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Sample records for altered cellular priorities

  1. A celiac cellular phenotype, with altered LPP sub-cellular distribution, is inducible in controls by the toxic gliadin peptide P31-43.

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    Merlin Nanayakkara

    Full Text Available Celiac disease (CD is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides P31-43 and P57-68 induce innate and adaptive T cell-mediated immune responses, respectively. Alterations in the cell shape and actin cytoskeleton are present in celiac enterocytes, and gliadin peptides induce actin rearrangements in both the CD mucosa and cell lines. Cell shape is maintained by the actin cytoskeleton and focal adhesions, sites of membrane attachment to the extracellular matrix. The locus of the human Lipoma Preferred Partner (LPP gene was identified as strongly associated with CD using genome-wide association studies (GWAS. The LPP protein plays an important role in focal adhesion architecture and acts as a transcription factor in the nucleus. In this study, we examined the hypothesis that a constitutive alteration of the cell shape and the cytoskeleton, involving LPP, occurs in a cell compartment far from the main inflammation site in CD fibroblasts from skin explants. We analyzed the cell shape, actin organization, focal adhesion number, focal adhesion proteins, LPP sub-cellular distribution and adhesion to fibronectin of fibroblasts obtained from CD patients on a Gluten-Free Diet (GFD and controls, without and with treatment with A-gliadin peptide P31-43. We observed a "CD cellular phenotype" in these fibroblasts, characterized by an altered cell shape and actin organization, increased number of focal adhesions, and altered intracellular LPP protein distribution. The treatment of controls fibroblasts with gliadin peptide P31-43 mimics the CD cellular phenotype regarding the cell shape, adhesion capacity, focal adhesion number and LPP sub-cellular distribution, suggesting a close association between these alterations and CD pathogenesis.

  2. Epstein-Barr virus growth/latency III program alters cellular microRNA expression

    International Nuclear Information System (INIS)

    Cameron, Jennifer E.; Fewell, Claire; Yin, Qinyan; McBride, Jane; Wang Xia; Lin Zhen

    2008-01-01

    The Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cancers. Initial EBV infection alters lymphocyte gene expression, inducing cellular proliferation and differentiation as the virus transitions through consecutive latency transcription programs. Cellular microRNAs (miRNAs) are important regulators of signaling pathways and are implicated in carcinogenesis. The extent to which EBV exploits cellular miRNAs is unknown. Using micro-array analysis and quantitative PCR, we demonstrate differential expression of cellular miRNAs in type III versus type I EBV latency including elevated expression of miR-21, miR-23a, miR-24, miR-27a, miR-34a, miR-146a and b, and miR-155. In contrast, miR-28 expression was found to be lower in type III latency. The EBV-mediated regulation of cellular miRNAs may contribute to EBV signaling and associated cancers

  3. Plant Abiotic Stress Proteomics: The Major Factors Determining Alterations in Cellular Proteome

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    Kosová, Klára; Vítámvás, Pavel; Urban, Milan O.; Prášil, Ilja T.; Renaut, Jenny

    2018-01-01

    HIGHLIGHTS: Major environmental and genetic factors determining stress-related protein abundance are discussed.Major aspects of protein biological function including protein isoforms and PTMs, cellular localization and protein interactions are discussed.Functional diversity of protein isoforms and PTMs is discussed. Abiotic stresses reveal profound impacts on plant proteomes including alterations in protein relative abundance, cellular localization, post-transcriptional and post-translational modifications (PTMs), protein interactions with other protein partners, and, finally, protein biological functions. The main aim of the present review is to discuss the major factors determining stress-related protein accumulation and their final biological functions. A dynamics of stress response including stress acclimation to altered ambient conditions and recovery after the stress treatment is discussed. The results of proteomic studies aimed at a comparison of stress response in plant genotypes differing in stress adaptability reveal constitutively enhanced levels of several stress-related proteins (protective proteins, chaperones, ROS scavenging- and detoxification-related enzymes) in the tolerant genotypes with respect to the susceptible ones. Tolerant genotypes can efficiently adjust energy metabolism to enhanced needs during stress acclimation. Stress tolerance vs. stress susceptibility are relative terms which can reflect different stress-coping strategies depending on the given stress treatment. The role of differential protein isoforms and PTMs with respect to their biological functions in different physiological constraints (cellular compartments and interacting partners) is discussed. The importance of protein functional studies following high-throughput proteome analyses is presented in a broader context of plant biology. In summary, the manuscript tries to provide an overview of the major factors which have to be considered when interpreting data from proteomic

  4. Cell-to-cell communication and cellular environment alter the somatostatin status of delta cells

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    Kelly, Catriona, E-mail: catriona.kelly@qub.ac.uk [SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine (United Kingdom); Flatt, Peter R.; McClenaghan, Neville H. [SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine (United Kingdom)

    2010-08-20

    Research highlights: {yields} TGP52 cells display enhanced functionality in pseudoislet form. {yields} Somatostatin content was reduced, but secretion increased in high glucose conditions. {yields} Cellular interactions and environment alter the somatostatin status of TGP52 cells. -- Abstract: Introduction: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. Methods: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5 mM glucose) or DMEM (25 mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. Results: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P < 0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P < 0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. Conclusions: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells.

  5. Cell-to-cell communication and cellular environment alter the somatostatin status of delta cells

    International Nuclear Information System (INIS)

    Kelly, Catriona; Flatt, Peter R.; McClenaghan, Neville H.

    2010-01-01

    Research highlights: → TGP52 cells display enhanced functionality in pseudoislet form. → Somatostatin content was reduced, but secretion increased in high glucose conditions. → Cellular interactions and environment alter the somatostatin status of TGP52 cells. -- Abstract: Introduction: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. Methods: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5 mM glucose) or DMEM (25 mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. Results: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P < 0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P < 0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. Conclusions: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells.

  6. The crowded sea: incorporating multiple marine activities in conservation plans can significantly alter spatial priorities.

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    Tessa Mazor

    Full Text Available Successful implementation of marine conservation plans is largely inhibited by inadequate consideration of the broader social and economic context within which conservation operates. Marine waters and their biodiversity are shared by a host of stakeholders, such as commercial fishers, recreational users and offshore developers. Hence, to improve implementation success of conservation plans, we must incorporate other marine activities while explicitly examining trade-offs that may be required. In this study, we test how the inclusion of multiple marine activities can shape conservation plans. We used the entire Mediterranean territorial waters of Israel as a case study to compare four planning scenarios with increasing levels of complexity, where additional zones, threats and activities were added (e.g., commercial fisheries, hydrocarbon exploration interests, aquaculture, and shipping lanes. We applied the marine zoning decision support tool Marxan to each planning scenario and tested a the ability of each scenario to reach biodiversity targets, b the change in opportunity cost and c the alteration of spatial conservation priorities. We found that by including increasing numbers of marine activities and zones in the planning process, greater compromises are required to reach conservation objectives. Complex plans with more activities incurred greater opportunity cost and did not reach biodiversity targets as easily as simplified plans with less marine activities. We discovered that including hydrocarbon data in the planning process significantly alters spatial priorities. For the territorial waters of Israel we found that in order to protect at least 10% of the range of 166 marine biodiversity features there would be a loss of ∼15% of annual commercial fishery revenue and ∼5% of prospective hydrocarbon revenue. This case study follows an illustrated framework for adopting a transparent systematic process to balance biodiversity goals and

  7. Alteration of cellular immune responses in the seastar Asterias rubens following dietary exposure to cadmium

    International Nuclear Information System (INIS)

    Coteur, G.; Gillan, D.; Pernet, Ph.; Dubois, Ph.

    2005-01-01

    Several parameters of cellular immunity in seastars fed Cd-contaminated mussels were analyzed. The accumulation of cadmium in the seastars did not alter the concentration of amoebocytes in the coelomic fluid. On the contrary, the immune cells showed a reduced phagocytic activity and an increased production of reactive oxygen species. These effects may lead to an inability of the seastars to cope with bacterial infections and to oxidative damages to self tissue that could threaten the survival of the animals

  8. JC virus induces altered patterns of cellular gene expression: Interferon-inducible genes as major transcriptional targets

    International Nuclear Information System (INIS)

    Verma, Saguna; Ziegler, Katja; Ananthula, Praveen; Co, Juliene K.G.; Frisque, Richard J.; Yanagihara, Richard; Nerurkar, Vivek R.

    2006-01-01

    Human polyomavirus JC (JCV) infects 80% of the population worldwide. Primary infection, typically occurring during childhood, is asymptomatic in immunocompetent individuals and results in lifelong latency and persistent infection. However, among the severely immunocompromised, JCV may cause a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Virus-host interactions influencing persistence and pathogenicity are not well understood, although significant regulation of JCV activity is thought to occur at the level of transcription. Regulation of the JCV early and late promoters during the lytic cycle is a complex event that requires participation of both viral and cellular factors. We have used cDNA microarray technology to analyze global alterations in gene expression in JCV-permissive primary human fetal glial cells (PHFG). Expression of more than 400 cellular genes was altered, including many that influence cell proliferation, cell communication and interferon (IFN)-mediated host defense responses. Genes in the latter category included signal transducer and activator of transcription 1 (STAT1), interferon stimulating gene 56 (ISG56), myxovirus resistance 1 (MxA), 2'5'-oligoadenylate synthetase (OAS), and cig5. The expression of these genes was further confirmed in JCV-infected PHFG cells and the human glioblastoma cell line U87MG to ensure the specificity of JCV in inducing this strong antiviral response. Results obtained by real-time RT-PCR and Western blot analyses supported the microarray data and provide temporal information related to virus-induced changes in the IFN response pathway. Our data indicate that the induction of an antiviral response may be one of the cellular factors regulating/controlling JCV replication in immunocompetent hosts and therefore constraining the development of PML

  9. Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2

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    Salaita, Khalid; Nair, Pradeep M; Petit, Rebecca S; Neve, Richard M; Das, Debopriya; Gray, Joe W; Groves, Jay T

    2009-09-09

    Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.

  10. Oleic acid blocks EGF-induced [Ca2+]i release without altering cellular metabolism in fibroblast EGFR T17.

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    Zugaza, J L; Casabiell, X A; Bokser, L; Casanueva, F F

    1995-02-06

    EGFR-T17 cells were pretreated with oleic acid and 5-10 minutes later stimulated with EGF, to study if early ionic signals are instrumental in inducing metabolic cellular response. Oleic acid blocks EGF-induced [Ca2+]i rise and Ca2+ influx without altering 2-deoxyglucose and 2-aminobutiryc acid uptake nor acute, nor chronically. Oleic acid it is shown, in the first minutes favors the entrance of both molecules to modify the physico-chemical membrane state. On the other hand, oleic acid is unable to block protein synthesis. The results suggest that EGF-induced Ins(1,4,5)P3/Ca2+ pathway does not seem to be decisive in the control of cellular metabolic activity.

  11. Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses.

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    Webb, Tonya J; Carey, Gregory B; East, James E; Sun, Wenji; Bollino, Dominique R; Kimball, Amy S; Brutkiewicz, Randy R

    2016-08-01

    Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5(')-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways. We hypothesized that activation of AMPK during infection and malignancy could alter the repertoire of antigens presented by CD1d and serve as a danger signal to NKT cells. In this study, we examined the effect of alterations in metabolism on CD1d-mediated antigen presentation to NKT cells and found that an infection with lymphocytic choriomeningitis virus rapidly increased CD1d-mediated antigen presentation. Hypoxia inducible factors (HIF) enhance T-cell effector functions during infection, therefore antigen presenting cells pretreated with pharmacological agents that inhibit glycolysis, induce HIF and activate AMPK were assessed for their ability to induce NKT-cell responses. Pretreatment with 2-deoxyglucose, cobalt chloride, AICAR and metformin significantly enhanced CD1d-mediated NKT-cell activation. In addition, NKT cells preferentially respond to malignant B cells and B-cell lymphomas express HIF-1α. These data suggest that targeting cellular metabolism may serve as a novel means of inducing innate immune responses. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle.

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    Lee, Yang; Fluckey, James D; Chakraborty, Sanjukta; Muthuchamy, Mariappan

    2017-07-01

    Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance. Onset of insulin resistance significantly impaired glucose uptake, mitochondrial function, oxygen consumption rates, glycolysis, lactic acid, and ATP production in LMCs. Hyperglycemia and hyperinsulinemia also impaired the PI3K/Akt while enhancing the ERK/p38MAPK/JNK pathways in LMCs. Increased NF-κB nuclear translocation and macrophage chemoattractant protein-1 and VCAM-1 levels in insulin-resistant LMCs indicated activation of inflammatory mechanisms. In addition, increased phosphorylation of myosin light chain-20, a key regulator of lymphatic muscle contraction, was observed in insulin-resistant LMCs. Therefore, our data elucidate the mechanisms of insulin resistance in LMCs and provide the first evidence that hyperglycemia and hyperinsulinemia promote insulin resistance and impair lymphatic contractile status by reducing glucose uptake, altering cellular metabolic pathways, and activating inflammatory signaling cascades.-Lee, Y., Fluckey, J. D., Chakraborty, S., Muthuchamy, M. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle. © FASEB.

  13. Altered cellular redox status, sirtuin abundance and clock gene expression in a mouse model of developmentally primed NASH.

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    Bruce, Kimberley D; Szczepankiewicz, Dawid; Sihota, Kiran K; Ravindraanandan, Manoj; Thomas, Hugh; Lillycrop, Karen A; Burdge, Graham C; Hanson, Mark A; Byrne, Christopher D; Cagampang, Felino R

    2016-07-01

    We have previously shown that high fat (HF) feeding during pregnancy primes the development of non-alcoholic steatohepatits (NASH) in the adult offspring. However, the underlying mechanisms are unclear. Since the endogenous molecular clock can regulate hepatic lipid metabolism, we investigated whether exposure to a HF diet during development could alter hepatic clock gene expression and contribute to NASH onset in later life. Female mice were fed either a control (C, 7%kcal fat) or HF (45%kcal fat) diet. Offspring were fed either a C or HF diet resulting in four offspring groups: C/C, C/HF, HF/C and HF/HF. NAFLD progression, cellular redox status, sirtuin expression (Sirt1, Sirt3), and the expression of core clock genes (Clock, Bmal1, Per2, Cry2) and clock-controlled genes involved in lipid metabolism (Rev-Erbα, Rev-Erbβ, RORα, and Srebp1c) were measured in offspring livers. Offspring fed a HF diet developed NAFLD. However HF fed offspring of mothers fed a HF diet developed NASH, coupled with significantly reduced NAD(+)/NADH (pNASH in adulthood, involving altered cellular redox status, reduced sirtuin abundance, and desynchronized clock gene expression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Cellular zinc fluxes and the regulation of apoptosis/gene-directed cell death.

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    Truong-Tran, A Q; Ho, L H; Chai, F; Zalewski, P D

    2000-05-01

    The maintenance of discrete subcellular pools of zinc (Zn) is critical for the functional and structural integrity of cells. Among the important biological processes influenced by Zn is apoptosis, a process that is important in cellular homeostasis (an important cellular homeostatic process). It has also been identified as a major mechanism contributing to cell death in response to toxins and in disease, offering hope that novel therapies that target apoptotic pathways may be developed. Because Zn levels in the body can be increased in a relatively nontoxic manner, it may be possible to prevent or ameliorate degenerative disorders that are associated with high rates of apoptotic cell death. This review begins with brief introductions that address, first, the cellular biology of Zn, especially the critical labile Zn pools, and, second, the phenomenon of apoptosis. We then review the evidence relating Zn to apoptosis and address three major hypotheses: (1) that a specific pool or pools of intracellular labile Zn regulates apoptosis; (2) that systemic changes in Zn levels in the body, due to dietary factors, altered physiological states or disease, can influence cell susceptibility to apoptosis, and (3) that this altered susceptibility to apoptosis contributes to pathophysiological changes in the body. Other key issues are the identity of the molecular targets of Zn in the apoptotic cascade, the types of cells and tissues most susceptible to Zn-regulated apoptosis, the role of Zn as a coordinate regulator of mitosis and apoptosis and the apparent release of tightly bound intracellular pools of Zn during the later stages of apoptosis. This review concludes with a section highlighting areas of priority for future studies.

  15. Timing is everything: priority effects alter community invasibility after disturbance.

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    Symons, Celia C; Arnott, Shelley E

    2014-02-01

    Theory suggests that communities should be more open to the establishment of regional species following disturbance because disturbance may make more resources available to dispersers. However, after an initial period of high invasibility, growth of the resident community may lead to the monopolization of local resources and decreased probability of successful colonist establishment. During press disturbances (i.e., directional environmental change), it remains unclear what effect regional dispersal will have on local community structure if the establishment of later arriving species is affected by early arriving species (i.e., if priority effects are important). To determine the relationship between time-since-disturbance and invasibility, we conducted a fully factorial field mesocosm experiment that exposed tundra zooplankton communities to two emerging stressors - nutrient and salt addition, and manipulated the arrival timing of regional dispersers. Our results demonstrate that invasibility decreases with increasing time-since-disturbance as abundance (nutrient treatments) or species richness (salt treatments) increases in the resident community. Results suggest that the relative timing of dispersal and environmental change will modify the importance of priority effects in determining species composition after a press disturbance.

  16. High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium.

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    Lu, Zhongyan; Shen, Hong; Shen, Zanming

    2018-01-01

    In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive). In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. These results indicated that the alterations of cellular metabolism promote the alterations in cellular

  17. High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium

    Directory of Open Access Journals (Sweden)

    Zhongyan Lu

    2018-03-01

    Full Text Available Background/Aims: In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. Methods: RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive. In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. Results: The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. Conclusions: These results indicated that the

  18. Near-optimal downlink precoding for two-tier priority-based wireless networks

    KAUST Repository

    Park, Kihong; Alouini, Mohamed-Slim

    2015-01-01

    In this paper, we study a two-tier priority-based wireless cellular network in which the primary base station (BS) has multiple antennas and the other terminals have a single antenna. We assume that we have two classes of users: high priority users and low priority users. We consider a rate maximization problem of the low priority users under signal-to-interference-plus-noise-ratio constraints on the high priority user to guarantee a certain quality-of-service for the high priority user. Since the interference due to the low priority users which communicate with each other via direct transmission may severely degrade the performance of the high priority user, we propose a BS-aided two-way relaying approach in which the BS helps relay the low priority users' signals instead of allowing them to communicate with each other via a direct path between them. In addition, an algorithm to find a near-optimal beamforming solution at the BS is proposed. The asymptotic results in the high power regime are derived to verify the average sum rate performance in the proposed scheme. Finally, based on some selected numerical results, we show that the proposed scheme outperforms the direct transmission scheme over a wide transmit power range.

  19. Near-optimal downlink precoding for two-tier priority-based wireless networks

    KAUST Repository

    Park, Kihong

    2015-02-01

    In this paper, we study a two-tier priority-based wireless cellular network in which the primary base station (BS) has multiple antennas and the other terminals have a single antenna. We assume that we have two classes of users: high priority users and low priority users. We consider a rate maximization problem of the low priority users under signal-to-interference-plus-noise-ratio constraints on the high priority user to guarantee a certain quality-of-service for the high priority user. Since the interference due to the low priority users which communicate with each other via direct transmission may severely degrade the performance of the high priority user, we propose a BS-aided two-way relaying approach in which the BS helps relay the low priority users\\' signals instead of allowing them to communicate with each other via a direct path between them. In addition, an algorithm to find a near-optimal beamforming solution at the BS is proposed. The asymptotic results in the high power regime are derived to verify the average sum rate performance in the proposed scheme. Finally, based on some selected numerical results, we show that the proposed scheme outperforms the direct transmission scheme over a wide transmit power range.

  20. Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.

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    Mieda, Michihiro; Okamoto, Hitoshi; Sakurai, Takeshi

    2016-09-26

    As the central pacemaker in mammals, the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is a heterogeneous structure consisting of multiple types of GABAergic neurons with distinct chemical identities [1, 2]. Although individual cells have a cellular clock driven by autoregulatory transcriptional/translational feedback loops of clock genes, interneuronal communication among SCN clock neurons is likely essential for the SCN to generate a highly robust, coherent circadian rhythm [1]. However, neuronal mechanisms that determine circadian period length remain unclear. The SCN is composed of two subdivisions: a ventral core region containing vasoactive intestinal peptide (VIP)-producing neurons and a dorsal shell region characterized by arginine vasopressin (AVP)-producing neurons. Here we examined whether AVP neurons act as pacemaker cells that regulate the circadian period of behavior rhythm in mice. The deletion of casein kinase 1 delta (CK1δ) specific to AVP neurons, which was expected to lengthen the period of cellular clocks [3-6], lengthened the free-running period of circadian behavior as well. Conversely, the overexpression of CK1δ specific to SCN AVP neurons shortened the free-running period. PER2::LUC imaging in slices confirmed that cellular circadian periods of the SCN shell were lengthened in mice without CK1δ in AVP neurons. Thus, AVP neurons may be an essential component of circadian pacemaker cells in the SCN. Remarkably, the alteration of the shell-core phase relationship in the SCN of these mice did not impair the generation per se of circadian behavior rhythm, thereby underscoring the robustness of the SCN network. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The epidermis of grhl3-null mice displays altered lipid processing and cellular hyperproliferation.

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    Ting, Stephen B; Caddy, Jacinta; Wilanowski, Tomasz; Auden, Alana; Cunningham, John M; Elias, Peter M; Holleran, Walter M; Jane, Stephen M

    2005-04-01

    The presence of an impermeable surface barrier is an essential homeostatic mechanism in almost all living organisms. We have recently described a novel gene that is critical for the developmental instruction and repair of the integument in mammals. This gene, Grainy head-like 3 (Grhl3) is a member of a large family of transcription factors that are homologs of the Drosophila developmental gene grainy head (grh). Mice lacking Grhl3 fail to form an adequate skin barrier, and die at birth due to dehydration. These animals are also unable to repair the epidermis, exhibiting failed wound healing in both fetal and adult stages of development. These defects are due, in part, to diminished expression of a Grhl3 target gene, Transglutaminase 1 (TGase 1), which encodes a key enzyme involved in cross-linking of epidermal structural proteins and lipids into the cornified envelope (CE). Remarkably, the Drosophila grh gene plays an analogous role, regulating enzymes involved in the generation of quinones, which are essential for cross-linking structural components of the fly epidermis. In an extension of our initial analyses, we focus this report on additional defects observed in the Grhl3-null epidermis, namely defective extra-cellular lipid processing, altered lamellar lipid architecture and cellular hyperproliferation. These abnormalities suggest that Grhl3 plays diverse mechanistic roles in maintaining homeostasis in the skin.

  2. Cellular Signaling Pathway Alterations and Potential Targeted Therapies for Medullary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Serena Giunti

    2013-01-01

    Full Text Available Parafollicular C-cell-derived medullary thyroid cancer (MTC comprises 3% to 4% of all thyroid cancers. While cytotoxic treatments have been shown to have limited efficacy, targeted molecular therapies that inhibit rearranged during transfection (RET and other tyrosine kinase receptors that are mainly involved in angiogenesis have shown great promise in the treatment of metastatic or locally advanced MTC. Multi-tyrosine kinase inhibitors such as vandetanib, which is already approved for the treatment of progressive MTC, and cabozantinib have shown distinct advantages with regard to rates of disease response and control. However, these types of tyrosine kinase inhibitor compounds are able to concurrently block several types of targets, which limits the understanding of RET as a specific target. Moreover, important resistances to tyrosine kinase inhibitors can occur, which limit the long-term efficacy of these treatments. Deregulated cellular signaling pathways and genetic alterations in MTC, particularly the activation of the RAS/mammalian target of rapamycin (mTOR cascades and RET crosstalk signaling, are now emerging as novel and potentially promising therapeutic treatments for aggressive MTC.

  3. Altered Cellular Metabolism Drives Trained Immunity.

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    Sohrabi, Yahya; Godfrey, Rinesh; Findeisen, Hannes M

    2018-04-04

    Exposing innate immune cells to an initial insult induces a long-term proinflammatory response due to metabolic and epigenetic alterations which encompass an emerging new concept called trained immunity. Recent studies provide novel insights into mechanisms centered on metabolic reprogramming which induce innate immune memory in hematopoietic stem cells and monocytes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Altered protein networks and cellular pathways in severe west nile disease in mice.

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    Christophe Fraisier

    Full Text Available BACKGROUND: The recent West Nile virus (WNV outbreaks in developed countries, including Europe and the United States, have been associated with significantly higher neuropathology incidence and mortality rate than previously documented. The changing epidemiology, the constant risk of (re-emergence of more virulent WNV strains, and the lack of effective human antiviral therapy or vaccines makes understanding the pathogenesis of severe disease a priority. Thus, to gain insight into the pathophysiological processes in severe WNV infection, a kinetic analysis of protein expression profiles in the brain of WNV-infected mice was conducted using samples prior to and after the onset of clinical symptoms. METHODOLOGY/PRINCIPAL FINDINGS: To this end, 2D-DIGE and gel-free iTRAQ labeling approaches were combined, followed by protein identification by mass spectrometry. Using these quantitative proteomic approaches, a set of 148 proteins with modified abundance was identified. The bioinformatics analysis (Ingenuity Pathway Analysis of each protein dataset originating from the different time-point comparisons revealed that four major functions were altered during the course of WNV-infection in mouse brain tissue: i modification of cytoskeleton maintenance associated with virus circulation; ii deregulation of the protein ubiquitination pathway; iii modulation of the inflammatory response; and iv alteration of neurological development and neuronal cell death. The differential regulation of selected host protein candidates as being representative of these biological processes were validated by western blotting using an original fluorescence-based method. CONCLUSION/SIGNIFICANCE: This study provides novel insights into the in vivo kinetic host reactions against WNV infection and the pathophysiologic processes involved, according to clinical symptoms. This work offers useful clues for anti-viral research and further evaluation of early biomarkers for the diagnosis

  5. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

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    Giovanni Dalmasso

    Full Text Available Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis and the removal of damaged mitochondria by selective autophagy (mitophagy. While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1 mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2 restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3 maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4 our model suggests sources of, and stress conditions

  6. Analysis and study of a handoff scheme with multiple priority strategies

    Institute of Scientific and Technical Information of China (English)

    李波; 吴成柯; 椋本介士; 福田明

    2000-01-01

    A handoff scheme with the combination of channel reservation and preemptive priority in integrated voice/data cellular mobile systems is proposed. In the scheme, calls are divided into three different classes: handoff voice calls, originating voice calls, and data calls. An access strategy with the combination of channel reservation and preemptive priority is provided to a handoff voice call. Furthermore, in order to improve the system capacity for the total voice traffic, preemptive priority is also given to partial originating voice calls. The system is modeled by a two-dimensional Markov chain. Both the iteration method and the approximate method are used to calculate and analyze some of the most important performance measures of the system. It is shown that our scheme can provide better quality of services for mobile subscribers.

  7. Different Candida parapsilosis clinical isolates and lipase deficient strain trigger an altered cellular immune response

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    Renata eToth

    2015-10-01

    Full Text Available Numerous human diseases can be associated with fungal infections either as potential causative agents or as a result of changed immune status due to a primary disease. Fungal infections caused by Candida species can vary from mild to severe dependent upon the site of infection, length of exposure and past medical history. Patients with impaired immune status are at increased risk for chronic fungal infections. Recent epidemiologic studies have revealed the increasing incidence of candidiasis caused by non-albicans species such as C. parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response towards this species. In the first section of our study we compared the interaction of CLIB 214 and GA1 cells with murine and human macrophages. Both strains are commonly used to investigate C. parapsilosis virulence properties. CLIB 214 is a rapidly pseudohyphae-forming strain and GA1 is an isolate that mainly exists in a yeast form. Our results showed, that the phagocyte response was similar in terms of overall uptake, however differences were observed in macrophage migration and engulfment of fungal cells. As C. parapsilosis releases extracellular lipases in order to promote host invasion we further investigated the role of these secreted components during the distinct stages of the phagocytic process. Using a secreted lipase deficient mutant strain and the parental strain GA1 individually and simultaneously, we confirmed that fungal secreted lipases influence the fungi’s virulence by detecting altered innate cellular responses.In this study we report that two isolates of a single species can trigger markedly distinct host responses and that lipase secretion plays a role on the cellular level of host pathogen interactions.

  8. Oleate induces KATP channel-dependent hyperpolarization in mouse hypothalamic glucose-excited neurons without altering cellular energy charge.

    Science.gov (United States)

    Dadak, Selma; Beall, Craig; Vlachaki Walker, Julia M; Soutar, Marc P M; McCrimmon, Rory J; Ashford, Michael L J

    2017-03-27

    The unsaturated fatty acid, oleate exhibits anorexigenic properties reducing food intake and hepatic glucose output. However, its mechanism of action in the hypothalamus has not been fully determined. This study investigated the effects of oleate and glucose on GT1-7 mouse hypothalamic cells (a model of glucose-excited (GE) neurons) and mouse arcuate nucleus (ARC) neurons. Whole-cell and perforated patch-clamp recordings, immunoblotting and cell energy status measures were used to investigate oleate- and glucose-sensing properties of mouse hypothalamic neurons. Oleate or lowered glucose concentration caused hyperpolarization and inhibition of firing of GT1-7 cells by the activation of ATP-sensitive K + channels (K ATP ). This effect of oleate was not dependent on fatty acid oxidation or raised AMP-activated protein kinase activity or prevented by the presence of the UCP2 inhibitor genipin. Oleate did not alter intracellular calcium, indicating that CD36/fatty acid translocase may not play a role. However, oleate activation of K ATP may require ATP metabolism. The short-chain fatty acid octanoate was unable to replicate the actions of oleate on GT1-7 cells. Although oleate decreased GT1-7 cell mitochondrial membrane potential there was no change in total cellular ATP or ATP/ADP ratios. Perforated patch and whole-cell recordings from mouse hypothalamic slices demonstrated that oleate hyperpolarized a subpopulation of ARC GE neurons by K ATP activation. Additionally, in a separate small population of ARC neurons, oleate application or lowered glucose concentration caused membrane depolarization. In conclusion, oleate induces K ATP- dependent hyperpolarization and inhibition of firing of a subgroup of GE hypothalamic neurons without altering cellular energy charge. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway.

    Science.gov (United States)

    Kurokawa, Hirofumi; Sugiyama, Seigo; Nozaki, Toshimitsu; Sugamura, Koichi; Toyama, Kensuke; Matsubara, Junichi; Fujisue, Koichiro; Ohba, Keisuke; Maeda, Hirofumi; Konishi, Masaaki; Akiyama, Eiichi; Sumida, Hitoshi; Izumiya, Yasuhiro; Yasuda, Osamu; Kim-Mitsuyama, Shokei; Ogawa, Hisao

    2015-04-01

    Mitochondrial dysfunction plays an important role in cellular senescence and impaired function of vascular endothelium, resulted in cardiovascular diseases. Telmisartan is a unique angiotensin II type I receptor blocker that has been shown to prevent cardiovascular events in high risk patients. AMP-activated protein kinase (AMPK) plays a critical role in mitochondrial biogenesis and endothelial function. This study assessed whether telmisartan enhances mitochondrial function and alters cellular functions via AMPK in human coronary artery endothelial cells (HCAECs). In cultured HCAECs, telmisartan significantly enhanced mitochondrial activity assessed by mitochondrial reductase activity and intracellular ATP production and increased the expression of mitochondria related genes. Telmisartan prevented cellular senescence and exhibited the anti-apoptotic and pro-angiogenic properties. The expression of genes related anti-oxidant and pro-angiogenic properties were increased by telmisartan. Telmisartan increased endothelial NO synthase and AMPK phosphorylation. Peroxisome proliferator-activated receptor gamma signaling was not involved in telmisartan-induced improvement of mitochondrial function. All of these effects were abolished by inhibition of AMPK. Telmisartan enhanced mitochondrial activity and exhibited anti-senescence effects and improving endothelial function through AMPK in HCAECs. Telmisartan could provide beneficial effects on vascular diseases via enhancement of mitochondrial activity and modulating endothelial function through AMPK activation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. The surfactant protein C mutation A116D alters cellular processing, stress tolerance, surfactant lipid composition, and immune cell activation

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    Zarbock Ralf

    2012-03-01

    Full Text Available Abstract Background Surfactant protein C (SP-C is important for the function of pulmonary surfactant. Heterozygous mutations in SFTPC, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We also evaluated the ability of drugs currently used in ILD therapy to counteract these effects. Methods SP-CA116D was expressed in MLE-12 alveolar epithelial cells. We assessed in vitro the consequences for cellular homeostasis, immune response and effects of azathioprine, hydroxychloroquine, methylprednisolone and cyclophosphamide. Results Stable expression of SP-CA116D in MLE-12 alveolar epithelial cells resulted in increased intracellular accumulation of proSP-C processing intermediates. SP-CA116D expression further led to reduced cell viability and increased levels of the chaperones Hsp90, Hsp70, calreticulin and calnexin. Lipid analysis revealed decreased intracellular levels of phosphatidylcholine (PC and increased lyso-PC levels. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CA116D cells secreted soluble factors into the medium that modulated surface expression of CCR2 or CXCR1 receptors on CD4+ lymphocytes and neutrophils, suggesting a direct paracrine effect of SP-CA116D on neighboring cells in the alveolar space. Conclusions We show that the A116D mutation leads to impaired processing of proSP-C in alveolar epithelial cells, alters cell viability and lipid composition, and also activates cells of the immune system. In addition, we show that some of the effects of the mutation on cellular homeostasis can be antagonized by application of pharmaceuticals commonly applied in ILD therapy

  11. Cellular metabolism

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  12. Temperature-Dependent Species Interactions Shape Priority Effects and the Persistence of Unequal Competitors.

    Science.gov (United States)

    Grainger, Tess Nahanni; Rego, Adam Ivan; Gilbert, Benjamin

    2018-02-01

    The order of species arrival at a site can determine the outcome of competitive interactions when early arrivers alter the environment or deplete shared resources. These priority effects are predicted to be stronger at high temperatures, as higher vital rates caused by warming allow early arrivers to more rapidly impact a shared environment. We tested this prediction using a pair of congeneric aphid species that specialize on milkweed plants. We manipulated temperature and arrival order of the two aphid species and measured aphid population dynamics and milkweed survival and defensive traits. We found that warming increased the impact of aphids on the quantity and quality of milkweed, which amplified the importance of priority effects by increasing the competitive exclusion of the inferior competitor when it arrived late. Warming also enhanced interspecific differences in dispersal, which could alter relative arrival times at a regional scale. Our experiment provides a first link between temperature-dependent trophic interactions, priority effects, and dispersal. This study suggests that the indirect and cascading effects of temperature observed here may be important determinants of diversity in the temporally and spatially complex landscapes that characterize ecological communities.

  13. Multiscale evaluation of cellular adhesion alteration and cytoskeleton remodeling by magnetic bead twisting.

    Science.gov (United States)

    Isabey, Daniel; Pelle, Gabriel; André Dias, Sofia; Bottier, Mathieu; Nguyen, Ngoc-Minh; Filoche, Marcel; Louis, Bruno

    2016-08-01

    Cellular adhesion forces depend on local biological conditions meaning that adhesion characterization must be performed while preserving cellular integrity. We presently postulate that magnetic bead twisting provides an appropriate stress, i.e., basically a clamp, for assessment in living cells of both cellular adhesion and mechanical properties of the cytoskeleton. A global dissociation rate obeying a Bell-type model was used to determine the natural dissociation rate ([Formula: see text]) and a reference stress ([Formula: see text]). These adhesion parameters were determined in parallel to the mechanical properties for a variety of biological conditions in which either adhesion or cytoskeleton was selectively weakened or strengthened by changing successively ligand concentration, actin polymerization level (by treating with cytochalasin D), level of exerted stress (by increasing magnetic torque), and cell environment (by using rigid and soft 3D matrices). On the whole, this multiscale evaluation of the cellular and molecular responses to a controlled stress reveals an evolution which is consistent with stochastic multiple bond theories and with literature results obtained with other molecular techniques. Present results confirm the validity of the proposed bead-twisting approach for its capability to probe cellular and molecular responses in a variety of biological conditions.

  14. Effect of etoposide-induced alteration of the Mdm2-Rb signaling pathway on cellular senescence in A549 lung adenocarcinoma cells.

    Science.gov (United States)

    Dai, Wenjing; Jiang, Yi; Chen, Kairong; Qiu, Jing; Sun, Jian; Zhang, Wei; Zhou, Xiafei; Huang, Na; Li, Yunhui; Li, Wancheng

    2017-10-01

    The present study aimed to investigate the effect of various concentrations of etoposide (VP-16) on the E3 ubiquitin-protein ligase Mdm2 (Mdm2)-retinoblastoma (Rb) signaling pathway in the cellular senescence of A549 lung adenocarcinoma cells. A549 cells were randomly divided into the following four groups: Control group (no treatment), group 1 (1 µmol/l VP-16), group 2 (5 µmol/l VP-16) and group 3 (25 µmol/l VP-16). Each group was cultured for 48 h after treatment prior to observation of the alterations to cellular morphology. The cell cycle distribution of each group was also detected by flow cytometry. In addition, the activity of cellular senescence-associated β-galactosidase, and the expression of Mdm2 and phosphorylated (p-) Rb protein, was measured. The percentage of senescent cells was significantly higher following VP-16 treatment compared with the control group. The percentage of G 1 phase cells, and p-Rb protein and Mdm2 protein expression were also significantly different following VP-16 treatment compared with the control group. VP-16 increased the activity of β-galactosidase in the A459 cells. VP-16 also decreased the expression level of Mdm2 and p-Rb protein and inhibited cell cycle progression in G 1 . These results indicate that VP-16 induces the cellular senescence of A549 cells via the Mdm2-Rb signaling pathway. However, further investigations are required to validate the mechanisms underlying these effects of VP-16.

  15. 1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling

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    Lars-Oliver Klotz

    2014-09-01

    Full Text Available Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others to cellular and inter-cellular signaling processes are discussed: (i naphthoquinone-induced Nrf2-dependent modulation of gene expression and its potentially beneficial outcome; (ii the modulation of receptor tyrosine kinases, such as the epidermal growth factor receptor by naphthoquinones, resulting in altered gap junctional intercellular communication. Generation of reactive oxygen species and modulation of redox signaling are properties of naphthoquinones that render them interesting leads for the development of novel compounds of potential use in various therapeutic settings.

  16. Bronchoalveolar lavage as a tool for evaluation of cellular alteration during Aelurostrongylus abstrusus infection in cats

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    Vitor M. Ribeiro

    2014-10-01

    Full Text Available Bronchoalveolar lavage (BAL is a procedure that retrieves cells and other elements from the lungs for evaluation, which helps in the diagnosis of pulmonary diseases. The aim of this study was to perform this procedure for cellular analysis of BAL fluid alterations during experimental infection with Aelurostrongylus abstrusus in cats. Fourteen cats were individually inoculated with 800 third stage larvae of A. abstrusus and five non-infected cats lined as a control group. The BAL procedure was performed through the use of an endotracheal tube on the nineteen cats with a mean age of 18 months, on 0, 30, 60, 90, 120, 180 and 270 days after infection. Absolute cell counts in the infected cats revealed that alveolar macrophages and eosinophils were the predominant cells following infection. This study shows that the technique allows us to retrieve cells and first stage larvae what provides information about the inflammatory process caused by aelurostrongylosis.

  17. On the Action of General Anesthetics on Cellular Function: Barbiturate Alters the Exocytosis of Catecholamines in a Model Cell System.

    Science.gov (United States)

    Ye, Daixin; Ewing, Andrew

    2018-01-22

    General anesthetics are essential in many areas, however, the cellular mechanisms of anesthetic-induced amnesia and unconsciousness are incompletely understood. Exocytosis is the main mechanism of signal transduction and neuronal communication through the release of chemical transmitters from vesicles to the extracellular environment. Here, we use disk electrodes placed on top of PC12 cells to show that treatment with barbiturate induces fewer molecules released during exocytosis and changes the event dynamics perhaps by inducing a less stable fusion pore that is prone to close faster during partial exocytosis. Larger events are essentially abolished. However, use of intracellular vesicle impact electrochemical cytometry using a nano-tip electrode inserted into a cell shows that the distribution of vesicle transmitter content does not change after barbiturate treatment. This indicates that barbiturate selectively alters the pore size of larger events or perhaps differentially between types of vesicles. Alteration of exocytosis in this manner could be linked to the effects of general anesthetics on memory loss. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Communitarian claims and community capabilities: furthering priority setting?

    Science.gov (United States)

    Mooney, Gavin

    2005-01-01

    Priority setting in health care is generally not done well. This paper draws on ideas from Amartya Sen and Martha Nussbaum and adds some communitarian underpinnings to provide a way of improving on current uses of program budgeting and marginal analysis (PBMA) in priority setting. The paper suggests that shifting to a communitarian base for priority setting alters the distribution of property rights over health service decision making and increases the probability that recommendations from PBMA exercises will be implemented. The approach is built on a paradigm which departs from three tenets of welfarism as it is normally conceived: (i) individuals qua individuals seek to maximise their individual utility/well-being; (ii) individuals want to do this; and (iii) it is the values of individuals qua individuals that count. Some of the problems of PBMA, as it has been applied to date, are highlighted. It is argued that these are due largely to a lack of 'credible commitment'. Bringing in the community and communitarian values to PBMA priority setting exercises can help to overcome some of the barriers to getting PBMA recommendations implemented. The approach has the merit of reflecting Sen's concept of capabilities (but extending that to a community level). It avoids the often consequentialist base of a conventional welfarist framework, and it allows community values as opposed to individual values to come to the fore. How to elicit communitarian values is explored.

  19. Antioxidant-Rich Fraction of Urtica dioica Mediated Rescue of Striatal Mito-Oxidative Damage in MPTP-Induced Behavioral, Cellular, and Neurochemical Alterations in Rats.

    Science.gov (United States)

    Bisht, Rohit; Joshi, Bhuwan Chandra; Kalia, Ajudhiya Nath; Prakash, Atish

    2017-09-01

    Parkinson's disease (PD) having a complex and multi-factorial neuropathology includes mainly the degeneration of the dopaminergic nigrostriatal pathway, which is a cumulative effect of depleted endogenous antioxidant enzymes, increased oxidative DNA damage, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. The present study was designed to investigate the neuroprotective effect of a potent antioxidant from Urtica dioica in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. MPTP was administered intranigrally for the induction of PD in male Wistar rats. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical, cellular, and neurochemical parameters were measured. Intranigrally repeated administration of MPTP showed significant impairment of motor co-ordination and marked increase of mito-oxidative damage and neuroinflammation in rats. Intranigral MPTP significantly decreases the dopamine and its metabolites with impairment of dopaminergic cell density in rat brain. However, post-treatment with the potent antioxidant fraction of Urtica dioica Linn. (UD) (20, 40, 80 mg/kg) improved the motor function, mito-oxidative defense alteration significantly and dose dependently in MPTP-treated rats. In addition, the potent antioxidant fraction of UD attenuated the pro-inflammatory cytokines (TNF-α and IL-β) and restored the level of dopamine and its metabolites in MPTP-induced PD in rats. Moreover, minocycline (30 mg/kg) with lower dose of UD (20 mg/kg) had significantly potentiated the protective effect of minocycline as compared to its effect with other individual drug-treated groups. In conclusion, Urtica dioica protected the dopaminergic neurons probably by reducing mito-oxidative damage, neuroinflammation, and cellular alteration along with enhanced neurotrophic potential. The above results revealed that the antioxidant rich

  20. A novel root-index based prioritized random access scheme for 5G cellular networks

    Directory of Open Access Journals (Sweden)

    Taehoon Kim

    2015-12-01

    Full Text Available Cellular networks will play an important role in realizing the newly emerging Internet-of-Everything (IoE. One of the challenging issues is to support the quality of service (QoS during the access phase, while accommodating a massive number of machine nodes. In this paper, we show a new paradigm of multiple access priorities in random access (RA procedure and propose a novel root-index based prioritized random access (RIPRA scheme that implicitly embeds the access priority in the root index of the RA preambles. The performance evaluation shows that the proposed RIPRA scheme can successfully support differentiated performance for different access priority levels, even though there exist a massive number of machine nodes.

  1. Competitive outcome of Daphnia-Simocephalus experimental microcosms: salinity versus priority effects.

    Directory of Open Access Journals (Sweden)

    Cláudia Loureiro

    Full Text Available Competition is a major driving force in freshwaters, especially given the cyclic nature and dynamics of pelagic food webs. Competition is especially important in the initial species assortment during colonization and re-colonization events, which depends strongly on the environmental context. Subtle changes, such as saline intrusion, may disrupt competitive relationships and, thus, influence community composition. Bearing this in mind, our objective was to assess whether low salinity levels (using NaCl as a proxy alter the competitive outcome (measured as the rate of population biomass increase of Daphnia-Simocephalus experimental microcosms, taking into account interactions with priority effects (sequential species arrival order. With this approach, we aimed to experimentally demonstrate a putative mechanism of differential species sorting in brackish environments or in freshwaters facing secondary salinization. Experiments considered three salinity levels, regarding NaCl added (0.00, 0.75 and 1.50 g L(-1, crossed with three competition scenarios (no priority, priority of Daphnia over Simocephalus, and vice-versa. At lower NaCl concentrations (0.00 and 0.75 g L(-1, Daphnia was a significantly superior competitor, irrespective of the species inoculation order, suggesting negligible priority effects. However, the strong decrease in Daphnia population growth at 1.50 g L(-1 alleviated the competitive pressure on Simocephalus, causing an inversion of the competitive outcome in favour of Simocephalus. The intensity of this inversion depended on the competition scenario. This salinity-mediated disruption of the competitive outcome demonstrates that subtle environmental changes produce indirect effects in key ecological mechanisms, thus altering community composition, which may lead to serious implications in terms of ecosystem functioning (e.g. lake regime shifts due to reduced grazing and biodiversity.

  2. Ecosystems and Climate Change. Research Priorities for the U.S. Climate Change Science Program

    Science.gov (United States)

    2006-06-01

    photosynthesis ), evapotranspiration, and energy balance. 12 Climate change recommended research priorities Organic matter inputs to soils and aquatic...may be altered through changes in climate (e.g., coral reefs, seagrass ). Finally, services provided by a number of federally protected areas depend

  3. Multiple-integrations of HPV16 genome and altered transcription of viral oncogenes and cellular genes are associated with the development of cervical cancer.

    Directory of Open Access Journals (Sweden)

    Xulian Lu

    Full Text Available The constitutive expression of the high-risk HPV E6 and E7 viral oncogenes is the major cause of cervical cancer. To comprehensively explore the composition of HPV16 early transcripts and their genomic annotation, cervical squamous epithelial tissues from 40 HPV16-infected patients were collected for analysis of papillomavirus oncogene transcripts (APOT. We observed different transcription patterns of HPV16 oncogenes in progression of cervical lesions to cervical cancer and identified one novel transcript. Multiple-integration events in the tissues of cervical carcinoma (CxCa are significantly more often than those of low-grade squamous intraepithelial lesions (LSIL and high-grade squamous intraepithelial lesions (HSIL. Moreover, most cellular genes within or near these integration sites are cancer-associated genes. Taken together, this study suggests that the multiple-integrations of HPV genome during persistent viral infection, which thereby alters the expression patterns of viral oncogenes and integration-related cellular genes, play a crucial role in progression of cervical lesions to cervix cancer.

  4. Patterns of cellular phone use among young people in 12 countries : Implications for RF exposure

    NARCIS (Netherlands)

    Langer, Chelsea Eastman; de Llobet Viladoms, Patricia; Dalmau-Bueno, Albert; Wiart, Joe; Goedhart, Geertje; Hours, Martine; Benke, Geza P; Bouka, Evdoxia; Bruchim, Revital; Choi, Kyung-Hwa; Eng, Amanda; Ha, Mina; Karalexi, Maria; Kiyohara, Kosuke; Kojimahara, Noriko; Krewski, Daniel; Kromhout, Hans; Lacour, Brigitte; 't Mannetje, Andrea; Maule, Milena; Migliore, Enrica; Mohipp, Charmaine; Momoli, Franco; Petridou, Eleni; Radon, Katja; Remen, Thomas; Sadetzki, Siegal; Sim, Malcolm R; Weinmann, Tobias; Vermeulen, Roel; Cardis, Elisabeth; Vrijheid, Martine

    2017-01-01

    Characterizing exposure to radiofrequency (RF) fields from wireless telecommunications technologies during childhood and adolescence is a research priority in investigating the health effects of RF. The Mobi-Expo study aimed to describe characteristics and determinants of cellular phone use in 534

  5. Oxidative Stress and Heart Failure in Altered Thyroid States

    Directory of Open Access Journals (Sweden)

    Pallavi Mishra

    2012-01-01

    Full Text Available Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that hyperthyroidism induces a hyperdynamic cardiovascular state, which is associated with a faster heart rate, enhanced left ventricular systolic and diastolic function whereas hypothyroidism is characterized by the opposite changes. Hyperthyroidism and hypothyroidism represent opposite clinical conditions, albeit not mirror images. Recent experimental and clinical studies have suggested the involvement of ROS tissue damage under altered thyroid status. Altered-thyroid state-linked changes in heart modify their susceptibility to oxidants and the extent of the oxidative damage they suffer following oxidative challenge. Chronic increase in the cellular levels of ROS can lead to a catastrophic cycle of DNA damage, mitochondrial dysfunction, further ROS generation and cellular injury. Thus, these cellular events might play an important role in the development and progression of myocardial remodeling and heart failure in altered thyroid states (hypo- and hyper-thyroidism. The present review aims at elucidating the various signaling pathways mediated via ROS and their modulation under altered thyroid state and the possibility of antioxidant therapy.

