, the presence of free n-alkanes and isoprenoid alkanes in carbonaceous meteorites is usually explained either by microbial contamination during the period between the meteorite fall and collection or by contamination from the environment of analytical laboratories and museums. The goal of this research was to repeat analysis of hydrocarbon components in meteorites and to investigate possible meteorite contamination routes discussed in the literature. Experimental analysis of free organic constituents in five carbonaceous meteorites by infrared spectroscopy (IR) and gas chromatographic (GC) methods confirmed the presence of extractable aliphatic components, n-alkanes in the C 15H 32-C 27H 56 range and isoprenoid alkanes (phytane, pristane, and norpristane), in some of these meteorites. The contents of these compounds vary depending on the source. Insoluble organic components of two meteorites (meteorite kerogens) were isolated, and their composition was analyzed by IR and cracking/GC methods. Comparison with the data on several terrestrial contamination sources proposed in the literature shows that the presence of free saturated hydrocarbons in meteorites and the composition of the meteorite kerogen could not be explained either by microbial contamination or by contamination from the laboratory environment. The types of the hydrocarbons in meteorites resemble those typical of ancient terrestrial deposits of organic-rich sediments, except for the absence of lighter hydrocarbons, which apparently slowly evaporated in space, and multi-ring naphthenic compounds of the biologic origin, steranes, terpanes, etc. The prevailing current explanation for the presence of free linear saturated hydrocarbons in carbonaceous meteorites, apart from contamination, is the abiotic route from hydrogen and carbon monoxide. However, the data on the structure of meteorite kerogens require a search for different routes that initially produce complex polymeric structures containing

  13. 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

  14. 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...

  15. Hadron Contribution to Vacuum Polarisation

    Science.gov (United States)

    Davier, M.; Hoecker, A.; Malaescu, B.; Zhang, Z.

    2016-10-01

    Precision tests of the Standard Theory require theoretical predictions taking into account higher-order quantum corrections. Among these vacuum polarisation plays a predominant role. Vacuum polarisation originates from creation and annihilation of virtual particle-antiparticle states. Leptonic vacuum polarisation can be computed from quantum electrodynamics. Hadronic vacuum polarisation cannot because of the non-perturbative nature of QCD at low energy. The problem is remedied by establishing dispersion relations involving experimental data on the cross section for e+ e- annihilation into hadrons. This chapter sets the theoretical and experimental scene and reviews the progress achieved in the last decades thanks to more precise and complete data sets. Among the various applications of hadronic vacuum polarisation calculations, two are emphasised: the contribution to the anomalous magnetic moment of the muon, and the running of the fine structure constant α to the Z mass scale. They are fundamental ingredients to high precision tests of the Standard Theory.

  16. Hadron Contribution to Vacuum Polarisation

    CERN Document Server

    Davier, M; Malaescu, B; Zhang, Z

    2016-01-01

    Precision tests of the Standard Theory require theoretical predictions taking into account higher-order quantum corrections. Among these vacuum polarisation plays a predominant role. Vacuum polarisation originates from creation and annihilation of virtual particle–antiparticle states. Leptonic vacuum polarisation can be computed from quantum electrodynamics. Hadronic vacuum polarisation cannot because of the non-perturbative nature of QCD at low energy. The problem is remedied by establishing dispersion relations involving experimental data on the cross section for e+ e− annihilation into hadrons. This chapter sets the theoretical and experimental scene and reviews the progress achieved in the last decades thanks to more precise and complete data sets. Among the various applications of hadronic vacuum polarisation calculations, two are emphasised: the contribution to the anomalous magnetic moment of the muon, and the running of the fine structure constant α to the Z mass scale. They are fundamental ingre...

  17. Components of solar thermal systems

    OpenAIRE

    Mendes, J. Farinha; Carvalho, M. J.; Schossig, Peter

    2013-01-01

    The heat production sub-system is the part of the overall system which provides heat to a thermally driven air-conditioning system. With regards to the solar-driven equipment, the solar collector is the main component of the sub-system. A brief review on the present state-of-the-art with respect to performance characteristics and available certification schemes of solar collectors is given in the following chapter. Besides the solar collector field, the storage unit and the back-up heat sourc...

  18. 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...... 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...