  6. The unfunded priorities: an evaluation of priority setting for noncommunicable disease control in Uganda.

    Science.gov (United States)

    Essue, Beverley M; Kapiriri, Lydia

    2018-02-20

    The double burden of infectious diseases coupled with noncommunicable diseases poses unique challenges for priority setting and for achieving equitable action to address the major causes of disease burden in health systems already impacted by limited resources. Noncommunicable disease control is an important global health and development priority. However, there are challenges for translating this global priority into local priorities and action. The aim of this study was to evaluate the influence of national, sub-national and global factors on priority setting for noncommunicable disease control in Uganda and examine the extent to which priority setting was successful. A mixed methods design that used the Kapiriri & Martin framework for evaluating priority setting in low income countries. The evaluation period was 2005-2015. Data collection included a document review (policy documents (n = 19); meeting minutes (n = 28)), media analysis (n = 114) and stakeholder interviews (n = 9). Data were analysed according to the Kapiriri & Martin (2010) framework. Priority setting for noncommunicable diseases was not entirely fair nor successful. While there were explicit processes that incorporated relevant criteria, evidence and wide stakeholder involvement, these criteria were not used systematically or consistently in the contemplation of noncommunicable diseases. There were insufficient resources for noncommunicable diseases, despite being a priority area. There were weaknesses in the priority setting institutions, and insufficient mechanisms to ensure accountability for decision-making. Priority setting was influenced by the priorities of major stakeholders (i.e. development assistance partners) which were not always aligned with national priorities. There were major delays in the implementation of noncommunicable disease-related priorities and in many cases, a failure to implement. This evaluation revealed the challenges that low income countries are

  7. Priority setting: what constitutes success? A conceptual framework for successful priority setting.

    Science.gov (United States)

    Sibbald, Shannon L; Singer, Peter A; Upshur, Ross; Martin, Douglas K

    2009-03-05

    The sustainability of healthcare systems worldwide is threatened by a growing demand for services and expensive innovative technologies. Decision makers struggle in this environment to set priorities appropriately, particularly because they lack consensus about which values should guide their decisions. One way to approach this problem is to determine what all relevant stakeholders understand successful priority setting to mean. The goal of this research was to develop a conceptual framework for successful priority setting. Three separate empirical studies were completed using qualitative data collection methods (one-on-one interviews with healthcare decision makers from across Canada; focus groups with representation of patients, caregivers and policy makers; and Delphi study including scholars and decision makers from five countries). This paper synthesizes the findings from three studies into a framework of ten separate but interconnected elements germane to successful priority setting: stakeholder understanding, shifted priorities/reallocation of resources, decision making quality, stakeholder acceptance and satisfaction, positive externalities, stakeholder engagement, use of explicit process, information management, consideration of values and context, and revision or appeals mechanism. The ten elements specify both quantitative and qualitative dimensions of priority setting and relate to both process and outcome components. To our knowledge, this is the first framework that describes successful priority setting. The ten elements identified in this research provide guidance for decision makers and a common language to discuss priority setting success and work toward improving priority setting efforts.

  8. Setting conservation priorities.

    Science.gov (United States)

    Wilson, Kerrie A; Carwardine, Josie; Possingham, Hugh P

    2009-04-01

    A generic framework for setting conservation priorities based on the principles of classic decision theory is provided. This framework encapsulates the key elements of any problem, including the objective, the constraints, and knowledge of the system. Within the context of this framework the broad array of approaches for setting conservation priorities are reviewed. While some approaches prioritize assets or locations for conservation investment, it is concluded here that prioritization is incomplete without consideration of the conservation actions required to conserve the assets at particular locations. The challenges associated with prioritizing investments through time in the face of threats (and also spatially and temporally heterogeneous costs) can be aided by proper problem definition. Using the authors' general framework for setting conservation priorities, multiple criteria can be rationally integrated and where, how, and when to invest conservation resources can be scheduled. Trade-offs are unavoidable in priority setting when there are multiple considerations, and budgets are almost always finite. The authors discuss how trade-offs, risks, uncertainty, feedbacks, and learning can be explicitly evaluated within their generic framework for setting conservation priorities. Finally, they suggest ways that current priority-setting approaches may be improved.

  9. Alterations of Cellular Immune Reactions in Crew Members Overwintering in the Antarctic Research Station Concordia

    Science.gov (United States)

    Crucian, Brian; Feuerecker, Matthias; Moreels, Marjan; Crucian, Brian; Kaufmann, Ines; Salam, Alex Paddy; Rybka, Alex; Ulrike, Thieme; Quintens, Roel; Sams, Clarence F.; hide

    2012-01-01

    Background: Concordia Station is located inside Antarctica about 1000km from the coast at an altitude of 3200m (Dome C). Hence, individuals living in this harsh environment are exposed to two major conditions: 1.) hypobaric hypoxia and 2.) confinement and extreme isolation. Both hypoxia and confinement can affect human immunity and health, and are likely to be present during exploration class space missions. This study focused on immune alterations measured by a new global immunity test assay, similar to the phased out delayed type hypersensitivity (DTH) skin test. Methods: After informed written consent 14 healthy male subjects were included to the CHOICE-study (Consequences-of-longterm-Confinement-and-Hypobaric-HypOxia-on-Immunity-in-the Antarctic-Concordia-Environment). Data collection occurred during two winter-over periods lasting each one year. During the first campaign 6 healthy male were enrolled followed by a second campaign with 8 healthy males. Blood was drawn monthly and incubated for 48h with various bacterial, viral and fungal antigens followed by an analysis of plasma cytokine levels (TNF-alpha, IL2, IFN-gamma, IL10). As a control, blood was incubated without stimulation ("resting condition"). Goals: The scope of this study was to assess the consequences of hypoxia and confinement on cellular immunity as assessed by a new in vitro DTH-like test. Results: Initial results indicate that under resting conditions the in vitro DTH-like test showed low cytokine levels which remained almost unchanged during the entire observation period. However, cytokine responses to viral, bacterial and fungal antigens were remarkably reduced at the first month after arrival at Concordia when compared to levels measured in Europe prior to departure for Antarctica. With incrementing months of confinement this depressed DTH-like response tended to reverse, and in fact to show an "overshooting" immune reaction after stimulation. Conclusion: The reduced in vitro DTH-like test

  10. An Integrative Neuroscience Framework for the Treatment of Chronic Pain: From Cellular Alterations to Behavior

    Directory of Open Access Journals (Sweden)

    Jess D. Greenwald

    2018-05-01

    Full Text Available Chronic pain can result from many pain syndromes including complex regional pain syndrome (CRPS, phantom limb pain and chronic low back pain, among others. On a molecular level, chronic pain syndromes arise from hypersensitization within the dorsal horn of the spinal cord, a process known as central sensitization. Central sensitization involves an upregulation of ionotropic and metabotropic glutamate receptors (mGluRs similar to that of long-term potentiation (LTP. Regions of the brain in which LTP occurs, such as the amygdala and hippocampus, are implicated in fear- and memory-related brain circuity. Chronic pain dramatically influences patient quality of life. Individuals with chronic pain may develop pain-related anxiety and pain-related fear. The syndrome also alters functional connectivity in the default-mode network (DMN and salience network. On a cellular/molecular level, central sensitization may be reversed through degradative glutamate receptor pathways. This, however, rarely happens. Instead, cortical brain regions may serve in a top-down regulatory capacity for the maintenance or alleviation of pain. Specifically, the medial prefrontal cortex (mPFC, which plays a critical role in fear-related brain circuits, the DMN, and salience network may be the driving forces in this process. On a cellular level, the mPFC may form new neural circuits through LTP that may cause extinction of pre-existing pain pathways found within fear-related brain circuits, the DMN, and salience network. In order to promote new LTP connections between the mPFC and other key brain structures, such as the amygdala and insula, we propose a holistic rehabilitation program including cognitive behavioral therapy (CBT and revolving around: (1 cognitive reappraisals; (2 mindfulness meditation; and (3 functional rehabilitation. Unlike current medical interventions focusing upon pain-relieving medications, we do not believe that chronic pain treatment should focus on

  11. Thermal expansion behavior in fabricated cellular structures

    International Nuclear Information System (INIS)

    Oruganti, R.K.; Ghosh, A.K.; Mazumder, J.

    2004-01-01

    Thermal expansion behavior of cellular structures is of interest in applications where undesirable deformation and failure are caused by thermal expansion mismatch. This report describes the role of processing-induced effects and metallurgical aspects of melt-processed cellular structures, such as a bi-material structure designed to contract on heating, as well as uni-material structures of regular and stochastic topology. This bi-material structure utilized the principle of internal geometric constraints to alter the expansion behavior of the internal ligaments to create overall contraction of the structure. Homogenization design method was used to design the structure, and fabrication was by direct metal deposition by laser melting of powder in another part of a joint effort. The degree of porosity and grain size in the fabricated structure are characterized and related to the laser deposition parameters. The structure was found to contract upon heating over a short range of temperature subsequent to which normal expansion ensued. Also examined in this report are uni-material cellular structures, in which internal constraints arise from residual stress variations caused by the fabrication process, and thereby alter their expansion characteristics. A simple analysis of thermal strain of this material supports the observed thermal expansion behavior

  12. Niemann-pick type C1 (NPC1) overexpression alters cellular cholesterol homeostasis.

    Science.gov (United States)

    Millard, E E; Srivastava, K; Traub, L M; Schaffer, J E; Ory, D S

    2000-12-08

    The Niemann-Pick type C1 (NPC1) protein is a key participant in intracellular trafficking of low density lipoprotein cholesterol, but its role in regulation of sterol homeostasis is not well understood. To characterize further the function of NPC1, we generated stable Chinese hamster ovary (CHO) cell lines overexpressing the human NPC1 protein (CHO/NPC1). NPC1 overexpression increases the rate of trafficking of low density lipoprotein cholesterol to the endoplasmic reticulum and the rate of delivery of endosomal cholesterol to the plasma membrane (PM). CHO/NPC1 cells exhibit a 1.5-fold increase in total cellular cholesterol and up to a 2.9-fold increase in PM cholesterol. This increase in PM cholesterol is closely paralleled by a 3-fold increase in de novo cholesterol synthesis. Inhibition of cholesterol synthesis results in marked redistribution of PM cholesterol to intracellular sites, suggesting an unsuspected role for NPC1 in internalization of PM cholesterol. Despite elevated total cellular cholesterol, CHO/NPC1 cells exhibit increased cholesterol synthesis, which may be attributable to both resistance to oxysterol suppression of sterol-regulated gene expression and to reduced endoplasmic reticulum cholesterol levels under basal conditions. Taken together, these studies provide important new insights into the role of NPC1 in the determination of the levels and distribution of cellular cholesterol.

  13. Taming the sphinx: Mechanisms of cellular sphingolipid homeostasis.

    Science.gov (United States)

    Olson, D K; Fröhlich, F; Farese, R V; Walther, T C

    2016-08-01

    Sphingolipids are important structural membrane components of eukaryotic cells, and potent signaling molecules. As such, their levels must be maintained to optimize cellular functions in different cellular membranes. Here, we review the current knowledge of homeostatic sphingolipid regulation. We describe recent studies in Saccharomyces cerevisiae that have provided insights into how cells sense changes in sphingolipid levels in the plasma membrane and acutely regulate sphingolipid biosynthesis by altering signaling pathways. We also discuss how cellular trafficking has emerged as an important determinant of sphingolipid homeostasis. Finally, we highlight areas where work is still needed to elucidate the mechanisms of sphingolipid regulation and the physiological functions of such regulatory networks, especially in mammalian cells. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. Copyright © 2015. Published by Elsevier B.V.

  14. Intraspecific priority effects modify compensatory responses to changes in hatching phenology in an amphibian.

    Science.gov (United States)

    Murillo-Rincón, Andrea P; Kolter, Nora A; Laurila, Anssi; Orizaola, Germán

    2017-01-01

    In seasonal environments, modifications in the phenology of life-history events can alter the strength of time constraints experienced by organisms. Offspring can compensate for a change in timing of hatching by modifying their growth and development trajectories. However, intra- and interspecific interactions may affect these compensatory responses, in particular if differences in phenology between cohorts lead to significant priority effects (i.e. the competitive advantage that early-hatching individuals have over late-hatching ones). Here, we conducted a factorial experiment to determine whether intraspecific priority effects can alter compensatory phenotypic responses to hatching delay in a synchronic breeder by rearing moor frog (Rana arvalis) tadpoles in different combinations of phenological delay and food abundance. Tadpoles compensated for the hatching delay by speeding up their development, but only when reared in groups of individuals with identical hatching phenology. In mixed phenology groups, strong competitive effects by non-delayed tadpoles prevented the compensatory responses and delayed larvae metamorphosed later than in single phenology treatments. Non-delayed individuals gained advantage from developing with delayed larvae by increasing their developmental and growth rates as compared to single phenology groups. Food shortage prolonged larval period and reduced mass at metamorphosis in all treatments, but it did not prevent compensatory developmental responses in larvae reared in single phenology groups. This study demonstrates that strong intraspecific priority effects can constrain the compensatory growth and developmental responses to phenological change, and that priority effects can be an important factor explaining the maintenance of synchronic life histories (i.e. explosive breeding) in seasonal environments. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

  15. Building bridges between cellular and molecular structural biology.

    Science.gov (United States)

    Patwardhan, Ardan; Brandt, Robert; Butcher, Sarah J; Collinson, Lucy; Gault, David; Grünewald, Kay; Hecksel, Corey; Huiskonen, Juha T; Iudin, Andrii; Jones, Martin L; Korir, Paul K; Koster, Abraham J; Lagerstedt, Ingvar; Lawson, Catherine L; Mastronarde, David; McCormick, Matthew; Parkinson, Helen; Rosenthal, Peter B; Saalfeld, Stephan; Saibil, Helen R; Sarntivijai, Sirarat; Solanes Valero, Irene; Subramaniam, Sriram; Swedlow, Jason R; Tudose, Ilinca; Winn, Martyn; Kleywegt, Gerard J

    2017-07-06

    The integration of cellular and molecular structural data is key to understanding the function of macromolecular assemblies and complexes in their in vivo context. Here we report on the outcomes of a workshop that discussed how to integrate structural data from a range of public archives. The workshop identified two main priorities: the development of tools and file formats to support segmentation (that is, the decomposition of a three-dimensional volume into regions that can be associated with defined objects), and the development of tools to support the annotation of biological structures.

  16. Priority in Process Algebras

    Science.gov (United States)

    Cleaveland, Rance; Luettgen, Gerald; Natarajan, V.

    1999-01-01

    This paper surveys the semantic ramifications of extending traditional process algebras with notions of priority that allow for some transitions to be given precedence over others. These enriched formalisms allow one to model system features such as interrupts, prioritized choice, or real-time behavior. Approaches to priority in process algebras can be classified according to whether the induced notion of preemption on transitions is global or local and whether priorities are static or dynamic. Early work in the area concentrated on global pre-emption and static priorities and led to formalisms for modeling interrupts and aspects of real-time, such as maximal progress, in centralized computing environments. More recent research has investigated localized notions of pre-emption in which the distribution of systems is taken into account, as well as dynamic priority approaches, i.e., those where priority values may change as systems evolve. The latter allows one to model behavioral phenomena such as scheduling algorithms and also enables the efficient encoding of real-time semantics. Technically, this paper studies the different models of priorities by presenting extensions of Milner's Calculus of Communicating Systems (CCS) with static and dynamic priority as well as with notions of global and local pre- emption. In each case the operational semantics of CCS is modified appropriately, behavioral theories based on strong and weak bisimulation are given, and related approaches for different process-algebraic settings are discussed.

  17. An integrated approach to elucidate the intra-viral and viral-cellular protein interaction networks of a gamma-herpesvirus.

    Directory of Open Access Journals (Sweden)

    Shaoying Lee

    2011-10-01

    Full Text Available Genome-wide yeast two-hybrid (Y2H screens were conducted to elucidate the molecular functions of open reading frames (ORFs encoded by murine γ-herpesvirus 68 (MHV-68. A library of 84 MHV-68 genes and gene fragments was generated in a Gateway entry plasmid and transferred to Y2H vectors. All possible pair-wise interactions between viral proteins were tested in the Y2H assay, resulting in the identification of 23 intra-viral protein-protein interactions (PPIs. Seventy percent of the interactions between viral proteins were confirmed by co-immunoprecipitation experiments. To systematically investigate virus-cellular protein interactions, the MHV-68 Y2H constructs were screened against a cellular cDNA library, yielding 243 viral-cellular PPIs involving 197 distinct cellar proteins. Network analyses indicated that cellular proteins targeted by MHV-68 had more partners in the cellular PPI network and were located closer to each other than expected by chance. Taking advantage of this observation, we scored the cellular proteins based on their network distances from other MHV-68-interacting proteins and segregated them into high (Y2H-HP and low priority/not-scored (Y2H-LP/NS groups. Significantly more genes from Y2H-HP altered MHV-68 replication when their expression was inhibited with siRNAs (53% of genes from Y2H-HP, 21% of genes from Y2H-LP/NS, and 16% of genes randomly chosen from the human PPI network; p<0.05. Enriched Gene Ontology (GO terms in the Y2H-HP group included regulation of apoptosis, protein kinase cascade, post-translational protein modification, transcription from RNA polymerase II promoter, and IκB kinase/NFκB cascade. Functional validation assays indicated that PCBP1, which interacted with MHV-68 ORF34, may be involved in regulating late virus gene expression in a manner consistent with the effects of its viral interacting partner. Our study integrated Y2H screening with multiple functional validation approaches to create

  18. Priority setting and economic appraisal: whose priorities--the community or the economist?

    Science.gov (United States)

    Green, A; Barker, C

    1988-01-01

    Scarce resources for health require a process for setting priorities. The exact mechanism chosen has important implications for the type of priorities and plans set, and in particular their relationship to the principles of primary health care. One technique increasingly advocated as an aid to priority setting is economic appraisal. It is argued however that economic appraisal is likely to reinforce a selective primary health care approach through its espousal of a technocratic medical model and through its hidden but implicit value judgements. It is suggested that urgent attention is needed to develop approaches to priority setting that incorporate the strengths of economic appraisal, but that are consistent with comprehensive primary health care.

  19. Human T lymphotropic virus type-1 p30II alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes

    Directory of Open Access Journals (Sweden)

    Feuer Gerold

    2004-11-01

    Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 is a deltaretrovirus that causes adult T-cell leukemia/lymphoma and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13II and p30II, which are incompletely defined in the virus life cycle or HTLV-1 pathogenesis. Proviral clones of the virus with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. Exogenous expression of p30II differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and represses tax/rex RNA nuclear export. Results Herein, we further characterized the role of p30II in regulation of cellular gene expression, using stable p30II expression system employing lentiviral vectors to test cellular gene expression with Affymetrix U133A arrays, representing ~33,000 human genes. Reporter assays in Jurkat T cells and RT-PCR in Jurkat and primary CD4+ T-lymphocytes were used to confirm selected gene expression patterns. Our data reveals alterations of interrelated pathways of cell proliferation, T-cell signaling, apoptosis and cell cycle in p30II expressing Jurkat T cells. In all categories, p30II appeared to be an overall repressor of cellular gene expression, while selectively increasing the expression of certain key regulatory genes. Conclusions We are the first to demonstrate that p30II, while repressing the expression of many genes, selectively activates key gene pathways involved in T-cell signaling/activation. Collectively, our data suggests that this complex retrovirus, associated with lymphoproliferative diseases, relies upon accessory gene products to modify cellular environment to promote clonal expansion of the virus genome and thus maintain proviral loads in vivo.

  20. 45 CFR 2531.20 - Funding priorities.

    Science.gov (United States)

    2010-10-01

    ... priorities. The Corporation may choose to set priorities (and to periodically revise such priorities) that... given fiscal year. In setting these priorities, the Corporation will seek to concentrate funds on those... 45 Public Welfare 4 2010-10-01 2010-10-01 false Funding priorities. 2531.20 Section 2531.20 Public...

  1. Cellular basis of morphological variation and temperature-related plasticity in Drosophila melanogaster strains with divergent wing shapes.

    Science.gov (United States)

    Torquato, Libéria Souza; Mattos, Daniel; Matta, Bruna Palma; Bitner-Mathé, Blanche Christine

    2014-12-01

    Organ shape evolves through cross-generational changes in developmental patterns at cellular and/or tissue levels that ultimately alter tissue dimensions and final adult proportions. Here, we investigated the cellular basis of an artificially selected divergence in the outline shape of Drosophila melanogaster wings, by comparing flies with elongated or rounded wing shapes but with remarkably similar wing sizes. We also tested whether cellular plasticity in response to developmental temperature was altered by such selection. Results show that variation in cellular traits is associated with wing shape differences, and that cell number may play an important role in wing shape response to selection. Regarding the effects of developmental temperature, a size-related plastic response was observed, in that flies reared at 16 °C developed larger wings with larger and more numerous cells across all intervein regions relative to flies reared at 25 °C. Nevertheless, no conclusive indication of altered phenotypic plasticity was found between selection strains for any wing or cellular trait. We also described how cell area is distributed across different intervein regions. It follows that cell area tends to decrease along the anterior wing compartment and increase along the posterior one. Remarkably, such pattern was observed not only in the selected strains but also in the natural baseline population, suggesting that it might be canalized during development and was not altered by the intense program of artificial selection for divergent wing shapes.

  2. Priorities for Extension.

    Science.gov (United States)

    Hayward, J. A.

    Agricultural extension is one component in an array including research, training, education, marketing, international trade, etc. which develop together to bring about growth, and sustained growth determines the priorities for extension. These priorities depend inevitably on the stage of development of a country or region, and on the current…

  3. Priorities of statutory claimants

    International Nuclear Information System (INIS)

    Pawluck, B.K.; Prowse, J.T.

    1996-01-01

    The statutory rights that unpaid creditors have when an oil or gas operator is placed in bankruptcy, were evaluated. Those statutory rights may give priority to their claims against the operator. Fifteen topics dealing with statutory priorities were examined, focusing on the change in priorities which would occur if the insolvent operator were placed in bankruptcy. The topics were: (1) Summary of statutory federal and provincial priorities, (2) Revenue Canada - source deductions/deemed trust, (3) Revenue Canada - source deductions/enhanced requirement to pay, (4) Revenue Canada - goods and service tax (GST)/deemed trust, (5) Revenue Canada - GST/enhanced requirement to pay, (6) Federal income taxes, (7) Validity of provincially legislated priority provisions in bankruptcy, (8) Provincially authorized municipal taxes - real property, (9) Provincial workers' compensation board, (10) Provincially legislated wages, overtime pay and holiday pay, (11) Provincially legislated severance/termination pay, (12) Provincially legislated successor employer obligations, (13) Provincially legislated private employment pension plans, (14) Provincial health care insurance premiums, and (15) Provincial freehold mineral rights tax

  4. Altered Cell Mechanics from the Inside: Dispersed Single Wall Carbon Nanotubes Integrate with and Restructure Actin

    Directory of Open Access Journals (Sweden)

    Mohammad F. Islam

    2012-05-01

    Full Text Available With a range of desirable mechanical and optical properties, single wall carbon nanotubes (SWCNTs are a promising material for nanobiotechnologies. SWCNTs also have potential as biomaterials for modulation of cellular structures. Previously, we showed that highly purified, dispersed SWCNTs grossly alter F-actin inside cells. F-actin plays critical roles in the maintenance of cell structure, force transduction, transport and cytokinesis. Thus, quantification of SWCNT-actin interactions ranging from molecular, sub-cellular and cellular levels with both structure and function is critical for developing SWCNT-based biotechnologies. Further, this interaction can be exploited, using SWCNTs as a unique actin-altering material. Here, we utilized molecular dynamics simulations to explore the interactions of SWCNTs with actin filaments. Fluorescence lifetime imaging microscopy confirmed that SWCNTs were located within ~5 nm of F-actin in cells but did not interact with G-actin. SWCNTs did not alter myosin II sub-cellular localization, and SWCNT treatment in cells led to significantly shorter actin filaments. Functionally, cells with internalized SWCNTs had greatly reduced cell traction force. Combined, these results demonstrate direct, specific SWCNT alteration of F-actin structures which can be exploited for SWCNT-based biotechnologies and utilized as a new method to probe fundamental actin-related cellular processes and biophysics.

  5. Altered White Matter Microstructure in Children with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Nagel, Bonnie J.; Bathula, Deepti; Herting, Megan; Schmitt, Colleen; Kroenke, Christopher D.; Fair, Damien; Nigg, Joel T.

    2011-01-01

    Objective: Identification of biomarkers is a priority for attention-deficit/hyperactivity disorder (ADHD). Studies have documented macrostructural brain alterations in ADHD, but few have examined white matter microstructure, particularly in preadolescent children. Given dramatic white matter maturation across childhood, microstructural differences…

  6. Altering spatial priority maps via statistical learning of target selection and distractor filtering.

    Science.gov (United States)

    Ferrante, Oscar; Patacca, Alessia; Di Caro, Valeria; Della Libera, Chiara; Santandrea, Elisa; Chelazzi, Leonardo

    2018-05-01

    with the notion that both kinds of SL adjust the priority of specific locations within attentional priority maps of space. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Final priority; Rehabilitation Services Administration--Assistive Technology Alternative Financing Program. Final priority.

    Science.gov (United States)

    2014-08-14

    The Assistant Secretary for Special Education and Rehabilitative Services announces a priority under the Assistive Technology Alternative Financing Program administered by the Rehabilitation Services Administration (RSA). The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2014 and later years. This priority is designed to ensure that the Department funds high-quality assistive technology (AT) alternative financing programs (AFPs) that meet rigorous standards in order to enable individuals with disabilities to access and acquire assistive technology devices and services necessary to achieve education, community living, and employment goals.

  8. QUEUEING DISCIPLINES BASED ON PRIORITY MATRIX

    Directory of Open Access Journals (Sweden)

    Taufik I. Aliev

    2014-11-01

    Full Text Available The paper deals with queueing disciplines for demands of general type in queueing systems with multivendor load. A priority matrix is proposed to be used for the purpose of mathematical description of such disciplines, which represents the priority type (preemptive priority, not preemptive priority or no priority between any two demands classes. Having an intuitive and simple way of priority assignment, such description gives mathematical dependencies of system operation characteristics on its parameters. Requirements for priority matrix construction are formulated and the notion of canonical priority matrix is given. It is shown that not every matrix, constructed in accordance with such requirements, is correct. The notion of incorrect priority matrix is illustrated by an example, and it is shown that such matrixes do not ensure any unambiguousness and determinacy in design of algorithm, which realizes corresponding queueing discipline. Rules governing construction of correct matrixes are given for canonical priority matrixes. Residence time for demands of different classes in system, which is the sum of waiting time and service time, is considered as one of the most important characteristics. By introducing extra event method Laplace transforms for these characteristics are obtained, and mathematical dependencies are derived on their basis for calculation of two first moments for corresponding characteristics of demands queueing

  9. International Occupational Therapy Research Priorities.

    Science.gov (United States)

    Mackenzie, Lynette; Coppola, Susan; Alvarez, Liliana; Cibule, Lolita; Maltsev, Sergey; Loh, Siew Yim; Mlambo, Tecla; Ikiugu, Moses N; Pihlar, Zdenka; Sriphetcharawut, Sarinya; Baptiste, Sue; Ledgerd, Richard

    2017-04-01

    Occupational therapy is a global profession represented by the World Federation of Occupational Therapists (WFOT). International research priorities are needed for strategic guidance on global occupational therapy practice. The objective of this study was to develop international research priorities to reflect global occupational therapy practice. A Delphi study using three rounds of electronic surveys, distributed to WFOT member organizations and WFOT accredited universities, was conducted. Data were analyzed after each round, and priorities were presented for rating and ranking in order of importance. Forty-six (53%) out of 87 WFOT member countries participated in the Delphi process. Eight research priorities were confirmed by the final electronic survey round. Differences were observed in rankings given by member organizations and university respondents. Despite attrition at Round 3, the final research priorities will help to focus research efforts in occupational therapy globally. Follow-up research is needed to determine how the research priorities are being adopted internationally.

  10. A Survey on Priority Queues

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting

    2013-01-01

    Back in 1964 Williams introduced the binary heap as a basic priority queue data structure supporting the operations Insert and ExtractMin in logarithmic time. Since then numerous papers have been published on priority queues. This paper tries to list some of the directions research on priority qu...

  11. Spaceflight induces both transient and heritable alterations in DNA methylation and gene expression in rice (Oryza sativa L.)

    Energy Technology Data Exchange (ETDEWEB)

    Ou Xiufang [Key Laboratory of Molecular Epigenetic of MOE and Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Long Likun [Inspection and Quarantine Technology Centre of Zhongshan Entry-Exit Inspection and Quarantine Bureau, Zhongshan 528400, Guangdong Province (China); Zhang Yunhong; Xue Yiqun; Liu Jingchun; Lin Xiuyun [Key Laboratory of Molecular Epigenetic of MOE and Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China); Liu Bao [Key Laboratory of Molecular Epigenetic of MOE and Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024 (China)], E-mail: baoliu6677@yahoo.com.cn

    2009-03-09

    Spaceflight represents a complex environmental condition in which several interacting factors such as cosmic radiation, microgravity and space magnetic fields are involved, which may provoke stress responses and jeopardize genome integrity. Given the inherent property of epigenetic modifications to respond to intrinsic as well as external perturbations, it is conceivable that epigenetic markers like DNA methylation may undergo alterations in response to spaceflight. We report here that extensive alteration in both DNA methylation and gene expression occurred in rice plants subjected to a spaceflight, as revealed by a set of characterized sequences including 6 transposable elements (TEs) and 11 cellular genes. We found that several features characterize the alterations: (1) All detected alterations are hypermethylation events; (2) whereas alteration in both CG and CNG methylation occurred in the TEs, only alteration in CNG methylation occurred in the cellular genes; (3) alteration in expression includes both up- and down-regulations, which did not show a general correlation with alteration in methylation; (4) altered methylation patterns in both TEs and cellular genes are heritable to progenies at variable frequencies; however, stochastic reversion to wild-type patterns and further de novo changes in progenies are also apparent; and (5) the altered expression states in both TEs and cellular genes are also heritable to selfed progenies but with markedly lower transmission frequencies than altered DNA methylation states. Furthermore, we found that a set of genes encoding for the various putative DNA methyltransferases, 5-methylcytosine DNA glycosylases, the SWI/SNF chromatin remodeller (DDM1) and siRNA-related proteins are extremely sensitive to perturbation by spaceflight, which might be an underlying cause for the altered methylation patterns in the space-flown plants. We discuss implications of spaceflight-induced epigenetic variations with regard to health safety

  12. Spaceflight induces both transient and heritable alterations in DNA methylation and gene expression in rice (Oryza sativa L.)

    International Nuclear Information System (INIS)

    Ou Xiufang; Long Likun; Zhang Yunhong; Xue Yiqun; Liu Jingchun; Lin Xiuyun; Liu Bao

    2009-01-01

    Spaceflight represents a complex environmental condition in which several interacting factors such as cosmic radiation, microgravity and space magnetic fields are involved, which may provoke stress responses and jeopardize genome integrity. Given the inherent property of epigenetic modifications to respond to intrinsic as well as external perturbations, it is conceivable that epigenetic markers like DNA methylation may undergo alterations in response to spaceflight. We report here that extensive alteration in both DNA methylation and gene expression occurred in rice plants subjected to a spaceflight, as revealed by a set of characterized sequences including 6 transposable elements (TEs) and 11 cellular genes. We found that several features characterize the alterations: (1) All detected alterations are hypermethylation events; (2) whereas alteration in both CG and CNG methylation occurred in the TEs, only alteration in CNG methylation occurred in the cellular genes; (3) alteration in expression includes both up- and down-regulations, which did not show a general correlation with alteration in methylation; (4) altered methylation patterns in both TEs and cellular genes are heritable to progenies at variable frequencies; however, stochastic reversion to wild-type patterns and further de novo changes in progenies are also apparent; and (5) the altered expression states in both TEs and cellular genes are also heritable to selfed progenies but with markedly lower transmission frequencies than altered DNA methylation states. Furthermore, we found that a set of genes encoding for the various putative DNA methyltransferases, 5-methylcytosine DNA glycosylases, the SWI/SNF chromatin remodeller (DDM1) and siRNA-related proteins are extremely sensitive to perturbation by spaceflight, which might be an underlying cause for the altered methylation patterns in the space-flown plants. We discuss implications of spaceflight-induced epigenetic variations with regard to health safety

  13. Comprehensive analysis of temporal alterations in cellular proteome of Bacillus subtilis under curcumin treatment.

    Directory of Open Access Journals (Sweden)

    Panga Jaipal Reddy

    Full Text Available Curcumin is a natural dietary compound with antimicrobial activity against various gram positive and negative bacteria. This study aims to investigate the proteome level alterations in Bacillus subtilis due to curcumin treatment and identification of its molecular/cellular targets to understand the mechanism of action. We have performed a comprehensive proteomic analysis of B. subtilis AH75 strain at different time intervals of curcumin treatment (20, 60 and 120 min after the drug exposure, three replicates to compare the protein expression profiles using two complementary quantitative proteomic techniques, 2D-DIGE and iTRAQ. To the best of our knowledge, this is the first comprehensive longitudinal investigation describing the effect of curcumin treatment on B. subtilis proteome. The proteomics analysis revealed several interesting targets such UDP-N-acetylglucosamine 1-carboxyvinyltransferase 1, putative septation protein SpoVG and ATP-dependent Clp protease proteolytic subunit. Further, in silico pathway analysis using DAVID and KOBAS has revealed modulation of pathways related to the fatty acid metabolism and cell wall synthesis, which are crucial for cell viability. Our findings revealed that curcumin treatment lead to inhibition of the cell wall and fatty acid synthesis in addition to differential expression of many crucial proteins involved in modulation of bacterial metabolism. Findings obtained from proteomics analysis were further validated using 5-cyano-2,3-ditolyl tetrazolium chloride (CTC assay for respiratory activity, resazurin assay for metabolic activity and membrane integrity assay by potassium and inorganic phosphate leakage measurement. The gene expression analysis of selected cell wall biosynthesis enzymes has strengthened the proteomics findings and indicated the major effect of curcumin on cell division.

  14. Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States.

    Science.gov (United States)

    Kim, Jong Wook; Abudayyeh, Omar O; Yeerna, Huwate; Yeang, Chen-Hsiang; Stewart, Michelle; Jenkins, Russell W; Kitajima, Shunsuke; Konieczkowski, David J; Medetgul-Ernar, Kate; Cavazos, Taylor; Mah, Clarence; Ting, Stephanie; Van Allen, Eliezer M; Cohen, Ofir; Mcdermott, John; Damato, Emily; Aguirre, Andrew J; Liang, Jonathan; Liberzon, Arthur; Alexe, Gabriella; Doench, John; Ghandi, Mahmoud; Vazquez, Francisca; Weir, Barbara A; Tsherniak, Aviad; Subramanian, Aravind; Meneses-Cime, Karina; Park, Jason; Clemons, Paul; Garraway, Levi A; Thomas, David; Boehm, Jesse S; Barbie, David A; Hahn, William C; Mesirov, Jill P; Tamayo, Pablo

    2017-08-23

    The systematic sequencing of the cancer genome has led to the identification of numerous genetic alterations in cancer. However, a deeper understanding of the functional consequences of these alterations is necessary to guide appropriate therapeutic strategies. Here, we describe Onco-GPS (OncoGenic Positioning System), a data-driven analysis framework to organize individual tumor samples with shared oncogenic alterations onto a reference map defined by their underlying cellular states. We applied the methodology to the RAS pathway and identified nine distinct components that reflect transcriptional activities downstream of RAS and defined several functional states associated with patterns of transcriptional component activation that associates with genomic hallmarks and response to genetic and pharmacological perturbations. These results show that the Onco-GPS is an effective approach to explore the complex landscape of oncogenic cellular states across cancers, and an analytic framework to summarize knowledge, establish relationships, and generate more effective disease models for research or as part of individualized precision medicine paradigms. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Defining priorities

    CERN Multimedia

    2013-01-01

    Last week the European Strategy Group met in Erice (Italy) to distil reams of input and months of discussion into a concise document outlining an updated Strategy for European Particle Physics. The result is a document that will be presented to the Council for feedback next month, before final approval by the Council at a special meeting in Brussels on 29 May. The Strategy process was important when it began in 2005, and is even more so today with important discoveries behind us and a changing global landscape for particle physics ahead.   The draft update, it’s fair to say, contains few surprises, but there are nevertheless some weighty issues for the Council to deliberate. The top priority is, of course, the full exploitation of the LHC, but the Strategy goes further, stating unambiguously that Europe’s top priority should be the high-luminosity upgrade of the machine. Other high-priority items are accelerator R&D to ensure the long-term global future of the field. O...

  16. 15 CFR 700.11 - Priority ratings.

    Science.gov (United States)

    2010-01-01

    ... OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700.11 Priority ratings. (a) Levels of...

  17. Simulation of Regionally Ecological Land Based on a Cellular Automation Model: A Case Study of Beijing, China

    Directory of Open Access Journals (Sweden)

    Xiubin Li

    2012-08-01

    Full Text Available Ecological land is like the “liver” of a city and is very useful to public health. Ecological land change is a spatially dynamic non-linear process under the interaction between natural and anthropogenic factors at different scales. In this study, by setting up natural development scenario, object orientation scenario and ecosystem priority scenario, a Cellular Automation (CA model has been established to simulate the evolution pattern of ecological land in Beijing in the year 2020. Under the natural development scenario, most of ecological land will be replaced by construction land and crop land. But under the scenarios of object orientation and ecosystem priority, the ecological land area will increase, especially under the scenario of ecosystem priority. When considering the factors such as total area of ecological land, loss of key ecological land and spatial patterns of land use, the scenarios from priority to inferiority are ecosystem priority, object orientation and natural development, so future land management policies in Beijing should be focused on conversion of cropland to forest, wetland protection and prohibition of exploitation of natural protection zones, water source areas and forest parks to maintain the safety of the regional ecosystem.

  18. Simulation of regionally ecological land based on a cellular automation model: a case study of Beijing, China.

    Science.gov (United States)

    Xie, Hualin; Kung, Chih-Chun; Zhang, Yanting; Li, Xiubin

    2012-08-01

    Ecological land is like the "liver" of a city and is very useful to public health. Ecological land change is a spatially dynamic non-linear process under the interaction between natural and anthropogenic factors at different scales. In this study, by setting up natural development scenario, object orientation scenario and ecosystem priority scenario, a Cellular Automation (CA) model has been established to simulate the evolution pattern of ecological land in Beijing in the year 2020. Under the natural development scenario, most of ecological land will be replaced by construction land and crop land. But under the scenarios of object orientation and ecosystem priority, the ecological land area will increase, especially under the scenario of ecosystem priority. When considering the factors such as total area of ecological land, loss of key ecological land and spatial patterns of land use, the scenarios from priority to inferiority are ecosystem priority, object orientation and natural development, so future land management policies in Beijing should be focused on conversion of cropland to forest, wetland protection and prohibition of exploitation of natural protection zones, water source areas and forest parks to maintain the safety of the regional ecosystem.

  19. Methods for the Analysis of Protein Phosphorylation-Mediated Cellular Signaling Networks

    Science.gov (United States)

    White, Forest M.; Wolf-Yadlin, Alejandro

    2016-06-01

    Protein phosphorylation-mediated cellular signaling networks regulate almost all aspects of cell biology, including the responses to cellular stimulation and environmental alterations. These networks are highly complex and comprise hundreds of proteins and potentially thousands of phosphorylation sites. Multiple analytical methods have been developed over the past several decades to identify proteins and protein phosphorylation sites regulating cellular signaling, and to quantify the dynamic response of these sites to different cellular stimulation. Here we provide an overview of these methods, including the fundamental principles governing each method, their relative strengths and weaknesses, and some examples of how each method has been applied to the analysis of complex signaling networks. When applied correctly, each of these techniques can provide insight into the topology, dynamics, and regulation of protein phosphorylation signaling networks.

  20. Role of thiols in cellular response to radiation and drugs. Symposium: thiols

    International Nuclear Information System (INIS)

    Biaglow, J.E.; Varnes, M.E.; Clark, E.P.; Epp, E.R.

    1983-01-01

    Cellular nonprotein thiols (NPSH) consist of glutathione (GSH) and other low molecular weight species such as cysteine, cysteamine, and coenzyme. A GSH is usually less than the total cellular NPSH, and with thiol reactive agents, such as diethyl maleate (DEM), its rate of depletion is in part dependent upon the cellular capacity for its resynthesis. If resynthesis is blocked by buthionine-S,R-sulfoximine(BSO), the NPSH, including GSH, is depleted more rapidly, Cellular thiol depletion by diamide, N-ethylmaleimide, and BSO may render oxygenated cells more sensitive to radiation. These cells may or may not show a reduction in the oxygen enhancement ratio (OER). Human A549 lung carcinoma cells depleted of their NPSH either by prolonged culture or by BSO treatment do not show a reduced OER but do show increased aerobic responses to radiation. Other nitrocompounds, such as misonidazole, are activated under hypoxic conditions to radical intermediates. When cellular thiols are depleted peroxide is formed. Under hypoxic conditions thiols are depleted because metabolically reduced intermediates react with GSH instead of oxygen. Thiol depletion, under hypoxic conditions, may be the reason that misonidazole and other nitrocompounds show an extra enhancement ratio with hypoxic cells. Thiol depletion by DEM or BSO alters the radiation response of hypoxic cells to misonidazole. In conclusion, we propose an altered thiol model which includes a mechanism for thiol involvement in the aerobic radiation response of cells

  1. Estradiol-induced promotion of hepatocarcinogenesis in medaka: Relationship of foci of cellular alteration to neoplasia

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, J.B.; Hinton, D.E. [Univ. of California, Davis, CA (United States)

    1995-12-31

    In some laboratory and field studies, female fish have higher prevalences of liver tumors than do males. The authors hypothesize gender and site-specific differences in prevalence are due to variable exposures of previously initiated fish to tumor modulating compounds. Estradiol, a growth promoter, increases incidences of hepatic tumors in carcinogen-treated rainbow trout and medaka (Oryzias latipes). Estradiol also increases incidences of hepatic foci of cellular alteration (FCA) in medaka. FCA are found in subadults of tumor-bearing feral populations. Lack of knowledge about the relationship of various phenotypes of FCA to eventual tumors, however, has prevented use of FCA as a biomarker. The authors examined fate and growth of liver FCA using a 2-step, initiation-promotion protocol. Three week old medaka were exposed to 200 ppm diethylnitrosamine (DEN) for 24 hr. and then fed 0.1 ppm 17-{beta}-estradiol (E2) continuously through sampling at weeks 4--26. Percent volume of FCA and morphometric characteristics of normal and focal hepatocytes, including numerical density and average hepatocyte volume were quantified using computer-assisted stereology. E2 increased percentage of liver occupied by DEN-initiated amphophilic, basophilic and eosinophilic FCA in both sexes. Focal parameters of young, DEN-initiated and estradiol-treated medaka were not reached until much later in fish given only DEN. Non-focal hepatocytes in estradiol-treated medaka were smaller and more numerous than in DEN-only counterparts. Morphometric analysis is quantitatively tracking the fate of specific phenotypes of FCA to determine their role in progression to cancer.

  2. The thorny path linking cellular senescence to organismalaging

    Energy Technology Data Exchange (ETDEWEB)

    Patil, Christopher K.; Mian, Saira; Campisi, Judith

    2005-08-09

    Half a century is fast approaching since Hayflick and colleagues formally described the limited ability of normal human cells to proliferate in culture (Hayflick and Moorhead, 1961). This finding--that normal somatic cells, in contrast to cancer cells, cannot divide indefinitely--challenged the prevailing idea that cells from mortal multicellular organisms were intrinsically ''immortal'' (Carrell, 1912). It also spawned two hypotheses, essential elements of which persist today. The first held that the restricted proliferation of normal cells, now termed cellular senescence, suppresses cancer (Hayflick, 1965; Sager, 1991; Campisi, 2001). The second hypothesis, as explained in the article by Lorenzini et al., suggested that the limited proliferation of cells in culture recapitulated aspects of organismal aging (Hayflick, 1965; Martin, 1993). How well have these hypotheses weathered the ensuing decades? Before answering this question, we first consider current insights into the causes and consequences of cellular senescence. Like Lorenzini et al., we limit our discussion to mammals. We also focus on fibroblasts, the cell type studied by Lorenzini et al., but consider other types as well. We suggest that replicative capacity in culture is not a straightforward assessment, and that it correlates poorly with both longevity and body mass. We speculate this is due to the malleable and variable nature of replicative capacity, which renders it an indirect metric of qualitative and quantitative differences among cells to undergo senescence, a response that directly alters cellular phenotype and might indirectly alter tissue structure and function.

  3. Healthcare priority setting in Kenya

    DEFF Research Database (Denmark)

    Bukachi, Salome A.; Onyango-Ouma, Washington; Siso, Jared Maaka

    2014-01-01

    In resource-poor settings, the accountability for reasonableness (A4R) has been identified as an important advance in priority setting that helps to operationalize fair priority setting in specific contexts. The four conditions of A4R are backed by theory, not evidence, that conformance with them...... improves the priority setting decisions. This paper describes the healthcare priority setting processes in Malindi district, Kenya, prior to the implementation of A4R in 2008 and evaluates the process for its conformance with the conditions for A4R. In-depth interviews and focus group discussions with key...... players in the Malindi district health system and a review of key policy documents and national guidelines show that the priority setting process in the district relies heavily on guidelines from the national level, making it more of a vertical, top-down orientation. Multilateral and donor agencies...

  4. Cellular proliferation and infiltration following interstitial irradiation of normal dog brain is altered by an inhibitor of polyamine synthesis

    International Nuclear Information System (INIS)

    Fike, John R.; Gobbel, Glenn T.; Chou, Dean; Wijnhoven, Bas P. L.; Bellinzona, Mattia; Nakagawa, Minoru; Seilhan, Theresa M.

    1995-01-01

    Purpose: The objectives of this study were to quantitatively define proliferative and infiltrative cell responses after focal 125 I irradiation of normal brain, and to determine the effects of an intravenous infusion of α-difluoromethylornithine (DFMO) on those responses. Methods and Materials: Adult beagle dogs were irradiated using high activity 125 I sources. Saline (control) or DFMO (150 mg/kg/day) was infused for 18 days starting 2 days before irradiation. At varying times up to 8 weeks after irradiation, brain tissues were collected and the cell responses in and around the focal lesion were quantified. Immunohistochemical stains were used to label astrocytes (GFAP), vascular endothelial cells (Factor VIII), polymorphonuclear leukocytes (PMNs; MAC 387) and cells synthesizing deoxyribonucleic acid (DNA) (BrdU). Cellular responses were quantified using a histomorphometric analysis. Results: After radiation alone, cellular events included a substantial acute inflammatory response followed by increased BrdU labeling and progressive increases in numbers of capillaries and astrocytes. α-Difluoromethylornithine treatment significantly affected the measured cell responses. As in controls, an early inflammatory response was measured, but after 2 weeks there were more PMNs/unit area than in controls. The onset of measurable BrdU labeling was delayed in DFMO-treated animals, and the magnitude of labeling was significantly reduced. Increases in astrocyte and vessel numbers/mm 2 were observed after a 2-week delay. At the site of implant, astrocytes from DFMO-treated dogs were significantly smaller than those from controls. Conclusions: There is substantial cell proliferation and infiltration in response to interstitial irradiation of normal brain, and these responses are significantly altered by DFMO treatment. Although the precise mechanisms by which DFMO exerts its effects in this model are not known, the results from this study suggest that modification of radiation

  5. Politicians’ priorities and the determinants of priorities in the Swedish social services

    Directory of Open Access Journals (Sweden)

    Marie Wörlén

    2012-04-01

    Full Text Available The setting of priorities is an integrated part of social-work politics in Sweden as well as internationally. This article explores Swedish social services and how politicians on the political boards wish to make priorities and what these priorities involve. The use of regression analyses also reveals which circumstances are of importance for allocative precedence and the impact different distributive principles have. It is hard to detect clear-cut patterns of circumstances that guide the judgements in any one direction. The results show that political affiliation overall is not a determining factor for attitudes towards how priorities are made. Another result is a manifest area bias, suggesting that respondents tend to see to the interests of their own professional domain, a result most visible among the politicians involved with Care for the Elderly and Disabled (CED. Yet, with regard to allocative principles, political colour seems to matter. Conservative politicians, as expected, agree with the principles of economy and of capacity to benefit, while the socialist block, less expectedly, seems to embrace the principle of deservingness.

  6. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    Energy Technology Data Exchange (ETDEWEB)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Casas, Josefina [Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain); Lacorte, Sílvia, E-mail: slbqam@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Porte, Cinta, E-mail: cinta.porte@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)

    2014-06-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  7. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    International Nuclear Information System (INIS)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet; Casas, Josefina; Lacorte, Sílvia; Porte, Cinta

    2014-01-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  8. Alterations in the developing testis transcriptome following embryonic vinclozolin exposure.

    Science.gov (United States)

    Clement, Tracy M; Savenkova, Marina I; Settles, Matthew; Anway, Matthew D; Skinner, Michael K

    2010-11-01

    The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic days 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Categorization by major known functions of altered genes was performed. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Basic priority rating model 2.0: current applications for priority setting in health promotion practice.

    Science.gov (United States)

    Neiger, Brad L; Thackeray, Rosemary; Fagen, Michael C

    2011-03-01

    Priority setting is an important component of systematic planning in health promotion and also factors into the development of a comprehensive evaluation plan. The basic priority rating (BPR) model was introduced more than 50 years ago and includes criteria that should be considered in any priority setting approach (i.e., use of predetermined criteria, standardized comparisons, and a rubric that controls bias). Although the BPR model has provided basic direction in priority setting, it does not represent the broad array of data currently available to decision makers. Elements in the model also give more weight to the impact of communicable diseases compared with chronic diseases. For these reasons, several modifications are recommended to improve the BPR model and to better assist health promotion practitioners in the priority setting process. The authors also suggest a new name, BPR 2.0, to represent this revised model.

  10. Theoretical cell alteration model in the context of carcinogenesis

    International Nuclear Information System (INIS)

    Walsh, P.J.

    1976-01-01

    A model incorporating cell survival and alteration is used to discuss the general nature of cellular response to a toxic agent. Cell division and repair are discussed as regards their influence on dose-response relationships to bone-seeking radionuclides. The application of the model in its present form to specific biologic end points depends on the assumption that such end points are the result of some initial alteration

  11. Cellular roles of ADAM12 in health and disease

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Albrechtsen, Reidar; Couchman, John R

    2008-01-01

    and it is a potential biomarker for breast cancer. It is therefore important to understand ADAM12's functions. Many cellular roles for ADAM12 have been suggested. It is an active metalloprotease, and has been implicated in insulin-like growth factor (IGF) receptor signaling, through cleavage of IGF-binding proteins......, and in epidermal growth factor receptor (EGFR) pathways, via ectodomain shedding of membrane-tethered EGFR ligands. These proteolytic events may regulate diverse cellular responses, such as altered cell differentiation, proliferation, migration, and invasion. ADAM12 may also regulate cell-cell and cell...... to or from the cell interior. These ADAM12-mediated cellular effects appear to be critical events in both biological and pathological processes. This review presents current knowledge on ADAM12 functions gained from in vitro and in vivo observations, describes ADAM12's role in both normal physiology...