  19. Anthropological Component of Descartes’ Ontology

    Directory of Open Access Journals (Sweden)

    Anatolii M. Malivskyi

    2014-06-01

    Full Text Available The purpose of the article is to outline and comprehend the Descartes’ theory about anthropological component of ontology as the most important part of his philosophy. The accomplishment of this purpose covers the successive solution of the following tasks: 1 review of the research literature concerning the problem of human’s presence and the individual nature of truth; 2 emphasize the ambivalence of the basic intention of his legacy; 3 justify the thesis about constitutivity of human’s presence and comprehend passions as the form of disclosure of ontology’s anthropological component. Methodology. The use of the euristic potential of phenomenology, postpositivism and postmodernism makes it possible to emphasize the multiple-layer and multiple-meaning classical philosophy works, to comprehend the limitation and scarcity of the naïve-enlightening vision of human nature and to look for a new reception of European classics that provides the overcoming of established nihilism and pessimism concerning the interpretation of human nature. Scientific novelty. It is the first time that anthropological component of Descartes’ ontology became an object of particular attention. It previously lacked attention because of following main reasons: 1 traditional underestimating of the fact of Descartes’ legacy incompleteness as an unrealized anthropological project and 2 lack of proper attention to the individual nature of truth. The premise for its constructive overcoming is the attention to ambivalence of the basic intention and the significance of ethics in the philosopher’s legacy. His texts and research literature allow confirming the constitutive nature of human’s presence and passions as the key form of disclosure of the ontology anthropological component. Conclusions. The established tradition of interpretation the Descartes’ philosophizing nature as the filiation process of impersonal knowledge loses its cogency these days. The

  20. Astrophysical components from Planck maps

    CERN Document Server

    Burigana, Carlo; Paoletti, Daniela; Mandolesi, Nazzareno; Natoli, Paolo

    2016-01-01

    The Planck Collaboration has recently released maps of the microwave sky in both temperature and polarization. Diffuse astrophysical components (including Galactic emissions, cosmic far infrared (IR) background, y-maps of the thermal Sunyaev-Zeldovich (SZ) effect) and catalogs of many thousands of Galactic and extragalactic radio and far-IR sources, and galaxy clusters detected through the SZ effect are the main astrophysical products of the mission. A concise overview of these results and of astrophysical studies based on Planck data is presented.

  1. 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...

  2. Induced radioactivity in LDEF components

    Science.gov (United States)

    Harmon, B. A.; Fishman, G. J.; Parnell, T. A.; Laird, C. E.

    1992-01-01

    A systematic study of the induced radioactivity of the Long Duration Exposure Facility (LDEF) is being carried out in order to gather information about the low earth orbit radiation environment and its effects on materials. The large mass of the LDEF spacecraft, its stabilized configuration, and long mission duration have presented an opportunity to determine space radiation-induced radioactivities with a precision not possible before. Data presented include preliminary activities for steel and aluminum structural samples, and activation subexperiment foils. Effects seen in the data show a clear indication of the trapped proton anisotropy in the South Atlantic Anomaly and suggest contributions from different sources of external radiation fluxes.

  3. The search for putative unifying genetic factors for components of the metabolic syndrome

    DEFF Research Database (Denmark)

    Sjögren, M; Lyssenko, V; Jonsson, Anna Elisabet;

    2008-01-01

    The metabolic syndrome is a cluster of factors contributing to increased risk of cardiovascular disease and type 2 diabetes but unifying mechanisms have not been identified. Our aim was to study whether common variations in 17 genes previously associated with type 2 diabetes or components...... of the metabolic syndrome and variants in nine genes with inconsistent association with at least two components of the metabolic syndrome would also predict future development of components of the metabolic syndrome, individually or in combination....

  4. A software component platform for the coordination of multiple adaptations in dynamic environments

    OpenAIRE

    Chefrour, Djalel

    2005-01-01

    The aim of this thesis is to contribute to the development of methods and tools forthe adaptation of software components and for their coordination in dynamic environments.We propose to capture the mechanisms of adaptability in a generic component modelbased on reflexivity and object-oriented techniques. The components use an underlyingservice for monitoring the environment and a middleware for coordinating multipleadaptations. Coordination includes the management of dependencies between inte...

  5. Cosmic Ray Excesses from Multi-component Dark Matter Decays

    CERN Document Server

    Geng, Chao-Qiang; Tsai, Lu-Hsing

    2014-01-01

    We use multi-component decaying dark matter (DM) scenario to explain the possible cosmic ray excesses in the positron fraction recently confirmed by AMS-02 and the total $e^+ +e^-$ flux observed by Fermi-LAT. In the two-component DM models, we find an interesting variation of the flavor structure along with the cutoff of the heavy DM. For the three-component DM case, we focus on a particular parameter range in which the best fits prefer to open only 2 DM decay channels with a third DM contributing nothing to the electron and positron spectra. We show that all models give the reasonable fits to both the AMS-02 positron fraction and the Fermi-LAT total $e^++e^-$ flux, which are also consistent with the measured diffuse $\\gamma$-ray flux by Fermi-LAT.

  6. A probabilistic model for component-based shape synthesis

    KAUST Repository

    Kalogerakis, Evangelos

    2012-07-01

    We present an approach to synthesizing shapes from complex domains, by identifying new plausible combinations of components from existing shapes. Our primary contribution is a new generative model of component-based shape structure. The model represents probabilistic relationships between properties of shape components, and relates them to learned underlying causes of structural variability within the domain. These causes are treated as latent variables, leading to a compact representation that can be effectively learned without supervision from a set of compatibly segmented shapes. We evaluate the model on a number of shape datasets with complex structural variability and demonstrate its application to amplification of shape databases and to interactive shape synthesis. © 2012 ACM 0730-0301/2012/08-ART55.

  7. Comparison of conforming and nonconforming retrieved glenoid components.

    Science.gov (United States)

    Nho, Shane J; Ala, Owen L; Dodson, Christopher C; Figgie, Mark P; Wright, Timothy M; Craig, Edward V; Warren, Russell F

    2008-01-01

    The purpose of this study was to compare differences in wear performance of conforming and nonconforming glenoid designs, using clinical, radiographic, and retrieved polyethylene glenoid component outcome Sixty-three glenoids met the study criteria, and each glenoid was assigned to the conforming group (if the radii of curvature of the humeral and glenoid components were identical) or the nonconforming group (if a mismatch existed between the radii of curvature). The mean length of implantation was 5.6 +/- 5.5 years in the conforming group and 3.1 +/- 3.1 years for the nonconforming group (P conforming group and 2.4 +/- 1.2 in the nonconforming one (P conforming group had greater abrasion and delamination scores (P conformity contributes to differences observed from retrieved polyethylene glenoid components, which are consistent with differences in performance that may influence loosening.

  8. An Analysis of the Systematic Components of Calorimetry Uncertainty.

    Energy Technology Data Exchange (ETDEWEB)

    Smith, M. K. (Morag K.); Bracken, D. S. (David S.); Rudy, C. R. (Clifford R.); Santi, P. A. (Peter A.)

    2005-01-01

    There is a long-standing qualitative observation that the components of the measurement uncertainty in a calorimeter measurement of special nuclear materials are dominated by the random components with the systematic components treated as negligible. The small to zero biases seen in calorimeter measurements are attributed to the very small contribution of systematic effects. An effort to quantify the systematic contributors has been made to verify the correctness of the qualitative understanding. Possible systematic contributors to the uncertainty have been identified, the magnitude of the individual variations assessed, and the size of the effect of each individual variation on the final uncertainty in the measured item power output evaluated. This paper discusses and summarizes the results of each of these steps.

  9. An Analysis of the Systematic Components of Calorimetry Uncertainty

    International Nuclear Information System (INIS)

    There is a long-standing qualitative observation that the components of the measurement uncertainty in a calorimeter measurement of special nuclear materials are dominated by the random components with the systematic components treated as negligible. The small to zero biases seen in calorimeter measurements are attributed to the very small contribution of systematic effects. An effort to quantify the systematic contributors has been made to verify the correctness of the qualitative understanding. Possible systematic contributors to the uncertainty have been identified, the magnitude of the individual variations assessed, and the size of the effect of each individual variation on the final uncertainty in the measured item power output evaluated. This paper discusses and summarizes the results of each of these steps.

  10. RAPD Analysis for Determination of Components in Herbal Medicine

    Directory of Open Access Journals (Sweden)

    V. M. Shinde

    2007-01-01

    Full Text Available In this study, the RAPD (Random Amplified Polymorphic DNA technique was employed for determination of the components in an Ayurvedic herbal prescription, Rasayana Churna. One-hundred-and-twenty decamer oligonucleotide primers were screened in the RAPD analysis to identify three Ayurvedic medicines, dried stem of Tinospora cordifolia, dried fruit of Emblica officinalis and dried fruit of Tribulus terestris, the Ayurvedic prescription. Primer OPC-6 simultaneously generated three distinct amplicons, each specific to one component. The marker with 600 bp is specific to Tinospora cordifolia; the marker 500 bp is specific to Emblica officinalis and the remaining marker >1000 bp was present in Tribulus terestris. Presence of three herbal medicines was determined when RAPD reaction with OPC-6 was performed. The technique was proved to contribute to the identification of components in Ayurvedic herbal preparation and thus helping to serve as a complementary tool for quality control.

  11. Two-component picture of e+e- inclusive processes

    International Nuclear Information System (INIS)

    From the hypothesis that the characteristics of hadronic production in e+e- are those seen in transverse distributions of hadron-hadron collisions we are lead to consider the inclusive distributions in e+e- annihilation as composed of two contributions, a cluster component which contains the e+e- resonances, and a parton component. The decay of the cluster is described by the same production radii as those observed in hadron-hadron collisions. The parton component obeys asymptotically Bjorken scaling, and the approach to scaling is set by a mass of 1.2 GeV. Within this picture we give a simple explanation of the energy dependence of the average charged energy and the multiplicity. (orig.)