  12. Pathogenesis of pulmonary emphysema – cellular and molecular events

    Directory of Open Access Journals (Sweden)

    Antonio Di Petta

    2010-06-01

    Full Text Available Pulmonary emphysema is a chronic obstructive disease, resulting fromimportant alterations in the whole distal structure of terminal bronchioles, either by enlargement of air spaces or by destruction of the alveolar wall, leading to loss of respiratory surface, decreased elastic recoil and lung hyperinflation. For many years, the hypothesis of protease-antiprotease unbalance prevailed as the central theme in the pathogenesis of pulmonary emphysema. According to this hypothesis, the release of active proteolytic enzymes, produced mainly by neutrophils and macrophages, degrades the extracellular matrix, affecting the integrity of its components, especially collagen and elastic fibers. However, new concepts involving cellular and molecular events were proposed, including oxidative stress, cell apoptosis, cellular senescence and failed lung tissue repair. The aim of this review paper was to evaluate the cellular and molecular mechanisms seen in the pathogenesis of pulmonary emphysema.

  13. Priority for sustainability. Final report

    International Nuclear Information System (INIS)

    2007-12-01

    The Dutch Minister of Economic Affairs (EZ) has been asked to realize priority in connection to the grid for sustainable production capacity. Currently there are waiting lists for connection of new production capacity to the grid in some areas, due to a shortage in transport capacity. The Dutch connection policy (first come, first serve) may possibly lead to delays in connecting sustainable production capacity, which is not desirable in view of the incentivisation of sustainability. EZ and TenneT have asked Booz Allen to examine the options for giving priority to sustainability (wind and CHP). Priority in connection applies only to new sustainable production capacity, but priority in transport also applies to existing sustainable production capacity. [mk] [nl

  14. Priority Queues Resilient to Memory Faults

    DEFF Research Database (Denmark)

    Jørgensen, Allan Grønlund; Moruz, Gabriel; Mølhave, Thomas

    2007-01-01

    In the faulty-memory RAM model, the content of memory cells can get corrupted at any time during the execution of an algorithm, and a constant number of uncorruptible registers are available. A resilient data structure in this model works correctly on the set of uncorrupted values. In this paper we...... introduce a resilient priority queue. The deletemin operation of a resilient priority queue returns either the minimum uncorrupted element or some corrupted element. Our resilient priority queue uses $O(n)$ space to store $n$ elements. Both insert and deletemin operations are performed in $O(\\log n......+\\delta)$ time amortized, where $\\delta$ is the maximum amount of corruptions tolerated. Our priority queue matches the performance of classical optimal priority queues in the RAM model when the number of corruptions tolerated is $O(\\log n)$. We prove matching worst case lower bounds for resilient priority...

  15. Experimental tests of priority effects and light availability on relative performance of Myriophyllum spicatum and Elodea nuttallii propagules in artificial stream channels.

    Directory of Open Access Journals (Sweden)

    Emily P Zefferman

    Full Text Available Submersed macrophytes have important ecological functions in many streams, but fostering growth of beneficial native species while suppressing weedy invasives may be challenging. Two approaches commonly used in management of terrestrial plant communities may be useful in this context: (1 altering resource availability and (2 establishing desirable species before weeds can invade (priority effects. However, these approaches are rarely used in aquatic systems, despite widespread need for sustainable solutions to aquatic weed problems. In artificial stream channels in California, USA, I conducted experiments with asexual propagules of non-native invasive Myriophyllum spicatum (Eurasian watermilfoil and native Elodea nuttallii (western waterweed to address the questions: (1 How does light availability affect relative performance of the two species?; (2 Does planting the native earlier than the invasive decrease survival or growth rate of the invasive?; and (3 Do light level and priority effects interact? The relative performance between E. nuttallii and M. spicatum had an interesting and unexpected pattern: M. spicatum had higher growth rates than E. nuttallii in the zero and medium shade levels, but had similar performance in the low and high shade levels. This pattern is most likely the result of E. nutallii's sensitivity to both very low and very high light, and M. spicatum's sensitivity to very low light only. Native priority did not significantly affect growth rate or survival of M. spicatum, possibly because of unexpectedly poor growth of the E. nuttallii planted early. This study suggests that altering light levels could be effective in reducing growth of an invasive macrophyte, and for changing the competitive balance between a native and a non-native species in the establishment phase. Further investigations into the use of priority effects and resource alteration for submersed macrophyte management are warranted, given their mixed results

  16. Experimental tests of priority effects and light availability on relative performance of Myriophyllum spicatum and Elodea nuttallii propagules in artificial stream channels.

    Science.gov (United States)

    Zefferman, Emily P

    2015-01-01

    Submersed macrophytes have important ecological functions in many streams, but fostering growth of beneficial native species while suppressing weedy invasives may be challenging. Two approaches commonly used in management of terrestrial plant communities may be useful in this context: (1) altering resource availability and (2) establishing desirable species before weeds can invade (priority effects). However, these approaches are rarely used in aquatic systems, despite widespread need for sustainable solutions to aquatic weed problems. In artificial stream channels in California, USA, I conducted experiments with asexual propagules of non-native invasive Myriophyllum spicatum (Eurasian watermilfoil) and native Elodea nuttallii (western waterweed) to address the questions: (1) How does light availability affect relative performance of the two species?; (2) Does planting the native earlier than the invasive decrease survival or growth rate of the invasive?; and (3) Do light level and priority effects interact? The relative performance between E. nuttallii and M. spicatum had an interesting and unexpected pattern: M. spicatum had higher growth rates than E. nuttallii in the zero and medium shade levels, but had similar performance in the low and high shade levels. This pattern is most likely the result of E. nutallii's sensitivity to both very low and very high light, and M. spicatum's sensitivity to very low light only. Native priority did not significantly affect growth rate or survival of M. spicatum, possibly because of unexpectedly poor growth of the E. nuttallii planted early. This study suggests that altering light levels could be effective in reducing growth of an invasive macrophyte, and for changing the competitive balance between a native and a non-native species in the establishment phase. Further investigations into the use of priority effects and resource alteration for submersed macrophyte management are warranted, given their mixed results in other

  17. 49 CFR 260.7 - Priority consideration.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Priority consideration. 260.7 Section 260.7... REHABILITATION AND IMPROVEMENT FINANCING PROGRAM Overview § 260.7 Priority consideration. When evaluating applications, the Administrator will give priority consideration (but not necessarily in the following order...

  18. Final priority; National Institute on Disability and Rehabilitation Research--Rehabilitation Engineering Research Centers. Final priority.

    Science.gov (United States)

    2014-07-09

    The Assistant Secretary for Special Education and Rehabilitative Services announces a priority under the Disability and Rehabilitation Research Projects and Centers Program administered by the National Institute on Disability and Rehabilitation Research (NIDRR). Specifically, we announce a priority for a Rehabilitation Engineering Research Center (RERC) on Improving the Accessibility, Usability, and Performance of Technology for Individuals who are Deaf or Hard of Hearing. The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2014 and later years. We take this action to focus research attention on an area of national need. We intend the priority to contribute to improving the accessibility, usability, and performance of technology for individuals who are deaf or hard of hearing.

  19. Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction

    Directory of Open Access Journals (Sweden)

    Corina T. Madreiter-Sokolowski

    2018-03-01

    Full Text Available Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS ensures a supply of adenosine triphosphate (ATP, but is also the main source of potentially harmful levels of reactive oxygen species (ROS. Moreover, mitochondrial function is strongly linked to mitochondrial Ca2+ homeostasis and mitochondrial shape, which undergo various alterations during aging. Since mitochondria play such a critical role in an organism’s process of aging, they also offer promising targets for manipulation of senescent cellular functions. Accordingly, interventions delaying the onset of age-associated disorders involve the manipulation of mitochondrial function, including caloric restriction (CR or exercise, as well as drugs, such as metformin, aspirin, and polyphenols. In this review, we discuss mitochondria’s role in and impact on cellular aging and their potential to serve as a target for therapeutic interventions against age-related cellular dysfunction.

  20. Cellular membrane accommodation of copper-induced oxidative conditions in the coral Seriatopora caliendrum

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chuan-Ho, E-mail: chtang@nmmba.gov.tw [Institute of Marine Biodiversity and Evolutionary Biology, National Dong Hwa University, Pingtung, Taiwan, ROC (China); National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China); Lin, Ching-Yu [Institute of Environmental Health, National Taiwan University, Taipei City, Taiwan, ROC (China); Lee, Shu-Hui [Center of General Education, National Kaohsiung Marine University, Kaohsiung, Taiwan, ROC (China); Wang, Wei-Hsien [National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China); Department of Marine Biotechnology and Resources and Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC (China)

    2014-03-01

    Highlights: • Coral cells alter membrane lipid to accommodate copper-induce oxidative conditions • Coral membrane repair occur due to lipid alterations • Zooxanthellae release results from membrane repair by symbiosome fusion • Copper-induced lipid alterations perturb membrane-related functions in coral cells • Copper chronic effect on coral fitness are related to long-term membrane perturbation - Abstract: Oxidative stress has been associated with copper-induced toxicity in scleractinian corals. To gain insight into the accommodation of the cellular membrane to oxidative conditions, a pocilloporid coral, Seriatopora caliendrum, was exposed to copper at distinct, environmentally relevant dose for various lengths of time. Glycerophosphocholine profiling of the response of the coral to copper exposure was characterized using a validated method. The results indicate that coral lipid metabolism is programmed to induce membrane alterations in response to the cellular deterioration that occurs during the copper exposure period. Decreasing lyso-phosphatidylcholines and exchanging polyunsaturated phosphatidylcholines for polyunsaturated plasmanylcholines were the initial actions taken to prevent membrane permeabilization. To relax/resist the resulting membrane strain caused by cell/organelle swelling, the coral cells inversely exchanged polyunsaturated plasmanylcholines for polyunsaturated phosphatidylcholines and further increased the levels of monounsaturated glycerophosphocholines. At the same time, the levels of saturated phosphatidylcholines were also increased to increase membrane rigidity and protect against oxidative attack. Interestingly, such alterations in lipid metabolism were also required for membrane fusion to repair the deteriorated membranes by repopulating them with proximal lipid reservoirs, similar to symbiosome membranes. Additionally, increasing saturated and monounsaturated plasmanylcholines and inhibiting the suppression of saturated lyso

  1. Cellular membrane accommodation of copper-induced oxidative conditions in the coral Seriatopora caliendrum

    International Nuclear Information System (INIS)

    Tang, Chuan-Ho; Lin, Ching-Yu; Lee, Shu-Hui; Wang, Wei-Hsien

    2014-01-01

    Highlights: • Coral cells alter membrane lipid to accommodate copper-induce oxidative conditions • Coral membrane repair occur due to lipid alterations • Zooxanthellae release results from membrane repair by symbiosome fusion • Copper-induced lipid alterations perturb membrane-related functions in coral cells • Copper chronic effect on coral fitness are related to long-term membrane perturbation - Abstract: Oxidative stress has been associated with copper-induced toxicity in scleractinian corals. To gain insight into the accommodation of the cellular membrane to oxidative conditions, a pocilloporid coral, Seriatopora caliendrum, was exposed to copper at distinct, environmentally relevant dose for various lengths of time. Glycerophosphocholine profiling of the response of the coral to copper exposure was characterized using a validated method. The results indicate that coral lipid metabolism is programmed to induce membrane alterations in response to the cellular deterioration that occurs during the copper exposure period. Decreasing lyso-phosphatidylcholines and exchanging polyunsaturated phosphatidylcholines for polyunsaturated plasmanylcholines were the initial actions taken to prevent membrane permeabilization. To relax/resist the resulting membrane strain caused by cell/organelle swelling, the coral cells inversely exchanged polyunsaturated plasmanylcholines for polyunsaturated phosphatidylcholines and further increased the levels of monounsaturated glycerophosphocholines. At the same time, the levels of saturated phosphatidylcholines were also increased to increase membrane rigidity and protect against oxidative attack. Interestingly, such alterations in lipid metabolism were also required for membrane fusion to repair the deteriorated membranes by repopulating them with proximal lipid reservoirs, similar to symbiosome membranes. Additionally, increasing saturated and monounsaturated plasmanylcholines and inhibiting the suppression of saturated lyso

  2. Cell phone use and parotid salivary gland alterations: no molecular evidence.

    Science.gov (United States)

    de Souza, Fabrício T A; Correia-Silva, Jeane F; Ferreira, Efigênia F; Siqueira, Elisa C; Duarte, Alessandra P; Gomez, Marcus Vinícius; Gomez, Ricardo S; Gomes, Carolina C

    2014-07-01

    The association between cell phone use and the development of parotid tumors is controversial. Because there is unequivocal evidence that the microenvironment is important for tumor formation, we investigated in the parotid glands whether cell phone use alters the expression of gene products related to cellular stress. We used the saliva produced by the parotid glands of 62 individuals to assess molecular alterations compatible with cellular stress, comparing the saliva from the gland exposed to cell phone radiation (ipsilateral) to the saliva from the opposite, unexposed parotid gland (contralateral) of each individual. We compared salivary flow, total protein concentration, p53, p21, reactive oxygen species (ROS), and salivary levels of glutathione (GSH), heat shock proteins 27 and 70, and IgA between the ipsilateral and contralateral parotids. No difference was found for any of these parameters, even when grouping individuals by period of cell phone use in years or by monthly average calls in minutes. We provide molecular evidence that the exposure of parotid glands to cell phone use does not alter parotid salivary flow, protein concentration, or levels of proteins of genes that are directly or indirectly affected by heat-induced cellular stress. ©2014 American Association for Cancer Research.

  3. Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations.

    Science.gov (United States)

    Yadav, Monu; Jindal, Deepak Kumar; Dhingra, Mamta Sachdeva; Kumar, Anil; Parle, Milind; Dhingra, Sameer

    2018-04-01

    Gallic acid has been reported to possess a number of psychopharmacological activities. These activities are attributed to the antioxidant potential due to the presence of phenolic moeity. The present study was carried out to investigate the protective effects of gallic acid in an experimental model of ketamine-induced psychosis in mice. Ketamine (50 mg/kg, i.p.) was used to induce stereotyped psychotic behavioural symptoms in mice. Behavioural studies (locomotor activity, stereotype behaviour, immobility duration and memory retention) were carried out to investigate the protective of gallic acid on ketamine-induced psychotic symptoms, followed by biochemical and neurochemical changes and cellular alterations in the brain. Chronic treatment with gallic acid for 15 consecutive days significantly attenuated stereotyped behavioural symptoms in mice. Biochemical estimations revealed that gallic acid reduced the lipid peroxidation and restored the total brain proteins. Furthermore, gallic acid remarkably reduced the dopamine levels, AChE activity and inflammatory surge (serum TNF-α), and increased the levels of GABA and increased glutathione in mice. The study revealed that gallic acid could ameliorate psychotic symptoms and biochemical changes in mice, indicating protective effects in psychosis.

  4. Priority actions (Environmental protection in Macedonia)

    International Nuclear Information System (INIS)

    1997-01-01

    The priority actions were based on environmental needs in the short to medium term, keeping in mind that there are severe budgetary constraints and the environmental institutions are still being developed. The private sector will be encouraged to participate, wherever possible in implementing the priority actions.Based on the evaluation of all the environmental priorities, the following are considered priority actions which should be addressed within the next five years: air quality improvement; water quality improvement; solid waste management; biodiversity conservation; renewal and preservation of forests; technical assistance. (author)

  5. Final priority. Rehabilitation Training: Job-Driven Vocational Rehabilitation Technical Assistance Center. Final priority.

    Science.gov (United States)

    2014-08-19

    The Assistant Secretary for Special Education and Rehabilitative Services announces a priority under the Rehabilitation Training program to establish a Job-Driven Vocational Rehabilitation Technical Assistance Center (JDVRTAC). The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2014 and later years. We take this action to focus on training in an area of national need. Specifically, this priority responds to the Presidential Memorandum to Federal agencies directing them to take action to address job-driven training for the Nation's workers. The JDVRTAC will provide technical assistance (TA) to State vocational rehabilitation (VR) agencies to help them develop for individuals with disabilities training and employment opportunities that meet the needs of today's employers.

  6. Community views and public health priority setting: how do health department priorities, community views, and health indicator data compare?

    Science.gov (United States)

    Earle-Richardson, Giulia; Scribani, Melissa; Wyckoff, Lynae; Strogatz, David; May, John; Jenkins, Paul

    2015-01-01

    New York, like many other states, provides county-level health statistics for use in local priority settings but does not provide any data on public views about priority health issues. This study assessed whether health department priorities are notably different from community concerns about health, and how both groups' priorities compare with local health statistics. Data from a 2009 rural survey on community health concerns were compared to priorities named by the seven area county health departments, and to local health indicator data. Health care/insurance cost (60%), obesity (53%), and prescription cost (41%) were leading community concerns, regardless of age, education, sex, or Internet in the home. Six of seven county health departments selected access to quality health care (which includes health care/insurance cost) as a leading public health priority, but only three identified obesity. The following leading local health issues were suggested by health indicators: Physical activity and nutrition, Smoking, and Unintentional injury. Health departments diverged from community priorities, from health indicator data, and from one another in choosing priorities. Adding a question about community health priorities to existing state telephone surveys on health behavior and lifestyle would provide an important tool to local health departments. © 2014 Society for Public Health Education.

  7. Setting priorities for safeguards upgrades

    International Nuclear Information System (INIS)

    Al-Ayat, R.A.; Judd, B.R.; Patenaude, C.J.; Sicherman, A.

    1987-01-01

    This paper describes an analytic approach and a computer program for setting priorities among safeguards upgrades. The approach provides safeguards decision makers with a systematic method for allocating their limited upgrade resources. The priorities are set based on the upgrades cost and their contribution to safeguards effectiveness. Safeguards effectiveness is measured by the probability of defeat for a spectrum of potential insider and outsider adversaries. The computer program, MI$ER, can be used alone or as a companion to ET and SAVI, programs designed to evaluate safeguards effectiveness against insider and outsider threats, respectively. Setting the priority required judgments about the relative importance (threat likelihoods and consequences) of insider and outsider threats. Although these judgments are inherently subjective, MI$ER can analyze the sensitivity of the upgrade priorities to these weights and determine whether or not they are critical to the priority ranking. MI$ER produces tabular and graphical results for comparing benefits and identifying the most cost-effective upgrades for a given expenditure. This framework provides decision makers with an explicit and consistent analysis to support their upgrades decisions and to allocate the safeguards resources in a cost-effective manner

  8. Research priorities for public mental health in Europe

    DEFF Research Database (Denmark)

    Forsman, Anna K; Wahlbeck, Kristian; Aarø, Leif Edvard

    2015-01-01

    experts were involved in the priority setting process. RESULTS: Twenty priorities for public mental health research were identified through the consensus process. The research priorities were divided into summary principles-encompassing overall recommendations for future public mental health research...... field. METHODS: Experts were invited to compile and discuss research priorities in a series of topic-based scientific workshops. In addition, a Delphi process was carried out to reach consensus on the list of research priorities and their rank order. Three web-based surveys were conducted. Nearly 60...... in Europe-and thematic research priorities, including area-specific top priorities on research topics and methods. The priorities represent three overarching goals mirroring societal challenges, that is, to identify causes, risk and protective factors for mental health across the lifespan; to advance...

  9. Movies of cellular and sub-cellular motion by digital holographic microscopy

    Directory of Open Access Journals (Sweden)

    Yu Lingfeng

    2006-03-01

    Full Text Available Abstract Background Many biological specimens, such as living cells and their intracellular components, often exhibit very little amplitude contrast, making it difficult for conventional bright field microscopes to distinguish them from their surroundings. To overcome this problem phase contrast techniques such as Zernike, Normarsky and dark-field microscopies have been developed to improve specimen visibility without chemically or physically altering them by the process of staining. These techniques have proven to be invaluable tools for studying living cells and furthering scientific understanding of fundamental cellular processes such as mitosis. However a drawback of these techniques is that direct quantitative phase imaging is not possible. Quantitative phase imaging is important because it enables determination of either the refractive index or optical thickness variations from the measured optical path length with sub-wavelength accuracy. Digital holography is an emergent phase contrast technique that offers an excellent approach in obtaining both qualitative and quantitative phase information from the hologram. A CCD camera is used to record a hologram onto a computer and numerical methods are subsequently applied to reconstruct the hologram to enable direct access to both phase and amplitude information. Another attractive feature of digital holography is the ability to focus on multiple focal planes from a single hologram, emulating the focusing control of a conventional microscope. Methods A modified Mach-Zender off-axis setup in transmission is used to record and reconstruct a number of holographic amplitude and phase images of cellular and sub-cellular features. Results Both cellular and sub-cellular features are imaged with sub-micron, diffraction-limited resolution. Movies of holographic amplitude and phase images of living microbes and cells are created from a series of holograms and reconstructed with numerically adjustable

  10. Ozone effects on radish (Raphanus sativus L. cv. Cherry Belle): morphological and cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Athanassious, R.; Klyne, M.A.; Phan, C.T.

    1978-01-01

    Morphological symptoms of ozone damage were related to cellular alterations. The different degrees of damage reflected by the severity of plasmolysis, membrane destruction and coagulation were shown at different levels of microscopy.

  11. Iodinated contrast media alter immune responses in pro-inflammatory states.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2010-07-01

    Hypertonic saline causes a transient elevation of blood osmolality and has been shown to alter cellular inflammatory responses in pro-inflammatory states. Intravascular administration of iodine contrast media also causes a transient elevation of blood osmolarity.

  12. Community Priority Index: utility, applicability and validation for priority setting in community-based participatory research

    Directory of Open Access Journals (Sweden)

    Hamisu M. Salihu

    2015-07-01

    Full Text Available Background. Providing practitioners with an intuitive measure for priority setting that can be combined with diverse data collection methods is a necessary step to foster accountability of the decision-making process in community settings. Yet, there is a lack of easy-to-use, but methodologically robust measures, that can be feasibly implemented for reliable decision-making in community settings. To address this important gap in community based participatory research (CBPR, the purpose of this study was to demonstrate the utility, applicability, and validation of a community priority index in a community-based participatory research setting. Design and Methods. Mixed-method study that combined focus groups findings, nominal group technique with six key informants, and the generation of a Community Priority Index (CPI that integrated community importance, changeability, and target populations. Bootstrapping and simulation were performed for validation. Results. For pregnant mothers, the top three highly important and highly changeable priorities were: stress (CPI=0.85; 95%CI: 0.70, 1.00, lack of affection (CPI=0.87; 95%CI: 0.69, 1.00, and nutritional issues (CPI=0.78; 95%CI: 0.48, 1.00. For non-pregnant women, top priorities were: low health literacy (CPI=0.87; 95%CI: 0.69, 1.00, low educational attainment (CPI=0.78; 95%CI: 0.48, 1.00, and lack of self-esteem (CPI=0.72; 95%CI: 0.44, 1.00. For children and adolescents, the top three priorities were: obesity (CPI=0.88; 95%CI: 0.69, 1.00, low self-esteem (CPI=0.81; 95%CI: 0.69, 0.94, and negative attitudes toward education (CPI=0.75; 95%CI: 0.50, 0.94. Conclusions. This study demonstrates the applicability of the CPI as a simple and intuitive measure for priority setting in CBPR.

  13. Effect of radiation on reconstitution of skin equivalent (dermal alterations); Effet de l`irradiation sur la reconstruction d`une peau equivalente (alterations dermiques)

    Energy Technology Data Exchange (ETDEWEB)

    Gentilhomme, E.; Bergier, J.; Richard, M.; Neveux, Y.

    1994-12-31

    Dermal equivalents have been treated by single doses of gamma irradiation of 10, 20, 30 and 50 Gray. Numerations at different times show a dose and time dependant diminution of cellular population. This diminution is histologically observed in dermal part of reconstituted skin, in association with cellular and functional alterations of fibroblast cells. Modifications of epidermal epithelia are also noted in some reconstituted skin. This model would be useful to apprehend the effect of a dermal irradiation lesion on the later epidermization. (author). 4 refs.

  14. Priority Setting for Occupational Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Cheryl E. Peters

    2018-06-01

    Full Text Available Background: Selecting priority occupational carcinogens is important for cancer prevention efforts; however, standardized selection methods are not available. The objective of this paper was to describe the methods used by CAREX Canada in 2015 to establish priorities for preventing occupational cancer, with a focus on exposure estimation and descriptive profiles. Methods: Four criteria were used in an expert assessment process to guide carcinogen prioritization: (1 the likelihood of presence and/or use in Canadian workplaces; (2 toxicity of the substance (strength of evidence for carcinogenicity and other health effects; (3 feasibility of producing a carcinogen profile and/or an occupational estimate; and (4 special interest from the public/scientific community. Carcinogens were ranked as high, medium or low priority based on specific conditions regarding these criteria, and stakeholder input was incorporated. Priorities were set separately for the creation of new carcinogen profiles and for new occupational exposure estimates. Results: Overall, 246 agents were reviewed for inclusion in the occupational priorities list. For carcinogen profile generation, 103 were prioritized (11 high, 33 medium, and 59 low priority, and 36 carcinogens were deemed priorities for occupational exposure estimation (13 high, 17 medium, and 6 low priority. Conclusion: Prioritizing and ranking occupational carcinogens is required for a variety of purposes, including research, resource allocation at different jurisdictional levels, calculations of occupational cancer burden, and planning of CAREX-type projects in different countries. This paper outlines how this process was achieved in Canada; this may provide a model for other countries and jurisdictions as a part of occupational cancer prevention efforts. Keywords: cancer prevention, carcinogen exposure, occupational health

  15. Optimal Priority Structure, Capital Structure, and Investment

    OpenAIRE

    Dirk Hackbarth; David C. Mauer

    2012-01-01

    We study the interaction between financing and investment decisions in a dynamic model, where the firm has multiple debt issues and equityholders choose the timing of investment. Jointly optimal capital and priority structures can virtually eliminate investment distortions because debt priority serves as a dynamically optimal contract. Examining the relative efficiency of priority rules observed in practice, we develop several predictions about how firms adjust their priority structure in res...

  16. Priority setting in practice: participants opinions on vertical and horizontal priority setting for reallocation.

    Science.gov (United States)

    Waldau, Susanne; Lindholm, Lars; Wiechel, Anna Helena

    2010-08-01

    In the Västerbotten County Council in Sweden a priority setting process was undertaken to reallocate existing resources for funding of new methods and activities. Resources were created by limiting low priority services. A procedure for priority setting was constructed and fully tested by engaging the entire organisation. The procedure included priority setting within and between departments and political decision making. Participants' views and experiences were collected as a basis for future improvement of the process. Results indicate that participants appreciated the overall approach and methodology and wished to engage in their improvement. Among the improvement proposals is prolongation of the process in order to improve the knowledge base quality. The procedure for identification of new items for funding also needs to be revised. The priority setting process was considered an overall success because it fulfilled its political goals. Factors considered crucial for success are a wish among managers for an economic strategy that addresses existing internal resource allocation; process management characterized by goal orientation and clear leadership; an elaborate communications strategy integrated early in the process and its management; political unity in support of the procedure, and a strong political commitment throughout the process. Generalizability has already been demonstrated by several health care organisations that performed processes founded on this working model. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Dreissenid mussel research priorities workshop

    Science.gov (United States)

    Sytsma, Mark; Phillips, Stephen; Counihan, Timothy D.

    2015-01-01

    Currently, dreissenid mussels have yet to be detected in the northwestern part of the United States and western Canada. Infestation of one of the jurisdictions within the mussel-free Pacific Northwest would likely have significant economic, soci­etal and environmental implications for the entire region. Understanding the biology and environmental tolerances of dreissenid mussels, and effectiveness of various man­agement strategies, is key to prevention.On November 4-5, 2015, the Aquatic Bioinvasion Research and Policy Institute and the Center for Lakes and Reservoirs at Portland State University, the US Geological Survey, and the Pacific States Marine Fisheries Commission, convened a Dreissenid Mussel Research Priorities Workshop funded by the Great Northern Landscape Conservation Cooperative. The purpose of the workshop was to review dreissenid research priorities in the 2010 Quagga-Zebra Mussel Action Plan for Western U.S. Waters, reassess those priorities, incorporate new information and emerging trends, and develop priorities to strategically focus research efforts on zebra and quagga mussels in the Pacific Northwest and ensure that future research is focused on the highest priorities. It is important to note that there is some repetition among dreissenid research priority categories (e.g., prevention, detection, control, monitoring, and biology).Workshop participants with research experience in dreissenid mussel biology and management were identified by a literature review. State and federal agency managers were also invited to the workshop to ensure relevancy and practicality of the work­shop outcomes. A total of 28 experts (see sidebar) in mussel biology, ecology, and management attended the workshop.

  18. A strategy to improve priority setting in developing countries.

    Science.gov (United States)

    Kapiriri, Lydia; Martin, Douglas K

    2007-09-01

    Because the demand for health services outstrips the available resources, priority setting is one of the most difficult issues faced by health policy makers, particularly those in developing countries. Priority setting in developing countries is fraught with uncertainty due to lack of credible information, weak priority setting institutions, and unclear priority setting processes. Efforts to improve priority setting in these contexts have focused on providing information and tools. In this paper we argue that priority setting is a value laden and political process, and although important, the available information and tools are not sufficient to address the priority setting challenges in developing countries. Additional complementary efforts are required. Hence, a strategy to improve priority setting in developing countries should also include: (i) capturing current priority setting practices, (ii) improving the legitimacy and capacity of institutions that set priorities, and (iii) developing fair priority setting processes.

  19. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium.

    Science.gov (United States)

    Walker, Nancy M; Liu, Jinghua; Stein, Sydney R; Stefanski, Casey D; Strubberg, Ashlee M; Clarke, Lane L

    2016-01-15

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl(-) and HCO3 (-) efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl(-)/HCO3 (-) exchange with maximized gradients, it also had increased intracellular Cl(-) concentration relative to wild-type. Pharmacological reduction of intracellular Cl(-) concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl(-) and HCO3 (-) efflux, which impairs pHi regulation by Ae2. Retention of Cl(-) and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. Copyright © 2016 the American Physiological Society.

  20. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium

    Science.gov (United States)

    Walker, Nancy M.; Liu, Jinghua; Stein, Sydney R.; Stefanski, Casey D.; Strubberg, Ashlee M.

    2015-01-01

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl− and HCO3− efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3−)-loading proteins and upregulation of the basolateral membrane HCO3−-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl−/HCO3− exchange with maximized gradients, it also had increased intracellular Cl− concentration relative to wild-type. Pharmacological reduction of intracellular Cl− concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl− and HCO3− efflux, which impairs pHi regulation by Ae2. Retention of Cl− and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. PMID:26542396

  1. Chatty Mitochondria: Keeping Balance in Cellular Protein Homeostasis.

    Science.gov (United States)

    Topf, Ulrike; Wrobel, Lidia; Chacinska, Agnieszka

    2016-08-01

    Mitochondria are multifunctional cellular organelles that host many biochemical pathways including oxidative phosphorylation (OXPHOS). Defective mitochondria pose a threat to cellular homeostasis and compensatory responses exist to curtail the source of stress and/or its consequences. The mitochondrial proteome comprises proteins encoded by the nuclear and mitochondrial genomes. Disturbances in protein homeostasis may originate from mistargeting of nuclear encoded mitochondrial proteins. Defective protein import and accumulation of mistargeted proteins leads to stress that triggers translation alterations and proteasomal activation. These cytosolic pathways are complementary to the mitochondrial unfolded protein response (UPRmt) that aims to increase the capacity of protein quality control mechanisms inside mitochondria. They constitute putative targets for interventions aimed at increasing the fitness, stress resistance, and longevity of cells and organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Influence of microgravity on cellular differentiation in root caps of Zea mays

    Science.gov (United States)

    Moore, R.; Fondren, W. M.; McClelen, C. E.; Wang, C. L.

    1987-01-01

    We launched imbibed seeds of Zea mays into outer space aboard the space shuttle Columbia to determine the influence of microgravity on cellular differentiation in root caps. The influence of microgravity varied with different stages of cellular differentiation. Overall, microgravity tended to 1) increase relative volumes of hyaloplasm and lipid bodies, 2) decrease the relative volumes of plastids, mitochondria, dictyosomes, and the vacuome, and 3) exert no influence on the relative volume of nuclei in cells comprising the root cap. The reduced allocation of dictyosomal volume in peripheral cells of flight-grown seedlings correlated positively with their secretion of significantly less mucilage than peripheral cells of Earth-grown seedlings. These results indicate that 1) microgravity alters the patterns of cellular differentiation and structures of all cell types comprising the root cap, and 2) the influence of microgravity on cellular differentiation in root caps of Zea mays is organelle specific.

  3. Setting research priorities for Type 1 diabetes.

    Science.gov (United States)

    Gadsby, R; Snow, R; Daly, A C; Crowe, S; Matyka, K; Hall, B; Petrie, J

    2012-10-01

    Research priorities are often set by academic researchers or the pharmaceutical industry. The interests of patients, carers and clinicians may therefore be overlooked and research questions that matter may be neglected. The aims of this study were to collect uncertainties about the treatment of Type 1 diabetes from patients, carers and health professionals, and to collate and prioritize these uncertainties to develop a top 10 list of research priorities, using a structured priority-setting partnership of patients, carers, health professionals and diabetes organizations, as described by the James Lind Alliance. A partnership of interested organizations was set up, and from this a steering committee of 10 individuals was formed. An online and paper survey was used to identify uncertainties. These were collated, and the steering group carried out an interim priority-setting exercise with partner organizations. This group of uncertainties was then voted on to give a smaller list that went forward to the final priority-setting workshop. At this meeting, a final list of the top 10 research priorities was agreed. An initial 1141 uncertainties were described. These were reduced to 88 indicative questions, 47 of which went out for voting. Twenty-four were then taken forward to a final priority-setting workshop. This workshop resulted in a list of top 10 research priorities in Type 1 diabetes. We have shown that it is possible using the James Lind Alliance process to develop an agreed top 10 list of research priorities for Type 1 diabetes from health professionals, patients and carers. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  4. Monocyte Activation in Immunopathology: Cellular Test for Development of Diagnostics and Therapy

    Directory of Open Access Journals (Sweden)

    Ekaterina A. Ivanova

    2016-01-01

    Full Text Available Several highly prevalent human diseases are associated with immunopathology. Alterations in the immune system are found in such life-threatening disorders as cancer and atherosclerosis. Monocyte activation followed by macrophage polarization is an important step in normal immune response to pathogens and other relevant stimuli. Depending on the nature of the activation signal, macrophages can acquire pro- or anti-inflammatory phenotypes that are characterized by the expression of distinct patterns of secreted cytokines and surface antigens. This process is disturbed in immunopathologies resulting in abnormal monocyte activation and/or bias of macrophage polarization towards one or the other phenotype. Such alterations could be used as important diagnostic markers and also as possible targets for the development of immunomodulating therapy. Recently developed cellular tests are designed to analyze the phenotype and activity of living cells circulating in patient’s bloodstream. Monocyte/macrophage activation test is a successful example of cellular test relevant for atherosclerosis and oncopathology. This test demonstrated changes in macrophage activation in subclinical atherosclerosis and breast cancer and could also be used for screening a panel of natural agents with immunomodulatory activity. Further development of cellular tests will allow broadening the scope of their clinical implication. Such tests may become useful tools for drug research and therapy optimization.

  5. Human equilibrative nucleoside transporter-1 knockdown tunes cellular mechanics through epithelial-mesenchymal transition in pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Yeonju Lee

    Full Text Available We report cell mechanical changes in response to alteration of expression of the human equilibrative nucleoside transporter-1 (hENT1, a most abundant and widely distributed plasma membrane nucleoside transporter in human cells and/or tissues. Modulation of hENT1 expression level altered the stiffness of pancreatic cancer Capan-1 and Panc 03.27 cells, which was analyzed by atomic force microscopy (AFM and correlated to microfluidic platform. The hENT1 knockdown induced reduction of cellular stiffness in both of cells up to 70%. In addition, cellular phenotypic changes such as cell morphology, migration, and expression level of epithelial-mesenchymal transition (EMT markers were observed after hENT1 knockdown. Cells with suppressed hENT1 became elongated, migrated faster, and had reduced E-cadherin and elevated N-cadherin compared to parental cells which are consistent with epithelial-mesenchymal transition (EMT. Those cellular phenotypic changes closely correlated with changes in cellular stiffness. This study suggests that hENT1 expression level affects cellular phenotype and cell elastic behavior can be a physical biomarker for quantify hENT1 expression and detect phenotypic shift. Furthermore, cell mechanics can be a critical tool in detecting disease progression and response to therapy.

  6. Setting Priorities Personal Values, Organizational Results

    CERN Document Server

    (CCL), Center for Creative Leadership

    2011-01-01

    To be a successful leader, you need to get results. To get results, you need to set priorities. This book can help you do a better job of setting priorities, recognizing the personal values that motivate your decision making, the probable trade-offs and consequences of your decisions, and the importance of aligning your priorities with your organization's expectations. In this way you can successfully meet organizational objectives and consistently produce results.

  7. [Epigenetic alterations in acute lymphoblastic leukemia].

    Science.gov (United States)

    Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  8. QoE-Driven D2D Media Services Distribution Scheme in Cellular Networks

    Directory of Open Access Journals (Sweden)

    Mingkai Chen

    2017-01-01

    Full Text Available Device-to-device (D2D communication has been widely studied to improve network performance and considered as a potential technological component for the next generation communication. Considering the diverse users’ demand, Quality of Experience (QoE is recognized as a new degree of user’s satisfaction for media service transmissions in the wireless communication. Furthermore, we aim at promoting user’s Mean of Score (MOS value to quantify and analyze user’s QoE in the dynamic cellular networks. In this paper, we explore the heterogeneous media service distribution in D2D communications underlaying cellular networks to improve the total users’ QoE. We propose a novel media service scheme based on different QoE models that jointly solve the massive media content dissemination issue for cellular networks. Moreover, we also investigate the so-called Media Service Adaptive Update Scheme (MSAUS framework to maximize users’ QoE satisfaction and we derive the popularity and priority function of different media service QoE expression. Then, we further design Media Service Resource Allocation (MSRA algorithm to schedule limited cellular networks resource, which is based on the popularity function to optimize the total users’ QoE satisfaction and avoid D2D interference. In addition, numerical simulation results indicate that the proposed scheme is more effective in cellular network content delivery, which makes it suitable for various media service propagation.

  9. Safety training priorities

    Science.gov (United States)

    Thompson, N. A.; Ruck, H. W.

    1984-04-01

    The Air Force is interested in identifying potentially hazardous tasks and prevention of accidents. This effort proposes four methods for determining safety training priorities for job tasks in three enlisted specialties. These methods can be used to design training aimed at avoiding loss of people, time, materials, and money associated with on-the-job accidents. Job tasks performed by airmen were measured using task and job factor ratings. Combining accident reports and job inventories, subject-matter experts identified tasks associated with accidents over a 3-year period. Applying correlational, multiple regression, and cost-benefit analysis, four methods were developed for ordering hazardous tasks to determine safety training priorities.

  10. 7 CFR 1775.11 - Priority.

    Science.gov (United States)

    2010-01-01

    ... management problems. (j) Cash or in kind support of project from non-federal sources. (k) Ability to... program. (a) Projects proposing to give priority for available services to rural communities having a population less than 5,500 and/or below 2,500. (b) Projects proposing to give priority for available services...

  11. 40 CFR 35.925-3 - Priority determination.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Priority determination. 35.925-3 Section 35.925-3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL... Priority determination. That such works are entitled to priority in accordance with § 35.915, and that the...

  12. Streptozotocin alters glucose transport, connexin expression and endoplasmic reticulum functions in neurons and astrocytes.

    Science.gov (United States)

    Biswas, Joyshree; Gupta, Sonam; Verma, Dinesh Kumar; Singh, Sarika

    2017-07-25

    The study was undertaken to explore the cell-specific streptozotocin (STZ)-induced mechanistic alterations. STZ-induced rodent model is a well-established experimental model of Alzheimer's disease (AD) and in our previous studies we have established it as an in vitro screening model of AD by employing N2A neuronal cells. Therefore, STZ was selected in the present study to understand the STZ-induced cell-specific alterations by utilizing neuronal N2A and astrocytes C6 cells. Both neuronal and astrocyte cells were treated with STZ at 10, 50, 100 and 1000μM concentrations for 48h. STZ exposure caused significant decline in cellular viability and augmented cytotoxicity of cells involving astrocytes activation. STZ treatment also disrupted the energy metabolism by altered glucose uptake and its transport in both cells as reflected with decreased expression of glucose transporters (GLUT) 1/3. The consequent decrease in ATP level and decreased mitochondrial membrane potential was also observed in both the cells. STZ caused increased intracellular calcium which could cause the initiation of endoplasmic reticulum (ER) stress. Significant upregulation of ER stress-related markers were observed in both cells after STZ treatment. The cellular communication of astrocytes and neurons was altered as reflected by increased expression of connexin 43 along with DNA fragmentation. STZ-induced apoptotic death was evaluated by elevated expression of caspase-3 and PI/Hoechst staining of cells. In conclusion, study showed that STZ exert alike biochemical alterations, ER stress and cellular apoptosis in both neuronal and astrocyte cells. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Decentralized health care priority-setting in Tanzania

    DEFF Research Database (Denmark)

    Maluka, Stephen; Kamuzora, Peter; Sebastiån, Miguel San

    2010-01-01

    Priority-setting has become one of the biggest challenges faced by health decision-makers worldwide. Fairness is a key goal of priority-setting and Accountability for Reasonableness has emerged as a guiding framework for fair priority-setting. This paper describes the processes of setting health...... care priorities in Mbarali district, Tanzania, and evaluates the descriptions against Accountability for Reasonableness. Key informant interviews were conducted with district health managers, local government officials and other stakeholders using a semi-structured interview guide. Relevant documents...... no formal mechanisms in place to ensure that this information reached the public. There were neither formal mechanisms for challenging decisions nor an adequate enforcement mechanism to ensure that decisions were made in a fair and equitable manner. Therefore, priority-setting in Mbarali district did...

  14. Wnt Signaling Alteration in the Spinal Cord of Amyotrophic Lateral Sclerosis Transgenic Mice: Special Focus on Frizzled-5 Cellular Expression Pattern.

    Directory of Open Access Journals (Sweden)

    Carlos González-Fernández

    Full Text Available Amyotrophic lateral sclerosis is a chronic neurodegenerative disease characterized by progressive paralysis due to degeneration of motor neurons by unknown causes. Recent evidence shows that Wnt signaling is involved in neurodegenerative processes, including Amyotrophic Lateral Sclerosis. However, to date, little is known regarding the expression of Wnt signaling components in this fatal condition. In the present study we used transgenic SOD1G93A mice to evaluate the expression of several Wnt signaling components, with special focus on Frizzled-5 cellular expression alteration along disease progression.Based on previous studies demonstrating the expression of Wnts and their transcriptional regulation during Amyotrophic lateral sclerosis development, we have analyzed the mRNA expression of several Wnt signaling components in the spinal cord of SOD1G93A transgenic mice at different stages of the disease by using real time quantitative PCR analysis. Strikingly, one of the molecules that seemed not to be altered at mRNA level, Frizzled-5, showed a clear up-regulation at late stages in neurons, as evidenced by immunofluorescence assays. Moreover, increased Frizzled-5 appears to correlate with a decrease in NeuN signal in these cells, suggesting a correlation between neuronal affectation and the increased expression of this receptor.Our data suggest the involvement of Wnt signaling pathways in the pathophysiology of Amyotrophic Lateral Sclerosis and, more specifically, the implication of Frizzled-5 receptor in the response of neuronal cells against neurodegeneration. Nevertheless, further experimental studies are needed to shed light on the specific role of Frizzled-5 and the emerging but increasing Wnt family of proteins research field as a potential target for this neuropathology.

  15. 7 CFR 632.12 - Funding priorities.

    Science.gov (United States)

    2010-01-01

    ... AGRICULTURE LONG TERM CONTRACTING RURAL ABANDONED MINE PROGRAM Qualifications § 632.12 Funding priorities. (a... extreme danger. (3) Priority 3. Restoration of the land and water resources and the environment where...

  16. Traumatic brain injury alters methionine metabolism: implications for pathophysiology

    Directory of Open Access Journals (Sweden)

    Pramod K Dash

    2016-04-01

    Full Text Available Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S-adenosylmethionine (SAM that serves as the principal methyl (-CH3 donor for DNA and histone methyltransferases to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling.. Under conditions of oxidative stress, homocysteine (which is derived from SAM enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (n = 20 and patients with mild TBI (GCS > 12; n = 20 or severe TBI (GCS < 8; n = 20 within the first 24 hours of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS. Severe TBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to healthy volunteers, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline. Mild TBI also decreased the levels of methionine, α-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser

  17. 14 CFR 250.3 - Boarding priority rules.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Boarding priority rules. 250.3 Section 250...) ECONOMIC REGULATIONS OVERSALES § 250.3 Boarding priority rules. (a) Every carrier shall establish priority... boarding on an oversold flight in the event that an insufficient number of volunteers come forward. Such...

  18. 15 CFR 700.15 - Extension of priority ratings.

    Science.gov (United States)

    2010-01-01

    ...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700.15 Extension of priority ratings. (a...

  19. Consumer design priorities for upper limb prosthetics.

    Science.gov (United States)

    Biddiss, Elaine; Beaton, Dorcas; Chau, Tom

    2007-11-01

    To measure consumer satisfaction with upper limb prosthetics and provide an enumerated list of design priorities for future developments. A self-administered, anonymous survey collected information on participant demographics, history of and goals for prosthesis use, satisfaction, and design priorities. The questionnaire was available online and in paper format and was distributed through healthcare providers, community support groups, and one prosthesis manufacturer; 242 participants of all ages and levels of upper limb absence completed the survey. Rates of rejection for myoelectric hands, passive hands, and body-powered hooks were 39%, 53%, and 50%, respectively. Prosthesis wearers were generally satisfied with their devices while prosthesis rejecters were dissatisfied. Reduced prosthesis weight emerged as the highest priority design concern of consumers. Lower cost ranked within the top five design priorities for adult wearers of all device types. Life-like appearance is a priority for passive/cosmetic prostheses, while improved harness comfort, wrist movement, grip control and strength are required for body-powered devices. Glove durability, lack of sensory feedback, and poor dexterity were also identified as design priorities for electric devices. Design priorities reflect consumer goals for prosthesis use and vary depending on the type of prosthesis used and age. Future design efforts should focus on the development of more light-weight, comfortable prostheses.

  20. Defining Priorities for Future Research: Results of the UK Kidney Transplant Priority Setting Partnership.

    Science.gov (United States)

    Knight, Simon R; Metcalfe, Leanne; O'Donoghue, Katriona; Ball, Simon T; Beale, Angela; Beale, William; Hilton, Rachel; Hodkinson, Keith; Lipkin, Graham W; Loud, Fiona; Marson, Lorna P; Morris, Peter J

    2016-01-01

    It has been suggested that the research priorities of those funding and performing research in transplantation may differ from those of end service users such as patients, carers and healthcare professionals involved in day-to-day care. The Kidney Transplant Priority Setting Partnership (PSP) was established with the aim of involving all stakeholders in prioritising future research in the field. The PSP methodology is as outlined by the James Lind Alliance. An initial survey collected unanswered research questions from patients, carers and clinicians. Duplicate and out-of-scope topics were excluded and the existing literature searched to identify topics answered by current evidence. An interim prioritisation survey asked patients and professionals to score the importance of the remaining questions to create a ranked long-list. These were considered at a final consensus workshop using a modified nominal group technique to agree a final top ten. The initial survey identified 497 questions from 183 respondents, covering all aspects of transplantation from assessment through to long-term follow-up. These were grouped into 90 unanswered "indicative" questions. The interim prioritisation survey received 256 responses (34.8% patients/carers, 10.9% donors and 54.3% professionals), resulting in a ranked list of 25 questions that were considered during the final workshop. Participants agreed a top ten priorities for future research that included optimisation of immunosuppression (improved monitoring, choice of regimen, personalisation), prevention of sensitisation and transplanting the sensitised patient, management of antibody-mediated rejection, long-term risks to live donors, methods of organ preservation, induction of tolerance and bioengineering of organs. There was evidence that patient and carer involvement had a significant impact on shaping the final priorities. The final list of priorities relates to all stages of the transplant process, including access to

  1. Final priorities; National Institute on Disability and Rehabilitation Research--Disability and Rehabilitation Research Projects and Centers Program--Rehabilitation Engineering Research Centers. Final priorities.

    Science.gov (United States)

    2013-06-11

    The Assistant Secretary for Special Education and Rehabilitative Services announces priorities under the Disability and Rehabilitation Research Projects and Centers Program administered by the National Institute on Disability and Rehabilitation Research (NIDRR). Specifically, we announce priorities for a Rehabilitation Engineering Research Center (RERC) on Rehabilitation Strategies, Techniques, and Interventions (Priority 1), Information and Communication Technologies Access (Priority 2), Individual Mobility and Manipulation (Priority 3), and Physical Access and Transportation (Priority 4). The Assistant Secretary may use one or more of these priorities for competitions in fiscal year (FY) 2013 and later years. We take this action to focus research attention on areas of national need. We intend these priorities to improve community living and participation, health and function, and employment outcomes of individuals with disabilities.

  2. Cellular reprogramming dynamics follow a simple 1D reaction coordinate

    Science.gov (United States)

    Teja Pusuluri, Sai; Lang, Alex H.; Mehta, Pankaj; Castillo, Horacio E.

    2018-01-01

    Cellular reprogramming, the conversion of one cell type to another, induces global changes in gene expression involving thousands of genes, and understanding how cells globally alter their gene expression profile during reprogramming is an ongoing problem. Here we reanalyze time-course data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple 1D reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of the experimental protocol used. Using Monte-Carlo simulations, we show that such a reaction coordinate emerges from epigenetic landscape models where cellular reprogramming is viewed as a ‘barrier-crossing’ process between cell fates. Overall, our analysis and model suggest that gene expression dynamics during reprogramming follow a canonical trajectory consistent with the idea of an ‘optimal path’ in gene expression space for reprogramming.