  12. Components of Adenovirus Genome Packaging

    Science.gov (United States)

    Ahi, Yadvinder S.; Mittal, Suresh K.

    2016-01-01

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

  13. Interpretable functional principal component analysis.

    Science.gov (United States)

    Lin, Zhenhua; Wang, Liangliang; Cao, Jiguo

    2016-09-01

    Functional principal component analysis (FPCA) is a popular approach to explore major sources of variation in a sample of random curves. These major sources of variation are represented by functional principal components (FPCs). The intervals where the values of FPCs are significant are interpreted as where sample curves have major variations. However, these intervals are often hard for naïve users to identify, because of the vague definition of "significant values". In this article, we develop a novel penalty-based method to derive FPCs that are only nonzero precisely in the intervals where the values of FPCs are significant, whence the derived FPCs possess better interpretability than the FPCs derived from existing methods. To compute the proposed FPCs, we devise an efficient algorithm based on projection deflation techniques. We show that the proposed interpretable FPCs are strongly consistent and asymptotically normal under mild conditions. Simulation studies confirm that with a competitive performance in explaining variations of sample curves, the proposed FPCs are more interpretable than the traditional counterparts. This advantage is demonstrated by analyzing two real datasets, namely, electroencephalography data and Canadian weather data.

  14. Bioactive components in fish venoms.

    Science.gov (United States)

    Ziegman, Rebekah; Alewood, Paul

    2015-05-01

    Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

  15. The components of paraphrase evaluations.

    Science.gov (United States)

    McCarthy, Philip M; Guess, Rebekah H; McNamara, Danielle S

    2009-08-01

    Two sentences are paraphrases if their meanings are equivalent but their words and syntax are different. Paraphrasing can be used to aid comprehension, stimulate prior knowledge, and assist in writing-skills development. As such, paraphrasing is a feature of fields as diverse as discourse psychology, composition, and computer science. Although automated paraphrase assessment is both commonplace and useful, research has centered solely on artificial, edited paraphrases and has used only binary dimensions (i.e., is or is not a paraphrase). In this study, we use an extensive database (N=1,998) of natural paraphrases generated by high school students that have been assessed along 10 dimensions (e.g., semantic completeness, lexical similarity, syntactical similarity). This study investigates the components of paraphrase quality emerging from these dimensions and examines whether computational approaches can simulate those human evaluations. The results suggest that semantic and syntactic evaluations are the primary components of paraphrase quality, and that computationally light systems such as latent semantic analysis (semantics) and minimal edit distances (syntax) present promising approaches to simulating human evaluations of paraphrases.

  16. Preventive maintenance for mechanical components

    International Nuclear Information System (INIS)

    In nuclear power stations as in other industrial plants, there are active and passive components whose failure is permissible only in exceptional cases both from a safety and/or economic view. Failure in this context means loss of integrity of a supporting wall, insufficient function and/or unstoppable leakage. A systematic defect must be excluded as cause of failure; the consequences of failure must be manageable. During operation, measures must be taken to maintain the required quality and detect consequences of damage mechanisms at an early stage, prior to failure. This is achieved by preventive maintenance in accordance with the latest state of knowledge. To exclude systematic errors, the quality standard of components must be re-checked every once in a while as the effects of damage mechanisms and the state of knowledge are time-dependent parameters. This requires an integrated concept, e.g. for life and ageing management, in whose context a comprehensive knowledge base is developed and regularly updated. (orig.)

  17. Determinations of H(10) and its dose components onboard aircraft.

    Science.gov (United States)

    Lindborg, L; Beck, P; Bottolier-Depois, J F; Latocha, M; Lillhök, J; Rollet, S; Roos, H; Roth, J; Schraube, H; Spurny, F; Stehno, G; Trompier, F; Wissmann, F

    2007-01-01

    Aircrew is in general receiving a higher average annual dose than other occupationally exposed personnel, and about half of the effective dose is deposited by high-LET neutron secondaries. A recent investigation of the cancer incidence following the atomic bombs at Hiroshima and Nagasaki has put forward the possibility that the relative biological efficiency for neutrons could be underestimated. If so, the effective dose to aircrew from this component would increase and the estimation of this component will become even more important. Different ambient dose equivalent measurement techniques and calculation methods have recently been compared on a dedicated flight. The experimental results are compared with calculations made with the codes EPCARD 3.2 and an updated version of FLUKA and different galactic proton spectra. The aircraft circulated within the target areas at two constant altitudes with a flight route variation of only about 1 degrees in longitude and latitude to reduce the influence from variations in atmospheric and geomagnetic shielding. The instrumentation consisted of tissue-equivalent proportional counters (TEPC) and a silicon diode spectrometer. Measurements were performed for 2 h to reduce the statistical uncertainties in the results. The TEPCs were evaluated either according to single-event analysis techniques or the variance-covariance method. Besides the total ambient dose equivalent, the instruments can be evaluated to reveal the low- and high-LET components. The EPCARD and FLUKA simulations can determine the contribution from each type of particle directly. The ratio between the calculated and the measured average value of the ambient dose equivalent rate was 1.00 +/- 0.08 with all instruments included for EPCARD and 0.97 +/- 0.07 when FLUKA was used. The measured high-LET component and the calculated neutron component are not quite identical, but should be similar. The agreement was always within 20%. The high-LET component contributed with

  18. Student Scientific Conference, 2010. Proceedings of reviewed contributions

    International Nuclear Information System (INIS)

    The conference included the following sections: (i) Biology (154 contributions); (ii) Chemistry (39 contributions); (iii) Geography; (41 contributions); (iv) Geology (22 contributions); (v) Environment (45 contributions); (vi) Didactics (6 contributions). Contributions relevant of INIS interest has been inputted to INIS.

  19. Student Scientific Conference, 2009. Proceedings of reviewed contributions

    International Nuclear Information System (INIS)

    The conference included the following sections: (i) Biology (145 contributions); (ii) Chemistry (42 contributions); (iii) Geology (42 contributions); (iv) Environment (40 contributions); (v) Geography (28 contributions); (vi) Didactics (13 contributions). Contributions relevant of INIS interest has been inputted to INIS.

  20. Uruguay geology contributions no. 2

    International Nuclear Information System (INIS)

    This Group is characterized by a volcano-sedimentary sequence of low grade into which are found the main Pb, Zn, Cu, Mo occurrences and vast limestones deposits and a laterally associated sequence of medium metamorphism. From a structural point of view it is characterized by a poly phasic evolution. At low metamorphic sequence is distinguished a volcanic-sedimentary series (s.s.) and a sedimentogenous series. The synchronism between both series is showed by transition by lateral facies changes. There is a pelitic carbonate zone associated to a basic calc o-alkaline and tholeitic volcanism and the another zone represented by a carbonaceous platform subjected lo de tri tic contribution of varied nature. The Iithologic succession permits establishing at the volcano-sedimentary sequence, five levels from base to top: -a phyllitic and meta pelitic level (500 meters thick), with basic volcanic rocks intercalated, -a level of limestones which evolves to the top by detritic contributions to a flisch alternation (300 m. thick) with basic volcanic rocks intercalated, -a level of rit mic alternation of rnetapelites, melasandstones, limes tones and phyllites (200 m. thick), -a basic volcanic unit, with intercalation of acid vulcanite s, at the lop are intercalated volcanoclastic rocks as tuffs and breccia s, 1000 meters thick, -a n el sedimentary unit integrated by limestones and phyllites wich evolve to the top of the series lo levels of dolomites. coarse-grained phyllites and jasper, 300 m. thick. Laterally this level passes lo a set integrated by quartzites, metaarcoses, limestones, acid tuffs and rarely rhyolites. The sedimentogenous series has the following base to top sequence: -150 m. of quartzites and meta sandstones wich lay unconformbly over a qranitic-gneissic set, -100 m. 01 phyllites, coarse-grained phyllites and metaarcoses, -ritmic alternance of calcareous, phyllites, coarse-grained phyllites, 800 m. thick (flisch). The megastructures were formed al the second

  1. Stochastic Modeling Of Wind Turbine Drivetrain Components

    DEFF Research Database (Denmark)

    Rafsanjani, Hesam Mirzaei; Sørensen, John Dalsgaard

    2014-01-01

    reliable components are needed for wind turbine. In this paper focus is on reliability of critical components in drivetrain such as bearings and shafts. High failure rates of these components imply a need for more reliable components. To estimate the reliability of these components, stochastic models...... are needed for initial defects and damage accumulation. In this paper, stochastic models are formulated considering some of the failure modes observed in these components. The models are based on theoretical considerations, manufacturing uncertainties, size effects of different scales. It is illustrated how...... the stochastic models can be used to obtain estimates of failure rates for wind turbine components....