  3. Priority setting and health policy and systems research

    Directory of Open Access Journals (Sweden)

    Bennett Sara C

    2009-12-01

    Full Text Available Abstract Health policy and systems research (HPSR has been identified as critical to scaling-up interventions to achieve the millennium development goals, but research priority setting exercises often do not address HPSR well. This paper aims to (i assess current priority setting methods and the extent to which they adequately include HPSR and (ii draw lessons regarding how HPSR priority setting can be enhanced to promote relevant HPSR, and to strengthen developing country leadership of research agendas. Priority setting processes can be distinguished by the level at which they occur, their degree of comprehensiveness in terms of the topic addressed, the balance between technical versus interpretive approaches and the stakeholders involved. When HPSR is considered through technical, disease-driven priority setting processes it is systematically under-valued. More successful approaches for considering HPSR are typically nationally-driven, interpretive and engage a range of stakeholders. There is still a need however for better defined approaches to enable research funders to determine the relative weight to assign to disease specific research versus HPSR and other forms of cross-cutting health research. While country-level research priority setting is key, there is likely to be a continued need for the identification of global research priorities for HPSR. The paper argues that such global priorities can and should be driven by country level priorities.

  4. HDACi: cellular effects, opportunities for restorative dentistry.

    LENUS (Irish Health Repository)

    Duncan, H F

    2011-12-01

    Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be \\'tipped\\' by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between \\'normal\\' and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage.

  5. Cellular effects of the microtubule-targeting agent peloruside A in hypoxia-conditioned colorectal carcinoma cells.

    Science.gov (United States)

    Řehulka, Jiří; Annadurai, Narendran; Frydrych, Ivo; Znojek, Pawel; Džubák, Petr; Northcote, Peter; Miller, John H; Hajdúch, Marián; Das, Viswanath

    2017-07-01

    Hypoxia is a prominent feature of solid tumors, dramatically remodeling microtubule structures and cellular pathways and contributing to paclitaxel resistance. Peloruside A (PLA), a microtubule-targeting agent, has shown promising anti-tumor effects in preclinical studies. Although it has a similar mode of action to paclitaxel, it binds to a distinct site on β-tubulin that differs from the classical taxane site. In this study, we examined the unexplored effects of PLA in hypoxia-conditioned colorectal HCT116 cancer cells. Cytotoxicity of PLA was determined by cell proliferation assay. The effects of a pre-exposure to hypoxia on PLA-induced cell cycle alterations and apoptosis were examined by flow cytometry, time-lapse imaging, and western blot analysis of selected markers. The hypoxia effect on stabilization of microtubules by PLA was monitored by an intracellular tubulin polymerization assay. Our findings show that the cytotoxicity of PLA is not altered in hypoxia-conditioned cells compared to paclitaxel and vincristine. Furthermore, hypoxia does not alter PLA-induced microtubule stabilization nor the multinucleation of cells. PLA causes cyclin B1 and G2/M accumulation followed by apoptosis. The cellular and molecular effects of PLA have been determined in normoxic conditions, but there are no reports of PLA effects in hypoxic cells. Our findings reveal that hypoxia preconditioning does not alter the sensitivity of HCT116 to PLA. These data report on the cellular and molecular effects of PLA in hypoxia-conditioned cells for the first time, and will encourage further exploration of PLA as a promising anti-tumor agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Cardiac troponin and tropomyosin: structural and cellular perspectives to unveil the Hypertrophic Cardiomyopathy phenotype

    Directory of Open Access Journals (Sweden)

    Mayra de A. Marques

    2016-09-01

    Full Text Available Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1,400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the disease of the sarcomere. The most common macroscopic phenotypes are left ventricle and interventricular septal thickening, but because the clinical profile of this disease is quite heterogeneous, these phenotypes are not suitable for an accurate diagnosis. The development of genomic approaches for clinical investigation allows for diagnostic progress and understanding at the molecular level. Meanwhile, the lack of accurate in vivo models to better comprehend the cellular events triggered by this pathology has become a challenge. Notwithstanding, the imbalance of Ca2+ concentrations, altered signaling pathways, induction of apoptotic factors, and heart remodeling leading to abnormal anatomy have already been reported. Of note, a misbalance of signaling biomolecules, such as kinases and tumor suppressors (e.g., Akt and p53, seems to participate in apoptotic and fibrotic events. In HCM, structural and cellular information about defective sarcomeric proteins and their altered interactome is emerging but still represents a bottleneck for developing new concepts in basic research and for future therapeutic interventions. This review focuses on the structural and cellular alterations triggered by HCM-causing mutations in troponin and tropomyosin proteins and how structural biology can aid in the discovery of new platforms for therapeutics. We

  7. Global conservation priorities for marine turtles.

    Directory of Open Access Journals (Sweden)

    Bryan P Wallace

    Full Text Available Where conservation resources are limited and conservation targets are diverse, robust yet flexible priority-setting frameworks are vital. Priority-setting is especially important for geographically widespread species with distinct populations subject to multiple threats that operate on different spatial and temporal scales. Marine turtles are widely distributed and exhibit intra-specific variations in population sizes and trends, as well as reproduction and morphology. However, current global extinction risk assessment frameworks do not assess conservation status of spatially and biologically distinct marine turtle Regional Management Units (RMUs, and thus do not capture variations in population trends, impacts of threats, or necessary conservation actions across individual populations. To address this issue, we developed a new assessment framework that allowed us to evaluate, compare and organize marine turtle RMUs according to status and threats criteria. Because conservation priorities can vary widely (i.e. from avoiding imminent extinction to maintaining long-term monitoring efforts we developed a "conservation priorities portfolio" system using categories of paired risk and threats scores for all RMUs (n = 58. We performed these assessments and rankings globally, by species, by ocean basin, and by recognized geopolitical bodies to identify patterns in risk, threats, and data gaps at different scales. This process resulted in characterization of risk and threats to all marine turtle RMUs, including identification of the world's 11 most endangered marine turtle RMUs based on highest risk and threats scores. This system also highlighted important gaps in available information that is crucial for accurate conservation assessments. Overall, this priority-setting framework can provide guidance for research and conservation priorities at multiple relevant scales, and should serve as a model for conservation status assessments and priority

  8. Setting Research Priorities for Kidney Cancer.

    Science.gov (United States)

    Jones, Jennifer M; Bhatt, Jaimin; Avery, Jonathan; Laupacis, Andreas; Cowan, Katherine; Basappa, Naveen S; Basiuk, Joan; Canil, Christina; Al-Asaaed, Sohaib; Heng, Daniel Y C; Wood, Lori; Stacey, Dawn; Kollmannsberger, Christian; Jewett, Michael A S

    2017-12-01

    Defining disease-specific research priorities in cancer can facilitate better allocation of limited resources. Involving patients and caregivers as well as expert clinicians in this process is of value. We undertook this approach for kidney cancer as an example. The Kidney Cancer Research Network of Canada sponsored a collaborative consensus-based priority-setting partnership that identified ten research priorities in the management of kidney cancer. These are discussed in the context of current initiatives and gaps in knowledge. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  9. Early leaf senescence is associated with an altered cellular redox balance in Arabidopsis cpr5/old1 mutants

    OpenAIRE

    Jing, H. -C.; Hebeler, R.; Oeljeklaus, S.; Sitek, B.; Stuehler, K.; Meyer, H. E.; Sturre, M. J. G.; Hille, J.; Warscheid, B.; Dijkwel, P. P.; Stühler, K.

    2008-01-01

    Reactive oxygen species (ROS) are the inevitable by-products of essential cellular metabolic and physiological activities. Plants have developed sophisticated gene networks of ROS generation and scavenging systems. However, ROS regulation is still poorly understood. Here, we report that mutations in the Arabidopsis CPR5/OLD1 gene may cause early senescence through deregulation of the cellular redox balance. Genetic analysis showed that blocking stress-related hormonal signalling pathways, suc...

  10. Priority setting in clinical nursing practice: literature review.

    Science.gov (United States)

    Hendry, Charles; Walker, Anne

    2004-08-01

    Time is a valuable resource. When nurses experience demands on their services which exceed their available time, then 'rationing' must occur. In clinical practice such rationing requires practitioners to set priorities for care. The aim of this paper is establish what is currently known about priority setting in nursing, including how nurses set priorities and what factors influence this. CINAHL, Medline, ASSIA, and PsychLit databases for the years 1982-2002 were searched, using the terms (clinical decision-making or problem-solving or planning) and (setting priorities or prioriti*). The publications found were used in a selective, descriptive review. Priority setting is an important skill in nursing, and a skill deficit can have serious consequences for patients. Recent studies have suggested that it is a difficult skill for newly qualified nurses to acquire and may not be given sufficient attention in nurse education. Priority setting can be defined as the ordering of nursing problems using notions of urgency and/or importance, in order to establish a preferential order for nursing actions. A number of factors that may impact on priority setting have been identified in the literature. These include: the expertise of the nurse; the patient's condition; the availability of resources; ward organization; philosophies and models of care; the nurse-patient relationship; and the cognitive strategy used by the nurse to set priorities. However, very little empirical work has been conducted in this area. Further study of priority setting in a range of clinical practice settings is necessary. This could inform both practice and education, promote better use of limited resources and maximize patient outcomes.

  11. 40 CFR 146.9 - Criteria for establishing permitting priorities.

    Science.gov (United States)

    2010-07-01

    ....9 Criteria for establishing permitting priorities. In determining priorities for setting times for... priorities. 146.9 Section 146.9 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER... (a), (c), (g) or § 144.22(f), the Director shall base these priorities upon consideration of the...

  12. 10 CFR 580.03 - Curtailment priorities.

    Science.gov (United States)

    2010-01-01

    ... DEPARTMENT OF ENERGY (CONTINUED) NATURAL GAS (ECONOMIC REGULATORY ADMINISTRATION) CURTAILMENT PRIORITIES FOR ESSENTIAL AGRICULTURAL USES § 580.03 Curtailment priorities. (a) Notwithstanding any provision of law other... curtailment of deliveries of natural gas for any essential agricultural use, unless: (1) Such curtailment does...

  13. Epigenetic Alterations in Epstein-Barr Virus-Associated Diseases.

    Science.gov (United States)

    Niller, Hans Helmut; Banati, Ferenc; Salamon, Daniel; Minarovits, Janos

    2016-01-01

    Latent Epstein-Bar virus genomes undergo epigenetic modifications which are dependent on the respective tissue type and cellular phenotype. These define distinct viral epigenotypes corresponding with latent viral gene expression profiles. Viral Latent Membrane Proteins 1 and 2A can induce cellular DNA methyltransferases, thereby influencing the methylation status of the viral and cellular genomes. Therefore, not only the viral genomes carry epigenetic modifications, but also the cellular genomes adopt major epigenetic alterations upon EBV infection. The distinct cellular epigenotypes of EBV-infected cells differ from the epigenotypes of their normal counterparts. In Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC) significant changes in the host cell methylome with a strong tendency towards CpG island hypermethylation are observed. Hypermethylated genes unique for EBVaGC suggest the existence of an EBV-specific "epigenetic signature". Contrary to the primary malignancies carrying latent EBV genomes, lymphoblastoid cells (LCs) established by EBV infection of peripheral B cells in vitro are characterized by a massive genome-wide demethylation and a significant decrease and redistribution of heterochromatic histone marks. Establishing complete epigenomes of the diverse EBV-associated malignancies shall clarify their similarities and differences and further clarify the contribution of EBV to the pathogenesis, especially for the epithelial malignancies, NPC and EBVaGC.

  14. 40 CFR 35.2103 - Priority determination.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Priority determination. 35.2103 Section 35.2103 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2103 Priority determination...

  15. In Vivo Bystander Effect: Cranial X-Irradiation Leads to Elevated DNA Damage, Altered Cellular Proliferation and Apoptosis, and Increased p53 Levels in Shielded Spleen

    International Nuclear Information System (INIS)

    Koturbash, Igor; Loree, Jonathan; Kutanzi, Kristy; Koganow, Clayton; Pogribny, Igor; Kovalchuk, Olga

    2008-01-01

    Purpose: It is well accepted that irradiated cells may 'forward' genome instability to nonirradiated neighboring cells, giving rise to the 'bystander effect' phenomenon. Although bystander effects were well studied by using cell cultures, data for somatic bystander effects in vivo are relatively scarce. Methods and Materials: We set out to analyze the existence and molecular nature of bystander effects in a radiation target-organ spleen by using a mouse model. The animal's head was exposed to X-rays while the remainder of the body was completely protected by a medical-grade shield. Using immunohistochemistry, we addressed levels of DNA damage, cellular proliferation, apoptosis, and p53 protein in the spleen of control animals and completely exposed and head-exposed/body bystander animals. Results: We found that localized head radiation exposure led to the induction of bystander effects in the lead-shielded distant spleen tissue. Namely, cranial irradiation led to increased levels of DNA damage and p53 expression and also altered levels of cellular proliferation and apoptosis in bystander spleen tissue. The observed bystander changes were not caused by radiation scattering and were observed in two different mouse strains; C57BL/6 and BALB/c. Conclusion: Our study proves that bystander effects occur in the distant somatic organs on localized exposures. Additional studies are required to characterize the nature of an enigmatic bystander signal and analyze the long-term persistence of these effects and possible contribution of radiation-induced bystander effects to secondary radiation carcinogenesis

  16. Toxicity of cadmium in Japanese quail: Evaluation of body weight, hepatic and renal function, and cellular immune response

    International Nuclear Information System (INIS)

    Sant'Ana, M.G.; Moraes, R.; Bernardi, M.M.

    2005-01-01

    Cadmium (Cd) is an environmental pollutant that is able to alter the immune function. Previous studies have shown that, in mammals, chronic exposure to Cd decreases the release of macrophagic cytokines such as IL1 and TNα and decreases phagocytosis activity. On the other hand contradictory results showed an increase in the humoral response. The cellular response could be decreased by exposure to Cd. These alterations were observed in mammals. The present study aimed to investigate some of the toxic effects of Cd exposure in birds. In particular, the main objective of this work was to elucidate the effects of exposure to this pollutant on the cellular immune function of the Japanese quail as a model for the study of toxicity in animals exposed in nature. The animals were exposed to the metal (100 ppm, per os) during development, i.e., from 1 to 28 days old. Body weight, biochemical parameters, and cellular immune response were measured during and at the end of treatment. The results showed that the exposure to Cd for 28 days significantly reduced the body weight and induced hepatic toxicity. The kidney function and cellular immune response were not affected by the Cd exposure

  17. Mutant p53 transfection of astrocytic cells results in altered cell cycle control, radiation sensitivity, and tumorigenicity

    International Nuclear Information System (INIS)

    Kanady, Kirk E.; Mei Su; Proulx, Gary; Malkin, David M.; Pardo, Francisco S.

    1995-01-01

    Introduction: Alterations in the p53 tumor suppressor gene are one of the most frequent genetic alterations in malignant gliomas. An understanding of the molecular genetic events leading to glial tumor progression would aid in designing therapeutic vectors for controlling these challenging tumor types. We investigated whether mutations in coding exons of the p53 gene result in functional changes altering cell cycle 'checkpoint' control and the intrinsic radiation sensitivity of glial cells. Methods: An astrocytic cell line was derived from a low grade astrocytoma and characterized to be of human karyotype and GFAP positivity. Additionally, the cellular population has never formed tumors in immune-deficient mice. At early passage ( 2 as parameters. Cell kinetic analyses after 2, 5, and 10 Gy of ionizing radiation were conducted using propidium iodide FACS analyses. Results: Overall levels of p53 expression were increased 5-10 fold in the transfected cellular populations. Astrocytic cellular populations transfected with mutant p53 revealed a statistically significant increase in levels of resistance to ionizing radiation in vitro (2-tailed test, SF2, MID). Astrocytic cellular populations transfected with mutant p53, unlike the parental cells, were tumorigenic in SCID mice. Cell kinetic analyses indicated that the untransfected cell line demonstrated dose dependent G1 and G2 arrests. Following transfection, however, the resultant cellular population demonstrated a predominant G2 arrest. Conclusions: Astrocytic cellular populations derived from low grade astrocytomas, are relatively radiation sensitive, non-tumorigenic, and have intact cell cycle ''checkpoints.'' Cellular populations resulting upon transfection of parental cells with a dominant negative p53 mutation, are relatively radiation resistant, when compared to both parental and mock-transfected cells. Transfected cells demonstrate abnormalities of cell cycle control at the G1/S checkpoint, increases in levels

  18. Setting stroke research priorities: The consumer perspective.

    Science.gov (United States)

    Sangvatanakul, Pukkaporn; Hillege, Sharon; Lalor, Erin; Levi, Christopher; Hill, Kelvin; Middleton, Sandy

    2010-12-01

    To test a method of engaging consumers in research priority-setting using a quantitative approach and to determine consumer views on stroke research priorities for clinical practice recommendations with lower levels of evidence (Level III and Level IV) and expert consensus opinion as published in the Australian stroke clinical practice guidelines. Survey Urban community Eighteen stroke survivors (n = 12) and carers (n = 6) who were members of the "Working Aged Group - Stroke" (WAGS) consumer support group. Phase I: Participants were asked whether recommendations were "worth" researching ("yes" or "no"); and, if researched, what potential impact they likely would have on patient outcomes. Phase II: Participants were asked to rank recommendations rated by more than 75% of participants in Phase I as "worth" researching and "highly likely" or "likely" to generate research with a significant effect on patient outcomes (n = 13) in order of priority for future stroke research. All recommendations were rated by at least half (n = 9, 50%) of participants as "worth" researching. The majority (67% to 100%) rated all recommendations as "highly likely" or "likely" that research would have a significant effect on patient outcomes. Thirteen out of 20 recommendations were ranked for their research priorities. Recommendations under the topic heading Getting to hospital were ranked highest and Organization of care and Living with stroke were ranked as a lower priority for research. This study provided an example of how to involve consumers in research priority setting successfully using a quantitative approach. Stroke research priorities from the consumer perspective were different from those of health professionals, as published in the literature; thus, consumer opinion should be considered when setting research priorities. Copyright © 2010 Society for Vascular Nursing, Inc. Published by Mosby, Inc. All rights reserved.

  19. The induction and regulation of radiogenic transformation in vitro: Cellular and molecular mechanisms

    International Nuclear Information System (INIS)

    Borek, C.

    1987-01-01

    Rodent and human cells in culture, transformed in vitro by ionizing radiation, ultraviolet light, or chemicals into malignant cells afford us the opportunity to probe into early and late events in the neoplastic process at a cellular and molecular level. Transformation can be regarded as an abnormal expression of cellular genes. The initiating agents disrupt the integrity of the genetic apparatus altering DNA in ways that result in the activation of cellular transforming genes (oncogenes) during some stage of the neoplastic process. Events associated with initiation and promotion may overlap to some degree, but in order for them to occur, cellular permissive conditions must prevail. Permissive factors include thyroid and steroid hormones, specific states of differentiation, certain stages in the cell cycle, specific genetic impairment, and inadequate antioxidants. Genetically susceptible cells require physiological states conducive to transformation. These may differ with age, tissue, and species and in part may be responsible for the observed lower sensitivity of human cells to transformation

  20. Ion channel signaling influences cellular proliferation and phagocyte activity during axolotl tail regeneration.

    Science.gov (United States)

    Franklin, Brandon M; Voss, S Randal; Osborn, Jeffrey L

    2017-08-01

    Little is known about the potential for ion channels to regulate cellular behaviors during tissue regeneration. Here, we utilized an amphibian tail regeneration assay coupled with a chemical genetic screen to identify ion channel antagonists that altered critical cellular processes during regeneration. Inhibition of multiple ion channels either partially (anoctamin1/Tmem16a, anoctamin2/Tmem16b, K V 2.1, K V 2.2, L-type Ca V channels and H/K ATPases) or completely (GlyR, GABA A R, K V 1.5 and SERCA pumps) inhibited tail regeneration. Partial inhibition of tail regeneration by blocking the calcium activated chloride channels, anoctamin1&2, was associated with a reduction of cellular proliferation in tail muscle and mesenchymal regions. Inhibition of anoctamin 1/2 also altered the post-amputation transcriptional response of p44/42 MAPK signaling pathway genes, including decreased expression of erk1/erk2. We also found that complete inhibition via voltage gated K + channel blockade was associated with diminished phagocyte recruitment to the amputation site. The identification of H + pumps as required for axolotl tail regeneration supports findings in Xenopus and Planaria models, and more generally, the conservation of ion channels as regulators of tissue regeneration. This study provides a preliminary framework for an in-depth investigation of the mechanistic role of ion channels and their potential involvement in regulating cellular proliferation and other processes essential to wound healing, appendage regeneration, and tissue repair. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Setting research priorities by applying the combined approach matrix.

    Science.gov (United States)

    Ghaffar, Abdul

    2009-04-01

    Priority setting in health research is a dynamic process. Different organizations and institutes have been working in the field of research priority setting for many years. In 1999 the Global Forum for Health Research presented a research priority setting tool called the Combined Approach Matrix or CAM. Since its development, the CAM has been successfully applied to set research priorities for diseases, conditions and programmes at global, regional and national levels. This paper briefly explains the CAM methodology and how it could be applied in different settings, giving examples and describing challenges encountered in the process of setting research priorities and providing recommendations for further work in this field. The construct and design of the CAM is explained along with different steps needed, including planning and organization of a priority-setting exercise and how it could be applied in different settings. The application of the CAM are described by using three examples. The first concerns setting research priorities for a global programme, the second describes application at the country level and the third setting research priorities for diseases. Effective application of the CAM in different and diverse environments proves its utility as a tool for setting research priorities. Potential challenges encountered in the process of research priority setting are discussed and some recommendations for further work in this field are provided.

  2. Determining climate change management priorities: A case study from Wisconsin

    Science.gov (United States)

    LeDee, Olivia E.; Ribic, Christine

    2015-01-01

    A burgeoning dialogue exists regarding how to allocate resources to maximize the likelihood of long-term biodiversity conservation within the context of climate change. To make effective decisions in natural resource management, an iterative, collaborative, and learning-based decision process may be more successful than a strictly consultative approach. One important, early step in a decision process is to identify priority species or systems. Although this promotes the conservation of select species or systems, it may inadvertently alter the future of non-target species and systems. We describe a process to screen terrestrial wildlife for potential sensitivity to climate change and then use the results to engage natural resource professionals in a process of identifying priorities for monitoring, research, and adaptation strategy implementation. We demonstrate this approach using a case study from Wisconsin. In Wisconsin, experts identified 23 out of 353 species with sufficient empirical research and management understanding to inform targeted action. Habitat management and management of hydrological conditions were the common strategies for targeted action. Although there may be an interest in adaptation strategy implementation for many species and systems, experts considered existing information inadequate to inform targeted action. According to experts, 40% of the vertebrate species in Wisconsin will require near-term intervention for climate adaptation. These results will inform state-wide conservation planning as well as regional efforts.

  3. On Setting Priorities among Human Rights

    NARCIS (Netherlands)

    Philips, Jos

    2014-01-01

    Should conflicts among human rights be dealt with by including general principles for priority setting at some prominent place in the practice of human rights? This essay argues that neither setting prominent and principled priorities nor a case-by-case approach are likely to be defensible as

  4. Game-Theoretic Social-Aware Resource Allocation for Device-to-Device Communications Underlaying Cellular Network

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2018-01-01

    Full Text Available Device-to-Device communication underlaying cellular network can increase the spectrum efficiency due to direct proximity communication and frequency reuse. However, such performance improvement is influenced by the power interference caused by spectrum sharing and social characteristics in each social community jointly. In this investigation, we present a dynamic game theory with complete information based D2D resource allocation scheme for D2D communication underlaying cellular network. In this resource allocation method, we quantify both the rate influence from the power interference caused by the D2D transmitter to cellular users and rate enhancement brought by the social relationships between mobile users. Then, the utility function maximization game is formulated to optimize the overall transmission rate performance of the network, which synthetically measures the final influence from both power interference and sociality enhancement. Simultaneously, we discuss the Nash Equilibrium of the proposed utility function maximization game from a theoretical point of view and further put forward a utility priority searching algorithm based resource allocation scheme. Simulation results show that our proposed scheme attains better performance compared with the other two advanced proposals.

  5. Setting priorities for ambient air quality objectives

    International Nuclear Information System (INIS)

    2004-10-01

    Alberta has ambient air quality objectives in place for several pollutants, toxic substances and other air quality parameters. A process is in place to determine if additional air quality objectives are required or if existing objectives should be changed. In order to identify the highest priority substances that may require an ambient air quality objective to protect ecosystems and public health, a rigorous, transparent and cost effective priority setting methodology is required. This study reviewed, analyzed and assessed successful priority setting techniques used by other jurisdictions. It proposed an approach for setting ambient air quality objective priorities that integrates the concerns of stakeholders with Alberta Environment requirements. A literature and expert review were used to examine existing priority-setting techniques used by other jurisdictions. An analysis process was developed to identify the strengths and weaknesses of various techniques and their ability to take into account the complete pathway between chemical emissions and damage to human health or the environment. The key strengths and weaknesses of each technique were identified. Based on the analysis, the most promising technique was the tool for the reduction and assessment of chemical and other environmental impacts (TRACI). Several considerations for using TRACI to help set priorities for ambient air quality objectives were also presented. 26 refs, 8 tabs., 4 appendices

  6. Phylogenetically-informed priorities for amphibian conservation.

    Science.gov (United States)

    Isaac, Nick J B; Redding, David W; Meredith, Helen M; Safi, Kamran

    2012-01-01

    The amphibian decline and extinction crisis demands urgent action to prevent further large numbers of species extinctions. Lists of priority species for conservation, based on a combination of species' threat status and unique contribution to phylogenetic diversity, are one tool for the direction and catalyzation of conservation action. We describe the construction of a near-complete species-level phylogeny of 5713 amphibian species, which we use to create a list of evolutionarily distinct and globally endangered species (EDGE list) for the entire class Amphibia. We present sensitivity analyses to test the robustness of our priority list to uncertainty in species' phylogenetic position and threat status. We find that both sources of uncertainty have only minor impacts on our 'top 100' list of priority species, indicating the robustness of the approach. By contrast, our analyses suggest that a large number of Data Deficient species are likely to be high priorities for conservation action from the perspective of their contribution to the evolutionary history.

  7. Phylogenetically-informed priorities for amphibian conservation.

    Directory of Open Access Journals (Sweden)

    Nick J B Isaac

    Full Text Available The amphibian decline and extinction crisis demands urgent action to prevent further large numbers of species extinctions. Lists of priority species for conservation, based on a combination of species' threat status and unique contribution to phylogenetic diversity, are one tool for the direction and catalyzation of conservation action. We describe the construction of a near-complete species-level phylogeny of 5713 amphibian species, which we use to create a list of evolutionarily distinct and globally endangered species (EDGE list for the entire class Amphibia. We present sensitivity analyses to test the robustness of our priority list to uncertainty in species' phylogenetic position and threat status. We find that both sources of uncertainty have only minor impacts on our 'top 100' list of priority species, indicating the robustness of the approach. By contrast, our analyses suggest that a large number of Data Deficient species are likely to be high priorities for conservation action from the perspective of their contribution to the evolutionary history.

  8. Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Kjaer, M; Mackey, A L

    2011-01-01

    The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging......-links and a buildup of advanced glycation end-product cross-links. Altered mechanotransduction, poorer activation of satellite cells, poorer chemotactic and delayed inflammatory responses, and a change in modulators of the ECM are important cellular changes. It is possible that the structural and biochemical changes...... in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some...

  9. Cave Conservation Priority Index to Adopt a Rapid Protection Strategy: A Case Study in Brazilian Atlantic Rain Forest

    Science.gov (United States)

    Souza Silva, Marconi; Martins, Rogério Parentoni; Ferreira, Rodrigo Lopes

    2015-02-01

    Cave environments are characterized by possessing specialized fauna living in high environmental stability with limited food conditions. These fauna are highly vulnerable to impacts, because this condition can frequently be easily altered. Moreover, environmental determinants of the biodiversity patterns of caves remain poorly understood and protected. Therefore, the main goal of this work is to propose a cave conservation priority index (CCPi) for a rapid assessment for troglobiotic and troglophile protection. Furthermore, the troglobiotic diversity, distribution and threats have been mapped in the Brazilian Atlantic forest. To propose the CCPi, the human impacts and richness of troglobiotic and troglophile species of 100 caves were associated. Data related to troglomorphic/troglobiotic fauna from another 200 caves were used to map the troglobiotic diversity and distribution. The CCPi reveals extremely high conservation priority for 15 % of the caves, high for 36 % and average for 46 % of the caves. Fourteen caves with extremely high priorities should have urgent conservation and management actions. The geographical distribution of the 221 known troglobiotic/troglomorphic species allowed us to select 19 karst areas that need conservation actions. Seven areas were considered to have urgent priority for conservation actions. The two richest areas correspond to the "iron quadrangle" with iron ore caves (67 spp.) and the "Açungui limestone group" (56 spp.). Both areas have several caves and are important aquifers. The use of the CCPi can prevent future losses because it helps assessors to select caves with priorities for conservation which should receive emergency attention in relation to protection, management and conservation actions.

  10. Prostate cancer-associated gene expression alterations determined from needle biopsies.

    Science.gov (United States)

    Qian, David Z; Huang, Chung-Ying; O'Brien, Catherine A; Coleman, Ilsa M; Garzotto, Mark; True, Lawrence D; Higano, Celestia S; Vessella, Robert; Lange, Paul H; Nelson, Peter S; Beer, Tomasz M

    2009-05-01

    To accurately identify gene expression alterations that differentiate neoplastic from normal prostate epithelium using an approach that avoids contamination by unwanted cellular components and is not compromised by acute gene expression changes associated with tumor devascularization and resulting ischemia. Approximately 3,000 neoplastic and benign prostate epithelial cells were isolated using laser capture microdissection from snap-frozen prostate biopsy specimens provided by 31 patients who subsequently participated in a clinical trial of preoperative chemotherapy. cDNA synthesized from amplified total RNA was hybridized to custom-made microarrays composed of 6,200 clones derived from the Prostate Expression Database. Expression differences for selected genes were verified using quantitative reverse transcription-PCR. Comparative analyses identified 954 transcript alterations associated with cancer (q transport. Genes down-regulated in prostate cancers were enriched in categories related to immune response, cellular responses to pathogens, and apoptosis. A heterogeneous pattern of androgen receptor expression changes was noted. In exploratory analyses, androgen receptor down-regulation was associated with a lower probability of cancer relapse after neoadjuvant chemotherapy followed by radical prostatectomy. Assessments of tumor phenotypes based on gene expression for treatment stratification and drug targeting of oncogenic alterations may best be ascertained using biopsy-based analyses where the effects of ischemia do not complicate interpretation.

  11. Priority for sustainability. Study of the effects on investment climate

    International Nuclear Information System (INIS)

    2007-12-01

    The Dutch cabinet has been asked to make sure that sustainable electricity plants can be connected to the grid with high priority. By request of the Dutch Ministry of Economic Affairs, the effects on the investment climate have been examined (both for sustainable and conventional) if priority (with regard to connection and transport) is given to sustainable generated electricity. Five models for priority for sustainable have been defined, i.e. (1) Sustainable is only given priority on the waiting list for connection; (2) Connect sustainable immediately, but no priority for transport; (3) Connect sustainable immediately and priority granted in transport; (4) Connect sustainable and conventional immediately, no priority for transport; (5) Connect sustainable and conventional immediately and give priority in transport to sustainable. [mk] [nl

  12. Priority Queues Resilient to Memory Faults

    DEFF Research Database (Denmark)

    Jørgensen, Allan Grønlund; Moruz, Gabriel; Mølhave, Thomas

    2007-01-01

    In the faulty-memory RAM model, the content of memory cells can get corrupted at any time during the execution of an algorithm, and a constant number of uncorruptible registers are available. A resilient data structure in this model works correctly on the set of uncorrupted values. In this paper we...... introduce a resilient priority queue. The deletemin operation of a resilient priority queue returns either the minimum uncorrupted element or some corrupted element. Our resilient priority queue uses $O(n)$ space to store $n$ elements. Both insert and deletemin operations are performed in $O(\\log n...... queues storing only structural information in the uncorruptible registers between operations....

  13. The cellular magnetic response and biocompatibility of biogenic zinc- and cobalt-doped magnetite nanoparticles

    Science.gov (United States)

    Moise, Sandhya; Céspedes, Eva; Soukup, Dalibor; Byrne, James M.; El Haj, Alicia J.; Telling, Neil D.

    2017-01-01

    The magnetic moment and anisotropy of magnetite nanoparticles can be optimised by doping with transition metal cations, enabling their properties to be tuned for different biomedical applications. In this study, we assessed the suitability of bacterially synthesized zinc- and cobalt-doped magnetite nanoparticles for biomedical applications. To do this we measured cellular viability and activity in primary human bone marrow-derived mesenchymal stem cells and human osteosarcoma-derived cells. Using AC susceptibility we studied doping induced changes in the magnetic response of the nanoparticles both as stable aqueous suspensions and when associated with cells. Our findings show that the magnetic response of the particles was altered after cellular interaction with a reduction in their mobility. In particular, the strongest AC susceptibility signal measured in vitro was from cells containing high-moment zinc-doped particles, whilst no signal was observed in cells containing the high-anisotropy cobalt-doped particles. For both particle types we found that the moderate dopant levels required for optimum magnetic properties did not alter their cytotoxicity or affect osteogenic differentiation of the stem cells. Thus, despite the known cytotoxicity of cobalt and zinc ions, these results suggest that iron oxide nanoparticles can be doped to sufficiently tailor their magnetic properties without compromising cellular biocompatibility.

  14. The role of thiols in cellular response to radiation and drugs

    International Nuclear Information System (INIS)

    Biaglow, J.E.; Varnes, M.E.; Clark, E.P.; Epp, E.R.

    1983-01-01

    Cellular nonprotein thiols (NPSH) consist of glutathione (GSH) and other low molecular weight species such as cysteine, cysteamine, and coenzyme A. GSH is usually less than the total cellular NPSH, and with thiol reactive agents, such as diethyl maleate (DEM), its rate of depletion is in part dependent upon the cellular capacity for its resynthesis. If resynthesis is blocked by buthionine-S,R-sulfoximine(BSO), the NPSH, including GSH, is depleted more rapidly, Cellular thiol depletion by diamide, N-ethylmaleimide, and BSO may render oxygenated cells more sensitive to radiation. These cells may or may not show a reduction in the oxygen enhancement ratio (OER). Human A549 lung carcinoma cells depleted of their NPSH either by prolonged culture or by BSO treatment do not show a reduced OER but do show increased aerobic responses to radiation. Some nitroheterocyclic radiosensitizing drugs also deplete cellular thiols under aerobic conditions. Such reactivity may be the reason that they show anomalous radiation sensitization (i.e., better than predicted on the basis of electron affinity). Other nitrocompounds, such as misonidazole, are activated under hypoxic conditions to radical intermediates. When cellular thiols are depleted peroxide is formed. Under hypoxic conditions thiols are depleted because metabolically reduced intermediates react with GSH instead of oxygen. Thiol depletion, under hypoxic conditions, may be the reason that misonidazole and other nitrocompounds show an extra enhancement ratio with hypoxic cells. Thiol depletion by DEM or BSO alters the radiation response of hypoxic cells to misonidazole

  15. Final priority; Technical Assistance on State Data Collection--IDEA Data Management Center. Final priority.

    Science.gov (United States)

    2014-08-05

    The Assistant Secretary for the Office of Special Education and Rehabilitative Services (OSERS) announces a priority under the Technical Assistance on State Data Collection program. The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2014 and later years. We take this action to fund a cooperative agreement to establish and operate an IDEA Data Management Center (Center) that will provide technical assistance (TA) to improve the capacity of States to meet the data collection requirements of the Individuals with Disabilities Education Act (IDEA).

  16. Leadership and priority setting: the perspective of hospital CEOs.

    Science.gov (United States)

    Reeleder, David; Goel, Vivek; Singer, Peter A; Martin, Douglas K

    2006-11-01

    The role of leadership in health care priority setting remains largely unexplored. While the management leadership literature has grown rapidly, the growing literature on priority setting in health care has looked in other directions to improve priority setting practices--to health economics and ethical approaches. Consequently, potential for improvement in hospital priority setting practices may be overlooked. A qualitative study involving interviews with 46 Ontario hospital CEOs was done to describe the role of leadership in priority setting through the perspective of hospital leaders. For the first time, we report a framework of leadership domains including vision, alignment, relationships, values and process to facilitate priority setting practices in health services' organizations. We believe this fledgling framework forms the basis for the sharing of good leadership practices for health reform. It also provides a leadership guide for decision makers to improve the quality of their leadership, and in so doing, we believe, the fairness of their priority setting.

  17. 10 CFR 216.7 - Conflict in priority orders.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Conflict in priority orders. 216.7 Section 216.7 Energy... DOMESTIC ENERGY SUPPLIES § 216.7 Conflict in priority orders. If it appears that the use of assistance pursuant to DPA section 101(c) creates or threatens to create a conflict with priorities and allocation...

  18. The priorities for ANSTO

    International Nuclear Information System (INIS)

    Garnett, H.M.

    1999-01-01

    As Australia's major centre of expertise in nuclear science, technology and its applications, ANSTO's priorities take account of the stated strategic and tactical needs of its various stakeholders, which in turn are considered as the Government (as owner), industry - including the health sector, the academic and research community and the public at large. Its priorities also take account of the opportunities perceived by its own staff in the light of the organisation's strengths, the activities of the international scientific, technology and industry community and a rapidly changing socioeconomic environment where environmental management and social accountability are becoming as important as fiscal responsibility and accountability

  19. Alteration of cellular radiation response as a consequence of defective DNA mismatch repair

    International Nuclear Information System (INIS)

    Weese, Theodore L. de; Bucci, Jennifer M.; Larrier, Nicole A.; Cutler, Richard G.; Riele, Hein te; Nelson, William G.

    1997-01-01

    Purpose/Objective: A number of genes have been implicated in the response of mammalian cells to ionizing radiation. Among these include the genes P53 and P21. Disruption of these genes can alter the predicted cellular behavior following radiation-induced DNA damage. Similarly, cells defective in mismatch repair are known to be tolerant to the lethal effects of alkylating agents. We hypothesized that mammalian cells which are defective in mismatch repair and tolerant to alkylating DNA damage might also be tolerant to the effects of oxidative DNA damage inflicted by ionizing radiation. Materials and Methods: Mouse embryonic stem cells homozygous for disrupted Msh2 alleles (Msh2-/-), heterozygous for a disrupted Msh2 allele (Msh2+/-) or intact cells (Msh2+/+) were exposed to both acute dose (1 Gy/min) and low dose rate (LDR) radiation (0.004 Gy/min) and cell survival was determined by clonogenic assay. Apoptosis induced by LDR was assessed by a terminal transferase assay. Immunoblot analysis was performed in order to evaluate induction of the polypeptides p53 and p21. Another measure of radiation damage tolerance may be accumulation of oxidative DNA species. Therefore, we monitored levels of 8-hydroxyguanine (8-OHG) and 8-hydroxyadenine (8-OHA) by gas chromatography - mass spectrometry with selected ion monitoring (GC-MS/SIM). Results: Cells containing either one or two disrupted Msh2 alleles (Msh2+/-, Msh2-/-) were found to be less sensitive to LDR than cells containing a complete complement of Msh2 alleles (Msh2+/+). Interestingly, all three cell lines had a nearly identical radiosensitivity to acute dose ionizing radiation despite differences in mismatch repair capacity. Apoptosis after LDR also varied between cells, with the Msh2+/+ cells exhibiting higher levels of apoptosis as compared to either the Msh2+/- or Msh2-/- cell lines. In addition, GC-MS/SIM revealed the Msh2+/- and Msh2-/- cell lines to have an approximately ten fold greater accumulation of the

  20. Gas priority users consultation : government response

    International Nuclear Information System (INIS)

    2007-01-01

    This consultation document presents the results of an updated analysis of gas priority users comments on the UK government's proposals for updating the current priority lists, amending the eligibility criteria for priority user status, and simplifying the administration of the scheme. The extension of Category C priority users to include sites where interruption of gas supplies would lead to damage exceeding fifty million pounds to a plant at another site is discussed. It is acknowledged that there is a preference for a reduction of gas demand as opposed to a cessation in the case of an emergency gas supply deficit and details are given of a Task Group set up to examine options for reducing demand rather than cessation for large industrial gas users. The role of the Network Emergency Co-ordinator, support for a more flexible approach, pre-agreed rota interruption, a long-duration emergency, demand reduction, and the establishment of a Government/Industry Gas/Electricity Task Group are discussed, and the raising of the load shedding threshold of 25,000 therms/yr is considered

  1. Economics and Security: Resourcing National Priorities

    Science.gov (United States)

    2010-05-21

    Papers Number 5 N um ber 5 Econom ics and Security: R esourcing N ational Priorities http://www.usnwc.edu Report Documentation Page Form ApprovedOMB No...2010 William B. Ruger Chair of National Security Economics Papers Number 5 N um ber 5 Econom ics and Security: R esourcing N ational Priorities http://www.usnwc.edu

  2. Priority setting partnership to identify the top 10 research priorities for the management of Parkinson's disease.

    Science.gov (United States)

    Deane, Katherine H O; Flaherty, Helen; Daley, David J; Pascoe, Roland; Penhale, Bridget; Clarke, Carl E; Sackley, Catherine; Storey, Stacey

    2014-12-14

    This priority setting partnership was commissioned by Parkinson's UK to encourage people with direct and personal experience of the condition to work together to identify and prioritise the top 10 evidential uncertainties that impact on everyday clinical practice for the management of Parkinson's disease (PD). The UK. Anyone with experience of PD including: people with Parkinson's (PwP), carers, family and friends, healthcare and social care professionals. Non-clinical researchers and employees of pharmaceutical or medical devices companies were excluded. 1000 participants (60% PwP) provided ideas on research uncertainties, 475 (72% PwP) initially prioritised them and 27 (37% PwP) stakeholders agreed a final top 10. Using a modified nominal group technique, participants were surveyed to identify what issues for the management of PD needed research. Unique research questions unanswered by current evidence were identified and participants were asked to identify their top 10 research priorities from this list. The top 26 uncertainties were presented to a consensus meeting with key stakeholders to agree the top 10 research priorities. 1000 participants provided 4100 responses, which contained 94 unique unanswered research questions that were initially prioritised by 475 participants. A consensus meeting with 27 stakeholders agreed the top 10 research priorities. The overarching research aspiration was an effective cure for PD. The top 10 research priorities for PD management included the need to address motor symptoms (balance and falls, and fine motor control), non-motor symptoms (sleep and urinary dysfunction), mental health issues (stress and anxiety, dementia and mild cognitive impairments), side effects of medications (dyskinesia) and the need to develop interventions specific to the phenotypes of PD and better monitoring methods. These research priorities identify crucial gaps in the existing evidence to address everyday practicalities in the management of the

  3. Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

    Science.gov (United States)

    Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

    2011-01-01

    It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

  4. The kidney cancer research priority-setting partnership: Identifying the top 10 research priorities as defined by patients, caregivers, and expert clinicians.

    Science.gov (United States)

    Jones, Jennifer; Bhatt, Jaimin; Avery, Jonathan; Laupacis, Andreas; Cowan, Katherine; Basappa, Naveen; Basiuk, Joan; Canil, Christina; Al-Asaaed, Sohaib; Heng, Daniel; Wood, Lori; Stacey, Dawn; Kollmannsberger, Christian; Jewett, Michael A S

    2017-12-01

    It is critically important to define disease-specific research priorities to better allocate limited resources. There is growing recognition of the value of involving patients and caregivers, as well as expert clinicians in this process. To our knowledge, this has not been done this way for kidney cancer. Using the transparent and inclusive process established by the James Lind Alliance, the Kidney Cancer Research Network of Canada (KCRNC) sponsored a collaborative consensus-based priority-setting partnership (PSP) to identify research priorities in the management of kidney cancer. The final result was identification of 10 research priorities for kidney cancer, which are discussed in the context of current initiatives and gaps in knowledge. This process provided a systematic and effective way to collaboratively establish research priorities with patients, caregivers, and clinicians, and provides a valuable resource for researchers and funding agencies.

  5. Polling, production & priorities

    NARCIS (Netherlands)

    Winands, E.M.M.

    2007-01-01

    Polling, Production & Priorities The present monograph focuses on the so-called stochastic economic lot scheduling problem (SELSP), which deals with the make-to-stock production of multiple standardized products on a single machine with limited capacity under random demands, possibly random setup

  6. Optimal purely functional priority queues

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Okasaki, Chris

    1996-01-01

    Brodal recently introduced the first implementation of imperative priority queues to support findMin, insert and meld in O(1) worst-case time, and deleteMin in O(log n) worst-case time. These bounds are asymptotically optimal among all comparison-based priority queues. In this paper, we adapt...... Brodal's data structure to a purely functional setting. In doing so, we both simplify the data structure and clarify its relationship to the binomial queues of Vuillemin, which support all four operations in O(log n) time. Specifically, we derive our implementation from binomial queues in three steps......: first, we reduce the running time of insert to O(1) by eliminating the possibility of cascading links; second, we reduce the running time of findMin to O(1) by adding a global root to hold the minimum element; and finally, we reduce the running time of meld to O(1) by allowing priority queues to contain...

  7. Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

    Science.gov (United States)

    McAllister, Kimberly; Worth, Leroy; Haugen, Astrid C.; Meyer, Joel N.; Domann, Frederick E.; Van Houten, Bennett; Mostoslavsky, Raul; Bultman, Scott J.; Baccarelli, Andrea A.; Begley, Thomas J.; Sobol, Robert W.; Hirschey, Matthew D.; Ideker, Trey; Santos, Janine H.; Copeland, William C.; Tice, Raymond R.; Balshaw, David M.; Tyson, Frederick L.

    2014-01-01

    Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria–nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25–26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria–cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to

  8. Hematological alterations in protein malnutrition.

    Science.gov (United States)

    Santos, Ed W; Oliveira, Dalila C; Silva, Graziela B; Tsujita, Maristela; Beltran, Jackeline O; Hastreiter, Araceli; Fock, Ricardo A; Borelli, Primavera

    2017-11-01

    Protein malnutrition is one of the most serious nutritional problems worldwide, affecting 794 million people and costing up to $3.5 trillion annually in the global economy. Protein malnutrition primarily affects children, the elderly, and hospitalized patients. Different degrees of protein deficiency lead to a broad spectrum of signs and symptoms of protein malnutrition, especially in organs in which the hematopoietic system is characterized by a high rate of protein turnover and, consequently, a high rate of protein renewal and cellular proliferation. Here, the current scientific information about protein malnutrition and its effects on the hematopoietic process is reviewed. The production of hematopoietic cells is described, with special attention given to the hematopoietic microenvironment and the development of stem cells. Advances in the study of hematopoiesis in protein malnutrition are also summarized. Studies of protein malnutrition in vitro, in animal models, and in humans demonstrate several alterations that impair hematopoiesis, such as structural changes in the extracellular matrix, the hematopoietic stem cell niche, the spleen, the thymus, and bone marrow stromal cells; changes in mesenchymal and hematopoietic stem cells; increased autophagy; G0/G1 cell-cycle arrest of progenitor hematopoietic cells; and functional alterations in leukocytes. Structural and cellular changes of the hematopoietic microenvironment in protein malnutrition contribute to bone marrow atrophy and nonestablishment of hematopoietic stem cells, resulting in impaired homeostasis and an impaired immune response. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. The long Tramp from Cellular Pathology to Molecular Pathology

    Directory of Open Access Journals (Sweden)

    Hans Guski

    2017-05-01

    Derivatives: The observation of principal identity of biological meaningful elements can be agglutinated to a ‘general theory of live’ and its manifestation. All of the investigated elements posses the same regularities, which are altered, destroyed or newly built by external influences such as disease, physical and psychological forces. Not all magnification levels that display with these elements are of the same significance. Already Virchow suggested that ‘smaller elements (molecules might be responsible for changes that are visible ‘in larger elements’ (at cellular level.  The reflection on these ideas can be associated with the implementation of molecular techniques which has been developed in the 20th century and are still ongoing today. Perspectives: Thus, cellular and molecular pathology can be integrated under one umbrella. This umbrella will lead to newly man-formed structures, such as artificial DNA and gene components or functional chip implantations.

  10. A Mathematical Analysis of Air Traffic Priority Rules

    Science.gov (United States)

    Nakawicz, Anthony J.; Munoz, Cesar A.; Maddalon, Jeffrey M.

    2012-01-01

    This paper analyzes priority rules, such as those in Part 91.113 of the Federal Aviation Regulations. Such rules determine which of two aircraft should maneuver in a given conflict scenario. While the rules in 91.113 are well accepted, other concepts of operation for NextGen, such as self separation, may allow for different priority rules. A mathematical framework is presented that can be used to analyze a general set of priority rules and enables proofs of important properties. Specific properties considered in this paper include safety, effectiveness, and stability. A set of rules is said to be safe if it ensures that it is never the case that both aircraft have priority. They are effective if exactly one aircraft has priority in every situation. Finally, a set of rules is called stable if it produces compatible results even under small changes to input data.

  11. Matriptase autoactivation is tightly regulated by the cellular chemical environments.

    Directory of Open Access Journals (Sweden)

    Jehng-Kang Wang

    Full Text Available The ability of cells to rapidly detect and react to alterations in their chemical environment, such as pH, ionic strength and redox potential, is essential for cell function and survival. We present here evidence that cells can respond to such environmental alterations by rapid induction of matriptase autoactivation. Specifically, we show that matriptase autoactivation can occur spontaneously at physiological pH, and is significantly enhanced by acidic pH, both in a cell-free system and in living cells. The acid-accelerated autoactivation can be attenuated by chloride, a property that may be part of a safety mechanism to prevent unregulated matriptase autoactivation. Additionally, the thio-redox balance of the environment also modulates matriptase autoactivation. Using the cell-free system, we show that matriptase autoactivation is suppressed by cytosolic reductive factors, with this cytosolic suppression being reverted by the addition of oxidizing agents. In living cells, we observed rapid induction of matriptase autoactivation upon exposure to toxic metal ions known to induce oxidative stress, including CoCl2 and CdCl2. The metal-induced matriptase autoactivation is suppressed by N-acetylcysteine, supporting the putative role of altered cellular redox state in metal induced matriptase autoactivation. Furthermore, matriptase knockdown rendered cells more susceptible to CdCl2-induced cell death compared to control cells. This observation implies that the metal-induced matriptase autoactivation confers cells with the ability to survive exposure to toxic metals and/or oxidative stress. Our results suggest that matriptase can act as a cellular sensor of the chemical environment of the cell that allows the cell to respond to and protect itself from changes in the chemical milieu.