  2. Pulmonary vasculature in COPD: The silent component.

    Science.gov (United States)

    Blanco, Isabel; Piccari, Lucilla; Barberà, Joan Albert

    2016-08-01

    Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction that results from an inflammatory process affecting the airways and lung parenchyma. Despite major abnormalities taking place in bronchial and alveolar structures, changes in pulmonary vessels also represent an important component of the disease. Alterations in vessel structure are highly prevalent and abnormalities in their function impair gas exchange and may result in pulmonary hypertension (PH), an important complication of the disease associated with reduced survival and worse clinical course. The prevalence of PH is high in COPD, particularly in advanced stages, although it remains of mild to moderate severity in the majority of cases. Endothelial dysfunction, with imbalance between vasodilator/vasoconstrictive mediators, is a key determinant of changes taking place in pulmonary vasculature in COPD. Cigarette smoke products may perturb endothelial cells and play a critical role in initiating vascular changes. The concurrence of inflammation, hypoxia and emphysema further contributes to vascular damage and to the development of PH. The use of drugs that target endothelium-dependent signalling pathways, currently employed in pulmonary arterial hypertension, is discouraged in COPD due to the lack of efficacy observed in randomized clinical trials and because there is compelling evidence indicating that these drugs may worsen pulmonary gas exchange. The subgroup of patients with severe PH should be ideally managed in centres with expertise in both PH and chronic lung diseases because alterations of pulmonary vasculature might resemble those observed in pulmonary arterial hypertension. Because this condition entails poor prognosis, it warrants specialist treatment. PMID:27028849

  3. Aspects for Run-time Component Integration

    DEFF Research Database (Denmark)

    Truyen, Eddy; Jørgensen, Bo Nørregaard; Joosen, Wouter;

    2000-01-01

    Component framework technology has become the cornerstone of building a family of systems and applications. A component framework defines a generic architecture into which specialized components can be plugged. As such, the component framework leverages the glue that connects the different insert...... dynamically integrate into the architecture of middleware systems new services that support non-functional aspects such as security, transactions, real-time.......Component framework technology has become the cornerstone of building a family of systems and applications. A component framework defines a generic architecture into which specialized components can be plugged. As such, the component framework leverages the glue that connects the different inserted...... components together. We have examined a middle ground between aspect-oriented programming and computational reflection that improves the dynamics of this gluing process such that interaction between components can be refined at run-time. In this paper, we show how we have used this middle ground to...

  4. ECN contributions to ADTT `96

    Energy Technology Data Exchange (ETDEWEB)

    Koning, A.J.

    1996-07-01

    An outline is presented of the status of nuclear data evaluation for accelerator-driven systems. The international effort consists mainly of measuring, compiling and calculating nuclear data for elements and isotopes relevant for transmutation of radioactive waste (ATW), energy amplification and other accelerator-related nuclear applications. We argue that input for global, macroscopic calculation schemes for hybrid nuclear systems basically should consist of three types of nuclear data: (a) High-energy transport codes for energies above about 150 MeV, (b) neutron and proton transport data files for energies below about 150 MeV and (c) neutron and proton transmutation/activation libraries below about 150 MeV. Our specific contribution to the field concerns (b) and (c). The progress of the evaluation of high-energy nuclear data files for the most important materials and the related compilation of nuclear reaction information is reported. The evaluated data are calculated with the computer codes ECIS95, MINGUS and GNASH and are stored in ENDF6-format. We illustrate the library production with a short outline of the employed physical methods. Finally, we briefly discuss the application of the activation/transmutation library ECNAF96. (orig.).

  5. Minisuperspace models as infrared contributions

    Science.gov (United States)

    Bojowald, Martin; Brahma, Suddhasattwa

    2016-06-01

    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 cutoff) 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 be well described by minisuperspace truncations, some related phenomena such as signature change, confirmed and clarified here for modified scalar field theories, require at least a perturbative treatment of inhomogeneity beyond a strict minisuperspace model. The new methods suggest a systematic extension of minisuperspace models by a canonical effective formulation of perturbative inhomogeneity.

  6. Quarkonium Contribution to Meson Molecules

    CERN Document Server

    Cincioglu, E; Ozpineci, A; Yilmazer, A U

    2016-01-01

    Starting from a molecular picture for the X(3872) resonance, this state and its J^{PC}=2++ HQSS partner [X2(4012)] are analyzed within a model which incorporates possible mixings with 2P charmonium states. Since it is reasonable to expect the bare chi_{c1}(2P) to be located above the D\\bar D* threshold, but relatively close to it, the presence of the charmonium state provides an effective attraction that will contribute to bind the X(3872), but it will not appear in the 2++ sector. Indeed in this latter sector, the chi_{c2}(2P) should provide an effective small repulsion, because it is placed well below the D*\\bar D* threshold. We show how the 1++ and 2++ bare charmonium poles are modified due to the D(*)\\bar D(*) loop effects, and the first one is moved to the complex plane. The meson loops produce, besides some shifts in the masses of the charmonia, a finite width for the 1++ dressed charmonium state. On the other hand, the X(3872) and X2(4012) start developing some charmonium content, which is estimated by...