  12. Priority setting in general practice: health priorities of older patients differ from treatment priorities of their physicians.

    Science.gov (United States)

    Voigt, Isabel; Wrede, Jennifer; Diederichs-Egidi, Heike; Dierks, Marie-Luise; Junius-Walker, Ulrike

    2010-12-01

    To ascertain health priorities of older patients and treatment priorities of their general practitioners (GP) on the basis of a geriatric assessment and to determine the agreement between these priorities. The study included a sample of 9 general practitioners in Hannover, Germany, and a stratified sample of 35 patients (2-5 patients per practice, 18 female, average age 77.7 years). Patients were given a geriatric assessment using the Standardized Assessment for Elderly Patients in Primary Care (STEP) to gain an overview of their health and everyday problems. On the basis of these results, patients and their physicians independently rated the importance of each problem disclosed by the assessment. Whereas patients assessed the importance for their everyday lives, physicians assessed the importance for patients' medical care and patients' everyday lives. Each patient had a mean ± standard deviation of 18 ± 9.2 health problems. Thirty five patients disclosed a total of 634 problems; 537 (85%) were rated by patients and physicians. Of these 537 problems, 332 (62%) were rated by patients and 334 (62%) by physicians as important for patients' everyday lives. In addition, 294 (55%) were rated by physicians as important for patients' medical care. Although these proportions of important problems were similar between patients and physicians, there was little overlap in the specific problems that each group considered important. The chance-corrected agreement (Cohen κ) between patients and physicians on the importance of problems for patients' lives was low (κ=0.23). Likewise, patients and physicians disagreed on the problems that physicians considered important for patients' medical care (κ=0.18, Ppriorities between patients and physicians necessitates better communication between the two parties to strengthen mutual understanding.

  13. Top ten research priorities for spinal cord injury: the methodology and results of a British priority setting partnership.

    Science.gov (United States)

    van Middendorp, J J; Allison, H C; Ahuja, S; Bracher, D; Dyson, C; Fairbank, J; Gall, A; Glover, A; Gray, L; Masri, W El; Uttridge, A; Cowan, K

    2016-05-01

    This is a mixed-method consensus development project. The objective of this study was to identify a top ten list of priorities for future research into spinal cord injury (SCI). The British Spinal Cord Injury Priority Setting Partnership was established in 2013 and completed in 2014. Stakeholders included consumer organisations, healthcare professional societies and caregivers. This partnership involved the following four key stages: (i) gathering of research questions, (ii) checking of existing research evidence, (iii) interim prioritisation and (iv) a final consensus meeting to reach agreement on the top ten research priorities. Adult individuals with spinal cord dysfunction because of trauma or non-traumatic causes, including transverse myelitis, and individuals with a cauda equina syndrome (henceforth grouped and referred to as SCI) were invited to participate in this priority setting partnership. We collected 784 questions from 403 survey respondents (290 individuals with SCI), which, after merging duplicate questions and checking systematic reviews for evidence, were reduced to 109 unique unanswered research questions. A total of 293 people (211 individuals with SCI) participated in the interim prioritisation process, leading to the identification of 25 priorities. At a final consensus meeting, a representative group of individuals with SCI, caregivers and health professionals agreed on their top ten research priorities. Following a comprehensive, rigorous and inclusive process, with participation from individuals with SCI, caregivers and health professionals, the SCI research agenda has been defined by people to whom it matters most and should inform the scope and future activities of funders and researchers for the years to come. The NIHR Oxford Biomedical Research Centre provided core funding for this project.

  14. Cellular modelling of river catchments and reaches: Advantages, limitations and prospects

    Science.gov (United States)

    Coulthard, T. J.; Hicks, D. M.; Van De Wiel, M. J.

    2007-10-01

    The last decade has witnessed the development of a series of cellular models that simulate the processes operating within river channels and drive their geomorphic evolution. Their proliferation can be partly attributed to the relative simplicity of cellular models and their ability to address some of the shortcomings of other numerical models. By using relaxed interpretations of the equations determining fluid flow, cellular models allow rapid solutions of water depths and velocities. These can then be used to drive (usually) conventional sediment transport relations to determine erosion and deposition and alter the channel form. The key advance of using these physically based yet simplified approaches is that they allow us to apply models to a range of spatial scales (1-100 km 2) and time periods (1-100 years) that are especially relevant to contemporary management and fluvial studies. However, these approaches are not without their limitations and technical problems. This paper reviews the findings of nearly 10 years of research into modelling fluvial systems with cellular techniques, principally focusing on improvements in routing water and how fluvial erosion and deposition (including lateral erosion) are represented. These ideas are illustrated using sample simulations of the River Teifi, Wales. A detailed case study is then presented, demonstrating how cellular models can explore the interactions between vegetation and the morphological dynamics of the braided Waitaki River, New Zealand. Finally, difficulties associated with model validation and the problems, prospects and future issues important to the further development and application of these cellular fluvial models are outlined.

  15. DNA Mismatch Repair System: Repercussions in Cellular Homeostasis and Relationship with Aging

    Directory of Open Access Journals (Sweden)

    Juan Cristóbal Conde-Pérezprina

    2012-01-01

    Full Text Available The mechanisms that concern DNA repair have been studied in the last years due to their consequences in cellular homeostasis. The diverse and damaging stimuli that affect DNA integrity, such as changes in the genetic sequence and modifications in gene expression, can disrupt the steady state of the cell and have serious repercussions to pathways that regulate apoptosis, senescence, and cancer. These altered pathways not only modify cellular and organism longevity, but quality of life (“health-span”. The DNA mismatch repair system (MMR is highly conserved between species; its role is paramount in the preservation of DNA integrity, placing it as a necessary focal point in the study of pathways that prolong lifespan, aging, and disease. Here, we review different insights concerning the malfunction or absence of the DNA-MMR and its impact on cellular homeostasis. In particular, we will focus on DNA-MMR mechanisms regulated by known repair proteins MSH2, MSH6, PMS2, and MHL1, among others.

  16. Global Priorities for Marine Biodiversity Conservation

    Science.gov (United States)

    Selig, Elizabeth R.; Turner, Will R.; Troëng, Sebastian; Wallace, Bryan P.; Halpern, Benjamin S.; Kaschner, Kristin; Lascelles, Ben G.; Carpenter, Kent E.; Mittermeier, Russell A.

    2014-01-01

    In recent decades, many marine populations have experienced major declines in abundance, but we still know little about where management interventions may help protect the highest levels of marine biodiversity. We used modeled spatial distribution data for nearly 12,500 species to quantify global patterns of species richness and two measures of endemism. By combining these data with spatial information on cumulative human impacts, we identified priority areas where marine biodiversity is most and least impacted by human activities, both within Exclusive Economic Zones (EEZs) and Areas Beyond National Jurisdiction (ABNJ). Our analyses highlighted places that are both accepted priorities for marine conservation like the Coral Triangle, as well as less well-known locations in the southwest Indian Ocean, western Pacific Ocean, Arctic and Antarctic Oceans, and within semi-enclosed seas like the Mediterranean and Baltic Seas. Within highly impacted priority areas, climate and fishing were the biggest stressors. Although new priorities may arise as we continue to improve marine species range datasets, results from this work are an essential first step in guiding limited resources to regions where investment could best sustain marine biodiversity. PMID:24416151

  17. Global priorities for marine biodiversity conservation.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Selig

    Full Text Available In recent decades, many marine populations have experienced major declines in abundance, but we still know little about where management interventions may help protect the highest levels of marine biodiversity. We used modeled spatial distribution data for nearly 12,500 species to quantify global patterns of species richness and two measures of endemism. By combining these data with spatial information on cumulative human impacts, we identified priority areas where marine biodiversity is most and least impacted by human activities, both within Exclusive Economic Zones (EEZs and Areas Beyond National Jurisdiction (ABNJ. Our analyses highlighted places that are both accepted priorities for marine conservation like the Coral Triangle, as well as less well-known locations in the southwest Indian Ocean, western Pacific Ocean, Arctic and Antarctic Oceans, and within semi-enclosed seas like the Mediterranean and Baltic Seas. Within highly impacted priority areas, climate and fishing were the biggest stressors. Although new priorities may arise as we continue to improve marine species range datasets, results from this work are an essential first step in guiding limited resources to regions where investment could best sustain marine biodiversity.

  18. Cellular cholesterol efflux to plasma from proteinuric patients is elevated and remains unaffected by antiproteinuric treatment

    NARCIS (Netherlands)

    Vogt, L; Laverman, GD; van Tol, A; Groen, AK; Navis, G; Dullaart, RPF

    Background. Lipid derangements are assumed to contribute to the elevated cardiovascular risk in proteinuric patients. The impact of proteinuria on reverse cholesterol transport (RCT) is unknown. The first step in RCT, cellular cholesterol efflux to plasma, may be altered in proteinuria, consequent

  19. The Altered Hepatic Tubulin Code in Alcoholic Liver Disease.

    Science.gov (United States)

    Groebner, Jennifer L; Tuma, Pamela L

    2015-09-18

    The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the "tubulin code" are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.

  20. Appraisal of Priority Sector Lending by Commercial Banks in India

    OpenAIRE

    C Bhujanga Rao

    2014-01-01

    This report provides an overview of the performance of priority sector lending by commercial banks in India. The review captures the changing contours of Reserve Bank of India policy on priority sector advances. The paper analyses the trends in priority sector lending for the period 1995-2011, the burden of non-performing assets of commercial bank in priority sector lending and the extent to which priority sector targets are achieved by individual banks. It is observed that the scheduled comm...

  1. Priority to organ donors: Personal responsibility, equal access and the priority rule in organ procurement

    DEFF Research Database (Denmark)

    Albertsen, Andreas

    2017-01-01

    recently and the preliminary reports indicate increased donation rates. How should we evaluate such initiatives from an ethical perspective? Luck egalitarianism, a responsibility-sensitive approach to distributive justice, provides one possible justification: Those who decide against being organ donors...... limit the health care resources available to others. As such, a priority rule can be justified by a luck egalitarian approach to distributive justice. Furthermore, a priority rule inspired by luck egalitarianism is well equipped to avoid prominent criticisms of such a procurement system. Luck...

  2. Symposium cellular response to DNA damage the role of poly(ADP-ribose) poly(ADP-ribose) in the cellular response to DNA damage

    International Nuclear Information System (INIS)

    Berger, N.A.

    1985-01-01

    Poly(ADP-ribose) polymerase is a chromatin-bound enzyme which, on activation by DNA strand breaks, catalyzes the successive transfer of ADP-ribose units from NAD to nuclear proteins. Poly(ADP-ribose) synthesis is stimulated by DNA strand breaks, and the polymer may alter the structure and/or function of chromosomal proteins to facilitate the DNA repair process. Inhibitors of Poly(ADP-ribose) polymerase or deficiencies of the substrate, NAD, lead to retardation of the DNA repair process. When DNA strand breaks are extensive or when breaks fail to be repaired, the stimulus for activation of Poly(ADP-ribose) persists and the activated enzyme is capable of totaly consuming cellular pools of NAD. Depletion of NAD and consequent lowering of cellular ATP pools, due to activation of Poly(ADP-ribose) polymerase, may account for rapid cell death before DNA repair takes place and before the genetic effects of DNA damage become manifest

  3. Phylogenetic relatedness predicts priority effects in nectar yeast communities

    Science.gov (United States)

    Peay, Kabir G.; Belisle, Melinda; Fukami, Tadashi

    2012-01-01

    Priority effects, in which the outcome of species interactions depends on the order of their arrival, are a key component of many models of community assembly. Yet, much remains unknown about how priority effects vary in strength among species in a community and what factors explain this variation. We experimented with a model natural community in laboratory microcosms that allowed us to quantify the strength of priority effects for most of the yeast species found in the floral nectar of a hummingbird-pollinated shrub at a biological preserve in northern California. We found that priority effects were widespread, with late-arriving species experiencing strong negative effects from early-arriving species. However, the magnitude of priority effects varied across species pairs. This variation was phylogenetically non-random, with priority effects stronger between closer relatives. Analysis of carbon and amino acid consumption profiles indicated that competition between closer relatives was more intense owing to higher ecological similarity, consistent with Darwin's naturalization hypothesis. These results suggest that phylogenetic relatedness between potential colonists may explain the strength of priority effects and, as a consequence, the degree to which community assembly is historically contingent. PMID:21775330

  4. Priority setting for existing chemicals : automated data selection routine

    NARCIS (Netherlands)

    Haelst, A.G. van; Hansen, B.G.

    2000-01-01

    One of the four steps within Council Regulation 793/93/EEC on the evaluation and control of existing chemicals is the priority setting step. The priority setting step is concerned with selecting high-priority substances from a large number of substances, initially starting with 2,474

  5. NRPC ServCat priorities

    Data.gov (United States)

    Department of the Interior — This document lists the Natural Resource Program Center’s priority ServCat documents. It is recommended that these documents- which include annual narrative reports,...

  6. Priority Systems

    OpenAIRE

    Gössler , Gregor; Sifakis , Joseph

    2004-01-01

    Projet POP_ART; We present a framework for the incremental construction of deadlock-free systems meeting given safety properties. The framework borrows concepts and basic results from the controller synthesis paradigm by considering a step in the construction process as a controller synthesis problem. We show that priorities are expressive enough to represent restrictions induced by deadlock-free controllers preserving safety properties. We define a correspondence between such restrictions an...

  7. Cellular network entropy as the energy potential in Waddington's differentiation landscape

    Science.gov (United States)

    Banerji, Christopher R. S.; Miranda-Saavedra, Diego; Severini, Simone; Widschwendter, Martin; Enver, Tariq; Zhou, Joseph X.; Teschendorff, Andrew E.

    2013-01-01

    Differentiation is a key cellular process in normal tissue development that is significantly altered in cancer. Although molecular signatures characterising pluripotency and multipotency exist, there is, as yet, no single quantitative mark of a cellular sample's position in the global differentiation hierarchy. Here we adopt a systems view and consider the sample's network entropy, a measure of signaling pathway promiscuity, computable from a sample's genome-wide expression profile. We demonstrate that network entropy provides a quantitative, in-silico, readout of the average undifferentiated state of the profiled cells, recapitulating the known hierarchy of pluripotent, multipotent and differentiated cell types. Network entropy further exhibits dynamic changes in time course differentiation data, and in line with a sample's differentiation stage. In disease, network entropy predicts a higher level of cellular plasticity in cancer stem cell populations compared to ordinary cancer cells. Importantly, network entropy also allows identification of key differentiation pathways. Our results are consistent with the view that pluripotency is a statistical property defined at the cellular population level, correlating with intra-sample heterogeneity, and driven by the degree of signaling promiscuity in cells. In summary, network entropy provides a quantitative measure of a cell's undifferentiated state, defining its elevation in Waddington's landscape. PMID:24154593

  8. New directions in research priority-setting

    DEFF Research Database (Denmark)

    Nielsen, Morten Velsing

    2017-01-01

    The way governments set priorities for research and innovation in Europe is changing. The new focus on responsible research and innovation (RRI) emphasises broader inclusion, increased dialogue, and a focus on societal challenges. The case of RESEARCH2015 in Denmark is one of the first European...... priority-setting processes to incorporate such criteria. This paper develops a theoretical model to explore how RESEARCH2015 contributes to mutual responsiveness among actors, a main objective of RRI. Studying mutual responsiveness means going beyond the often-stated focus on policy impact to look...... at the creation of trust, interdependence and mutual understanding among participants. The study finds that mutual responsiveness is an important precondition for priority-setting, but that the process's contribution to mutual responsiveness is limited, due to the limited attention to social impacts. Still...

  9. Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kastrup, I.B.; Worm, J.; Ralfkiaer, E.

    2008-01-01

    The reduced folate carrier (RFC) is a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs, including methotrexate (MTX). Acquired alterations of the RFC gene have been associated with resistance to MTX in cancer cell lines and primary osteosarcomas. Here, w...... with adverse outcome. In DLBCL, genetic and epigenetic alterations of RFC were detected at diagnosis in the absence of a selective MTX pressure, suggesting that these alterations may possibly contribute to the development of lymphoma Udgivelsesdato: 2008/1...

  10. Shared research priorities for pessary use in women with prolapse: results from a James Lind Alliance Priority Setting Partnership.

    Science.gov (United States)

    Lough, Kate; Hagen, Suzanne; McClurg, Doreen; Pollock, Alex

    2018-04-28

    To identify the shared priorities for future research of women affected by and clinicians involved with pessary use for the management of prolapse. A priority setting project using a consensus method. A James Lind Alliance Pessary use for prolapse Priority Setting Partnership (JLA Pessary PSP) conducted from May 2016 to September 2017 in the UK. The PSP was run by a Steering Group of three women with experience of pessary use, three experienced clinicians involved with management of prolapse, two researchers with relevant experience, a JLA adviser and a PSP leader. Two surveys were conducted in 2016 and 2017. The first gathered questions about pessaries, and the second asked respondents to prioritise a list of questions. A final workshop was held on 8 September 2017 involving 10 women and 13 clinician representatives with prolapse and pessary experience. A top 10 list of priorities for future research in pessary use for prolapse was agreed by consensus. Women with experience of pessary use and clinicians involved with prolapse management have worked together to determine shared priorities for future research. Aligning the top 10 results with existing research findings will highlight the gaps in current evidence and signpost future research to areas of priority. Effective dissemination of the results will enable research funding bodies to focus on gathering the evidence to answer the questions that matter most to those who will be affected. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. 15 CFR 700.20 - Use of priority ratings.

    Science.gov (United States)

    2010-01-01

    ...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities for Energy Programs § 700.20 Use of...

  12. Occupational health research priorities in Malaysia: a Delphi study.

    Science.gov (United States)

    Sadhra, S; Beach, J R; Aw, T C; Sheikh-Ahmed, K

    2001-07-01

    As part of a consultancy project on occupational health, the Delphi method was used to identify research priorities in occupational health in Malaysia. Participation was sought from government ministries, industry, and professional organisations, and university departments with an interest in occupational and public health. Two rounds of questionnaires resulted in a final list of priorities, with noticeable differences between participants depending on whether they worked in industry or were from government organisations. The participation rate of 71% (55 of 78) was obtained for the first questionnaire and 76% (72 of 95) for the second questionnaire. The participants identified occupational health problems for specific groups and industries as the top research priority area (ranked as top priority by 25% of participants). Ministry of Health participants placed emphasis on healthcare workers (52% ranking it as top priority), whereas those from industry identified construction and plantation workers as groups, which should be accorded the highest priority. Evaluation of research and services was given a low priority. The priorities for occupational health determined with the Delphi approach showed differences between Malaysia, a developing country, and findings from similar European studies. This may be expected, as differences exist in stages of economic development, types of industries, occupational activities, and cultural attitudes to occupational health and safety. Chemical poisonings and workplace accidents were accorded a high priority. By contrast with findings from western countries, workplace psychosocial problems and musculoskeletal injuries were deemed less important. There also seemed to be greater emphasis on adopting interventions for identified problems based on experience in other countries rather than the need to evaluate local occupational health provisions.

  13. What are the macro-social health research priorities?

    Directory of Open Access Journals (Sweden)

    Narges Tabrizchi

    2016-10-01

    Full Text Available   Background: Setting research priorities is a scientific process to allocate resources to the best use. In low- and middle-income countries, allocation of limited resources to fundamental issues is more important. So, the present study was conducted to determine social health research priorities.  Methods: In the first step, important issues and research topics of social health were extracted from documents and studies conducted at the national level.In qualitative phase, reciprocating questionnaires were sent and interviews were conducted with experts and stakeholders, social health issues (as members of Delphi. In the next step, the research topics extracted were discussed in small groups (suggested by Council on Health Research for Development to score the proposed priority topics by Delphi members. Finally, the list of priorities (titles that acquired more than 80% of the total score was sent to Delphi members for final approval.  Results: During the study, 220 topics were obtained in four research domains: “description of the problem and its consequences”, “cause finding”, “intervention to eliminate or reduce problems”, and “Management-Policymaking”. Finally, 30 of these topics remained as priority topics. High priority research topics in social health were equity, happiness, economics, and ethics, respectively.  Conclusion: The findings provide a list of research priorities that help researchers carrying out studies that will have the greatest social health impact. Some targeting areas such as happiness and ethics were identified as less attended subjects that need more investment in research policies, management, and governance.

  14. Worst-case efficient external-memory priority queues

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Katajainen, Jyrki

    1998-01-01

    A priority queue Q is a data structure that maintains a collection of elements, each element having an associated priority drawn from a totally ordered universe, under the operations Insert, which inserts an element into Q, and DeleteMin, which deletes an element with the minimum priority from Q....... In this paper a priority-queue implementation is given which is efficient with respect to the number of block transfers or I/Os performed between the internal and external memories of a computer. Let B and M denote the respective capacity of a block and the internal memory measured in elements. The developed...... data structure handles any intermixed sequence of Insert and DeleteMin operations such that in every disjoint interval of B consecutive priorityqueue operations at most clogM/B N/M I/Os are performed, for some positive constant c. These I/Os are divided evenly among the operations: if B ≥ clogM/B N...

  15. Microbial community changes in biological phosphate-removal systems on altering sludge phosphorus content

    NARCIS (Netherlands)

    Liu, WT; Linning, KD; Nakamura, K; Mino, T; Matsuo, T; Forney, LJ

    Biomarkers (respiratory quinones and cellular fatty acids) and denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA genes were used to characterize the microbial community structure of lab-scale enhanced biological phosphate-removal (EBPR) systems in response to altering sludge

  16. Interplay of drug metabolizing enzymes with cellular transporters.

    Science.gov (United States)

    Böhmdorfer, Michaela; Maier-Salamon, Alexandra; Riha, Juliane; Brenner, Stefan; Höferl, Martina; Jäger, Walter

    2014-11-01

    Many endogenous and xenobiotic substances and their metabolites are substrates for drug metabolizing enzymes and cellular transporters. These proteins may not only contribute to bioavailability of molecules but also to uptake into organs and, consequently, to overall elimination. The coordinated action of uptake transporters, metabolizing enzymes, and efflux pumps, therefore, is a precondition for detoxification and elimination of drugs. As the understanding of the underlying mechanisms is important to predict alterations in drug disposal, adverse drug reactions and, finally, drug-drug interactions, this review illustrates the interplay between selected uptake/efflux transporters and phase I/II metabolizing enzymes.

  17. Research Priorities in Spasmodic Dysphonia

    Science.gov (United States)

    Ludlow, Christy L.; Adler, Charles H.; Berke, Gerald S.; Bielamowicz, Steven A.; Blitzer, Andrew; Bressman, Susan B.; Hallett, Mark; Jinnah, H. A.; Juergens, Uwe; Martin, Sandra B.; Perlmutter, Joel S.; Sapienza, Christine; Singleton, Andrew; Tanner, Caroline M.; Woodson, Gayle E.

    2009-01-01

    OBJECTIVE To identify research priorities for increasing understanding of the pathogenesis, diagnosis and improved treatment of spasmodic dysphonia. STUDY DESIGN AND SETTING A multidisciplinary working group was formed including both scientists and clinicians from multiple disciplines, otolaryngology, neurology, speech pathology, genetics and neuroscience, to review currently available information on spasmodic dysphonia and to identify research priorities. RESULTS Operational definitions for spasmodic dysphonia at different levels of certainty were recommended for diagnosis and recommendations made for a multi-center multidisciplinary validation study. CONCLUSIONS The highest priority is to characterize the disorder and identify risk factors that may contribute to its onset. Future research should compare and contrast spasmodic dysphonia with other forms of focal dystonia. Development of animal models is recommended to explore hypotheses related to pathogenesis. Improved understanding of the pathophysiology of SD should provide the basis for developing new treatment options and exploratory clinical trials. SIGNIFICANCE This document should foster future research to improve the care of patients with this chronic debilitating voice and speech disorder by otolaryngology, neurology, and speech pathology. PMID:18922334

  18. Functional and genetic deconstruction of the cellular origin in liver cancer

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B; Thorgeirsson, Snorri S

    2015-01-01

    During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation......, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance...... of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution...

  19. Using repair priorities in systems with redundacies

    NARCIS (Netherlands)

    Sleptchenko, A.V.; Adan, I.J.B.F.; Van Houtum, G.-J.

    2014-01-01

    In this paper, we present and analyze a mathematical model for the computation of the system availability for a system of parallel machines with redundancies and repair priorities. Using the presented models, we show that the repair priorities have a strong effect on the performance of the system.

  20. Synchrony of plant cellular circadian clocks with heterogeneous properties under light/dark cycles.

    Science.gov (United States)

    Okada, Masaaki; Muranaka, Tomoaki; Ito, Shogo; Oyama, Tokitaka

    2017-03-22

    Individual cells in a plant can work independently as circadian clocks, and their properties are the basis of various circadian phenomena. The behaviour of individual cellular clocks in Lemna gibba was orderly under 24-h light/dark cycles despite their heterogeneous free-running periods (FRPs). Here, we reveal the entrainment habits of heterogeneous cellular clocks using non-24-h light/dark cycles (T-cycles). The cellular rhythms of AtCCA1::LUC under T = 16 h cycles showed heterogeneous entrainment that was associated with their heterogeneous FRPs. Under T = 12 h cycles, most cells showed rhythms having ~24-h periods. This suggested that the lower limit of entrainment to the light/dark cycles of heterogeneous cellular circadian clocks is set to a period longer than 12 h, which enables them to be synchronous under ~24-h daily cycles without being perturbed by short light/dark cycles. The entrainment habits of individual cellular clocks are likely to be the basis of the circadian behaviour of plant under the natural day-night cycle with noisy environmental fluctuations. We further suggest that modifications of EARLY FLOWERING3 (ELF3) in individual cells deviate the entrainability to shorter T-cycles possibly by altering both the FRPs and light responsiveness.

  1. Scientists’ perspectives on global ocean research priorities

    Directory of Open Access Journals (Sweden)

    Murray Alan Rudd

    2014-08-01

    Full Text Available Diverse natural and social science research is needed to support policies to recover and sustain healthy oceans. While a wide variety of expert-led prioritization initiatives have identified research themes and priorities at national and regional scale, over the past several years there has also been a surge in the number of scanning exercises that have identified important environmental research questions and issues ‘from the bottom-up’. From those questions, winnowed from thousands of contributions by scientists and policy-makers around the world who participated in terrestrial, aquatic and domain-specific horizon scanning and big question exercises, I identified 657 research questions potentially important for informing decisions regarding ocean governance and sustainability. These were distilled to a short list of 67 distinctive research questions that, in an internet survey, were ranked by 2179 scientists from 94 countries. Five of the top 10 research priorities were shared by respondents globally. Despite significant differences between physical and ecological scientists’ priorities regarding specific research questions, they shared seven common priorities among their top 10. Social scientists’ priorities were, however, much different, highlighting their research focus on managerial solutions to ocean challenges and questions regarding the role of human behavior and values in attaining ocean sustainability. The results from this survey provide a comprehensive and timely assessment of current ocean research priorities among research-active scientists but highlight potential challenges in stimulating crossdisciplinary research. As ocean and coastal research necessarily becomes more transdisciplinary to address complex ocean challenges, it will be critical for scientists and research funders to understand how scientists from different disciplines and regions might collaborate and strengthen the overall evidence base for ocean

  2. Multiprocessor Priority Ceiling Emulation for Safety-Critical Java

    DEFF Research Database (Denmark)

    Strøm, Torur Biskopstø; Schoeberl, Martin

    2015-01-01

    Priority ceiling emulation has preferable properties on uniprocessor systems, such as avoiding priority inversion and being deadlock free. This has made it a popular locking protocol. According to the safety-critical Java specication, priority ceiling emulation is a requirement for implementations....... However, implementing the protocol for multiprocessor systemsis more complex so implementations might perform worse than non-preemptive implementations. In this paper we compare two multiprocessor lock implementations with hardware support for the Java optimized processor: non-preemptive locking...

  3. Emotion strengthens high-priority memory traces but weakens low-priority memory traces.

    Science.gov (United States)

    Sakaki, Michiko; Fryer, Kellie; Mather, Mara

    2014-02-01

    When people encounter emotional events, their memory for those events is typically enhanced. But it has been unclear how emotionally arousing events influence memory for preceding information. Does emotional arousal induce retrograde amnesia or retrograde enhancement? The current study revealed that this depends on the top-down goal relevance of the preceding information. Across three studies, we found that emotional arousal induced by one image facilitated memory for the preceding neutral item when people prioritized that neutral item. In contrast, an emotionally arousing image impaired memory for the preceding neutral item when people did not prioritize that neutral item. Emotional arousal elicited by both negative and positive pictures showed this pattern of enhancing or impairing memory for the preceding stimulus depending on its priority. These results indicate that emotional arousal amplifies the effects of top-down priority in memory formation.

  4. Histomorphometric analysis of nuclear and cellular volumetric alterations in oral lichen planus, lichenoid lesions and normal oral mucosa using image analysis software.

    Science.gov (United States)

    Venkatesiah, Sowmya S; Kale, Alka D; Hallikeremath, Seema R; Kotrashetti, Vijayalakshmi S

    2013-01-01

    Lichen planus is a chronic inflammatory mucocutaneous disease that clinically and histologically resembles lichenoid lesions, although the latter has a different etiology. Though criteria have been suggested for differentiating oral lichen planus from lichenoid lesions, confusion still prevails. To study the cellular and nuclear volumetric features in the epithelium of normal mucosa, lichen planus, and lichenoid lesions to determine variations if any. A retrospective study was done on 25 histologically diagnosed cases each of oral lichen planus, oral lichenoid lesions, and normal oral mucosa. Cellular and nuclear morphometric measurements were assessed on hematoxylin and eosin sections using image analysis software. Analysis of variance test (ANOVA) and Tukey's post-hoc test. The basal cells of oral lichen planus showed a significant increase in the mean nuclear and cellular areas, and in nuclear volume; there was a significant decrease in the nuclear-cytoplasmic ratio as compared to normal mucosa. The suprabasal cells showed a significant increase in nuclear and cellular areas, nuclear diameter, and nuclear and cellular volumes as compared to normal mucosa. The basal cells of oral lichenoid lesions showed significant difference in the mean cellular area and the mean nuclear-cytoplasmic ratio as compared to normal mucosa, whereas the suprabasal cells differed significantly from normal mucosa in the mean nuclear area and the nuclear and cellular volumes. Morphometry can differentiate lesions of oral lichen planus and oral lichenoid lesions from normal oral mucosa. Thus, morphometry may serve to discriminate between normal and premalignant lichen planus and lichenoid lesions. These lesions might have a high risk for malignant transformation and may behave in a similar manner with respect to malignant transformation.

  5. Setting priorities for space research: An experiment in methodology

    Science.gov (United States)

    1995-01-01

    In 1989, the Space Studies Board created the Task Group on Priorities in Space Research to determine whether scientists should take a role in recommending priorities for long-term space research initiatives and, if so, to analyze the priority-setting problem in this context and develop a method by which such priorities could be established. After answering the first question in the affirmative in a previous report, the task group set out to accomplish the second task. The basic assumption in developing a priority-setting process is that a reasoned and structured approach for ordering competing initiatives will yield better results than other ways of proceeding. The task group proceeded from the principle that the central criterion for evaluating a research initiative must be its scientific merit -- the value of the initiative to the proposing discipline and to science generally. The group developed a two-stage methodology for priority setting and constructed a procedure and format to support the methodology. The first of two instruments developed was a standard format for structuring proposals for space research initiatives. The second instrument was a formal, semiquantitative appraisal procedure for evaluating competing proposals. This report makes available complete templates for the methodology, including the advocacy statement and evaluation forms, as well as an 11-step schema for a priority-setting process. From the beginning of its work, the task group was mindful that the issue of priority setting increasingly pervades all of federally supported science and that its work would have implications extending beyond space research. Thus, although the present report makes no recommendations for action by NASA or other government agencies, it provides the results of the task group's work for the use of others who may study priority-setting procedures or take up the challenge of implementing them in the future.

  6. THE MECHANISMS OF FORMATION OF STRATEGIC SOCIO-ECONOMIC PRIORITIES

    Directory of Open Access Journals (Sweden)

    Klimanov V. V.

    2016-12-01

    Full Text Available The article is devoted to definition of methods and techniques to identify priorities of socioeconomic development, applicable at the Federal level. The initial data for the study was strategic planning documents, as well as the decrees, resolutions and orders of the Executive authorities of the Russian Federation and of constituent entities of the Russian Federation, defining the strategic priorities of socio-economic development in the 20-year period. The article presents the defining the term ‘priorities of economic and development’ and the approaches to their formation, which are represented at Russia’s normative acts and other federal documents. The content analysis of priorities in the strategic planning documents has allowed drawing the typology of economic and social development priorities of the Russian Federation. The authors determined the mechanism of creating the priorities under the influence of main endogenous (foreign trade, foreign policy, macro, etc. and exogenous (the interests of business, communities, regional authorities factors which could be recommended for consideration at the strategy developing process at federal level.

  7. Comparison of Cellular Alterations in Fat Cells Harvested With Laser-Assisted Liposuction and Suction-Assisted Liposuction.

    Science.gov (United States)

    Yildiz, Kemalettin; Taşli, Pakize Neslihan; Şahin, Fikrettin; Güneren, Ethem

    2016-05-01

    The aim of the present study was to evaluate the viability and proliferative capacity of adipose-derived stem cells obtained by laser-assisted liposuction (LAL). Fat tissue was obtained from 7 male patients treated surgically for gynecomastia. On one side, harvesting was made before LAL, while it was implemented after LAL on the contralateral side. Viability, cell surface antigens, pluripotency, and apoptosis were assessed and compared in these samples. Cells harvested before and after LAL did not exhibit any significant difference in terms of surface cell markers. Number of viable stem cells was lower initially after exposure to laser, while this difference was reversed at the end of 72 hours. Genetic indicators of cellular differentiation were similar in both groups. Apoptosis indicators were increased remarkably after laser exposure in the first 24 hours, but this increase was absent 72 hours after LAL procedure. The authors' results have promising clinical relevance since mesenchymal stem cells harvested during LAL have maintained appropriate cellular features to be used for autologous fat transfer and fat grafting.

  8. Regulating a Monopoly Offering Priority Service

    OpenAIRE

    Matsukawa, Isamu

    2006-01-01

    This paper investigates the effects of alternative forms of regulation on the market penetration and capacity, which are determined by a profit-maximizing monopolist providing priority service to consumers. For continuous priority service, a minimum reliability standard, price cap and rate of return regulation lead to larger capacity than in the absence of regulation. A minimum reliability standard reduces the market penetration while price cap and rate of return regulation increase it. T...

  9. IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Takahashi, Yutaka, E-mail: takahash@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

  10. IGF-I enhances cellular senescence via the reactive oxygen species–p53 pathway

    International Nuclear Information System (INIS)

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro; Takahashi, Yutaka

    2012-01-01

    Highlights: ► Cellular senescence plays an important role in tumorigenesis and aging process. ► We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. ► IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. ► These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated β-galactosidase (SA-β-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, γH2AX, the increased levels of p53 and p21 proteins, and activated SA-β-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-β-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

  11. Examining changes in cellular communication in neuroendocrine cells after noble metal nanoparticle exposure.

    Science.gov (United States)

    Love, Sara A; Liu, Zhen; Haynes, Christy L

    2012-07-07

    As nanoparticles enjoy increasingly widespread use in commercial applications, the potential for unintentional exposure has become much more likely during any given day. Researchers in the field of nanotoxicity are working to determine the physicochemical nanoparticle properties that lead to toxicity in an effort to establish safe design rules. This work explores the effects of noble metal nanoparticle exposure in murine chromaffin cells, focusing on examining the effects of size and surface functionality (coating) in silver and gold, respectively. Carbon-fibre microelectrode amperometry was utilized to examine the effect of exposure on exocytosis function, at the single cell level, and provided new insights into the compromised functions of cells. Silver nanoparticles of varied size, between 15 and 60 nm diameter, were exposed to cells and found to alter the release kinetics of exocytosis for those cells exposed to the smallest examined size. Effects of gold were examined after modification with two commonly used 'bio-friendly' polymers, either heparin or poly (ethylene glycol), and gold nanoparticles were found to induce altered cellular adhesion or the number of chemical messenger molecules released, respectively. These results support the body of work suggesting that noble metal nanoparticles perturb exocytosis, typically altering the number of molecules and kinetics of release, and supports a direct disruption of the vesicle matrix by the nanoparticle. Overall, it is clear that various nanoparticle physicochemical properties, including size and surface coating, do modulate changes in cellular communication via exocytosis.

  12. [The Danish Debate on Priority Setting in Medicine--An Update].

    Science.gov (United States)

    Pornak, S C; Raspe, H

    2015-09-01

    In the last years, the Danish debate about priority setting in medicine has gained new strength. This paper shows the main focuses of the current discussion based on a research of Danish primary literature. For the first time since the 1990s the Danish Council of Ethics has been involved with priority setting in medicine in a project running from 2011 to 2013. The Council emphasises the importance of legitimate processes and calls for visible values and criteria. A focus of the debate is how to deal with new expensive drugs. Politicians, physicians, health economists and the Council of Ethics have called for a national institution for priority setting in medicine. They have mainly looked to the Norwegian National Council for Priority Setting in Health Care and the British National Institute for Health and Care Excellence for inspiration. The Danish Government considered establishing a national institute for priority setting, but the plans were not put into practice. In the year 2012 a new national project was launched to create clinical guidelines. Danish doctors welcome the guidelines as a good basis for priority setting. Just like in earlier Danish priority setting debates, a coordinating institution is lacking to bundle the discussion and keep it going. The debate seems to have come to an end once again. The fact that it was seriously considered to establish an institute for priority setting is a new development. It can be expected that the discussion will be resumed in the near future, possibly the idea of an institute for priority setting will be readopted. The general conditions for priority setting in health care have improved. © Georg Thieme Verlag KG Stuttgart · New York.

  13. NEW MULTIANUAL FINANCIAL FRAMEWORK: PRIORITIES FOR THE EUROPEAN UNION, PRIORITIES FOR ROMANIA

    Directory of Open Access Journals (Sweden)

    ROXANA-DANIELA PĂUN

    2013-05-01

    Full Text Available This article proposes a brief foray into the situation of the European economy, but especially of the banking system of the Member States affected differently by the current world economic crisis, or recession, but especially for a detailed analysis of the New Multiannual Financial Framework for the period 2014-2020, with the priorities which appear to be distinct for the EU and for Romania. After a comparative analysis of European regulations on the agreements of the previous financial negotiated for the period 2014-2020, and Delors I (1988-1992, Delors II (1993-1999, the Agenda 2000 (2000-2006 and multiannual financial framework (2007- 2013 and ultimately the provisions of the Treaty of Lisbon (which convert multiannual financial framework in an essential act from a legal point of view; express personal opinions on Romania’s priorities and on the challenges and perspectives in the actual European and global context.

  14. Key Nuclear Verification Priorities: Safeguards and Beyond

    International Nuclear Information System (INIS)

    Carlson, J.

    2010-01-01

    In addressing nuclear verification priorities, we should look beyond the current safeguards system. Non-proliferation, which the safeguards system underpins, is not an end in itself, but an essential condition for achieving and maintaining nuclear disarmament. Effective safeguards are essential for advancing disarmament, and safeguards issues, approaches and techniques are directly relevant to the development of future verification missions. The extent to which safeguards challenges are successfully addressed - or otherwise - will impact not only on confidence in the safeguards system, but on the effectiveness of, and confidence in, disarmament verification. To identify the key nuclear verification priorities, we need to consider the objectives of verification, and the challenges to achieving these. The strategic objective of IAEA safeguards might be expressed as: To support the global nuclear non-proliferation regime by: - Providing credible assurance that states are honouring their safeguards commitments - thereby removing a potential motivation to proliferate; and - Early detection of misuse of nuclear material and technology - thereby deterring proliferation by the risk of early detection, enabling timely intervention by the international community. Or to summarise - confidence-building, detection capability, and deterrence. These will also be essential objectives for future verification missions. The challenges to achieving these involve a mix of political, technical and institutional dimensions. Confidence is largely a political matter, reflecting the qualitative judgment of governments. Clearly assessments of detection capability and deterrence have a major impact on confidence. Detection capability is largely thought of as 'technical', but also involves issues of legal authority, as well as institutional issues. Deterrence has both political and institutional aspects - including judgments on risk of detection and risk of enforcement action being taken. The

  15. Key Nuclear Verification Priorities - Safeguards and Beyond

    International Nuclear Information System (INIS)

    Carlson, J.

    2010-01-01

    In addressing nuclear verification priorities, we should look beyond the current safeguards system. Non-proliferation, which the safeguards system underpins, is not an end in itself, but an essential condition for achieving and maintaining nuclear disarmament. Effective safeguards are essential for advancing disarmament, and safeguards issues, approaches and techniques are directly relevant to the development of future verification missions. The extent to which safeguards challenges are successfully addressed - or otherwise - will impact not only on confidence in the safeguards system, but on the effectiveness of, and confidence in, disarmament verification. To identify the key nuclear verification priorities, we need to consider the objectives of verification, and the challenges to achieving these. The strategic objective of IAEA safeguards might be expressed as: To support the global nuclear non-proliferation regime by: - Providing credible assurance that states are honouring their safeguards commitments - thereby removing a potential motivation to proliferate; and - Early detection of misuse of nuclear material and technology - thereby deterring proliferation by the risk of early detection, enabling timely intervention by the international community. Or to summarise - confidence-building, detection capability, and deterrence. These will also be essential objectives for future verification missions. The challenges to achieving these involve a mix of political, technical and institutional dimensions. Confidence is largely a political matter, reflecting the qualitative judgment of governments. Clearly assessments of detection capability and deterrence have a major impact on confidence. Detection capability is largely thought of as 'technical', but also involves issues of legal authority, as well as institutional issues. Deterrence has both political and institutional aspects - including judgments on risk of detection and risk of enforcement action being taken. The

  16. Research priorities in medical education: A national study.

    Science.gov (United States)

    Tootoonchi, Mina; Yamani, Nikoo; Changiz, Tahereh; Yousefy, Alireza

    2012-01-01

    One preliminary step to strengthen medical education research would be determining the research priorities. The aim of this study was to determine the research priorities of medical education in Iran in 2007-2008. This descriptive study was carried out in two phases. Phase one was performed in 3 stages and used Delphi technique among academic staffs of Isfahan University of Medical Sciences. The three stages included a brainstorming workshop for 140 faculty members and educational experts resulting in a list of research priorities, then, in the second and third stages 99 and 76 questionnaires were distributed among faculty members. In the second phase, the final questionnaires were mailed to educational research center managers of universities type I, II and III, and were distributed among 311 academic members and educational experts to rate the items on a numerical scale ranging from 1 to 10. The most important research priorities included faculty members' development methods, faculty members' motives, satisfaction and welfare, criteria and procedures of faculty members' promotion, teaching methods and learning techniques, job descriptions and professional skills of graduates, quality management in education, second language, clinical education, science production in medicine, faculty evaluation and information technology. This study shows the medial education research priorities in national level and in different types of medical universities in Iran. It is recommended that faculty members and research administrators consider the needs and requirements of education and plan the researches in education according to these priorities.

  17. Inhibitory effects of OK-432 (Picibanil) on cellular proliferation and adhesive capacity of breast carcinoma cells.

    Science.gov (United States)

    Horii, Yoshio; Iino, Yuichi; Maemura, Michio; Horiguchi, Jun; Morishita, Yasuo

    2005-02-01

    We investigated the potent inhibitory effects of OK-432 (Picibanil) on both cellular adhesion and cell proliferation of estrogen-dependent (MCF-7) or estrogen-independent (MDA-MB-231) breast carcinoma cells. Cellular proliferation of both MCF-7 and MDA-MB-231 cells was markedly inhibited in a dose-dependent manner, when the carcinoma cells were exposed to OK-432. Cell attachment assay demonstrated that incubation with OK-432 for 24 h reduced integrin-mediated cellular adhesion of both cell types. However, fluorescence activated cell sorter (FACS) analysis revealed that incubation with OK-432 for 24 h did not decrease the cell surface expressions of any integrins. These results suggest that the binding avidity of integrins is reduced by OK-432 without alteration of the integrin expression. We conclude that OK-432 inhibits integrin-mediated cellular adhesion as well as cell proliferation of breast carcinoma cells regardless of estrogen-dependence, and that these actions of OK-432 contribute to prevention or inhibition of breast carcinoma invasion and metastasis.

  18. Utilization Bound of Non-preemptive Fixed Priority Schedulers

    Science.gov (United States)

    Park, Moonju; Chae, Jinseok

    It is known that the schedulability of a non-preemptive task set with fixed priority can be determined in pseudo-polynomial time. However, since Rate Monotonic scheduling is not optimal for non-preemptive scheduling, the applicability of existing polynomial time tests that provide sufficient schedulability conditions, such as Liu and Layland's bound, is limited. This letter proposes a new sufficient condition for non-preemptive fixed priority scheduling that can be used for any fixed priority assignment scheme. It is also shown that the proposed schedulability test has a tighter utilization bound than existing test methods.

  19. VT Priority Stream/River

    Data.gov (United States)

    Vermont Center for Geographic Information — Vermont List of Priority Surface Waters outside CWA Section 303(d) is divided in to 4 parts; Parts B, D, E and F. The four-part list has managed by the Vermont...

  20. VT Priority Lake/Pond

    Data.gov (United States)

    Vermont Center for Geographic Information — Vermont List of Priority Surface Waters outside CWA Section 303(d) is divided in to 4 parts; Parts B, D, E and F. The four-part list has managed by the Vermont...

  1. Extending RTA/Linux with fixed-priority scheduling with deferred preemption

    NARCIS (Netherlands)

    Bergsma, M.; Holenderski, M.J.; Bril, R.J.; Lukkien, J.J.; Petters, S.M.; Zijlstra, P.

    2009-01-01

    Fixed-Priority Scheduling with Deferred Preemption (FPDS) is a middle ground between Fixed-Priority Pre-emptive Scheduling and Fixed-Priority Non-preemptive Scheduling, and offers advantages with respect to context switch overhead and resource access control. In this paper we present our work on

  2. Conditional Selection of Genomic Alterations Dictates Cancer Evolution and Oncogenic Dependencies.

    Science.gov (United States)

    Mina, Marco; Raynaud, Franck; Tavernari, Daniele; Battistello, Elena; Sungalee, Stephanie; Saghafinia, Sadegh; Laessle, Titouan; Sanchez-Vega, Francisco; Schultz, Nikolaus; Oricchio, Elisa; Ciriello, Giovanni

    2017-08-14

    Cancer evolves through the emergence and selection of molecular alterations. Cancer genome profiling has revealed that specific events are more or less likely to be co-selected, suggesting that the selection of one event depends on the others. However, the nature of these evolutionary dependencies and their impact remain unclear. Here, we designed SELECT, an algorithmic approach to systematically identify evolutionary dependencies from alteration patterns. By analyzing 6,456 genomes from multiple tumor types, we constructed a map of oncogenic dependencies associated with cellular pathways, transcriptional readouts, and therapeutic response. Finally, modeling of cancer evolution shows that alteration dependencies emerge only under conditional selection. These results provide a framework for the design of strategies to predict cancer progression and therapeutic response. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant.

    Science.gov (United States)

    Ivey, Jill W; Latouche, Eduardo L; Richards, Megan L; Lesser, Glenn J; Debinski, Waldemar; Davalos, Rafael V; Verbridge, Scott S

    2017-07-25

    Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration. However, we have recently demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a key predictor of response for cells treated with high-frequency irreversible electroporation (IRE). In this study, we leverage a targeted molecular therapy, ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2 receptor, to investigate how biophysical cellular changes resulting from NCR manipulation affect the response to IRE at varying frequencies. We present evidence that the increase in the NCR mitigates the cell death response to conventional electroporation pulsed-electric fields (∼100 μs), consistent with the previously noted size dependence. However, this same molecular treatment enhanced the cell death response to high-frequency electric fields (∼1 μs). This finding demonstrates the importance of considering cellular biophysics and frequency-dependent effects in developing electroporation protocols, and our approach provides, to our knowledge, a novel and direct experimental methodology to quantify the relationship between cell morphology, pulse frequency, and electroporation response. Finally, this novel, to our knowledge, combinatorial approach may provide a paradigm to enhance in vivo tumor ablation through a molecular manipulation of cellular morphology before IRE application. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. The Altered Hepatic Tubulin Code in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Jennifer L. Groebner

    2015-09-01

    Full Text Available The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the “tubulin code” are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.

  5. Effects of motexafin gadolinium on tumor oxygenation and cellular oxygen consumption

    International Nuclear Information System (INIS)

    Donnelly, E.T.; Liu, Y.; Rockwell, S.; Magda, D.

    2003-01-01

    Full text: Recent work in our laboratory showed that motexafin gadolinium (MGd, Xcytrin), a drug currently in Phase III clinical trials as an adjuvant to radiation therapy, modulates the oxygen tensions in EMT6 tumors. The median pO 2 increased from the control value of 1.5±0.4 mmHg to 7.4 ± 3.8 mmHg six hours after treatment with 40 μmol/kg MGd and the percentage of severely hypoxic readings in the tumors ( 7 plateau phase EMT6 cells in 3 mL Dulbecco's Modified Eagle's Medium supplemented with 10% dialyzed fetal bovine serum, which contains no ascorbic acid. In the absence of ascorbic acid, 100 μM MGd did not alter the cellular oxygen consumption rate for EMT6 cells significantly. Marked inhibition of cellular oxygen consumption was observed when cells were incubated with 100 μM MGd in medium supplemented with equimolar ascorbic acid (a 31.5% decrease in consumption was observed after 6 hours of treatment). The 5% mannitol vehicle solution with equimolar ascorbic acid had no discernible effect on cellular oxygen consumption. Ascorbic acid may facilitate cellular uptake of MGd via the intermediate formation of a MGd-oxalate complex. These studies suggest that changes in cellular oxygen consumption could contribute to the changes in tumor oxygenation seen after administration of MGd. These experiments were supported by Pharmacyclics and training grant T32CA09085 from the NIH (E.T.D.). We thank Dr. Raymond Russell for allowing us to use his oxygen electrode apparatus

  6. Comprehensive framework for preventive maintenance priority of medical equipment.

    Science.gov (United States)

    Saleh, Neven; Balestra, Gabriella

    2015-08-01

    Throughout the medical equipment life cycle, preventive maintenance is considered one of the most important stages that should be managed properly. However, the need for better management and control by giving a reasonable prioritization for preventive maintenance becomes essential. The purpose of this study is to develop a comprehensive framework for preventive maintenance priority of medical equipment using Quality Function Deployment (QFD) and Fuzzy Logic (FL). The quality function deployment is proposed in order to identify the most important criteria that could impact preventive maintenance priority decision; meanwhile the role of the fuzzy logic is to generate a priority index of the list of equipment considering those criteria. The model validation was carried out on 140 pieces of medical equipment belonging to two hospitals. In application, we propose to classify the priority index into five classes. The results indicate that the strong correlation existence between risk-based criteria and preventive maintenance priority decision.

  7. The badness of death and priorities in health.

    Science.gov (United States)

    Solberg, Carl Tollef; Gamlund, Espen

    2016-04-14

    The state of the world is one with scarce medical resources where longevity is not equally distributed. Given such facts, setting priorities in health entails making difficult yet unavoidable decisions about which lives to save. The business of saving lives works on the assumption that longevity is valuable and that an early death is worse than a late death. There is a vast literature on health priorities and badness of death, separately. Surprisingly, there has been little cross-fertilisation between the academic fields of priority setting and badness of death. Our aim is to connect philosophical discussions on the badness of death to contemporary debates in health priorities. Two questions regarding death are especially relevant to health priorities. The first question is why death is bad. Death is clearly bad for others, such as family, friends and society. Many philosophers also argue that death can be bad for those who die. This distinction is important for health priorities, because it concerns our fundamental reasons for saving lives. The second question is, 'When is the worst time to die?' A premature death is commonly considered worse than a late death. Thus, the number of good life years lost seems to matter to the badness of death. Concerning young individuals, some think the death of infants is worse than the death of adolescents, while others have contrary intuitions. Our claim is that to prioritise between age groups, we must consider the question of when it is worst to die. Deprivationism provides a more plausible approach to health priorities than Epicureanism. If Deprivationism is accepted, we will have a firmer basis for claiming that individuals, in addition to having a health loss caused by morbidity, will have a loss of good life years due to mortality. Additionally, Deprivationism highlights the importance of age and values for health priorities. Regarding age, both variants of Deprivationism imply that stillbirths are included in the Global

  8. Hypertension management research priorities from patients, caregivers, and healthcare providers: A report from the Hypertension Canada Priority Setting Partnership Group.

    Science.gov (United States)

    Khan, Nadia; Bacon, Simon L; Khan, Samia; Perlmutter, Sara; Gerlinsky, Carline; Dermer, Mark; Johnson, Lonni; Alves, Finderson; McLean, Donna; Laupacis, Andreas; Pui, Mandy; Berg, Angelique; Flowitt, Felicia

    2017-11-01

    Patient- and stakeholder-oriented research is vital to improving the relevance of research. The authors aimed to identify the 10 most important research priorities of patients, caregivers, and healthcare providers (family physicians, nurses, nurse practitioners, pharmacists, and dietitians) for hypertension management. Using the James Lind Alliance approach, a national web-based survey asked patients, caregivers, and care providers to submit their unanswered questions on hypertension management. Questions already answered from randomized controlled trial evidence were removed. A priority setting process of patient, caregiver, and healthcare providers then ranked the final top 10 research priorities in an in-person meeting. There were 386 respondents who submitted 598 questions after exclusions. Of the respondents, 78% were patients or caregivers, 29% lived in rural areas, 78% were aged 50 to 80 years, and 75% were women. The 598 questions were distilled to 42 unique questions and from this list, the top 10 research questions prioritized included determining the combinations of healthy lifestyle modifications to reduce the need for antihypertensive medications, stress management interventions, evaluating treatment strategies based on out-of-office blood pressure compared with conventional (office) blood pressure, education tools and technologies to improve patient motivation and health behavior change, management strategies for ethnic groups, evaluating natural and alternative treatments, and the optimal role of different healthcare providers and caregivers in supporting patients with hypertension. These priorities can be used to guide clinicians, researchers, and funding bodies on areas that are a high priority for hypertension management research for patients, caregivers, and healthcare providers. This also highlights priority areas for improved knowledge translation and delivering patient-centered care. ©2017 Wiley Periodicals, Inc.

  9. Cellular energy metabolism in T-lymphocytes.

    Science.gov (United States)

    Gaber, Timo; Strehl, Cindy; Sawitzki, Birgit; Hoff, Paula; Buttgereit, Frank

    2015-01-01

    Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders.

  10. A unifying property for distribution-sensitive priority queues

    DEFF Research Database (Denmark)

    Elmasry, Amr Ahmed Abd Elmoneim; Farzan, Arash; Iacono, John

    2011-01-01

    , before) the last access of x and are still in the priority queue at the time when the corresponding operation is performed. Our priority queue then has both the working-set and the queueish properties; and, more strongly, it satisfies these properties in the worst-case sense. We also argue...... that these bounds are the best possible with respect to the considered measures. Moreover, we modify our priority queue to satisfy a new unifying property - the time-finger property - which encapsulates both the working-set and the queueish properties. In addition, we prove that the working-set bound......We present a priority queue that supports the operations: insert in worst-case constant time, and delete, delete-min, find-min and decrease-key on an element x in worst-case O(lg(min{wx, qx} + 2)) time, where wx (respectively, qx) is the number of elements that were accessed after (respectively...

  11. Setting priorities in health care organizations: criteria, processes, and parameters of success.

    Science.gov (United States)

    Gibson, Jennifer L; Martin, Douglas K; Singer, Peter A

    2004-09-08

    Hospitals and regional health authorities must set priorities in the face of resource constraints. Decision-makers seek practical ways to set priorities fairly in strategic planning, but find limited guidance from the literature. Very little has been reported from the perspective of Board members and senior managers about what criteria, processes and parameters of success they would use to set priorities fairly. We facilitated workshops for board members and senior leadership at three health care organizations to assist them in developing a strategy for fair priority setting. Workshop participants identified 8 priority setting criteria, 10 key priority setting process elements, and 6 parameters of success that they would use to set priorities in their organizations. Decision-makers in other organizations can draw lessons from these findings to enhance the fairness of their priority setting decision-making. Lessons learned in three workshops fill an important gap in the literature about what criteria, processes, and parameters of success Board members and senior managers would use to set priorities fairly.

  12. Appearance and cellular distribution of lectin-like receptors for alpha 1-acid glycoprotein in the developing rat testis

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1996-01-01

    A histochemical avidin-biotin technique with three different alpha 1-acid glycoprotein glycoforms showed pronounced alterations in the cellular localization of two alpha 1-acid glycoprotein lectin-like receptors during cell differentiation in the developing rat testis. The binding of alpha 1-acid...

  13. Metabolic alterations during ascosporogenesis of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Carvalho, Sandra; Nadkarni, G.B.

    1977-01-01

    Sporulation of S. cerevisiae has been shown to alter the profiles of enzymes involved in gluconeogenesis and glycolysis. The enhancement in the levels of total cellular carbohydrates could be correlated with the enhancement in fructose 1,6-diphosphatase and trehalose-phosphate synthetase. The latter activity could account for the 15-fold increase in trehalose levels in sporulating cells. Glucose-6-phosphatase, pyruvate kinase and phosphofructokinase showed continuous decline during ascosporogenesis. The relative incorporation of radioactivity from possible precursors of gluconeogenesis indicated that acetate-2- 14 C alone could contribute to carbohydrate synthesis. (author)

  14. Novel cellular targets of AhR underlie alterations in neutrophilic inflammation and iNOS expression during influenza virus infection

    Science.gov (United States)

    Head Wheeler, Jennifer L.; Martin, Kyle C.; Lawrence, B. Paige

    2012-01-01

    The underlying reasons for variable clinical outcomes from respiratory viral infections remain uncertain. Several studies suggest that environmental factors contribute to this variation, but limited knowledge of cellular and molecular targets of these agents hampers our ability to quantify or modify their contribution to disease and improve public health. The aryl hydrocarbon receptor (AhR) is an environment sensing transcription factor that binds many anthropogenic and natural chemicals. The immunomodulatory properties of AhR ligands are best characterized with extensive studies of changes in CD4+ T cell responses. Yet, AhR modulates other aspects of immune function. We previously showed that during influenza virus infection, AhR activation modulates neutrophil accumulation in the lung, and this contributes to increased mortality in mice. Enhanced levels of inducible nitric oxide synthase (iNOS) in infected lungs are observed during the same timeframe as AhR-mediated increased pulmonary neutrophilia. In this study, we evaluated whether these two consequences of AhR activation are causally linked. Reciprocal inhibition of AhR-mediated elevations in iNOS and pulmonary neutrophilia reveal that, although they are contemporaneous, they are not causally related. We show using Cre/loxP technology that elevated iNOS levels and neutrophil number in the infected lung result from separate, AhR-dependent signaling in endothelial and respiratory epithelial cells, respectively. Studies using mutant mice further reveal that AhR-mediated alterations in these innate responses to infection require a functional nuclear localization signal and DNA binding domain. Thus, gene targets of AhR in non-hematopoietic cells are important new considerations for understanding AhR-mediated changes in innate anti-viral immunity. PMID:23233726

  15. Research priorities in medical education: A national study

    Directory of Open Access Journals (Sweden)

    Mina Tootoonchi

    2012-01-01

    Full Text Available Background: One preliminary step to strengthen medical education research would be determining the research prior-ities. The aim of this study was to determine the research priorities of medical education in Iran in 2007-2008. Methods: This descriptive study was carried out in two phases. Phase one was performed in 3 stages and used Delphi technique among academic staffs of Isfahan University of Medical Sciences. The three stages included a brainstorming workshop for 140 faculty members and educational experts resulting in a list of research priorities, then, in the second and third stages 99 and 76 questionnaires were distributed among faculty members. In the second phase, the final ques-tionnaires were mailed to educational research center managers of universities type I, II and III, and were distributed among 311 academic members and educational experts to rate the items on a numerical scale ranging from 1 to 10. Results: The most important research priorities included faculty members′ development methods, faculty members′ motives, satisfaction and welfare, criteria and procedures of faculty members′ promotion, teaching methods and learning techniques, job descriptions and professional skills of graduates, quality management in education, second language, clinical education, science production in medicine, faculty evaluation and information technology. Conclusions: This study shows the medial education research priorities in national level and in different types of medical universities in Iran. It is recommended that faculty members and research administrators consider the needs and requirements of education and plan the researches in education according to these priorities.

  16. Priority Setting, Cost-Effectiveness, and the Affordable Care Act.

    Science.gov (United States)

    Persad, Govind

    2015-01-01

    The Affordable Care Act (ACA) may be the most important health law statute in American history, yet much of the most prominent legal scholarship examining it has focused on the merits of the court challenges it has faced rather than delving into the details of its priority-setting provisions. In addition to providing an overview of the ACA's provisions concerning priority setting and their developing interpretations, this Article attempts to defend three substantive propositions. First, I argue that the ACA is neither uniformly hostile nor uniformly friendly to efforts to set priorities in ways that promote cost and quality. Second, I argue that the ACA does not take a single, unified approach to priority setting; rather, its guidance varies depending on the aspect of the healthcare system at issue (Patient Centered Outcomes Research Institute, Medicare, essential health benefits) and the factors being excluded from priority setting (age, disability, life expectancy). Third, I argue that cost-effectiveness can be achieved within the ACA's constraints, but that doing so will require adopting new approaches to cost-effectiveness and priority setting. By limiting the use of standard cost-effectiveness analysis, the ACA makes the need for workable rivals to cost-effectiveness analysis a pressing practical concern rather than a mere theoretical worry.

  17. Differences between patients' and clinicians' research priorities from the Anaesthesia and Peri-operative Care Priority Setting Partnership.

    Science.gov (United States)

    Boney, O; Nathanson, M H; Grocott, M P W; Metcalf, L

    2017-09-01

    The James Lind Alliance Anaesthesia and Peri-operative Care Priority Setting Partnership was a recent collaborative venture bringing approximately 2000 patients, carers and clinicians together to agree priorities for future research into anaesthesia and critical care. This secondary analysis compares the research priorities of 303 service users, 1068 clinicians and 325 clinicians with experience as service users. All three groups prioritised research to improve patient safety. Service users prioritised research about improving patient experience, whereas clinicians prioritised research about clinical effectiveness. Clinicians who had experience as service users consistently prioritised research more like clinicians than like service users. Individual research questions about patient experience were more popular with patients and carers than with clinicians in all but one case. We conclude that patients, carers and clinicians prioritise research questions differently. All groups prioritise research into patient safety, but service users also favour research into patient experience, whereas clinicians favour research into clinical effectiveness. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

  18. Loss of DNA topoisomerase I activity alters many cellular functions in Salmonella typhimurium

    International Nuclear Information System (INIS)

    Overbye, K.M.; Basu, S.K.; Margolin, P.

    1983-01-01

    In this paper is reported the absence of DNA topoisomerase I in S. typhimurium results in an increased level of the recBC DNase (exonuclease V) enzyme, an almost total abolition of both direct and indirect mutagenesis by alkylating agents, and altered characteristics in the formation of chromosomal tandem duplications. We also present evidence that modifications in DNA superhelicity may strongly affect the pattern of DNA degrafation initiated by treatment of recA mutant cells with bleomycin and mitomycin C. 43 references, 3 figures, 3 tables

  19. Cellular reprogramming by gram-positive bacterial components: a review.

    LENUS (Irish Health Repository)

    Buckley, Julliette M

    2012-02-03

    LPS tolerance has been the focus of extensive scientific and clinical research over the last several decades in an attempt to elucidate the sequence of changes that occur at a molecular level in tolerized cells. Tolerance to components of gram-positive bacterial cell walls such as bacterial lipoprotein and lipoteichoic acid is a much lesser studied, although equally important, phenomenon. This review will focus on cellular reprogramming by gram-positive bacterial components and examines the alterations in cell surface receptor expression, changes in intracellular signaling, gene expression and cytokine production, and the phenomenon of cross-tolerance.

  20. Fungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway

    Directory of Open Access Journals (Sweden)

    Peter Belenky

    2013-02-01

    Full Text Available Amphotericin, miconazole, and ciclopirox are antifungal agents from three different drug classes that can effectively kill planktonic yeast, yet their complete fungicidal mechanisms are not fully understood. Here, we employ a systems biology approach to identify a common oxidative-damage cellular death pathway triggered by these representative fungicides in Candida albicans and Saccharomyces cerevisiae. This mechanism utilizes a signaling cascade involving the GTPases Ras1 and Ras2 and protein kinase A, and it culminates in death through the production of toxic reactive oxygen species in a tricarboxylic-acid-cycle- and respiratory-chain-dependent manner. We also show that the metabolome of C. albicans is altered by antifungal drug treatment, exhibiting a shift from fermentation to respiration, a jump in the AMP/ATP ratio, and elevated production of sugars; this coincides with elevated mitochondrial activity. Lastly, we demonstrate that DNA damage plays a critical role in antifungal-induced cellular death and that blocking DNA-repair mechanisms potentiates fungicidal activity.

  1. Priority issues affecting operators' and suppliers' liens: the Alberta perspective

    International Nuclear Information System (INIS)

    Corbett, W.T.

    1996-01-01

    Selected aspects of priority issues in contractual obligations in the petroleum industry were discussed, focusing on the priority issues claimed by suppliers and operators with respect to Alberta properties. Discussions touched upon suppliers' lien rights in Alberta, operators' set-off rights, and on some of the priority issues involving operators' liens

  2. Biochemical and cellular mechanisms of low-dose effects

    International Nuclear Information System (INIS)

    Feinendegen, L.E.; Booz, J.; Muehlensiepen, H.

    1988-01-01

    The question of health effects from small radiation doses remains open. Individual cells, when being hit by single elemental doses - in low-dose irradiation - react acutely and temporarily by altering control of enzyme activity, as is demonstrated for the case of thymidine kinase. This response is not constant in that it provides a temporary protection of enzyme activity against a second irradiation, by a mechanism likely to be via improved detoxification of intracellular radicals. It must be considered that in the low-dose region radiation may also exert protection against other challenges involving radicals, causing a net beneficial effect by temporarily shielding the hit cell against radicals produced by metabolism. Since molecular alterations leading to late effects are considered a consequence of the initial cellular response, late effects from small radiation doses do not necessarily adhere to a linear dose-effect relationship. The reality of the linear relationship between the risk of late effects from high doses to small doses is an assumption, for setting dose limits, but it must not be taken for predicting health detriment from low doses. (author)

  3. Using evaluation theory in priority setting and resource allocation.

    Science.gov (United States)

    Smith, Neale; Mitton, Craig; Cornelissen, Evelyn; Gibson, Jennifer; Peacock, Stuart

    2012-01-01

    Public sector interest in methods for priority setting and program or policy evaluation has grown considerably over the last several decades, given increased expectations for accountable and efficient use of resources and emphasis on evidence-based decision making as a component of good management practice. While there has been some occasional effort to conduct evaluation of priority setting projects, the literatures around priority setting and evaluation have largely evolved separately. In this paper, the aim is to bring them together. The contention is that evaluation theory is a means by which evaluators reflect upon what it is they are doing when they do evaluation work. Theories help to organize thinking, sort out relevant from irrelevant information, provide transparent grounds for particular implementation choices, and can help resolve problematic issues which may arise in the conduct of an evaluation project. A detailed review of three major branches of evaluation theory--methods, utilization, and valuing--identifies how such theories can guide the development of efforts to evaluate priority setting and resource allocation initiatives. Evaluation theories differ in terms of their guiding question, anticipated setting or context, evaluation foci, perspective from which benefits are calculated, and typical methods endorsed. Choosing a particular theoretical approach will structure the way in which any priority setting process is evaluated. The paper suggests that explicitly considering evaluation theory makes key aspects of the evaluation process more visible to all stakeholders, and can assist in the design of effective evaluation of priority setting processes; this should iteratively serve to improve the understanding of priority setting practices themselves.

  4. High priority tank sampling and analysis report

    Energy Technology Data Exchange (ETDEWEB)

    Brown, T.M.

    1998-03-05

    In July 1993, the Defense Nuclear Facilities Safety Board (DNFSB) transmitted Recommendation 93-5 (Conway 1993) to the US Department of Energy (DOE). Recommendation 93-5 noted that there was insufficient tank waste technical information and the pace to obtain it was too slow to ensure that Hanford Site wastes could be safely stored, that associated operations could be conducted safely, and that future disposal data requirements could be met. In May 1996, the DOE issued Revision 1 of the Recommendation 93-5 Implementation Plan (DOE-RL 1996). The Implementation Plan revision presented a modified approach to achieve the original plan`s objectives. The approach concentrated on actions necessary to ensure that wastes can be safely stored, that operations can be safely conducted, and that timely characterization information for the tank waste Disposal Program could be obtained. The Implementation Plan proposed 28 High Priority tanks, which, if sampled and analyzed, were expected to provide information to answer questions regarding safety and disposal issues. The High Priority tank list was originally developed in Section 9.0 of the Tank Waste Characterization Basis (Brown et al. 1995) by integrating the needs of the various safety and disposal programs. The High Priority tank list represents a set of tanks that were expected to provide the highest information return for characterization resources expended. The High Priority tanks were selected for near-term core sampling and were not expected to be the only tanks that would provide meaningful information. Sampling and analysis of non-High Priority tanks also could be used to provide scientific and technical data to confirm assumptions, calibrate models, and measure safety related phenomenological characteristics of the waste. When the sampling and analysis results of the High Priority and other tanks were reviewed, it was expected that a series of questions should be answered allowing key decisions to be made. The first

  5. High priority tank sampling and analysis report

    International Nuclear Information System (INIS)

    Brown, T.M.

    1998-01-01

    In July 1993, the Defense Nuclear Facilities Safety Board (DNFSB) transmitted Recommendation 93-5 (Conway 1993) to the US Department of Energy (DOE). Recommendation 93-5 noted that there was insufficient tank waste technical information and the pace to obtain it was too slow to ensure that Hanford Site wastes could be safely stored, that associated operations could be conducted safely, and that future disposal data requirements could be met. In May 1996, the DOE issued Revision 1 of the Recommendation 93-5 Implementation Plan (DOE-RL 1996). The Implementation Plan revision presented a modified approach to achieve the original plan's objectives. The approach concentrated on actions necessary to ensure that wastes can be safely stored, that operations can be safely conducted, and that timely characterization information for the tank waste Disposal Program could be obtained. The Implementation Plan proposed 28 High Priority tanks, which, if sampled and analyzed, were expected to provide information to answer questions regarding safety and disposal issues. The High Priority tank list was originally developed in Section 9.0 of the Tank Waste Characterization Basis (Brown et al. 1995) by integrating the needs of the various safety and disposal programs. The High Priority tank list represents a set of tanks that were expected to provide the highest information return for characterization resources expended. The High Priority tanks were selected for near-term core sampling and were not expected to be the only tanks that would provide meaningful information. Sampling and analysis of non-High Priority tanks also could be used to provide scientific and technical data to confirm assumptions, calibrate models, and measure safety related phenomenological characteristics of the waste. When the sampling and analysis results of the High Priority and other tanks were reviewed, it was expected that a series of questions should be answered allowing key decisions to be made. The first

  6. Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

    Directory of Open Access Journals (Sweden)

    Roberto G. Pozner

    2013-01-01

    Full Text Available Viral hemorrhagic fevers (VHFs caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

  7. Setting Priorities: Personal Values, Organizational Results. Ideas into Action Guidebooks

    Science.gov (United States)

    Cartwright, Talula

    2007-01-01

    Successful leaders get results. To get results, you need to set priorities. This book can help you do a better job of setting priorities, recognizing the personal values that motivate your decision making, the probable trade-offs and consequences of your decisions, and the importance of aligning your priorities with your organization's…

  8. A Delphi study to establish national cost-effectiveness research priorities for positron emission tomography

    International Nuclear Information System (INIS)

    Robert, Glenn; Milne, Ruairidh

    1999-01-01

    Objective: This study aimed to determine the key cost-effectiveness research questions relating to positron emission tomography (PET) in the UK. Methods: A systematic literature review was conducted to establish the existing knowledge base relating to the cost-effectiveness of PET in the various conditions for which it has been proposed. A three-round postal Delphi study of relevant individuals was used to determine the key cost-effectiveness research questions relating to PET in the UK. The content and structure of the Delphi study was informed by the results of the literature review. Results: The most important cost-effectiveness research priorities for the National Health Service (NHS) relating to PET were in the clinical areas of lung cancer, breast cancer and the assessment of myocardial viability. Gamma camera PET using coincidence imaging was highlighted as a modality whose clinical role needed to be determined urgently. Conclusion: Underlying the cost-effectiveness research priorities which were established is the need for evidence that the use of the various PET modalities as a diagnostic technique will alter patient management as compared to existing diagnostic strategies. The findings of the project provide a contemporary overview of the potential role for PET in the NHS and will be relevant to other countries

  9. Potential priority pollutants in sewage sludge

    DEFF Research Database (Denmark)

    Eriksson, Eva; Christensen, Nina; Schmidt, Jens Ejbye

    2008-01-01

    compounds using their inherent properties and environmental fate it was shown that 99 XOCs could be classified as being hazardous with regard to the solid phase and 23 were found to be priority pollutants in the subsequent hazard assessment. The final selected priority pollutants can act as indicators when...... assessing sludge quality. They were compared with European legislations and discussed in regard for pointing out the need for mitigation such as substitution. Furthermore, the potential need for implementation of sludge treatment trains in order to meet the society's needs was addressed....

  10. Setting priorities in health care organizations: criteria, processes, and parameters of success

    Directory of Open Access Journals (Sweden)

    Martin Douglas K

    2004-09-01

    Full Text Available Abstract Background Hospitals and regional health authorities must set priorities in the face of resource constraints. Decision-makers seek practical ways to set priorities fairly in strategic planning, but find limited guidance from the literature. Very little has been reported from the perspective of Board members and senior managers about what criteria, processes and parameters of success they would use to set priorities fairly. Discussion We facilitated workshops for board members and senior leadership at three health care organizations to assist them in developing a strategy for fair priority setting. Workshop participants identified 8 priority setting criteria, 10 key priority setting process elements, and 6 parameters of success that they would use to set priorities in their organizations. Decision-makers in other organizations can draw lessons from these findings to enhance the fairness of their priority setting decision-making. Summary Lessons learned in three workshops fill an important gap in the literature about what criteria, processes, and parameters of success Board members and senior managers would use to set priorities fairly.

  11. Relation of murine thoracic aortic structural and cellular changes with aging to passive and active mechanical properties.

    Science.gov (United States)

    Wheeler, Jason B; Mukherjee, Rupak; Stroud, Robert E; Jones, Jeffrey A; Ikonomidis, John S

    2015-02-25

    Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood. Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following potassium stimulation was reduced in old versus young mice. Furthermore, collagen gel contraction by aortic smooth muscle cells was reduced with age. These results demonstrate that numerous age-related structural changes occurred in the thoracic aorta and were related to alterations in mechanical properties. Aortic contractility decreased with age, likely because of a reduction in medial cell number in addition to a smooth muscle contractile deficit. Together, these unique findings provide evidence that the age-related changes in structure and mechanical function coalesce to provide an aortic substrate that may be predisposed to aortopathies. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  12. 32 CFR 728.3 - General restrictions and priorities.

    Science.gov (United States)

    2010-07-01

    ... AND DENTAL CARE FOR ELIGIBLE PERSONS AT NAVY MEDICAL DEPARTMENT FACILITIES General § 728.3 General... domiciliary care. Routine dental care, other than dental prosthesis or orthodontia, may be rendered on a space...) Priorities. When care cannot be rendered to all eligible beneficiaries, the priorities in the following chart...

  13. 29 CFR 4044.11 - Priority category 1 benefits.

    Science.gov (United States)

    2010-07-01

    ... priority category 1 with respect to that participant is the present value of that annuity. ... 29 Labor 9 2010-07-01 2010-07-01 false Priority category 1 benefits. 4044.11 Section 4044.11 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION PLAN TERMINATIONS ALLOCATION OF...

  14. Cellular gravity

    NARCIS (Netherlands)

    F.C. Gruau; J.T. Tromp (John)

    1999-01-01

    textabstractWe consider the problem of establishing gravity in cellular automata. In particular, when cellular automata states can be partitioned into empty, particle, and wall types, with the latter enclosing rectangular areas, we desire rules that will make the particles fall down and pile up on

  15. Nanomechanical and electrical characterization of a new cellular electret sensor-actuator

    International Nuclear Information System (INIS)

    Windmill, J F C; Zorab, A; Bedwell, D J; Robert, D

    2008-01-01

    Electrically charged cellular polymers are known to display pseudo-piezoelectric effects that endow them with interesting mechano-electrical characteristics. When a film of such a polymer is compressed, charge is generated across its thickness, and conversely, applying an oscillatory or static potential elicits mechanical motions. This dual sensor-actuator behaviour can be embedded in one material and presents distinct advantages of functional integration. A novel electroactive foam is presented here that embeds such a sensor-actuator function. The foam has a sensitivity constant (d 33 ) of 330 pC N -1 . Interestingly, the resonant behaviour of the cellular film can be altered by variation in the DC offset across the material. Such adaptive capacity could be of great advantage for tuning polymer-based mechanical devices to be either efficient sound radiators and mechanical actuators, or sensitive and coherent sensors. Possible applications in microfluidics are also discussed

  16. Priority issues affecting operators' and suppliers' liens: the Saskatchewan perspective

    International Nuclear Information System (INIS)

    Milani, M.W.

    1996-01-01

    Priority issues in contractual obligations in the petroleum industry were discussed from the perspective of Saskatchewan. In Saskatchewan, the priority issues relative to builders' and suppliers' liens are similar to those of Alberta, but there are some subtle differences, which were addressed. Priority issues claimed by suppliers and operators with respect to Saskatchewan properties were given special attention

  17. The cellular distribution of extracellular superoxide dismutase in macrophages is altered by cellular activation but unaffected by the natural occurring R213G substitution

    DEFF Research Database (Denmark)

    Gottfredsen, Randi Heidemann; Goldstrohm, David; Hartney, John

    2014-01-01

    and associated with the cell surface via the extracellular matrix (ECM)-binding region. Upon cellular activation induced by lipopolysaccharide, EC-SOD is relocated and detected both in the cell culture medium and in lipid raft structures. Although the secreted material presented a significantly reduced ligand......-binding capacity, this could not be correlated to proteolytic removal of the ECM-binding region, because the integrity of the material recovered from the medium was comparable to that of the cell surface-associated protein. The naturally occurring R213G amino acid substitution located in the ECM-binding region...

  18. Danazol alters mitochondria metabolism of fibrocystic breast Mcf10A cells.

    Science.gov (United States)

    Irgebay, Zhazira; Yeszhan, Banu; Sen, Bhaswati; Tuleukhanov, Sultan; Brooks, Ari D; Sensenig, Richard; Orynbayeva, Zulfiya

    2017-10-01

    Fibrocystic Breast Disease (FBD) or Fibrocystic change (FC) affects about 60% of women at some time during their life. Although usually benign, it is often associated with pain and tenderness (mastalgia). The synthetic steroid danazol has been shown to be effective in reducing the pain associated with FBD, but the cellular and molecular mechanisms for its action have not been elucidated. We investigated the hypothesis that danazol acts by affecting energy metabolism. Effects of danazol on Mcf10A cells homeostasis, including mechanisms of oxidative phosphorylation, cytosolic calcium signaling and oxidative stress, were assessed by high-resolution respirometry and flow cytometry. In addition to fast physiological responses the associated genomic modulations were evaluated by Affimetrix microarray analysis. The alterations of mitochondria membrane potential and respiratory activity, downregulation of energy metabolism transcripts result in suppression of energy homeostasis and arrest of Mcf10A cells growth. The data obtained in this study impacts the recognition of direct control of mitochondria by cellular mechanisms associated with altered energy metabolism genes governing the breast tissue susceptibility and response to medication by danazol. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. On the holistic approach in cellular and cancer biology: nonlinearity, complexity, and quasi-determinism of the dynamic cellular network.

    Science.gov (United States)

    Waliszewski, P; Molski, M; Konarski, J

    1998-06-01

    A keystone of the molecular reductionist approach to cellular biology is a specific deductive strategy relating genotype to phenotype-two distinct categories. This relationship is based on the assumption that the intermediary cellular network of actively transcribed genes and their regulatory elements is deterministic (i.e., a link between expression of a gene and a phenotypic trait can always be identified, and evolution of the network in time is predetermined). However, experimental data suggest that the relationship between genotype and phenotype is nonbijective (i.e., a gene can contribute to the emergence of more than just one phenotypic trait or a phenotypic trait can be determined by expression of several genes). This implies nonlinearity (i.e., lack of the proportional relationship between input and the outcome), complexity (i.e. emergence of the hierarchical network of multiple cross-interacting elements that is sensitive to initial conditions, possesses multiple equilibria, organizes spontaneously into different morphological patterns, and is controlled in dispersed rather than centralized manner), and quasi-determinism (i.e., coexistence of deterministic and nondeterministic events) of the network. Nonlinearity within the space of the cellular molecular events underlies the existence of a fractal structure within a number of metabolic processes, and patterns of tissue growth, which is measured experimentally as a fractal dimension. Because of its complexity, the same phenotype can be associated with a number of alternative sequences of cellular events. Moreover, the primary cause initiating phenotypic evolution of cells such as malignant transformation can be favored probabilistically, but not identified unequivocally. Thermodynamic fluctuations of energy rather than gene mutations, the material traits of the fluctuations alter both the molecular and informational structure of the network. Then, the interplay between deterministic chaos, complexity, self

  20. Final priority; National Institute on Disability and Rehabilitation Research--Disability and Rehabilitation Projects and Centers Program--Rehabilitation Engineering Research Centers. Final priority.

    Science.gov (United States)

    2013-06-19

    The Assistant Secretary for Special Education and Rehabilitative Services announces a priority for a Rehabilitation Engineering Research Center (RERC) on Technologies to Support Successful Aging with Disability under the Disability and Rehabilitation Research Projects and Centers Program administered by the National Institute on Disability and Rehabilitation Research (NIDRR). The Assistant Secretary may use this priority for a competition in fiscal year (FY) 2013 and later years. We take this action to focus research attention on areas of national need. We intend to use this priority to improve outcomes for individuals with disabilities.

  1. Early leaf senescence is associated with an altered cellular redox balance in Arabidopsis cpr5/old1 mutants

    NARCIS (Netherlands)

    Jing, H. -C.; Hebeler, R.; Oeljeklaus, S.; Sitek, B.; Stuehler, K.; Meyer, H. E.; Sturre, M. J. G.; Hille, J.; Warscheid, B.; Dijkwel, P. P.; Stühler, K.

    Reactive oxygen species (ROS) are the inevitable by-products of essential cellular metabolic and physiological activities. Plants have developed sophisticated gene networks of ROS generation and scavenging systems. However, ROS regulation is still poorly understood. Here, we report that mutations in

  2. Priority Setting for Improvement of Cervical Cancer Prevention in Iran

    DEFF Research Database (Denmark)

    Majidi, A.; Ghiasvand, R.; Hadji, M.

    2016-01-01

    , ICC has low incidence in Iran and many other Muslim countries. There is no organized cervical screening in these countries. Therefore, ICC is usually diagnosed in advanced stages with poor prognosis in these countries. We performed a priority setting exercise and suggested priorities for prevention...... of ICC in this setting. Methods: We invited experts and researchers to a workshop and asked them to list important suggestions for ICC prevention in Iran. After merging similar items and removing the duplicates, we asked the experts to rank the list of suggested items. We used a strategy grid and Go......-zone analysis to determine final list of priorities for ICC prevention in Iran. Results: From 26 final items suggested as priorities for prevention of ICC, the most important priorities were developing national guidelines for cervical screening and quality control protocol for patient follow-up and management...

  3. The MAP, M/G1,G2/1 queue with preemptive priority

    Directory of Open Access Journals (Sweden)

    Bong Dae Choi

    1997-01-01

    Full Text Available We consider the MAP, M/G1,G2/1 queue with preemptive resume priority, where low priority customers arrive to the system according to a Markovian arrival process (MAP and high priority customers according to a Poisson process. The service time density function of low (respectively: high priority customers is g1(x (respectively: g2(x. We use the supplementary variable method with Extended Laplace Transforms to obtain the joint transform of the number of customers in each priority queue, as well as the remaining service time for the customer in service in the steady state. We also derive the probability generating function for the number of customers of low (respectively, high priority in the system just after the service completion epochs for customers of low (respectively, high priority.

  4. 1991 Acceptance priority ranking

    International Nuclear Information System (INIS)

    1991-12-01

    The Standard Contract for Disposal of Spent Nuclear Fuel and/or High- Level Radioactive Waste (10 CFR Part 961) that the Department of Energy (DOE) has executed with the owners and generators of civilian spent nuclear fuel requires annual publication of the Acceptance Priority Ranking (APR). The 1991 APR details the order in which DOE will allocate Federal waste acceptance capacity. As required by the Standard Contract, the ranking is based on the age of permanently discharged spent nuclear fuel (SNF), with the owners of the oldest SNF, on an industry-wide basis, given the highest priority. the 1991 APR will be the basis for the annual allocation of waste acceptance capacity to the Purchasers in the 1991 Annual Capacity Report (ACR), to be issued later this year. This document is based on SNF discharges as of December 31, 1990, and reflects Purchaser comments and corrections, as appropriate, to the draft APR issued on May 15, 1991

  5. Setting priorities for reducing risk and advancing patient safety.

    Science.gov (United States)

    Gaffey, Ann D

    2016-04-01

    We set priorities every day in both our personal and professional lives. Some decisions are easy, while others require much more thought, participation, and resources. The difficult or less appealing priorities may not be popular, may receive push-back, and may be resource intensive. Whether personal or professional, the urgency that accompanies true priorities becomes a driving force. It is that urgency to ensure our patients' safety that brings many of us to work each day. This is not easy work. It requires us to be knowledgeable about the enterprise we are working in and to have the professional skills and competence to facilitate setting the priorities that allow our organizations to minimize risk and maximize value. © 2016 American Society for Healthcare Risk Management of the American Hospital Association.

  6. Static magnetic field exposure reproduces cellular effects of the Parkinson's disease drug candidate ZM241385.

    Directory of Open Access Journals (Sweden)

    Zhiyun Wang

    2010-11-01

    Full Text Available This study was inspired by coalescing evidence that magnetic therapy may be a viable treatment option for certain diseases. This premise is based on the ability of moderate strength fields (i.e., 0.1 to 1 Tesla to alter the biophysical properties of lipid bilayers and in turn modulate cellular signaling pathways. In particular, previous results from our laboratory (Wang et al., BMC Genomics, 10, 356 (2009 established that moderate strength static magnetic field (SMF exposure altered cellular endpoints associated with neuronal function and differentiation. Building on this background, the current paper investigated SMF by focusing on the adenosine A(2A receptor (A(2AR in the PC12 rat adrenal pheochromocytoma cell line that displays metabolic features of Parkinson's disease (PD.SMF reproduced several responses elicited by ZM241385, a selective A(2AR antagonist, in PC12 cells including altered calcium flux, increased ATP levels, reduced cAMP levels, reduced nitric oxide production, reduced p44/42 MAPK phosphorylation, inhibited proliferation, and reduced iron uptake. SMF also counteracted several PD-relevant endpoints exacerbated by A(2AR agonist CGS21680 in a manner similar to ZM241385; these include reduction of increased expression of A(2AR, reversal of altered calcium efflux, dampening of increased adenosine production, reduction of enhanced proliferation and associated p44/42 MAPK phosphorylation, and inhibition of neurite outgrowth.When measured against multiple endpoints, SMF elicited qualitatively similar responses as ZM241385, a PD drug candidate. Provided that the in vitro results presented in this paper apply in vivo, SMF holds promise as an intriguing non-invasive approach to treat PD and potentially other neurological disorders.

  7. Research priorities in mesothelioma: A James Lind Alliance Priority Setting Partnership.

    Science.gov (United States)

    Stephens, R J; Whiting, C; Cowan, K

    2015-08-01

    In the UK, despite the import and use of all forms of asbestos being banned more than 15 years ago, the incidence of mesothelioma continues to rise. Mesothelioma is almost invariably fatal, and more research is required, not only to find more effective treatments, but also to achieve an earlier diagnosis and improve palliative care. Following a debate in the House of Lords in July 2013, a package of measures was agreed, which included a James Lind Alliance Priority Setting Partnership, funded by the National Institute for Health Research. The partnership brought together patients, carers, health professionals and support organisations to agree the top 10 research priorities relating to the diagnosis, treatment and care of patients with mesothelioma. Following the established James Lind Alliance priority setting process, mesothelioma patients, current and bereaved carers, and health professionals were surveyed to elicit their concerns regarding diagnosis, treatment and care. Research questions were generated from the survey responses, and following checks that the questions were currently unanswered, an interim prioritisation survey was conducted to identify a shortlist of questions to take to a final consensus meeting. Four hundred and fifty-three initial surveys were returned, which were refined into 52 unique unanswered research questions. The interim prioritisation survey was completed by 202 responders, and the top 30 questions were taken to a final meeting where mesothelioma patients, carers, and health professionals prioritised all the questions, and reached a consensus on the top 10. The top 10 questions cover a wide portfolio of research (including assessing the value of immunotherapy, individualised chemotherapy, second-line treatment and immediate chemotherapy, monitoring patients with pleural thickening, defining the management of ascites in peritoneal mesothelioma, and optimising follow-up strategy). This list is an invaluable resource, which should be

  8. Quantification of nanoscale density fluctuations by electron microscopy: probing cellular alterations in early carcinogenesis

    International Nuclear Information System (INIS)

    Pradhan, Prabhakar; Damania, Dhwanil; Turzhitsky, Vladimir; Subramanian, Hariharan; Backman, Vadim; Joshi, Hrushikesh M; Dravid, Vinayak P; Roy, Hemant K; Taflove, Allen

    2011-01-01

    Most cancers are curable if they are diagnosed and treated at an early stage. Recent studies suggest that nanoarchitectural changes occur within cells during early carcinogenesis and that such changes precede microscopically evident tissue alterations. It follows that the ability to comprehensively interrogate cell nanoarchitecture (e.g., macromolecular complexes, DNA, RNA, proteins and lipid membranes) could be critical to the diagnosis of early carcinogenesis. We present a study of the nanoscale mass-density fluctuations of biological tissues by quantifying their degree of disorder at the nanoscale. Transmission electron microscopy images of human tissues are used to construct corresponding effective disordered optical lattices. The properties of nanoscale disorder are then studied by statistical analysis of the inverse participation ratio (IPR) of the spatially localized eigenfunctions of these optical lattices at the nanoscale. Our results show an increase in the disorder of human colonic epithelial cells in subjects harboring early stages of colon neoplasia. Furthermore, our findings strongly suggest that increased nanoscale disorder correlates with the degree of tumorigenicity. Therefore, the IPR technique provides a practicable tool for the detection of nanoarchitectural alterations in the earliest stages of carcinogenesis. Potential applications of the technique for early cancer screening and detection are also discussed

  9. [The Danish debate on priority setting in medicine - characteristics and results].

    Science.gov (United States)

    Pornak, S; Meyer, T; Raspe, H

    2011-10-01

    Priority setting in medicine helps to achieve a fair and transparent distribution of health-care resources. The German discussion about priority setting is still in its infancy and may benefit from other countries' experiences. This paper aims to analyse the Danish priority setting debate in order to stimulate the German discussion. The methods used are a literature analysis and a document analysis as well as expert interviews. The Danish debate about priority setting in medicine began in the 1970s, when a government committee was constituted to evaluate health-care priorities at the national level. In the 1980s a broader debate arose in politics, ethics, medicine and health economy. The discussions reached a climax in the 1990s, when many local activities - always involving the public - were initiated. Some Danish counties tried to implement priority setting in the daily routine of health care. The Council of Ethics was a major player in the debate of the 1990s and published a detailed statement on priority setting in 1996. With the new century the debate about priority setting seemed to have come to an end, but in 2006 the Technology Council and the Danish Regions resumed the discussion. In 2009 the Medical Association called for a broad debate in order to achieve equity among all patients. The long lasting Danish debate on priority setting has entailed only very little practical consequences on health care. The main problems seem to have been the missing effort to bundle the various local initiatives on a national level and the lack of powerful players to put results of the discussion into practice. Nevertheless, today the attitude towards priority setting is predominantly positive and even politicians talk freely about it. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Priorities for research in miscarriage: a priority setting partnership between people affected by miscarriage and professionals following the James Lind Alliance methodology.

    Science.gov (United States)

    Prior, Matthew; Bagness, Carmel; Brewin, Jane; Coomarasamy, Arri; Easthope, Lucy; Hepworth-Jones, Barbara; Hinshaw, Kim; O'Toole, Emily; Orford, Julie; Regan, Lesley; Raine-Fenning, Nick; Shakespeare, Judy; Small, Rachel; Thornton, Jim; Metcalf, Leanne

    2017-08-23

    To identify and prioritise important research questions for miscarriage. A priority setting partnership using prospective surveys and consensus meetings following methods advocated by the James Lind Alliance. UK. Women and those affected by miscarriage working alongside healthcare professionals. In the initial survey, 1093 participants (932 women who have experienced miscarriage, 8 partners, 17 family members, friends or colleagues, 104 healthcare professionals and eight charitable organisations) submitted 3279 questions. A review of existing literature identified a further 64. Non-questions were removed, and the remaining questions were categorised and summarised into 58 questions. In an interim electronic survey, 2122 respondents chose their top 10 priorities from the 58 summary questions. The 25 highest ranked in the survey were prioritised at a final face-to-face workshop. In summary, the top 10 priorities were ranked as follows: research into preventative treatment, emotional aspects in general, investigation, relevance of pre-existing medical conditions, emotional support as a treatment, importance of lifestyle factors, importance of genetic and chromosomal causes, preconception tests, investigation after different numbers of miscarriage and male causal factors. These results should be the focus of future miscarriage research. Presently, studies are being conducted to address the top priority; however, many other priorities, especially psychological and emotional support, are less well researched areas. We hope our results will encourage both researchers and funders to focus on these priorities. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Promoting community participation in priority setting in district health systems

    DEFF Research Database (Denmark)

    Kamuzora, Peter; Maluka, Stephen; Ndawi, Benedict

    2013-01-01

    Community participation in priority setting in health systems has gained importance all over the world, particularly in resource-poor settings where governments have often failed to provide adequate public-sector services for their citizens. Incorporation of public views into priority setting...... is perceived as a means to restore trust, improve accountability, and secure cost-effective priorities within healthcare. However, few studies have reported empirical experiences of involving communities in priority setting in developing countries. The aim of this article is to provide the experience...... of implementing community participation and the challenges of promoting it in the context of resource-poor settings, weak organizations, and fragile democratic institutions....

  12. Determining priorities of current and long-range pollution control projects

    Energy Technology Data Exchange (ETDEWEB)

    Clark, E O

    1977-01-01

    The dilemma facing corporations of setting priorities on pollution control projects is reviewed and procedural guidelines outlined. The management must support those assigned to analyze priorities so that they have the opportunity to experiment and make quantitative studies, to evaluate their results, and to make independent recommendations. Priority is then given to the problems of air, noise, water, and land pollution in accordance with the company's environmental record. Each of the four categories, however, has its own legal, technical, and financial aspects that require further priority analysis. Each company must adopt and publish a regularly updated environmental policy that will have public visibility. (DCK)

  13. Energy-related indoor environmental quality research: A priority agenda

    Energy Technology Data Exchange (ETDEWEB)

    Fisk, W.J.; Brager, G.; Burge, H.; Cummings, J.; Levin, H.; Loftness, V.; Mendell, M.J.; Persily, A.; Taylor, S.; Zhang, J.S.

    2002-08-01

    A multidisciplinary team of IEQ and energy researchers has defined a program of priority energy-related IEQ research. This paper describes the methods employed to develop the agenda, and 35 high priority research and development (R&D) project areas related to four broad goals: (1) identifying IEQ problems and opportunities; (2) developing and evaluating energy-efficient technologies for improving IEQ; (3) developing and evaluating energy-efficient practices for improving IEQ; and (4) encouraging or assisting the implementation of technologies or practices for improving IEQ. The identified R&D priorities reflect a strong need to benchmark IEQ conditions in small commercial buildings, schools, and residences. The R&D priorities also reflect the need to better understand how people are affected by IEQ conditions and by the related building characteristics and operation and maintenance practices. The associated research findings will provide a clearer definition of acceptable IEQ that is required to guide the development of technologies, practices, standards, and guidelines. Quantifying the effects of building characteristics and practices on IEQ conditions, in order to provide the basis for development of energy efficient and effective IEQ control measures, was also considered a priority. The development or advancement in a broad range of IEQ tools, technologies, and practices are also a major component of the priority research agenda. Consistent with the focus on ''energy-related'' research priorities, building ventilation and heating, ventilating and air conditioning (HVAC) systems and processes are very prominent in the agenda. Research related to moisture and microbiological problems, particularly within hot and humid climates, is also prominent within the agenda. The agenda tends to emphasize research on residences, small commercial buildings, and schools because these types of buildings have been underrepresented in prior research. Most of

  14. Priority Settings in patients with Chronic Diseases and Cancer

    DEFF Research Database (Denmark)

    Arreskov, Anne Beiter; Graungaard, Anette Hauskov; Søndergaard, Jens

    Priority setting in patients with cancer and comorbidities Background and aim As both the cancer incidence and the number of patients diagnosed with chronic diseases are increasing, a growing population of cancer survivors will also deal with comorbid chronic diseases. The period after completed...... to comorbidities. Some studies show that participation in regular follow-up consultations concerning comorbid chronic diseases and lifestyle are lower among cancer survivors than non-cancer patients. This could be explained by changes in the patient’s priority setting or in the doctor’s priority and attempt...... to spare the patient for further treatment burden, perhaps resulting in comorbidities falling down the agenda. The overall purpose is to explore patients’ and doctors’ priority settings of comorbidities in patients who have been diagnosed with non-metastatic cancer. Method: The study will consist of three...

  15. Energy priorities and options for the European Community

    International Nuclear Information System (INIS)

    Audland, C.J.

    1984-01-01

    The paper discusses the energy priorities and options for the European Community. Reasons for the recent improvement in the efficiency of energy use are briefly discussed, as well as the outlook for 1990, priorities for the future, solid fuels. natural gas, electricity and nuclear energy. Energy policy considerations in the United Kingdom are also mentioned. (U.K.)

  16. An Emergency Medicine Research Priority Setting Partnership to establish the top 10 research priorities in emergency medicine.

    Science.gov (United States)

    Smith, Jason; Keating, Liza; Flowerdew, Lynsey; O'Brien, Rachel; McIntyre, Sam; Morley, Richard; Carley, Simon

    2017-07-01

    Defining research priorities in a specialty as broad as emergency medicine is a significant challenge. In order to fund and complete the most important research projects, it is imperative that we identify topics that are important to all clinicians, society and to our patients. We have undertaken a priority setting partnership to establish the most important questions facing emergency medicine. The top 10 questions reached through a consensus process are discussed. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Magnolol Affects Cellular Proliferation, Polyamine Biosynthesis and Catabolism-Linked Protein Expression and Associated Cellular Signaling Pathways in Human Prostate Cancer Cells in vitro

    Directory of Open Access Journals (Sweden)

    Brendan T. McKeown

    2015-01-01

    Full Text Available Background: Prostate cancer is the most commonly diagnosed form of cancer in men in Canada and the United States. Both genetic and environmental factors contribute to the development and progression of many cancers, including prostate cancer. Context and purpose of this study: This study investigated the effects of magnolol, a compound found in the roots and bark of the magnolia tree Magnolia officinalis, on cellular proliferation and proliferation-linked activities of PC3 human prostate cancer cells in vitro. Results: PC3 cells exposed to magnolol at a concentration of 80 μM for 6 hours exhibited decreased protein expression of ornithine decarboxylase, a key regulator in polyamine biosynthesis, as well as affecting the expression of other proteins involved in polyamine biosynthesis and catabolism. Furthermore, protein expression of the R2 subunit of ribonucleotide reductase, a key regulatory protein associated with DNA synthesis, was significantly decreased. Finally, the MAPK (mitogen-activated protein kinase, PI3K (phosphatidylinositol 3-kinase, NFκB (nuclear factor of kappa-light-chain-enhancer of activated B cells and AP-1 (activator protein 1 cellular signaling pathways were assayed to determine which, if any, of these pathways magnolol exposure would alter. Protein expressions of p-JNK-1 and c-jun were significantly increased while p-p38, JNK-1/2, PI3Kp85, p-PI3Kp85, p-Akt, NFκBp65, p-IκBα and IκBα protein expressions were significantly decreased. Conclusions: These alterations further support the anti-proliferative effects of magnolol on PC3 human prostate cancer cells in vitro and suggest that magnolol may have potential as a novel anti-prostate cancer agent.