  7. The magnet components database system

    Energy Technology Data Exchange (ETDEWEB)

    Baggett, M.J. (Brookhaven National Lab., Upton, NY (USA)); Leedy, R.; Saltmarsh, C.; Tompkins, J.C. (Superconducting Supercollider Lab., Dallas, TX (USA))

    1990-01-01

    The philosophy, structure, and usage MagCom, the SSC magnet components database, are described. The database has been implemented in Sybase (a powerful relational database management system) on a UNIX-based workstation at the Superconducting Super Collider Laboratory (SSCL); magnet project collaborators can access the database via network connections. The database was designed to contain the specifications and measured values of important properties for major materials, plus configuration information (specifying which individual items were used in each cable, coil, and magnet) and the test results on completed magnets. These data will facilitate the tracking and control of the production process as well as the correlation of magnet performance with the properties of its constituents. 3 refs., 10 figs.

  8. Parallel supercomputing with commodity components

    Energy Technology Data Exchange (ETDEWEB)

    Warren, M.S.; Goda, M.P. [Los Alamos National Lab., NM (United States); Becker, D.J. [Goddard Space Flight Center, Greenbelt, MD (United States)] [and others

    1997-09-01

    We have implemented a parallel computer architecture based entirely upon commodity personal computer components. Using 16 Intel Pentium Pro microprocessors and switched fast ethernet as a communication fabric, we have obtained sustained performance on scientific applications in excess of one Gigaflop. During one production astrophysics treecode simulation, we performed 1.2 x 10{sup 15} floating point operations (1.2 Petaflops) over a three week period, with one phase of that simulation running continuously for two weeks without interruption. We report on a variety of disk, memory and network benchmarks. We also present results from the NAS parallel benchmark suite, which indicate that this architecture is competitive with current commercial architectures. In addition, we describe some software written to support efficient message passing, as well as a Linux device driver interface to the Pentium hardware performance monitoring registers.

  9. Microelectromechanical components in electrical metrology

    CERN Document Server

    Manninen, Antti; Pesonen, Nadine; Oja, Aarne; Seppa, Heikki

    2007-01-01

    Microelectromechanical systems (MEMS) can offer a competitive alternative for conventional technology in electrical precision measurements. This article summarises recent work in development of MEMS solutions for electrical metrology. MEMS-based voltage references, RMS-to-DC converters, high frequency power sensors, and reference oscillators are discussed. The main principle of operation of the components is the balance between electrical forces and mechanical spring forces in micromachined silicon structures. In RMS sensors and RMS-to-DC converters, the quadratic voltage dependence of the force between plates of a moving-plate capacitor is utilised, and the operation of the MEMS voltage reference is based on the pull-in phenomenon of a moving-plate capacitor. Advantages of MEMS devices compared to more conventional solutions include small size, low power consumption, low price in mass production, and stability. The drift caused by electrostatic charging effects has turned out to be a major problem. This prob...

  10. Inelastic behavior of structural components

    Science.gov (United States)

    Hussain, N.; Khozeimeh, K.; Toridis, T. G.

    1980-01-01

    A more accurate procedure was developed for the determination of the inelastic behavior of structural components. The actual stress-strain curve for the mathematical of the structure was utilized to generate the force-deformation relationships for the structural elements, rather than using simplified models such as elastic-plastic, bilinear and trilinear approximations. relationships were generated for beam elements with various types of cross sections. In the generational of these curves, stress or load reversals, kinematic hardening and hysteretic behavior were taken into account. Intersections between loading and unloading branches were determined through an iterative process. Using the inelastic properties obtained, the plastic static response of some simple structural systems composed of beam elements was computed. Results were compared with known solutions, indicating a considerable improvement over response predictions obtained by means of simplified approximations used in previous investigations.

  11. Component codification and identification systems

    International Nuclear Information System (INIS)

    The lecture covers the codification in power stations during the erection phase and commercial operation phase. A diagram gives a survey. There are three basic-codifications for application; 1) Kraftwerk-Kennzeichen-System (KKS) for marking each component in orientated systems, for marking electrical orientated positions in cubicals, switch gears etc. and for marking rooms in buildings; 2) Ordnungssystem (OS) for cost calculation and ordering; 3) Unterlagenarten-Schluessel (UAS) for letters, reports etc. and for documentation. The OS is developed on the principle of cost account number and is therefore close to the organization of each supplier and his special form of design and constrution. KKS has only to mark hardware. Therefore all German owners, consultants, authorities and suppliers develop KKS together and conform to it in DIN 407119. (ORU)

  12. Components, Safety Interfaces, and Compositional Analysis

    OpenAIRE

    Elmqvist, Jonas

    2007-01-01

    Component-based software development has emerged as a promising approach for developing complex software systems by composing smaller independently developed components into larger component assemblies. This approach offers means to increase software reuse, achieve higher flexibility and shorter time-to-market by the use of off-the-shelf components (COTS). However, the use of COTS in safety-critical system is highly unexplored. This thesis addresses the problems appearing in component-based d...

  13. Library thermohydraulic components for training simulators

    International Nuclear Information System (INIS)

    The thermohydraulic components Library was modeled in MatLab/Simulink®. This library owns Pipe type components (pump, control valve and / or heaters), storage tanks (Open, Closed and Equilibrium Water Vapor-Air) and Heat Exchangers (Co-Current, Counter-Current and U-tubes). Each component can be attached to other components through the component library Header, in order to create a more complex thermal-hydraulic system which in turn can interact with other thermal-hydraulic systems. (author)

  14. Neural components of altruistic punishment

    Directory of Open Access Journals (Sweden)

    Emily eDu

    2015-02-01

    Full Text Available Altruistic punishment, which occurs when an individual incurs a cost to punish in response to unfairness or a norm violation, may play a role in perpetuating cooperation. The neural correlates underlying costly punishment have only recently begun to be explored. Here we review the current state of research on the neural basis of altruism from the perspectives of costly punishment, emphasizing the importance of characterizing elementary neural processes underlying a decision to punish. In particular, we emphasize three cognitive processes that contribute to the decision to altruistically punish in most scenarios: inequity aversion, cost-benefit calculation, and social reference frame to distinguish self from others. Overall, we argue for the importance of understanding the neural correlates of altruistic punishment with respect to the core computations necessary to achieve a decision to punish.

  15. Neural components of altruistic punishment

    Science.gov (United States)

    Du, Emily; Chang, Steve W. C.

    2015-01-01

    Altruistic punishment, which occurs when an individual incurs a cost to punish in response to unfairness or a norm violation, may play a role in perpetuating cooperation. The neural correlates underlying costly punishment have only recently begun to be explored. Here we review the current state of research on the neural basis of altruism from the perspectives of costly punishment, emphasizing the importance of characterizing elementary neural processes underlying a decision to punish. In particular, we emphasize three cognitive processes that contribute to the decision to altruistically punish in most scenarios: inequity aversion, cost-benefit calculation, and social reference frame to distinguish self from others. Overall, we argue for the importance of understanding the neural correlates of altruistic punishment with respect to the core computations necessary to achieve a decision to punish. PMID:25709565

  16. Peripheral contributions to visceral hyperalgesia.

    Science.gov (United States)

    Gebhart, G F

    1999-03-01

    and, along with activated mechanically insensitive receptors, increase the afferent barrage into the spinal cord, contributing to the development of visceral hyperalgesia.

  17. Generic component reliability data for research reactor PSA

    International Nuclear Information System (INIS)

    The purpose of this document is to provide reference generic component-reliability information for a variety of research reactor types. As noted in Section 2 and Table IV, component data accumulated over many years is in the database. It is expected that the report should provide representative data which will remain valid for a number of years. The database provides component failure rates on a time and/or demand related basis according to the operational modes of the components. No update of the database is presently planned. As a result of the implementation of data collection systems in the research reactors represented in these studies, updating of data from individual facilities could be made available by the contributing research reactor facilities themselves. As noted in Section 1.1, the report does not include a detailed discussion of information regarding component classification and reliability parameter definitions. The report does provide some insights and discussions regarding the practicalities of the data collection process and some guidelines for database usage. 9 refs, 7 tabs

  18. A Component Based Heuristic Search method with Adaptive Perturbations for Hospital Personnel Scheduling

    CERN Document Server

    Li, Jingpeng; Burke, Edmund

    2008-01-01

    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 adaptive perturbations, 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 mimic a natural evolutionary process on these components 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 a dynamic evaluation function which evaluates how well each component contributes towards the final objective. Two perturbation steps are then applied: the first perturbation eliminates a number of components that are deemed not worthy to stay in the current schedule; the second perturbation may also throw out, with a low level of probability, some worthy components. The eli...

  19. 7 CFR 966.45 - Contributions.

    Science.gov (United States)

    2010-01-01

    ... contributions but these shall only be used for production research, market research and development and..., or any person whose contributions would constitute a conflict of interest. Research and Development...

  20. "Uighur's Contributions to the Ancient Chinese Culture"

    OpenAIRE

    SHIMIN, Geng

    2010-01-01

    In this my paper I speak briefly on the contributions made by the Uighurs and their ancestors to the Chinese civilization. Of course, the Chinese people also made great contributions to the civilization of Uighur people