  18. Cellular MR Imaging

    Directory of Open Access Journals (Sweden)

    Michel Modo

    2005-07-01

    Full Text Available Cellular MR imaging is a young field that aims to visualize targeted cells in living organisms. In order to provide a different signal intensity of the targeted cell, they are either labeled with MR contrast agents in vivo or prelabeled in vitro. Either (ultrasmall superparamagnetic iron oxide [(USPIO] particles or (polymeric paramagnetic chelates can be used for this purpose. For in vivo cellular labeling, Gd3+- and Mn2+- chelates have mainly been used for targeted hepatobiliary imaging, and (USPIO-based cellular imaging has been focused on imaging of macrophage activity. Several of these magneto-pharmaceuticals have been FDA-approved or are in late-phase clinical trials. As for prelabeling of cells in vitro, a challenge has been to induce a sufficient uptake of contrast agents into nonphagocytic cells, without affecting normal cellular function. It appears that this issue has now largely been resolved, leading to an active research on monitoring the cellular biodistribution in vivo following transplantation or transfusion of these cells, including cell migration and trafficking. New applications of cellular MR imaging will be directed, for instance, towards our understanding of hematopoietic (immune cell trafficking and of novel guided (stem cell-based therapies aimed to be translated to the clinic in the future.

  19. Adaptive optics without altering visual perception.

    Science.gov (United States)

    Koenig, D E; Hart, N W; Hofer, H J

    2014-04-01

    Adaptive optics combined with visual psychophysics creates the potential to study the relationship between visual function and the retina at the cellular scale. This potential is hampered, however, by visual interference from the wavefront-sensing beacon used during correction. For example, we have previously shown that even a dim, visible beacon can alter stimulus perception (Hofer et al., 2012). Here we describe a simple strategy employing a longer wavelength (980nm) beacon that, in conjunction with appropriate restriction on timing and placement, allowed us to perform psychophysics when dark adapted without altering visual perception. The method was verified by comparing detection and color appearance of foveally presented small spot stimuli with and without the wavefront beacon present in 5 subjects. As an important caution, we found that significant perceptual interference can occur even with a subliminal beacon when additional measures are not taken to limit exposure. Consequently, the lack of perceptual interference should be verified for a given system, and not assumed based on invisibility of the beacon. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Setting healthcare priorities in hospitals: a review of empirical studies.

    Science.gov (United States)

    Barasa, Edwine W; Molyneux, Sassy; English, Mike; Cleary, Susan

    2015-04-01

    Priority setting research has focused on the macro (national) and micro (bedside) level, leaving the meso (institutional, hospital) level relatively neglected. This is surprising given the key role that hospitals play in the delivery of healthcare services and the large proportion of health systems resources that they absorb. To explore the factors that impact upon priority setting at the hospital level, we conducted a thematic review of empirical studies. A systematic search of PubMed, EBSCOHOST, Econlit databases and Google scholar was supplemented by a search of key websites and a manual search of relevant papers' reference lists. A total of 24 papers were identified from developed and developing countries. We applied a policy analysis framework to examine and synthesize the findings of the selected papers. Findings suggest that priority setting practice in hospitals was influenced by (1) contextual factors such as decision space, resource availability, financing arrangements, availability and use of information, organizational culture and leadership, (2) priority setting processes that depend on the type of priority setting activity, (3) content factors such as priority setting criteria and (4) actors, their interests and power relations. We observe that there is need for studies to examine these issues and the interplay between them in greater depth and propose a conceptual framework that might be useful in examining priority setting practices in hospitals. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.

  1. Suitability of the cellular viability technique as a control tool of the chlorine dosage on the activated sludge of a biological process affected by bulking

    International Nuclear Information System (INIS)

    Montaya Martinez, T.; Zornoza Zornoza, A.; Granell Munoz, P.; Fayos, G.; Fajarddo, V.; Zorrilla, F.; Alonso Molina, J. L.; Morenilla Martinez, J. J.; Bernacer Bonora, I.; Martinez Francisco, F. J.

    2009-01-01

    This work demonstrates the suitability of the cellular viability technique as a control tool of the chlorine dosage on the activated sludge of a biological process affected by the overabundance of the filamentous bacteria (Thiothrix-021N). This technique was used to establish the chlorine dosage according to the observed damages on cellular membranes of both, floc-forming bacteria as well as filamentous bacteria. To identify the filamentous bacteria responsible for the macro-structural alteration of the flocs, several criteria were, met, including morphologic characteristics as well as conventional microbiological stains: Gram, Neisser and polyhydroxy alkanoates. FISH was used to confirm the obtained results, providing a definitive identification of the filamentous bacteria responsible for the alteration. (Author) 11 refs

  2. Programmable cellular arrays. Faults testing and correcting in cellular arrays

    International Nuclear Information System (INIS)

    Cercel, L.

    1978-03-01

    A review of some recent researches about programmable cellular arrays in computing and digital processing of information systems is presented, and includes both combinational and sequential arrays, with full arbitrary behaviour, or which can realize better implementations of specialized blocks as: arithmetic units, counters, comparators, control systems, memory blocks, etc. Also, the paper presents applications of cellular arrays in microprogramming, in implementing of a specialized computer for matrix operations, in modeling of universal computing systems. The last section deals with problems of fault testing and correcting in cellular arrays. (author)

  3. Opinion evolution based on cellular automata rules in small world networks

    Science.gov (United States)

    Shi, Xiao-Ming; Shi, Lun; Zhang, Jie-Fang

    2010-03-01

    In this paper, we apply cellular automata rules, which can be given by a truth table, to human memory. We design each memory as a tracking survey mode that keeps the most recent three opinions. Each cellular automata rule, as a personal mechanism, gives the final ruling in one time period based on the data stored in one's memory. The key focus of the paper is to research the evolution of people's attitudes to the same question. Based on a great deal of empirical observations from computer simulations, all the rules can be classified into 20 groups. We highlight the fact that the phenomenon shown by some rules belonging to the same group will be altered within several steps by other rules in different groups. It is truly amazing that, compared with the last hundreds of presidential voting in America, the eras of important events in America's history coincide with the simulation results obtained by our model.

  4. A bead-based western for high-throughput cellular signal transduction analyses

    Science.gov (United States)

    Treindl, Fridolin; Ruprecht, Benjamin; Beiter, Yvonne; Schultz, Silke; Döttinger, Anette; Staebler, Annette; Joos, Thomas O.; Kling, Simon; Poetz, Oliver; Fehm, Tanja; Neubauer, Hans; Kuster, Bernhard; Templin, Markus F.

    2016-01-01

    Dissecting cellular signalling requires the analysis of large number of proteins. The DigiWest approach we describe here transfers the western blot to a bead-based microarray platform. By combining gel-based protein separation with immobilization on microspheres, hundreds of replicas of the initial blot are created, thus enabling the comprehensive analysis of limited material, such as cells collected by laser capture microdissection, and extending traditional western blotting to reach proteomic scales. The combination of molecular weight resolution, sensitivity and signal linearity on an automated platform enables the rapid quantification of hundreds of specific proteins and protein modifications in complex samples. This high-throughput western blot approach allowed us to identify and characterize alterations in cellular signal transduction that occur during the development of resistance to the kinase inhibitor Lapatinib, revealing major changes in the activation state of Ephrin-mediated signalling and a central role for p53-controlled processes. PMID:27659302

  5. Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.

    Science.gov (United States)

    Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko

    2017-07-17

    Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.

  6. Final priority; National Institute on Disability and Rehabilitation Research--Disability and Rehabilitation Research Projects and Centers Program--Rehabilitation Engineering Research Centers. Final priority.

    Science.gov (United States)

    2013-06-14

    The Assistant Secretary for Special Education and Rehabilitative Services announces a priority for a Rehabilitation Engineering Research Center (RERC) on Universal Interfaces and Information Technology Access under the Disability and Rehabilitation Research Projects and Centers Program administered by the National Institute on Disability and Rehabilitation Research (NIDRR). The Assistant Secretary may use this priority for a competition in fiscal year (FY) 2013 and later years. We take this action to focus research attention on areas of national need. We intend to use this priority to improve outcomes for individuals with disabilities.

  7. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation.

    Science.gov (United States)

    Irwin, Michael R; Wang, Minge; Campomayor, Capella O; Collado-Hidalgo, Alicia; Cole, Steve

    2006-09-18

    Inflammation is associated with increased risk of cardiovascular disorders, arthritis, diabetes mellitus, and mortality. The effects of sleep loss on the cellular and genomic mechanisms that contribute to inflammatory cytokine activity are not known. In 30 healthy adults, monocyte intracellular proinflammatory cytokine production was repeatedly assessed during the day across 3 baseline periods and after partial sleep deprivation (awake from 11 pm to 3 am). We analyzed the impact of sleep loss on transcription of proinflammatory cytokine genes and used DNA microarray analyses to characterize candidate transcription-control pathways that might mediate the effects of sleep loss on leukocyte gene expression. In the morning after a night of sleep loss, monocyte production of interleukin 6 and tumor necrosis factor alpha was significantly greater compared with morning levels following uninterrupted sleep. In addition, sleep loss induced a more than 3-fold increase in transcription of interleukin 6 messenger RNA and a 2-fold increase in tumor necrosis factor alpha messenger RNA. Bioinformatics analyses suggested that the inflammatory response was mediated by the nuclear factor kappaB inflammatory signaling system as well as through classic hormone and growth factor response pathways. Sleep loss induces a functional alteration of the monocyte proinflammatory cytokine response. A modest amount of sleep loss also alters molecular processes that drive cellular immune activation and induce inflammatory cytokines; mapping the dynamics of sleep loss on molecular signaling pathways has implications for understanding the role of sleep in altering immune cell physiologic characteristics. Interventions that target sleep might constitute new strategies to constrain inflammation with effects on inflammatory disease risk.

  8. Scale-dependent complementarity of climatic velocity and environmental diversity for identifying priority areas for conservation under climate change.

    Science.gov (United States)

    Carroll, Carlos; Roberts, David R; Michalak, Julia L; Lawler, Joshua J; Nielsen, Scott E; Stralberg, Diana; Hamann, Andreas; Mcrae, Brad H; Wang, Tongli

    2017-11-01

    As most regions of the earth transition to altered climatic conditions, new methods are needed to identify refugia and other areas whose conservation would facilitate persistence of biodiversity under climate change. We compared several common approaches to conservation planning focused on climate resilience over a broad range of ecological settings across North America and evaluated how commonalities in the priority areas identified by different methods varied with regional context and spatial scale. Our results indicate that priority areas based on different environmental diversity metrics differed substantially from each other and from priorities based on spatiotemporal metrics such as climatic velocity. Refugia identified by diversity or velocity metrics were not strongly associated with the current protected area system, suggesting the need for additional conservation measures including protection of refugia. Despite the inherent uncertainties in predicting future climate, we found that variation among climatic velocities derived from different general circulation models and emissions pathways was less than the variation among the suite of environmental diversity metrics. To address uncertainty created by this variation, planners can combine priorities identified by alternative metrics at a single resolution and downweight areas of high variation between metrics. Alternately, coarse-resolution velocity metrics can be combined with fine-resolution diversity metrics in order to leverage the respective strengths of the two groups of metrics as tools for identification of potential macro- and microrefugia that in combination maximize both transient and long-term resilience to climate change. Planners should compare and integrate approaches that span a range of model complexity and spatial scale to match the range of ecological and physical processes influencing persistence of biodiversity and identify a conservation network resilient to threats operating at

  9. Setting the top 10 research priorities to improve the health of people with Type 2 diabetes: a Diabetes UK-James Lind Alliance Priority Setting Partnership.

    Science.gov (United States)

    Finer, S; Robb, P; Cowan, K; Daly, A; Shah, K; Farmer, A

    2018-07-01

    To describe processes and outcomes of a priority setting partnership to identify the 'top 10 research priorities' in Type 2 diabetes, involving people living with the condition, their carers, and healthcare professionals. We followed the four-step James Lind Alliance Priority Setting Partnership process which involved: gathering uncertainties using a questionnaire survey distributed to 70 000 people living with Type 2 diabetes and their carers, and healthcare professionals; organizing the uncertainties; interim priority setting by resampling of participants with a second survey; and final priority setting in an independent group of participants, using the nominal group technique. At each step the steering group closely monitored and guided the process. In the first survey, 8227 uncertainties were proposed by 2587 participants, of whom 18% were from black, Asian and minority ethnic groups. Uncertainties were formatted and collated into 114 indicative questions. A total of 1506 people contributed to a second survey, generating a shortlist of 24 questions equally weighted to the contributions of people living with diabetes and their carers and those of healthcare professionals. In the final step the 'top 10 research priorities' were selected, including questions on cure and reversal, risk identification and prevention, and self-management approaches in Type 2 diabetes. Systematic and transparent methodology was used to identify research priorities in a large and genuine partnership of people with lived and professional experience of Type 2 diabetes. The top 10 questions represent consensus areas of research priority to guide future research, deliver responsive and strategic allocation of research resources, and improve the future health and well-being of people living with, and at risk of, Type 2 diabetes. © 2018 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

  10. EDTA treatment alters protein glycosylation in the cellular slime mold Dictyostelium discoideum

    International Nuclear Information System (INIS)

    West, C.M.; Brownstein, S.A.

    1988-01-01

    The authors have found that treatment of cells with EDTA resulted in the accumulation of lower molecular weight forms of two cell-type-specific glycoproteins. These new glycoproteins lacked a developmentally regulated glycoantigen defined by monoclonal antibody 54.2. Since EDTA dissociated the cells, the possible involvement of cell separation was tested by immobilizing cells in soft agarose. Glycoantigen expression on these proteins was found to be dependent on cAMP and high oxygen tension but not on cell contact, and was reversibly sensitive to EDTA regardless of the state of cell association. The EDTA effect was mimicked by other soluble, but not particulate, membrane impermeable chelators, could be completed by Zn 2+ better than Mg 2+ , and appeared to involve an intracellular mechanism. Studies with [ 14 C]EDTA showed that EDTA equilibrated with a cellular compartment in a temperature-dependent, Zn 2+ -insensitive fashion with half-time kinetics of loading and unloading of 30-40 min. The data suggest that this step in glycosylation, which was found to be delayed 1 or more hours subsequent to protein synthesis, involves an intracellular, transition metal-ion-dependent process which can be modulated by chelators entering the cell through the endocytic pathway

  11. 78 FR 26560 - Proposed Priority-National Institute on Disability and Rehabilitation Research-Rehabilitation...

    Science.gov (United States)

    2013-05-07

    ... in nonrural areas (U.S. Census Bureau, 2011b), and rural vocational rehabilitation clients with... priorities, we designate the type of each priority as absolute, competitive preference, or invitational...)). Competitive preference priority: Under a competitive preference priority, we give competitive preference to an...

  12. Hypergravity-induced altered behavior in Drosophila

    Science.gov (United States)

    Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila

    2012-07-01

    Microgravity and mechanical stress are important factors of the spaceflight environment, and affect astronaut health and behavior. Structural, functional, and behavioral mechanisms of all cells and organisms are adapted to Earth's gravitational force, 1G, while altered gravity can pose challenges to their adaptability to this new environment. On ground, hypergravity paradigms have been used to predict and complement studies on microgravity. Even small changes that take place at a molecular and genetic level during altered gravity may result in changes in phenotypic behavior. Drosophila provides a robust and simple, yet very reliable model system to understand the complexity of hypergravity-induced altered behavior, due to availability of a plethora of genetic tools. Locomotor behavior is a sensitive parameter that reflects the array of molecular adaptive mechanisms recruited during exposure to altered gravity. Thus, understanding the genetic basis of this behavior in a hypergravity environment could potentially extend our understanding of mechanisms of adaptation in microgravity. In our laboratory we are trying to dissect out the cellular and molecular mechanisms underlying hypergravity-induced oxidative stress, and its potential consequences on behavioral alterations by using Drosophila as a model system. In the present study, we employed pan-neuronal and mushroom body specific knock-down adult flies by using Gal4/UAS system to express inverted repeat transgenes (RNAi) to monitor and quantify the hypergravity-induced behavior in Drosophila. We established that acute hypergravity (3G for 60 min) causes a significant and robust decrease in the locomotor behavior in adult Drosophila, and that this change is dependent on genes related to Parkinson's disease, such as DJ-1α , DJ-1β , and parkin. In addition, we also showed that anatomically the control of this behavior is significantly processed in the mushroom body region of the fly brain. This work links a molecular

  13. Hardware Locks with Priority Ceiling Emulation for a Java Chip-Multiprocessor

    DEFF Research Database (Denmark)

    Strøm, Torur Biskopstø; Schoeberl, Martin

    2015-01-01

    According to the safety-critical Java specification, priority ceiling emulation is a requirement for implementations, as it has preferable properties, such as avoiding priority inversion and being deadlock free on uni-core systems. In this paper we explore our hardware supported implementation...... of priority ceiling emulation on the multicore Java optimized processor, and compare it to the existing hardware locks on the Java optimized processor. We find that the additional overhead for priority ceiling emulation on a multicore processor is several times higher than simpler, non-premptive locks, mainly...

  14. 47 CFR 22.970 - Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone...

    Science.gov (United States)

    2010-10-01

    ...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. 22.970 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.970 Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. (a) Definition...

  15. Increasing Capacity of Intersections with Transit Priority

    Directory of Open Access Journals (Sweden)

    Yanxi Hao

    2016-12-01

    Full Text Available Dedicated bus lane (DBL and transit signal priority (TSP are two effective and low-cost ways of improving the reliability of transits. However, these strategies reduce the capacity of general traffic. This paper presents an integrated optimization (IO model to improve the performance of intersections with dedicated bus lanes. The IO model integrated geometry layout, main-signal timing, pre-signal timing and transit priority. The optimization problem is formulated as a Mix-Integer-Non-Linear-Program (MINLP that can be transformed into a Mix-Integer-Linear-Program (MILP and then solved by the standard branch-and-bound technique. The applicability of the IO model is tested through numerical experiment under different intersection layouts and traffic demands. A VISSIM micro simulation model was developed and used to evaluate the performance of the proposed IO model. The test results indicate that the proposed model can increase the capacity and reduce the delay of general traffic when providing priority to buses.

  16. Priority setting for health in emerging markets.

    Science.gov (United States)

    Glassman, Amanda; Giedion, Ursula; McQueston, Kate

    2013-05-01

    The use of health technology assessment research in emerging economies is becoming an increasingly important tool to determine the uses of health spending. As low- and middle-income countries' gross domestic product grows, the funding available for health has increased in tandem. There is growing evidence that comparative effectiveness research and cost-effectiveness can be used to improve health outcomes within a predefined financial space. The use of these evaluation tools, combined with a systematized process of priority setting, can help inform national and global health payers. This review of country institutions for health technology assessment illustrates two points: the efforts underway to use research to inform priorities are widespread and not confined to wealthier countries; and many countries' efforts to create evidence-based policy are incomplete and more country-specific research will be needed. Further evidence shows that there is scope to reduce these gaps and opportunity to support better incorporation of data through better-defined priority-setting processes.

  17. Fast meldable priority queues

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting

    1995-01-01

    We present priority queues that support the operations Find-Min, Insert, MakeQueue and Meld in worst case time O(1) and Delete and DeleteMin in worst case time O(log n). They can be implemented on the pointer machine and require linear space. The time bounds are optimal for all implementations wh...

  18. The epigenetic alterations of endogenous retroelements in aging.

    Science.gov (United States)

    Cardelli, Maurizio

    2018-02-16

    Endogenous retroelements, transposons that mobilize through RNA intermediates, include some of the most abundant repetitive sequences of the human genome, such as Alu and LINE-1 sequences, and human endogenous retroviruses. Recent discoveries demonstrate that these mobile genetic elements not only act as intragenomic parasites, but also exert regulatory roles in living cells. The risk of genomic instability represented by endogenous retroelements is normally counteracted by a series of epigenetic control mechanisms which include, among the most important, CpG DNA methylation. Indeed, most of the genomic CpG sites subjected to DNA methylation in the nuclear DNA are carried by these repetitive elements. As other parts of the genome, endogenous retroelements and other transposable elements are subjected to deep epigenetic alterations during aging, repeatedly observed in the context of organismal and cellular senescence, in human and other species. This review summarizes the current status of knowledge about the epigenetic alterations occurring in this large, non-genic portion of the genome in aging and age-related conditions, with a focus on the causes and the possible functional consequences of these alterations. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Obesity alters adipose tissue macrophage iron content and tissue iron distribution.

    Science.gov (United States)

    Orr, Jeb S; Kennedy, Arion; Anderson-Baucum, Emily K; Webb, Corey D; Fordahl, Steve C; Erikson, Keith M; Zhang, Yaofang; Etzerodt, Anders; Moestrup, Søren K; Hasty, Alyssa H

    2014-02-01

    Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFe(hi), and the remaining ATMs are referred to as MFe(lo). In lean mice, ~25% of the ATMs are MFe(hi); this percentage decreases in obesity owing to the recruitment of MFe(lo) macrophages. Similar to MFe(lo) cells, MFe(hi) ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFe(hi) ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFe(hi) iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFe(hi) ATM phenotype and their reduced capacity to handle iron.

  20. Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kastrup, Ingelise Bjerring; Worm, Jesper; Ralfkiaer, Elisabeth

    2007-01-01

    The reduced folate carrier (RFC) is a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs, including methotrexate (MTX). Acquired alterations of the RFC gene have been associated with resistance to MTX in cancer cell lines and primary osteosarcomas. Here, we...

  1. Heterogeneous cellular networks

    CERN Document Server

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  2. Implications of TGFβ on transcriptome and cellular biofunctions of palatal mesenchyme

    Directory of Open Access Journals (Sweden)

    Xiujuan eZhu

    2012-04-01

    Full Text Available Development of the palate comprises sequential stages of growth, elevation and fusion of the palatal shelves. The mesenchymal component of palates plays a major role in early phases of palatogenesis, such as growth and elevation. Failure in these steps may result in cleft palate, the second most common birth defect in the world. These early stages of palatogenesis require precise and chronological orchestration of key physiological processes, such as growth, proliferation, differentiation, migration, and apoptosis. There is compelling evidence for the vital role of TGFβ-mediated regulation of palate development. We hypothesized that the isoforms of TGFβ regulate different cellular biofunctions of the palatal mesenchyme to various extents. Human embryonic palatal mesenchyme (HEPM cells were treated with TGFβ1, β2, and β3 for microarray-based gene expression studies in order to identify the roles of TGFβ in the transcriptome of the palatal mesenchyme. Following normalization and modeling of 28,869 human genes, 566 transcripts were detected as differentially expressed in TGFβ-treated HEPM cells. Out of these altered transcripts, 234 of them were clustered in cellular biofunctions, including growth and proliferation, development, morphology, movement, cell cycle, and apoptosis. Biological interpretation and network analysis of the genes active in cellular biofunctions were performed using IPA. Among the differentially expressed genes, 11 of them were previously identified as being crucial for palatogenesis (EDN1, INHBA, LHX8, PDGFC, PIGA, RUNX1, SNAI1, SMAD3, TGFβ1, TGFβ2, and TGFβR1. These genes were used for a merged interaction network with cellular behaviors. Overall, we have determined that more than 2% of human transcripts were differentially expressed in response to TGFβ treatment in HEPM cells. Our results suggest that both TGFβ1 and TGFβ2 orchestrate major cellular biofunctions within the palatal mesenchyme in vitro by

  3. Cigarette smoke alters the secretome of lung epithelial cells.

    Science.gov (United States)

    Mossina, Alessandra; Lukas, Christina; Merl-Pham, Juliane; Uhl, Franziska E; Mutze, Kathrin; Schamberger, Andrea; Staab-Weijnitz, Claudia; Jia, Jie; Yildirim, Ali Ö; Königshoff, Melanie; Hauck, Stefanie M; Eickelberg, Oliver; Meiners, Silke

    2017-01-01

    Cigarette smoke is the most relevant risk factor for the development of lung cancer and chronic obstructive pulmonary disease. Many of its more than 4500 chemicals are highly reactive, thereby altering protein structure and function. Here, we used subcellular fractionation coupled to label-free quantitative MS to globally assess alterations in the proteome of different compartments of lung epithelial cells upon exposure to cigarette smoke extract. Proteomic profiling of the human alveolar derived cell line A549 revealed the most pronounced changes within the cellular secretome with preferential downregulation of proteins involved in wound healing and extracellular matrix organization. In particular, secretion of secreted protein acidic and rich in cysteine, a matricellular protein that functions in tissue response to injury, was consistently diminished by cigarette smoke extract in various pulmonary epithelial cell lines and primary cells of human and mouse origin as well as in mouse ex vivo lung tissue cultures. Our study reveals a previously unrecognized acute response of lung epithelial cells to cigarette smoke that includes altered secretion of proteins involved in extracellular matrix organization and wound healing. This may contribute to sustained alterations in tissue remodeling as observed in lung cancer and chronic obstructive pulmonary disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Hexokinase cellular trafficking in ischemia-reperfusion and ischemic preconditioning is altered in type I diabetic heart

    NARCIS (Netherlands)

    Gurel, Ebru; Ustunova, Savas; Kapucu, Aysegul; Yilmazer, Nadim; Eerbeek, Otto; Nederlof, Rianne; Hollmann, Markus W.; Demirci-Tansel, Cihan; Zuurbier, Coert J.

    2013-01-01

    Diabetes mellitus (DM) has been reported to alter the cardiac response to ischemia-reperfusion (IR). In addition, cardioprotection induced by ischemic preconditioning (IPC) is often impaired in diabetes. We have previously shown that the subcellular localisation of the glycolytic enzyme hexokinase

  5. Static Magnetic Field Exposure Reproduces Cellular Effects of the Parkinson's Disease Drug Candidate ZM241385

    Science.gov (United States)

    Wang, Zhiyun; Che, Pao-Lin; Du, Jian; Ha, Barbara; Yarema, Kevin J.

    2010-01-01

    Background This study was inspired by coalescing evidence that magnetic therapy may be a viable treatment option for certain diseases. This premise is based on the ability of moderate strength fields (i.e., 0.1 to 1 Tesla) to alter the biophysical properties of lipid bilayers and in turn modulate cellular signaling pathways. In particular, previous results from our laboratory (Wang et al., BMC Genomics, 10, 356 (2009)) established that moderate strength static magnetic field (SMF) exposure altered cellular endpoints associated with neuronal function and differentiation. Building on this background, the current paper investigated SMF by focusing on the adenosine A2A receptor (A2AR) in the PC12 rat adrenal pheochromocytoma cell line that displays metabolic features of Parkinson's disease (PD). Methodology and Principal Findings SMF reproduced several responses elicited by ZM241385, a selective A2AR antagonist, in PC12 cells including altered calcium flux, increased ATP levels, reduced cAMP levels, reduced nitric oxide production, reduced p44/42 MAPK phosphorylation, inhibited proliferation, and reduced iron uptake. SMF also counteracted several PD-relevant endpoints exacerbated by A2AR agonist CGS21680 in a manner similar to ZM241385; these include reduction of increased expression of A2AR, reversal of altered calcium efflux, dampening of increased adenosine production, reduction of enhanced proliferation and associated p44/42 MAPK phosphorylation, and inhibition of neurite outgrowth. Conclusions and Significance When measured against multiple endpoints, SMF elicited qualitatively similar responses as ZM241385, a PD drug candidate. Provided that the in vitro results presented in this paper apply in vivo, SMF holds promise as an intriguing non-invasive approach to treat PD and potentially other neurological disorders. PMID:21079735

  6. Establishing research priorities for patient safety in emergency medicine: a multidisciplinary consensus panel.

    Science.gov (United States)

    Plint, Amy C; Stang, Antonia S; Calder, Lisa A

    2015-01-01

    Patient safety in the context of emergency medicine is a relatively new field of study. To date, no broad research agenda for patient safety in emergency medicine has been established. The objective of this study was to establish patient safety-related research priorities for emergency medicine. These priorities would provide a foundation for high-quality research, important direction to both researchers and health-care funders, and an essential step in improving health-care safety and patient outcomes in the high-risk emergency department (ED) setting. A four-phase consensus procedure with a multidisciplinary expert panel was organized to identify, assess, and agree on research priorities for patient safety in emergency medicine. The 19-member panel consisted of clinicians, administrators, and researchers from adult and pediatric emergency medicine, patient safety, pharmacy, and mental health; as well as representatives from patient safety organizations. In phase 1, we developed an initial list of potential research priorities by electronically surveying a purposeful and convenience sample of patient safety experts, ED clinicians, administrators, and researchers from across North America using contact lists from multiple organizations. We used simple content analysis to remove duplication and categorize the research priorities identified by survey respondents. Our expert panel reached consensus on a final list of research priorities through an in-person meeting (phase 3) and two rounds of a modified Delphi process (phases 2 and 4). After phases 1 and 2, 66 unique research priorities were identified for expert panel review. At the end of phase 4, consensus was reached for 15 research priorities. These priorities represent four themes: (1) methods to identify patient safety issues (five priorities), (2) understanding human and environmental factors related to patient safety (four priorities), (3) the patient perspective (one priority), and (4) interventions for

  7. Cyclic delivery scheduling to customers with different priorities

    Directory of Open Access Journals (Sweden)

    Katarzyna Zofia Gdowska

    2013-12-01

    Full Text Available Background: In this paper a cyclic delivery scheduling problem for customers with different priorities is presented. Shops, which are provided with deliveries, are occasionally located in places which are crucial for the proper flow of traffic. In such places coordination of deliveries is crucial; therefore it allows to completely eliminate the phenomenon of the simultaneous arrivals of suppliers. Methods: In this paper the cyclic delivery scheduling problem for customers with different priorities was presented. To this theoretical problem a mix integer programming model was developed. Specific approach to the cyclic delivery scheduling problem is inspired by timetabling problem for urban public transport. Results: Mixed integer programming model was employed for solving four cases of cyclic delivery scheduling problem for customers with different priorities. When the value of the synchronization priority assigned to a single customer raised then the total number of synchronizations in the whole network decreased. In order to compare solutions a synchronization rate was utilized. A simple factor was utilized - the proportion of number of synchronizations of deliveries to a given customer to the total number of synchronizations obtained for the whole network. When the value of synchronization priority raised then the value of synchronization rate of this customer improved significantly. Conclusions: The mixed integer programming model for the cyclic delivery scheduling problem for customers with different priorities presented in this paper can be utilized for generating schedules of serving customers located in places where only one delivery can be received and unloaded at one go and where there is no space for other suppliers to wait in a queue. Such a schedule can be very useful for organizing deliveries to small shops united in a franchising network, since they operate in a way that is very similar to the network presented in this paper

  8. Exploring Citizen Infrastructure and Environmental Priorities in Mumbai, India

    Energy Technology Data Exchange (ETDEWEB)

    Sperling, Joshua; Romero-Lankao, Patricia; Beig, Gufran

    2016-06-01

    Many cities worldwide seek to understand local policy priorities among their general populations. This study explores how differences in local conditions and among citizens within and across Mumbai, India shape local infrastructure (e.g. energy, water, transport) and environmental (e.g. managing pollution, climate-related extreme weather events) policy priorities for change that may or may not be aligned with local government action or global environmental sustainability concerns such as low-carbon development. In this rapidly urbanizing city, multiple issues compete for prominence, ranging from improved management of pollution and extreme weather to energy and other infrastructure services. To inform a broader perspective of policy priorities for urban development and risk mitigation, a survey was conducted among over 1200 citizens. The survey explored the state of local conditions, the challenges citizens face, and the ways in which differences in local conditions (socio-institutional, infrastructure, and health-related) demonstrate inequities and influence how citizens perceive risks and rank priorities for the future design and implementation of local planning, policy, and community-based efforts. With growing discussion and tensions surrounding the new urban sustainable development goal, announced by the UN in late September 2015, and a new global urban agenda document to be agreed upon at 'Habitat III', issues on whether sustainable urbanization priorities should be set at the international, national or local level remain controversial. As such, this study aims to first understand determinants of and variations in local priorities across one city, with implications discussed for local-to-global urban sustainability. Findings from survey results indicate the determinants and variation in conditions such as age, assets, levels of participation in residential action groups, the health outcome of chronic asthma, and the infrastructure service of piped

  9. Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance

    Directory of Open Access Journals (Sweden)

    Anna E. Maciag

    2013-01-01

    Full Text Available JS-K is a nitric oxide (NO-releasing prodrug of the O2-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models both in vitro and in vivo. The current study of the metabolic actions of JS-K was undertaken to investigate mechanisms of its cytotoxicity. Consistent with model chemical reactions, the activating step in the metabolism of JS-K in the cell is the dearylation of the diazeniumdiolate by glutathione (GSH via a nucleophilic aromatic substitution reaction. The resulting product (CEP/NO anion spontaneously hydrolyzes, releasing two equivalents of NO. The GSH/GSSG redox couple is considered to be the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. We have quantified the effects of JS-K on cellular GSH content, and show that JS-K markedly depletes GSH, due to JS-K's rapid uptake and cascading release of NO and reactive nitrogen species. The depletion of GSH results in alterations in the redox potential of the cellular environment, initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing agent N-acetylcysteine prevented the signaling events that lead to apoptosis. These data indicate that multiplicative depletion of the reduced glutathione pool and deregulation of intracellular redox balance are important initial steps in the mechanism of JS-K's cytotoxic action.

  10. 47 CFR 22.909 - Cellular markets.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets...

  11. A Pulmonary Rehabilitation Decisional Score to Define Priority Access for COPD Patients

    Directory of Open Access Journals (Sweden)

    Michele Vitacca

    2017-01-01

    Full Text Available This retrospective study aimed to evaluate, through an ad hoc 17-item tool, the Pulmonary Rehabilitation Decisional Score (PRDS, the priority access to PR prescription by respiratory specialists. The PRDS, scoring functional, clinical, disability, frailty, and participation parameters from 0 = low priority to 34 = very high priority for PR access, was retrospectively calculated on 124 specialist reports sent to the GP of subjects (aged 71±11 years, FEV1%  51±17 consecutively admitted to our respiratory outpatient clinic. From the specialist’s report the final subject’s allocation could be low priority (LP (>60 days, high priority (HP (30–60 days, or very high priority (VHP (<30 days to rehabilitation. The PRDS calculation showed scores significantly higher in VHP versus LP (p<0.001 and significantly different between HP and VHP (p<0.001. Comparing the specialist’s allocation decision and priority choice based on PRDS cut-offs, PR prescription was significantly more appropriate in VHP than in HP (p=0.016. Specialists underprescribed PR in 49% of LP cases and overprescribed it in 46% and 30% of the HP and VHP prescriptions, respectively. A multicomprehensive score is feasible being useful for staging the clinical priorities for PR prescription and facilitating sustainability of the health system.

  12. Here, there be dragons: charting autophagy-related alterations in human tumors.

    Science.gov (United States)

    Lebovitz, Chandra B; Bortnik, Svetlana B; Gorski, Sharon M

    2012-03-01

    Macroautophagy (or autophagy) is a catabolic cellular process that is both homeostatic and stress adaptive. Normal cells rely on basal levels of autophagy to maintain cellular integrity (via turnover of long-lived proteins and damaged organelles) and increased levels of autophagy to buoy cell survival during various metabolic stresses (via nutrient and energy provision through lysosomal degradation of cytoplasmic components). Autophagy can function in both tumor suppression and tumor progression, and is under investigation in clinical trials as a novel target for anticancer therapy. However, its role in cancer pathogenesis has yet to be fully explored. In particular, it remains unknown whether in vitro observations will be applicable to human cancer patients. Another outstanding question is whether there exists tumor-specific selection for alterations in autophagy function. In this review, we survey reported mutations in autophagy genes and key autophagy regulators identified in human tumor samples and summarize the literature regarding expression levels of autophagy genes and proteins in various cancer tissues. Although it is too early to draw inferences from this collection of in vivo studies of autophagy-related alterations in human cancers, their results highlight the challenges that must be overcome before we can accurately assess the scope of autophagy's predicted role in tumorigenesis.

  13. Health Priorities in French-Speaking Swiss Cantons

    Directory of Open Access Journals (Sweden)

    Philippe Chastonay

    2018-01-01

    Full Text Available In Switzerland, the federal authorities, the cantons, and the communes share the responsibility of healthcare, disease prevention and health promotion policies. Yet, the cantons are in most health matters independent in their decisions, thus defining as a matter of fact their own health priorities. We examined and analysed the content of the disease prevention and health promotion plans elaborated during the last decade in six French-speaking cantons with different political contexts and resources, but quite similar population health data, in order to identify the set health priorities. The plans appear significantly inhomogeneous in their structure, scope and priorities. Most of the formal documents are short, in the 16 to 40 pages range. Core values such as equity, solidarity and sustainability are explicitly put forward in 2/6 cantonal plans. Priority health issues shared by all 6 cantons are “physical activity/sedentariness” and “nutrition/food.” Mental health is explicitly mentioned in 5 cantonal plans, whereas tobacco and alcohol consumptions are mentioned 4 times. Less attention has been given to topics that appear as major public health challenges at present and in the future in Switzerland, eg, ageing of the population, rise of social inequalities, increase of vulnerable populations. Little attention has also been paid to issues like domestic violence or healthy work environments. Despite some heterogeneity, there is a common base that should make inter-cantonal collaborations possible and coordination with national strategies easily feasible.

  14. ENTREPRENEURIAL ACTIVITY IN THE CONDITIONS OF PRIORITY DEVELOPMENT AREAS

    Directory of Open Access Journals (Sweden)

    E. V. Gruzdeva

    2016-01-01

    Full Text Available This article presents an analysis of the most important issues in priority development areas, including the commitment of the Kamchatka region in which such territory is focused primarily on the development of tourism. The relevance of the article due to the increase in the activity of creation of territories of operahouse development in Russia.Goal/objectives. The purpose of this article is to identify both advantages and disadvantages of priority development areas as a mechanism of economic development. To achieve this goal, the author formulated and solved two tasks – analysis of theoretical questions of development of territories of priority development and evaluation of a practical example of creating such a site.Methodology. The theoretical basis of the research was normative legal acts devoted to the question of priority development areas and strategic documents of the Kamchatka region. As a methodological basis of applied methods: analysis, synthesis, analogy, comparison, induction and deduction.Results. Found that despite the existing shortcomings and limitations, the creation of territories of priority development is an eff ective tool for the development of entrepreneurship.Conclusions/significance. Creation within the country's territory, favorable for attracting long-term investment, is a widespread global practice to attract large companies. In Russia, this tool is relatively new, but is already actively used for the development of entrepreneurial activities in troubled regions.This tool provides its residents with sufficient opportunities to gain competitive advantage, accordingly, is a critical study of all questions of implementation and follow-up work of priority development areas, given companies' business activities both within and outside the area.

  15. Setting health priorities in a community: a case example

    Directory of Open Access Journals (Sweden)

    Fábio Alexandre Melo do Rego Sousa

    Full Text Available ABSTRACT OBJECTIVE To describe the methodology used in the process of setting health priorities for community intervention in a community of older adults. METHODS Based on the results of a health diagnosis related to active aging, a prioritization process was conceived to select the priority intervention problem. The process comprised four successive phases of problem analysis and classification: (1 grouping by level of similarity, (2 classification according to epidemiological criteria, (3 ordering by experts, and (4 application of the Hanlon method. These stages combined, in an integrated manner, the views of health team professionals, community nursing and gerontology experts, and the actual community. RESULTS The first stage grouped the identified problems by level of similarity, comprising a body of 19 issues for analysis. In the second stage these problems were classified by the health team members by epidemiological criteria (size, vulnerability, and transcendence. The nine most relevant problems resulting from the second stage of the process were submitted to expert analysis and the five most pertinent problems were selected. The last step identified the priority issue for intervention in this specific community with the participation of formal and informal community leaders: Low Social Interaction in Community Participation. CONCLUSIONS The prioritization process is a key step in health planning, enabling the identification of priority problems to intervene in a given community at a given time. There are no default formulas for selecting priority issues. It is up to each community intervention team to define its own process with different methods/techniques that allow the identification of and intervention in needs classified as priority by the community.

  16. Public Issue Priority Formation: Media Agenda-Setting and Social Interaction.

    Science.gov (United States)

    Zhu, Jian-Hua; And Others

    1993-01-01

    Presents a mathematical model to explain the public's issue priority by integrating media agenda-setting and social interaction. Finds that the public's issue priority was influenced by both media and social interaction. (RS)

  17. Selective mRNA translation coordinates energetic and metabolic adjustments to cellular oxygen deprivation and reoxygenation in Arabidopsis thaliana.

    Science.gov (United States)

    Branco-Price, Cristina; Kaiser, Kayla A; Jang, Charles J H; Larive, Cynthia K; Bailey-Serres, Julia

    2008-12-01

    Cellular oxygen deprivation (hypoxia/anoxia) requires an acclimation response that enables survival during an energy crisis. To gain new insights into the processes that facilitate the endurance of transient oxygen deprivation, the dynamics of the mRNA translation state and metabolites were quantitatively monitored in Arabidopsis thaliana seedlings exposed to a short (2 h) or prolonged (9 h) period of oxygen and carbon dioxide deprivation and following 1 h of re-aeration. Hypoxia stress and reoxygenation promoted adjustments in the levels of polyribosomes (polysomes) that were highly coordinated with cellular ATP content. A quantitative comparison of steady-state and polysomal mRNA populations revealed that over half of the cellular mRNAs were restricted from polysome complexes during the stress, with little or no change in abundance. This selective repression of translation was rapidly reversed upon reoxygenation. Comparison of the adjustment in gene transcripts and metabolites demonstrated that profiling of polysomal mRNAs strongly augments the prediction of cellular processes that are altered during cellular oxygen deprivation. The selective translation of a subset of mRNAs promotes the conservation of ATP and facilitates the transition to anaerobic metabolism during low-oxygen stress.

  18. Priority pricing in electricity supply. An application for Israel

    Energy Technology Data Exchange (ETDEWEB)

    Beenstock, Michael; Goldin, Ephraim [Hebrew University of Jerusalem, Department of Economics, Mount Scopus, Jerusalem (Israel)

    1997-06-01

    It is well known that in the event of a shortage in generation capacity, it is inefficient if the electricity utility cuts off customers randomly. It is preferable to set up a market in service priority in which customers who have a greater need pay more for the right not to be cut off. We use an econometric model of outage costs in Israel to calculate the menu of priority rates by season and time of day. Top priority rates range from zero, when the loss-of-load probability (LOLP) is zero, to 8 cents (US) per kWh when the LOLP is greatest

  19. Inhibition of the alpha-ketoglutarate dehydrogenase complex alters mitochondrial function and cellular calcium regulation.

    Science.gov (United States)

    Huang, Hsueh-Meei; Zhang, Hui; Xu, Hui; Gibson, Gary E

    2003-01-20

    Mitochondrial dysfunction occurs in many neurodegenerative diseases. The alpha-ketoglutarate dehydrogenase complex (KGDHC) catalyzes a key and arguably rate-limiting step of the tricarboxylic acid cycle (TCA). A reduction in the activity of the KGDHC occurs in brains and cells of patients with many of these disorders and may underlie the abnormal mitochondrial function. Abnormalities in calcium homeostasis also occur in fibroblasts from Alzheimer's disease (AD) patients and in cells bearing mutations that lead to AD. Thus, the present studies test whether the reduction of KGDHC activity can lead to the alterations in mitochondrial function and calcium homeostasis. alpha-Keto-beta-methyl-n-valeric acid (KMV) inhibits KGDHC activity in living N2a cells in a dose- and time-dependent manner. Surprisingly, concentration of KMV that inhibit in situ KGDHC by 80% does not alter the mitochondrial membrane potential (MMP). However, similar concentrations of KMV induce the release of cytochrome c from mitochondria into the cytosol, reduce basal [Ca(2+)](i) by 23% (Pcalcium release from the endoplasmic reticulum (ER) by 46% (P<0.005). This result suggests that diminished KGDHC activities do not lead to the Ca(2+) abnormalities in fibroblasts from AD patients or cells bearing PS-1 mutations. The increased release of cytochrome c with diminished KGDHC activities will be expected to activate other pathways including cell death cascades. Reductions in this key mitochondrial enzyme will likely make the cells more vulnerable to metabolic insults that promote cell death.

  20. Lymphocyte maintenance during healthy aging requires no substantial alterations in cellular turnover.

    Science.gov (United States)

    Westera, Liset; van Hoeven, Vera; Drylewicz, Julia; Spierenburg, Gerrit; van Velzen, Jeroen F; de Boer, Rob J; Tesselaar, Kiki; Borghans, José A M

    2015-04-01

    In healthy humans, lymphocyte populations are maintained at a relatively constant size throughout life, reflecting a balance between lymphocyte production and loss. Given the profound immunological changes that occur during healthy aging, including a significant decline in T-cell production by the thymus, lymphocyte maintenance in the elderly is generally thought to require homeostatic alterations in lymphocyte dynamics. Surprisingly, using in vivo (2) H2 O labeling, we find similar dynamics of most lymphocyte subsets between young adult and elderly healthy individuals. As the contribution of thymic output to T-cell production is only minor from young adulthood onward, compensatory increases in peripheral T-cell division rates are not required to maintain the T-cell pool, despite a tenfold decline in thymic output. These fundamental insights will aid the interpretation of further research into aging and clinical conditions related to disturbed lymphocyte dynamics. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  1. Ethanol alters cellular activation and CD14 partitioning in lipid rafts

    International Nuclear Information System (INIS)

    Dai Qun; Zhang Jun; Pruett, Stephen B.

    2005-01-01

    Alcohol consumption interferes with innate immunity. In vivo EtOH administration suppresses cytokine responses induced through Toll-like receptor 4 (TLR4) and inhibits TLR4 signaling. Actually, EtOH exhibits a generalized suppressive effect on signaling and cytokine responses induced by through most TLRs. However, the underlying mechanism remains unknown. RAW264.7 cells were treated with LPS or co-treated with EtOH or with lipid raft-disrupting drugs. TNF-α production, IRAK-1 activation, and CD14 partition were evaluated. EtOH or nystatin, a lipid raft-disrupting drug, suppressed LPS-induced production of TNF-α. The suppressive effect of EtOH on LPS-induced TNF-α production was additive with that of methyl-β-cyclodextrin (MCD), another lipid raft-disrupting drug. EtOH interfered with IRAK-1 activation, an early TLR4 intracellular signaling event. Cell fractionation analyses show that acute EtOH altered LPS-related partition of CD14, a critical component of the LPS receptor complex. These results suggest a novel mechanism of EtOH action that involves interference with lipid raft clustering induced by LPS. This membrane action of EtOH might be one of the mechanisms by which EtOH acts as a generalized suppressor for TLR signaling

  2. Priorities for family building among patients and partners seeking treatment for infertility.

    Science.gov (United States)

    Duthie, Elizabeth A; Cooper, Alexandra; Davis, Joseph B; Sandlow, Jay; Schoyer, Katherine D; Strawn, Estil; Flynn, Kathryn E

    2017-04-05

    Infertility treatment decisions require people to balance multiple priorities. Within couples, partners must also negotiate priorities with one another. In this study, we assessed the family-building priorities of couples prior to their first consultations with a reproductive specialist. Participants were couples who had upcoming first consultations with a reproductive specialist (N = 59 couples (59 women; 59 men)). Prior to the consultation, couples separately completed the Family-Building Priorities Tool, which tasked them with ranking from least to most important 10 factors associated with family building. We describe the highest (top three) and lowest (bottom three) priorities, the alignment of priorities within couples, and test for differences in prioritization between men and women within couples (Wilcoxon signed rank test). Maintaining a close and satisfying relationship with one's partner was ranked as a high priority by majorities of men and women, and in 25% of couples, both partners ranked this factor as their most important priority for family building. Majorities of men and women also ranked building a family in a way that does not make infertility obvious to others as a low priority, and in 27% of couples, both partners ranked this factor as the least important priority for family building. There were also differences within couples that involved either men or women ranking a particular goal more highly than their partners. More women ranked two factors higher than did their partners: 1) that I become a parent one way or another (p = 0.015) and 2) that I have a child in the next year or two (p maintain a close relationship with my partner (p = 0.034), and 4) that I avoid side effects from treatment (p building paths should be aware that: (1) patients balance multiple priorities as a part of, or beside, becoming a parent; and (2) patients and their partners may not be aligned in their prioritization of achieving parenthood. For

  3. Setting Healthcare Priorities at the Macro and Meso Levels: A Framework for Evaluation.

    Science.gov (United States)

    Barasa, Edwine W; Molyneux, Sassy; English, Mike; Cleary, Susan

    2015-09-16

    Priority setting in healthcare is a key determinant of health system performance. However, there is no widely accepted priority setting evaluation framework. We reviewed literature with the aim of developing and proposing a framework for the evaluation of macro and meso level healthcare priority setting practices. We systematically searched Econlit, PubMed, CINAHL, and EBSCOhost databases and supplemented this with searches in Google Scholar, relevant websites and reference lists of relevant papers. A total of 31 papers on evaluation of priority setting were identified. These were supplemented by broader theoretical literature related to evaluation of priority setting. A conceptual review of selected papers was undertaken. Based on a synthesis of the selected literature, we propose an evaluative framework that requires that priority setting practices at the macro and meso levels of the health system meet the following conditions: (1) Priority setting decisions should incorporate both efficiency and equity considerations as well as the following outcomes; (a) Stakeholder satisfaction, (b) Stakeholder understanding, (c) Shifted priorities (reallocation of resources), and (d) Implementation of decisions. (2) Priority setting processes should also meet the procedural conditions of (a) Stakeholder engagement, (b) Stakeholder empowerment, (c) Transparency, (d) Use of evidence, (e) Revisions, (f) Enforcement, and (g) Being grounded on community values. Available frameworks for the evaluation of priority setting are mostly grounded on procedural requirements, while few have included outcome requirements. There is, however, increasing recognition of the need to incorporate both consequential and procedural considerations in priority setting practices. In this review, we adapt an integrative approach to develop and propose a framework for the evaluation of priority setting practices at the macro and meso levels that draws from these complementary schools of thought. © 2015

  4. Setting Healthcare Priorities at the Macro and Meso Levels: A Framework for Evaluation

    Science.gov (United States)

    Barasa, Edwine W.; Molyneux, Sassy; English, Mike; Cleary, Susan

    2015-01-01

    Background: Priority setting in healthcare is a key determinant of health system performance. However, there is no widely accepted priority setting evaluation framework. We reviewed literature with the aim of developing and proposing a framework for the evaluation of macro and meso level healthcare priority setting practices. Methods: We systematically searched Econlit, PubMed, CINAHL, and EBSCOhost databases and supplemented this with searches in Google Scholar, relevant websites and reference lists of relevant papers. A total of 31 papers on evaluation of priority setting were identified. These were supplemented by broader theoretical literature related to evaluation of priority setting. A conceptual review of selected papers was undertaken. Results: Based on a synthesis of the selected literature, we propose an evaluative framework that requires that priority setting practices at the macro and meso levels of the health system meet the following conditions: (1) Priority setting decisions should incorporate both efficiency and equity considerations as well as the following outcomes; (a) Stakeholder satisfaction, (b) Stakeholder understanding, (c) Shifted priorities (reallocation of resources), and (d) Implementation of decisions. (2) Priority setting processes should also meet the procedural conditions of (a) Stakeholder engagement, (b) Stakeholder empowerment, (c) Transparency, (d) Use of evidence, (e) Revisions, (f) Enforcement, and (g) Being grounded on community values. Conclusion: Available frameworks for the evaluation of priority setting are mostly grounded on procedural requirements, while few have included outcome requirements. There is, however, increasing recognition of the need to incorporate both consequential and procedural considerations in priority setting practices. In this review, we adapt an integrative approach to develop and propose a framework for the evaluation of priority setting practices at the macro and meso levels that draws from these

  5. Setting Healthcare Priorities at the Macro and Meso Levels: A Framework for Evaluation

    Directory of Open Access Journals (Sweden)

    Edwine W. Barasa

    2015-11-01

    Full Text Available Background Priority setting in healthcare is a key determinant of health system performance. However, there is no widely accepted priority setting evaluation framework. We reviewed literature with the aim of developing and proposing a framework for the evaluation of macro and meso level healthcare priority setting practices. Methods We systematically searched Econlit, PubMed, CINAHL, and EBSCOhost databases and supplemented this with searches in Google Scholar, relevant websites and reference lists of relevant papers. A total of 31 papers on evaluation of priority setting were identified. These were supplemented by broader theoretical literature related to evaluation of priority setting. A conceptual review of selected papers was undertaken. Results Based on a synthesis of the selected literature, we propose an evaluative framework that requires that priority setting practices at the macro and meso levels of the health system meet the following conditions: (1 Priority setting decisions should incorporate both efficiency and equity considerations as well as the following outcomes; (a Stakeholder satisfaction, (b Stakeholder understanding, (c Shifted priorities (reallocation of resources, and (d Implementation of decisions. (2 Priority setting processes should also meet the procedural conditions of (a Stakeholder engagement, (b Stakeholder empowerment, (c Transparency, (d Use of evidence, (e Revisions, (f Enforcement, and (g Being grounded on community values. Conclusion Available frameworks for the evaluation of priority setting are mostly grounded on procedural requirements, while few have included outcome requirements. There is, however, increasing recognition of the need to incorporate both consequential and procedural considerations in priority setting practices. In this review, we adapt an integrative approach to develop and propose a framework for the evaluation of priority setting practices at the macro and meso levels that draws from

  6. Research Priorities for Business Education

    Science.gov (United States)

    Schultheis, Robert A.

    1971-01-01

    Most pressing problems representing research priorities for the business education profession do not fit into such narrow functional categories as typewriting and shorthand. Rather the problems critical to survival of our discipline in the decade ahead are more of an interdisciplinary nature. (Author)

  7. TALENT MANAGEMENT - A STRATEGIC PRIORITY

    Directory of Open Access Journals (Sweden)

    Matei Mirabela-Constanta

    2009-05-01

    Full Text Available Companies facing the new economic world, dominated by demographic, macroeconomic, and technological changes need to see talent management as a business priority in order to survive. At the same time, the world economic crisis ads pressure over managers, f

  8. Involving patients in setting priorities for healthcare improvement: a cluster randomized trial.

    Science.gov (United States)

    Boivin, Antoine; Lehoux, Pascale; Lacombe, Réal; Burgers, Jako; Grol, Richard

    2014-02-20

    Patients are increasingly seen as active partners in healthcare. While patient involvement in individual clinical decisions has been extensively studied, no trial has assessed how patients can effectively be involved in collective healthcare decisions affecting the population. The goal of this study was to test the impact of involving patients in setting healthcare improvement priorities for chronic care at the community level. Cluster randomized controlled trial. Local communities were randomized in intervention (priority setting with patient involvement) and control sites (no patient involvement). Communities in a canadian region were required to set priorities for improving chronic disease management in primary care, from a list of 37 validated quality indicators. Patients were consulted in writing, before participating in face-to-face deliberation with professionals. Professionals established priorities among themselves, without patient involvement. A total of 172 individuals from six communities participated in the study, including 83 chronic disease patients, and 89 health professionals. The primary outcome was the level of agreement between patients' and professionals' priorities. Secondary outcomes included professionals' intention to use the selected quality indicators, and the costs of patient involvement. Priorities established with patients were more aligned with core generic components of the Medical Home and Chronic Care Model, including: access to primary care, self-care support, patient participation in clinical decisions, and partnership with community organizations (p Priorities established by professionals alone placed more emphasis on the technical quality of single disease management. The involvement intervention fostered mutual influence between patients and professionals, which resulted in a 41% increase in agreement on common priorities (95%CI: +12% to +58%, p priorities. Patient involvement can change priorities driving healthcare

  9. Sources of unbounded priority inversions in real-time systems and a comparative study of possible solutions

    Science.gov (United States)

    Davari, Sadegh; Sha, Lui

    1992-01-01

    In the design of real-time systems, tasks are often assigned priorities. Preemptive priority driven schedulers are used to schedule tasks to meet the timing requirements. Priority inversion is the term used to describe the situation when a higher priority task's execution is delayed by lower priority tasks. Priority inversion can occur when there is contention for resources among tasks of different priorities. The duration of priority inversion could be long enough to cause tasks to miss their dead lines. Priority inversion cannot be completely eliminated. However, it is important to identify sources of priority inversion and minimize the duration of priority inversion. In this paper, a comprehensive review of the problem of and solutions to unbounded priority inversion is presented.

  10. Priority-setting in health systems

    DEFF Research Database (Denmark)

    Byskov, Jens

    2013-01-01

    improvements work similarly in the vast array of social and other local contextual factors. Local, fair and accountable priority setting processes are neccessary to make the best of ever shifting national level strategies and priorities. An approach is described, which can assist in the involvement......DBL - under core funding from Danish International Development Agency (Danida) 2013 WHY HAVE HEALTH SYSTEMS WHEN EFFECTIVE INTERVENTIONS ARE KNOWN? Case: A teenage mother lives in a poor sub-Saharan village next to a big lake. The area is known to have malaria transmission all year around......, and surveys in nearby villages have shown a high prevalence of intestinal helminthiasis and schistosomiasis. The HIV prevalence in similar rural settings is about 10% in her age group. She has been losing weight over the last months and now her one-year-old child feels hot and is not eating well. She has...

  11. Prostate Cancer: Epigenetic Alterations, Risk Factors, and Therapy

    Directory of Open Access Journals (Sweden)

    Mankgopo M. Kgatle

    2016-01-01

    Full Text Available Prostate cancer (PCa is the most prevalent urological cancer that affects aging men in South Africa, and mechanisms underlying prostate tumorigenesis remain elusive. Research advancements in the field of PCa and epigenetics have allowed for the identification of specific alterations that occur beyond genetics but are still critically important in the pathogenesis of tumorigenesis. Anomalous epigenetic changes associated with PCa include histone modifications, DNA methylation, and noncoding miRNA. These mechanisms regulate and silence hundreds of target genes including some which are key components of cellular signalling pathways that, when perturbed, promote tumorigenesis. Elucidation of mechanisms underlying epigenetic alterations and the manner in which these mechanisms interact in regulating gene transcription in PCa are an unmet necessity that may lead to novel chemotherapeutic approaches. This will, therefore, aid in developing combination therapies that will target multiple epigenetic pathways, which can be used in conjunction with the current conventional PCa treatment.

  12. Application of economic principles in healthcare priority setting.

    Science.gov (United States)

    Bate, Angela; Mitton, Craig

    2006-06-01

    In healthcare, resources are often insufficient to meet all claims on them. In this respect, resources are considered scarce and have to be managed by prioritizing between competing claims. Economics as a discipline explicitly addresses this reality by acknowledging resource scarcity. However, the extent to which economics actually influences such prioritizing decisions in healthcare is unclear. The purpose of this paper is to review the use of economics in priority setting decision making. We outline the key principles of economics as they apply to priority setting and review the methods reported in the literature with respect to these. We find that these methods, even economic methods (e.g., those typically used in conducting economic evaluations such as cost-effectiveness analyses) do not tend to explicitly incorporate economic principles. We argue therefore that these methods, when applied to the context of priority setting, are not sufficient and that what is required is a broader framework that can incorporate the output from economic methods yet also be pragmatically applicable. We then go on to present an alternative approach - namely program budgeting and marginal analysis. Finally, we put forward our case for using program budgeting and marginal analysis in priority setting practice and set out some future research challenges.

  13. Priority pollutant analysis of MHD-derived combustion products

    Science.gov (United States)

    Parks, Katherine D.

    An important factor in developing Magnetohydrodynamics (MHD) for commercial applications is environmental impact. Consequently, an effort was initiated to identify and quantify any possible undesirable minute chemical constituents in MHD waste streams, with special emphasis on the priority pollutant species. This paper discusses how priority pollutant analyses were used to accomplish the following goals at the University of Tennessee Space Institute (UTSI): comparison of the composition of solid combustion products collected from various locations along a prototypical MHD flow train during the firing of Illinois No. 6 and Montana Rosebud coals; comparison of solid waste products generated from MHD and conventional power plant technologies; and identification of a suitable disposal option for various MHD derived combustion products. Results from our ongoing research plans for gas phase sampling and analysis of priority pollutant volatiles, semi-volatiles, and metals are discussed.

  14. Biomechanics of cellular solids.

    Science.gov (United States)

    Gibson, Lorna J

    2005-03-01

    Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

  15. DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

    Directory of Open Access Journals (Sweden)

    Mankgopo Magdeline Kgatle

    2017-01-01

    Full Text Available Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV, hepatitis B virus (HBV, and Epstein-Barr virus (EBV. Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.

  16. 40 CFR 60.16 - Priority list.

    Science.gov (United States)

    2010-07-01

    ... PERFORMANCE FOR NEW STATIONARY SOURCES General Provisions § 60.16 Priority list. Prioritized Major Source... and Resins: Polyethylene 19. Charcoal Production 20. Synthetic Rubber (a) Tire manufacture (b) SBR...

  17. Exploring stakeholders' views of medical education research priorities: a national survey.

    Science.gov (United States)

    Dennis, Ashley A; Cleland, Jennifer A; Johnston, Peter; Ker, Jean S; Lough, Murray; Rees, Charlotte E

    2014-11-01

    Setting research priorities is important when exploring complex issues with limited resources. Only two countries (Canada and New Zealand) have previously conducted priority-setting exercises for medical education research (MER). This study aimed to identify the views of multiple stakeholders on MER priorities in Scotland. This study utilised a two-stage design to explore the views of stakeholders across the medical education continuum using online questionnaires. In Stage 1, key informants outlined their top three MER priorities and justified their choices. In Stage 2, participants rated 21 topics generated in Stage 1 according to importance and identified or justified their top priorities. A combination of qualitative (i.e. framework analysis) and quantitative (e.g. exploratory factor analysis) data analyses were employed. Views were gathered from over 1300 stakeholders. A total of 21 subthemes (or priority areas) identified in Stage 1 were explored further in Stage 2. The 21 items loaded onto five factors: the culture of learning together in the workplace; enhancing and valuing the role of educators; curriculum integration and innovation; bridging the gap between assessment and feedback, and building a resilient workforce. Within Stage 2, the top priority subthemes were: balancing conflicts between service and training; providing useful feedback; promoting resiliency and well-being; creating an effective workplace learning culture; selecting and recruiting doctors to reflect need, and ensuring that curricula prepare trainees for practice. Participant characteristics were related to the perceived importance of the factors. Finally, five themes explaining why participants prioritised items were identified: patient safety; quality of care; investing for the future; policy and political agendas, and evidence-based education. This study indicates that, across the spectrum of stakeholders and geography, certain MER priorities are consistently identified. These

  18. Priority Questions and Horizon Scanning for Conservation: A Comparative Study

    Science.gov (United States)

    Kark, Salit; Sutherland, William J.; Shanas, Uri; Klass, Keren; Achisar, Hila; Dayan, Tamar; Gavrieli, Yael; Justo-Hanani, Ronit; Mandelik, Yael; Orion, Nir; Pargament, David; Portman, Michelle; Reisman-Berman, Orna; Safriel, Uriel N.; Schaffer, Gad; Steiner, Noa; Tauber, Israel; Levin, Noam

    2016-01-01

    Several projects aimed at identifying priority issues for conservation with high relevance to policy have recently been completed in several countries. Two major types of projects have been undertaken, aimed at identifying (i) policy-relevant questions most imperative to conservation and (ii) horizon scanning topics, defined as emerging issues that are expected to have substantial implications for biodiversity conservation and policy in the future. Here, we provide the first overview of the outcomes of biodiversity and conservation-oriented projects recently completed around the world using this framework. We also include the results of the first questions and horizon scanning project completed for a Mediterranean country. Overall, the outcomes of the different projects undertaken (at the global scale, in the UK, US, Canada, Switzerland and in Israel) were strongly correlated in terms of the proportion of questions and/or horizon scanning topics selected when comparing different topic areas. However, some major differences were found across regions. There was large variation among regions in the percentage of proactive (i.e. action and response oriented) versus descriptive (non-response oriented) priority questions and in the emphasis given to socio-political issues. Substantial differences were also found when comparing outcomes of priority questions versus horizon scanning projects undertaken for the same region. For example, issues related to climate change, human demography and marine ecosystems received higher priority as horizon scanning topics, while ecosystem services were more emphasized as current priority questions. We suggest that future initiatives aimed at identifying priority conservation questions and horizon scanning topics should allow simultaneous identification of both current and future priority issues, as presented here for the first time. We propose that further emphasis on social-political issues should be explicitly integrated into future

  19. Cellular Reflectarray Antenna

    Science.gov (United States)

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  20. Towards human exploration of space: The THESEUS review series on nutrition and metabolism research priorities.

    Science.gov (United States)

    Bergouignan, Audrey; Stein, T Peter; Habold, Caroline; Coxam, Veronique; O' Gorman, Donal; Blanc, Stéphane

    2016-01-01

    Nutrition has multiple roles during space flight from providing sufficient nutrients to meet the metabolic needs of the body and to maintain good health, to the beneficial psychosocial aspects related to the meals. Nutrition is central to the functioning of the body; poor nutrition compromises all the physiological systems. Nutrition is therefore likely to have a key role in counteracting the negative effects of space flight (e.g., radiation, immune deficits, oxidative stress, and bone and muscle loss). As missions increase in duration, any dietary/nutritional deficiencies will become progressively more detrimental. Moreover, it has been recognized that the human diet contains, in addition to essential macronutrients, a complex array of naturally occurring bioactive micronutrients that may confer significant long-term health benefits. It is therefore critical that astronauts be adequately nourished during missions. Problems of nutritional origin are often treatable by simply providing the appropriate nutrients and adequate recommendations. This review highlights six key issues that have been identified as space research priorities in nutrition field: in-flight energy balance; altered feeding behavior; development of metabolic stress; micronutrient deficiency; alteration of gut microflora; and altered fluid and electrolytes balance. For each of these topics, relevance for space exploration, knowledge gaps and proposed investigations are described. Finally, the nutritional questions related to bioastronautics research are very relevant to multiple ground-based-related health issues. The potential spin-offs are both interesting scientifically and potentially of great clinical importance.

  1. Identifying national freshwater ecosystem priority areas

    CSIR Research Space (South Africa)

    Nel, JL

    2012-10-01

    Full Text Available This presentation highlights the use of systematic conservation planning to identify priority areas for managing the health of freshwater ecosystems and their associated biodiversity and ecosystem services....

  2. Political priorities

    DEFF Research Database (Denmark)

    Ren, Jingzheng

    2016-01-01

    …THE POLITICAL LEADERS of the local government of Chongqing, China, vigorously promote a low-carbon economy and sustainable development to mitigate environmental pollution. Accordingly, research grants focused on this issue were supported by the government, and our group obtained a grant for a pr......…THE POLITICAL LEADERS of the local government of Chongqing, China, vigorously promote a low-carbon economy and sustainable development to mitigate environmental pollution. Accordingly, research grants focused on this issue were supported by the government, and our group obtained a grant...... for a project about industrial park planning and design.…In my view, political priorities based on correct decision-making and market requirements are beneficial for researchers....

  3. Adamantyl Glycosphingolipids Provide a New Approach to the Selective Regulation of Cellular Glycosphingolipid Metabolism*

    OpenAIRE

    Kamani, Mustafa; Mylvaganam, Murugesapillai; Tian, Robert; Rigat, Brigitte; Binnington, Beth; Lingwood, Clifford

    2011-01-01

    Mammalian glycosphingolipid (GSL) precursor monohexosylceramides are either glucosyl- or galactosylceramide (GlcCer or GalCer). Most GSLs derive from GlcCer. Substitution of the GSL fatty acid with adamantane generates amphipathic mimics of increased water solubility, retaining receptor function. We have synthesized adamantyl GlcCer (adaGlcCer) and adamantyl GalCer (adaGalCer). AdaGlcCer and adaGalCer partition into cells to alter GSL metabolism. At low dose, adaGlcCer increased cellular GSLs...

  4. Linearizable cellular automata

    International Nuclear Information System (INIS)

    Nobe, Atsushi; Yura, Fumitaka

    2007-01-01

    The initial value problem for a class of reversible elementary cellular automata with periodic boundaries is reduced to an initial-boundary value problem for a class of linear systems on a finite commutative ring Z 2 . Moreover, a family of such linearizable cellular automata is given

  5. 32 CFR 245.21 - ESCAT air traffic priority list.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false ESCAT air traffic priority list. 245.21 Section 245.21 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS PLAN FOR THE EMERGENCY SECURITY CONTROL OF AIR TRAFFIC (ESCAT) ESCAT Air Traffic Priority List (EATPL) § 245.21 ESCAT air traffic...

  6. Electromagnetic cellular interactions.

    Science.gov (United States)

    Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

    2011-05-01

    Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Prior acetaminophen consumption impacts the early adaptive cellular response of human skeletal muscle to resistance exercise.

    Science.gov (United States)

    D'Lugos, Andrew C; Patel, Shivam H; Ormsby, Jordan C; Curtis, Donald P; Fry, Christopher S; Carroll, Chad C; Dickinson, Jared M

    2018-04-01

    Resistance exercise (RE) is a powerful stimulus for skeletal muscle adaptation. Previous data demonstrate that cyclooxygenase (COX)-inhibiting drugs alter the cellular mechanisms regulating the adaptive response of skeletal muscle. The purpose of this study was to determine whether prior consumption of the COX inhibitor acetaminophen (APAP) alters the immediate adaptive cellular response in human skeletal muscle after RE. In a double-blinded, randomized, crossover design, healthy young men ( n = 8, 25 ± 1 yr) performed two trials of unilateral knee extension RE (8 sets, 10 reps, 65% max strength). Subjects ingested either APAP (1,000 mg/6 h) or placebo (PLA) for 24 h before RE (final dose consumed immediately after RE). Muscle biopsies (vastus lateralis) were collected at rest and 1 h and 3 h after exercise. Mammalian target of rapamycin (mTOR) complex 1 signaling was assessed through immunoblot and immunohistochemistry, and mRNA expression of myogenic genes was examined via RT-qPCR. At 1 h p-rpS6 Ser240/244 was increased in both groups but to a greater extent in PLA. At 3 h p-S6K1 Thr389 was elevated only in PLA. Furthermore, localization of mTOR to the lysosome (LAMP2) in myosin heavy chain (MHC) II fibers increased 3 h after exercise only in PLA. mTOR-LAMP2 colocalization in MHC I fibers was greater in PLA vs. APAP 1 h after exercise. Myostatin mRNA expression was reduced 1 h after exercise only in PLA. MYF6 mRNA expression was increased 1 h and 3 h after exercise only in APAP. APAP consumption appears to alter the early adaptive cellular response of skeletal muscle to RE. These findings further highlight the mechanisms through which COX-inhibiting drugs impact the adaptive response of skeletal muscle to exercise. NEW & NOTEWORTHY The extent to which the cellular reaction to acetaminophen impacts the mechanisms regulating the adaptive response of human skeletal muscle to resistance exercise is not well understood. Consumption of acetaminophen before

  8. 12 CFR 360.3 - Priorities.

    Science.gov (United States)

    2010-01-01

    ... include wages or salaries of employees of the association; (3) Claims for wages and salaries, including... proved to the satisfaction of the receiver shall have priority in the following order: (1) Administrative... reasonable expenses incurred by employees which were authorized and reimbursable under a pre-existing expense...

  9. High priority tank sampling and analysis report

    International Nuclear Information System (INIS)

    Brown, T.M.

    1998-01-01

    In July 1993, the Defense Nuclear Facilities Board issued Recommendation 93-5 (Conway 1993) which noted that there was insufficient tank waste technical information and the pace to obtain it was too slow to ensure that Hanford Site wastes could be safely stored, that associated operations could be conducted safely, and that future disposal data requirements could be met. In response, the US Department of Energy, in May 1996, issued Revision 1 of the Recommendation 93-5 Implementation Plan (DOE-RL 1996). The Implementation Plan presented a modified approach to achieve the original plan's objectives, concentrating on actions necessary to ensure that wastes can be safely stored, that operations can be safely conducted, and that timely characterization information for the tank waste Disposal Program could be obtained. The Implementation Plan proposed 28 High Priority tanks for near term core sampling and analysis, which along with sampling and analysis of other non-High Priority tanks, could provide the scientific and technical data to confirm assumptions, calibrate models, and.measure safety related phenomenology of the waste. When the analysis results of the High Priority and other-tank sampling were reviewed, it was expected that a series of 12 questions, 9 related to safety issues and 3 related to planning for the disposal process, should be answered allowing key decisions to be made. This report discusses the execution of the Implementation Plan and the results achieved in addressing the questions. Through sampling and analysis, all nine safety related questions have been answered and extensive data for the three disposal planning related questions have been collected, allowing for key decision making. Many more tanks than the original 28 High Priority tanks identified in the Implementation Plan were sampled and analyzed. Twenty-one High Priority tanks and 85 other tanks were core sampled and used to address the questions. Thirty-eight additional tanks were auger

  10. Multilevel processor-sharing algorithm for M/G/1 systems with priorities

    Energy Technology Data Exchange (ETDEWEB)

    Yassouridis, A.; Koller, R.

    1983-01-01

    The well-known multilevel processor-sharing algorithm for M/G/1 systems without priorities is extended to M/G/1 systems with priority classes. The average response time t/sub j/(x) and the average waiting time w/sub j/(x) for a j-class job, which requires a total service of x sec, are analytically calculated. Some figures demonstrate how the priority classes and the total number of different levels affect the behaviour of the functions t/sub j/(x) and w/sub j/(x). In addition, the foreground-background algorithm with priorities, which is not yet covered in the literature, is treated as a special case of the multilevel processor-sharing algorithm. 8 references.

  11. A dynamically reconfigurable logic cell: from artificial neural networks to quantum-dot cellular automata

    Science.gov (United States)

    Naqvi, Syed Rameez; Akram, Tallha; Iqbal, Saba; Haider, Sajjad Ali; Kamran, Muhammad; Muhammad, Nazeer

    2018-02-01

    Considering the lack of optimization support for Quantum-dot Cellular Automata, we propose a dynamically reconfigurable logic cell capable of implementing various logic operations by means of artificial neural networks. The cell can be reconfigured to any 2-input combinational logic gate by altering the strength of connections, called weights and biases. We demonstrate how these cells may appositely be organized to perform multi-bit arithmetic and logic operations. The proposed work is important in that it gives a standard implementation of an 8-bit arithmetic and logic unit for quantum-dot cellular automata with minimal area and latency overhead. We also compare the proposed design with a few existing arithmetic and logic units, and show that it is more area efficient than any equivalent available in literature. Furthermore, the design is adaptable to 16, 32, and 64 bit architectures.

  12. Priority classes and weighted constrained equal awards rules for the claims problem

    DEFF Research Database (Denmark)

    Szwagrzak, Karol

    2015-01-01

    . They are priority-augmented versions of the standard weighted constrained equal awards rules, also known as weighted gains methods (Moulin, 2000): individuals are sorted into priority classes; the resource is distributed among the individuals in the first priority class using a weighted constrained equal awards...... rule; if some of the resource is left over, then it is distributed among the individuals in the second priority class, again using a weighted constrained equal awards rule; the distribution carries on in this way until the resource is exhausted. Our characterization extends to a generalized version...

  13. Best Practices and Processes for Choosing Research Priorities

    Science.gov (United States)

    Briscoe, M. G.

    2015-12-01

    Individuals, teams, departments, organizations, funding agencies, committees, and others all need to select desirable research priorities from many possible alternatives. One cannot do everything, one cannot afford everything, so what to select? Essays and reports since Weinberg (1963) have suggested criteria for choosing science topics. Popper et al (2000) reviewed and summarized all that had gone before in the subject of setting priorities; their main conclusions were that the underlying principles were the promotion of excellence and relevance. Sea Change (2015) from the NRC/OSB focused on four criteria. From most important to least important, they were transformative science, societal impacts, readiness, and partnership potential; these four criteria embodied the essence of the suggestions from Weinberg on, framed with the pragmatism of ORPISS (2007). Getting to the final set of priorities from many candidates involves a sequence of formal or informal processes, only the last of which is the application of the selected, weighted criteria. As developed by professional prioritization experts, the best-practice steps and processes are: Collection of input candidates from the community. Clustering and parsing/rephrasing of the input to eliminate redundancy and repetition and develop statements at a useful level of specificity. (NOTE:there is no counting of input to see how many times a particular topic was mentioned. The goal is diversity in the input, not a popularity contest.) Development of the selection criteria, and weighting the chosen criteria. Application of the selection criteria to the clustered/adjusted candidates. Finally, two more best practices: Do continuing sanity checks, to avoid losing sight of the goals of the effort. Resist the temptation to just sit around a table and talk about it to arrive at the priorities, which depends too much on who the specific members of the prioritization team are, and provides no transparency or explanation of why

  14. Research Priorities for NCD Prevention and Climate Change: An International Delphi Survey.

    Science.gov (United States)

    Colagiuri, Ruth; Boylan, Sinead; Morrice, Emily

    2015-10-16

    Climate change and non-communicable diseases (NCDs) are arguably the greatest global challenges of the 21st Century. However, the confluence between them remains under-examined and there is little evidence of a comprehensive, systematic approach to identifying research priorities to mitigate their joint impact. Consequently, we: (i) convened a workshop of academics (n = 25) from the Worldwide Universities Network to identify priority areas at the interface between NCDs and climate change; (ii) conducted a Delphi survey of international opinion leaders in public health and relevant other disciplines; and (iii) convened an expert panel to review and advise on final priorities. Three research areas (water security; transport; conceptualising NCD harms to support policy formation) were listed among the top 10 priorities by >90% of Delphi respondents, and ranked among the top 12 priorities by >60% of respondents who ranked the order of priority. A fourth area (reducing the carbon footprint of cities) was ranked highest by the same >60% of respondents. Our results are consistent with existing frameworks on health and climate change, and extends them by focusing specifically on NCDs. Researching these priorities could progress understanding of climate change and NCDs, and inform global and national policy decisions for mitigating associated harms.

  15. Research Priorities for NCD Prevention and Climate Change: An International Delphi Survey

    Directory of Open Access Journals (Sweden)

    Ruth Colagiuri

    2015-10-01

    Full Text Available Climate change and non-communicable diseases (NCDs are arguably the greatest global challenges of the 21st Century. However, the confluence between them remains under-examined and there is little evidence of a comprehensive, systematic approach to identifying research priorities to mitigate their joint impact. Consequently, we: (i convened a workshop of academics (n = 25 from the Worldwide Universities Network to identify priority areas at the interface between NCDs and climate change; (ii conducted a Delphi survey of international opinion leaders in public health and relevant other disciplines; and (iii convened an expert panel to review and advise on final priorities. Three research areas (water security; transport; conceptualising NCD harms to support policy formation were listed among the top 10 priorities by >90% of Delphi respondents, and ranked among the top 12 priorities by >60% of respondents who ranked the order of priority. A fourth area (reducing the carbon footprint of cities was ranked highest by the same >60% of respondents. Our results are consistent with existing frameworks on health and climate change, and extends them by focusing specifically on NCDs. Researching these priorities could progress understanding of climate change and NCDs, and inform global and national policy decisions for mitigating associated harms.

  16. 76 FR 396 - Product Change-Priority Mail-Non-Published Rates

    Science.gov (United States)

    2011-01-04

    ... POSTAL SERVICE Product Change--Priority Mail--Non-Published Rates AGENCY: Postal Service TM . ACTION: Notice. SUMMARY: Postal Service notice of filing of a request with the Postal Regulatory... States Postal Service Concerning Priority Mail--Non-Published Rates and Notice of Filing Materials Under...

  17. Wolbachia infect ovaries in the course of their maturation: last minute passengers and priority travellers?

    Directory of Open Access Journals (Sweden)

    Lise-Marie Genty

    Full Text Available Wolbachia are widespread endosymbiotic bacteria of arthropods and nematodes. Studies on such models suggest that Wolbachia's remarkable aptitude to infect offspring may rely on a re-infection of ovaries from somatic tissues instead of direct cellular segregation between oogonia and oocytes. In the terrestrial isopod Armadillidium vulgare, Wolbachia are vertically transmitted to the host offspring, even though ovary cells are cyclically renewed. Using Fluorescence in situ hybridization (FISH, we showed that the proportion of infected oocytes increased in the course of ovary and oocyte maturation, starting with 31.5% of infected oocytes only. At the end of ovary maturation, this proportion reached 87.6% for the most mature oocytes, which is close to the known transmission rate to offspring. This enrichment can be explained by a secondary acquisition of the bacteria by oocytes (Wolbachia can be seen as last minute passengers and/or by a preferential selection of oocytes infected with Wolbachia (as priority travellers.

  18. Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

    Science.gov (United States)

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2012-01-01

    Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

  19. Global research priorities for interpersonal violence prevention: a modified Delphi study.

    Science.gov (United States)

    Mikton, Christopher R; Tanaka, Masako; Tomlinson, Mark; Streiner, David L; Tonmyr, Lil; Lee, Bandy X; Fisher, Jane; Hegadoren, Kathy; Pim, Joam Evans; Wang, Shr-Jie Sharlenna; MacMillan, Harriet L

    2017-01-01

    To establish global research priorities for interpersonal violence prevention using a systematic approach. Research priorities were identified in a three-round process involving two surveys. In round 1, 95 global experts in violence prevention proposed research questions to be ranked in round 2. Questions were collated and organized according to the four-step public health approach to violence prevention. In round 2, 280 international experts ranked the importance of research in the four steps, and the various substeps, of the public health approach. In round 3, 131 international experts ranked the importance of detailed research questions on the public health step awarded the highest priority in round 2. In round 2, "developing, implementing and evaluating interventions" was the step of the public health approach awarded the highest priority for four of the six types of violence considered (i.e. child maltreatment, intimate partner violence, armed violence and sexual violence) but not for youth violence or elder abuse. In contrast, "scaling up interventions and evaluating their cost-effectiveness" was ranked lowest for all types of violence. In round 3, research into "developing, implementing and evaluating interventions" that addressed parenting or laws to regulate the use of firearms was awarded the highest priority. The key limitations of the study were response and attrition rates among survey respondents. However, these rates were in line with similar priority-setting exercises. These findings suggest it is premature to scale up violence prevention interventions. Developing and evaluating smaller-scale interventions should be the funding priority.

  20. Cellular studies and interaction mechanisms of extremely low frequency fields

    Science.gov (United States)

    Liburdy, Robert P.

    1995-01-01

    Worldwide interest in the biological effects of ELF (extremely low frequency, level is to identify cellular responses to ELF fields, to develop a dose threshold for such interactions, and with such information to formulate and test appropriate interaction mechanisms. This review is selective and will discuss the most recent cellular studies directed at these goals which relate to power line, sinusoidal ELF fields. In these studies an interaction site at the cell membrane is by consensus a likely candidate, since changes in ion transport, ligand-receptor events such as antibody binding, and G protein activation have been reported. These changes strongly indicate that signal transduction (ST) can be influenced. Also, ELF fields are reported to influence enzyme activation, gene expression, protein synthesis, and cell proliferation, which are triggered by earlier ST events at the cell membrane. The concept of ELF fields altering early cell membrane events and thereby influencing intracellular cell function via the ST cascade is perhaps the most plausible biological framework currently being investigated for understanding ELF effects on cells. For example, the consequence of an increase due to ELF fields in mitogenesis, the final endpoint of the ST cascade, is an overall increase in the probability of mutagenesis and consequently cancer, according to the Ames epigenetic model of carcinogenesis. Consistent with this epigenetic mechanism and the ST pathway to carcinogenesis is recent evidence that ELF fields can alter breast cancer cell proliferation and can act as a copromoter in vitro. The most important dosimetric question being addressed currently is whether the electric (E) or the magnetic (B) field, or if combinations of static B and time-varying B fields represent an exposure metric for the cell. This question relates directly to understanding fundamental interaction mechanisms and to the development of a rationale for ELF dose threshold guidelines. The weight of

  1. Conclusions on severe accident research priorities

    International Nuclear Information System (INIS)

    Klein-Heßling, W.; Sonnenkalb, M.; Jacquemain, D.; Clément, B.; Raimond, E.; Dimmelmeier, H.; Azarian, G.; Ducros, G.; Journeau, C.; Herranz Puebla, L.E.; Schumm, A.; Miassoedov, A.; Kljenak, I.; Pascal, G.; Bechta, S.; Güntay, S.; Koch, M.K.; Ivanov, I.; Auvinen, A.; Lindholm, I.

    2014-01-01

    Highlights: • Estimation of research priorities related to severe accident phenomena. • Consideration of new topics, partly linked to the severe accidents at Fukushima. • Consideration of results of recent projects, e.g. SARNET, ASAMPSA2, OECD projects. - Abstract: The objectives of the SARNET network of excellence are to define and work on common research programs in the field of severe accidents in Gen. II–III nuclear power plants and to further develop common tools and methodologies for safety assessment in this area. In order to ensure that the research conducted on severe accidents is efficient and well-focused, it is necessary to periodically evaluate and rank the priorities of research. This was done at the end of 2008 by the Severe Accident Research Priority (SARP) group at the end of the SARNET project of the 6th Framework Programme of European Commission (FP6). This group has updated this work in the FP7 SARNET2 project by accounting for the recent experimental results, the remaining safety issues as e.g. highlighted by Level 2 PSA national studies and the results of the recent ASAMPSA2 FP7 project. These evaluation activities were conducted in close relation with the work performed under the auspices of international organizations like OECD or IAEA. The Fukushima-Daiichi severe accidents, which occurred while SARNET2 was running, had some effects on the prioritization and definition of new research topics. Although significant progress has been gained and simulation models (e.g. the ASTEC integral code, jointly developed by IRSN and GRS) were improved, leading to an increased confidence in the predictive capabilities for assessing the success potential of countermeasures and/or mitigation measures, most of the selected research topics in 2008 are still of high priority. But the Fukushima-Daiichi accidents underlined that research efforts had to focus still more to improve severe accident management efficiency

  2. A Fair Contention Access Scheme for Low-Priority Traffic in Wireless Body Area Networks

    Directory of Open Access Journals (Sweden)

    Shagufta Henna

    2017-08-01

    Full Text Available Recently, wireless body area networks (WBANs have attracted significant consideration in ubiquitous healthcare. A number of medium access control (MAC protocols, primarily derived from the superframe structure of the IEEE 802.15.4, have been proposed in literature. These MAC protocols aim to provide quality of service (QoS by prioritizing different traffic types in WBANs. A contention access period (CAPwith high contention in priority-based MAC protocols can result in higher number of collisions and retransmissions. During CAP, traffic classes with higher priority are dominant over low-priority traffic; this has led to starvation of low-priority traffic, thus adversely affecting WBAN throughput, delay, and energy consumption. Hence, this paper proposes a traffic-adaptive priority-based superframe structure that is able to reduce contention in the CAP period, and provides a fair chance for low-priority traffic. Simulation results in ns-3 demonstrate that the proposed MAC protocol, called traffic- adaptive priority-based MAC (TAP-MAC, achieves low energy consumption, high throughput, and low latency compared to the IEEE 802.15.4 standard, and the most recent priority-based MAC protocol, called priority-based MAC protocol (PA-MAC.

  3. Interaction of HSP20 with a viral RdRp changes its sub-cellular localization and distribution pattern in plants.

    Science.gov (United States)

    Li, Jing; Xiang, Cong-Ying; Yang, Jian; Chen, Jian-Ping; Zhang, Heng-Mu

    2015-09-11

    Small heat shock proteins (sHSPs) perform a fundamental role in protecting cells against a wide array of stresses but their biological function during viral infection remains unknown. Rice stripe virus (RSV) causes a severe disease of rice in Eastern Asia. OsHSP20 and its homologue (NbHSP20) were used as baits in yeast two-hybrid (YTH) assays to screen an RSV cDNA library and were found to interact with the viral RNA-dependent RNA polymerase (RdRp) of RSV. Interactions were confirmed by pull-down and BiFC assays. Further analysis showed that the N-terminus (residues 1-296) of the RdRp was crucial for the interaction between the HSP20s and viral RdRp and responsible for the alteration of the sub-cellular localization and distribution pattern of HSP20s in protoplasts of rice and epidermal cells of Nicotiana benthamiana. This is the first report that a plant virus or a viral protein alters the expression pattern or sub-cellular distribution of sHSPs.

  4. Ultrastructural and cellular damage to rat lung with x-rays: a search for target cell in lung tissue

    Energy Technology Data Exchange (ETDEWEB)

    Furuta, I

    1975-03-01

    Radiation effects on the peripheral alveoli of conventional rats were examined by means of electron microscopy. The right hemithorax alone was exposed to various single doses of x rays. The initial cellular lesions selectively involved the cytoplasms of alveolar capillary endothelial (Ed) and type 1 epithelial (Ep 1) cells in a dose-dependent fashion, where the major alterations were multifocal vacuolations and swellings. These lesions became visible as early as 1 hr after 1000 R (the assumed mean lethal dose for Ed cells) and more. However, progenitor Ep 2 cells exhibited no obvious cytoplasmic lesions by the doses below 2000 R, indicating that Ep 2 cells are more resistant to x rays. With time following 1000 R, the capillary Ed blebbing abruptly developed in various forms from the sites presumably other than the Ed junctions. The Ed blebs and interstitial edema progressed until about 2 weeks without recovery, while some signs of cellular recovery were recognized in Ep 1 cells during this period. The observations after a long period of 6 months following 1000 R showed that the typical pulmonary fibrotic changes were initiated in the interstitium perhaps around unrepaired capillaries. Further, inflammatory reaction characterized by massive cellular infiltations was superimposed on developing pulmonary fibrosis. Considering the current knowledge about the cell sensitivity and renewal in stable tissues, the present results imply that capillary Ed cell is the primary target for the radiation lesion leading to the secondary pulmonary alterations.

  5. Setting priorities for zinc-related health research to reduce children's disease burden worldwide: an application of the Child Health and Nutrition Research Initiative's research priority-setting method.

    Science.gov (United States)

    Brown, Kenneth H; Hess, Sonja Y; Boy, Erick; Gibson, Rosalind S; Horton, Susan; Osendarp, Saskia J; Sempertegui, Fernando; Shrimpton, Roger; Rudan, Igor

    2009-03-01

    To make the best use of limited resources for supporting health-related research to reduce child mortality, it is necessary to apply a suitable method to rank competing research options. The Child Health and Nutrition Research Initiative (CHNRI) developed a new methodology for setting health research priorities. To broaden experience with this priority-setting technique, we applied the method to rank possible research priorities concerning the control of Zn deficiency. Although Zn deficiency is not generally recognized as a direct cause of child mortality, recent research indicates that it predisposes children to an increased incidence and severity of several of the major direct causes of morbidity and mortality. Leading experts in the field of Zn research in child health were identified and invited to participate in a technical working group (TWG) to establish research priorities. The individuals were chosen to represent a wide range of expertise in Zn nutrition. The seven TWG members submitted a total of ninety research options, which were then consolidated into a final list of thirty-one research options categorized by the type of resulting intervention. The identified priorities were dominated by research investment options targeting Zn supplementation, and were followed by research on Zn fortification, general aspects of Zn nutrition, dietary modification and other new interventions. In general, research options that aim to improve the efficiency of an already existing intervention strategy received higher priority scores. Challenges identified during the implementation of the methodology and suggestions to modify the priority-setting procedures are discussed.

  6. The Theory of Dynamic Public Transit Priority with Dynamic Stochastic Park and Ride

    Directory of Open Access Journals (Sweden)

    Chengming Zhu

    2014-01-01

    Full Text Available Public transit priority is very important for relieving traffic congestion. The connotation of dynamic public transit priority and dynamic stochastic park and ride is presented. Based on the point that the travel cost of public transit is not higher than the travel cost of car, how to determine the level of dynamic public transit priority is discussed. The traffic organization method of dynamic public transit priority is introduced. For dynamic stochastic park and ride, layout principle, scale, and charging standard are discussed. Traveler acceptability is high through the analysis of questionnaire survey. Dynamic public transit priority with dynamic stochastic park and ride has application feasibility.

  7. What are the dietary treatment research priorities for inflammatory bowel disease? A short report based on a priority setting partnership with the James Lind Alliance.

    Science.gov (United States)

    Lomer, M C; Hart, A L; Verjee, A; Daly, A; Solomon, J; Mclaughlin, J

    2017-12-01

    Treatment of inflammatory bowel disease (IBD) involves a multidisciplinary approach comprising medical management and sometimes surgery. Although diet is central to IBD management, the optimal diet for patients with IBD is uncertain. A UK collaborative partnership within the James Lind Alliance was set up between patients, clinicians and other stakeholders to develop research priorities in IBD. The aim of this short report is to provide a comprehensive summary of the research priority findings relating to diet in the treatment of IBD. The James Lind Alliance Priority Setting Partnership process was used to develop research priorities in IBD. In brief, patients, clinicians and other stakeholders were invited to provide up to five treatment uncertainties in IBD. These uncertainties were collated, revised and ranked, leading to a final top 10 research questions in IBD. A total of 1671 uncertainties from 531 participants were collected and refined to exclude duplicates leaving 1253 uncertainties. Of these, 348 were categorised as diet-related and grouped according to topic. There were 206 uncertainties related to how diet can be used to treat IBD or alleviate symptoms. Seventy-two percent of diet-related questions came from patients. One broadly diet-related and two diet-specific treatment uncertainties were included in the top 10 research priorities for IBD. Dietary treatment options in the management of IBD are important research priorities. Almost three-quarters of diet related questions came from patients, who were particularly interested in how diet can impact disease activity and symptom control. © 2017 The British Dietetic Association Ltd.

  8. The priority queue as an example of hardware/software codesign

    DEFF Research Database (Denmark)

    Høeg, Flemming; Mellergaard, Niels; Staunstrup, Jørgen

    1994-01-01

    The paper identifies a number of issues that are believed to be important for hardware/software codesign. The issues are illustrated by a small comprehensible example: a priority queue. Based on simulations of a real application, we suggest a combined hardware/software realization of the priority...

  9. TOP PRIORITI QMS PRINCIPLES FOR ACHIEVING BUSINESS EXCELLENCE

    Directory of Open Access Journals (Sweden)

    Aleksandar Vujović

    2010-06-01

    Full Text Available The main target of this paper is to select top priority principles of QMS for achieving business excellence. This could be done from the standpoint of significant of principles. That means that. organization should make more attention to this principles in the way for making excellent results. This paper has been developed as a tendency of researchers in the Center for quality-Faculty of mechanical engineering in Podgorica to establish a model for improvement of business processes performances based on quality management system through comparison with top organizational performances characterized by criteria i.e. particularities of the business excellence model. Correlation of principles of the quality management system with QMS principles has been established to that effect. Weight coefficients have been also determined for each principle individually. Thereby key principles were identified, namely priorities in terms of achieving business excellence i.e. areas (principles were given priorities, that is to say principles that play the biggest part in achieving business excellence.

  10. Research priorities for shoulder surgery: results of the 2015 James Lind Alliance patient and clinician priority setting partnership.

    Science.gov (United States)

    Rangan, Amar; Upadhaya, Sheela; Regan, Sandra; Toye, Francine; Rees, Jonathan L

    2016-04-11

    To run a UK based James Lind Alliance Priority Setting Partnership for 'Surgery for Common Shoulder Problems'. This was a nationally funded and conducted process. It was organised from a musculoskeletal research centre and Biomedical Research Unit in Oxford. UK shoulder patients, carers and clinicians, involved in treating patients with shoulder pain and shoulder problems that might require surgery. These were national electronic and paper surveys capturing treatment uncertainties that are important to shoulder patients, carers and clinicians. The outcomes relevant to this study were the survey results and rankings. The process took 18 months to complete, with 371 participants contributing 404 in scope questions. The James Lind process then produced a final 10 research priorities and uncertainties that relate to the scope of 'Surgery for Common Shoulder Problems'. The final top 10 UK research priorities have been produced and are now being disseminated to partner organisations and funders to guide funding of shoulder research for the next 5-10 years on topics that are important to patients, their carers and clinicians. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  11. Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

    Science.gov (United States)

    McCune, Matthew; Kosztin, Ioan

    2013-03-01

    Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

  12. Cellular and Molecular Targets of Menthol Actions

    Directory of Open Access Journals (Sweden)

    Murat Oz

    2017-07-01

    Full Text Available Menthol belongs to monoterpene class of a structurally diverse group of phytochemicals found in plant-derived essential oils. Menthol is widely used in pharmaceuticals, confectionary, oral hygiene products, pesticides, cosmetics, and as a flavoring agent. In addition, menthol is known to have antioxidant, anti-inflammatory, and analgesic effects. Recently, there has been renewed awareness in comprehending the biological and pharmacological effects of menthol. TRP channels have been demonstrated to mediate the cooling actions of menthol. There has been new evidence demonstrating that menthol can significantly influence the functional characteristics of a number of different kinds of ligand and voltage-gated ion channels, indicating that at least some of the biological and pharmacological effects of menthol can be mediated by alterations in cellular excitability. In this article, we examine the results of earlier studies on the actions of menthol with voltage and ligand-gated ion channels.

  13. The Theory of Dynamic Public Transit Priority with Dynamic Stochastic Park and Ride

    OpenAIRE

    Zhu, Chengming; Chen, Yanyan; Ma, Changxi

    2014-01-01

    Public transit priority is very important for relieving traffic congestion. The connotation of dynamic public transit priority and dynamic stochastic park and ride is presented. Based on the point that the travel cost of public transit is not higher than the travel cost of car, how to determine the level of dynamic public transit priority is discussed. The traffic organization method of dynamic public transit priority is introduced. For dynamic stochastic park and ride, layout principle, scal...

  14. 1988 Delphi survey of nursing research priorities for New York State.

    Science.gov (United States)

    Shortridge, L; Doswell, W; Evans, M E; Levin, R F; Millor, G K; Carter, E

    1989-09-01

    In order to inform decisions about nursing research and health care policy, the Council on Nursing Research of the New York State Nurses Association (NYSNA) conducted a Delphi survey to identify the priorities for nursing research in New York state. The Delphi technique is a method of eliciting judgements from experts for the purpose of short-term forecasting and planning. The survey was conducted by mail in three rounds during 1988. Round I required participants to identify three primary research priorities for the nursing profession. In Round II participants ranked the 37 most frequently identified categories from Round I. The highest 16 categories from Round II were ranked by participants in Round III to provide the final 10 nursing research priority categories for New York state. All members of the New York State Nurses Association holding a minimum of a master's degree in nursing were invited to participate. The response rates were: Round I, 34% (N = 872); Round II, 38% (N = 985); Round III 37% (N = 974). Of the 10 nursing research priority categories identified in the final round, 5 relate to nurses, 2 relate to nursing, and 3 relate to clients. None of the high-risk conditions or populations with whom nurses work appear in the top 10, and only 2 of these are ranked in the top 15 priority categories. These priority categories will be used by the NYSNA Council on Nursing Research to influence its future agenda and activities. They can be used by the nursing profession and others for planning, policy making, and establishing nursing research funding priorities.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Speciation and determination of priority metals in sediments of Oyun ...

    African Journals Online (AJOL)

    This work was carried out to determine the concentrations, bioavailability and mobility of priority metals in sediments of Oyun River, Sango, Ilorin, Nigeria. The river sediments were sampled at six selected locations and the samples were analyzed for some certain priority metals to determine the concentration, speciation and ...

  16. Montessori Early Childhood Teacher Perceptions of Family Priorities and Stressors

    Science.gov (United States)

    Epstein, Ann

    2015-01-01

    Teachers of young children work closely with families. One component of teacher-family partnerships is teachers' understanding of family priorities and stressors. This study examines Montessori Early Childhood (ages three through six) teacher perceptions of family priorities and stressors through an analysis of responses to two parallel surveys.…

  17. Evaluating the impacts of priority dispatch in the European electricity market

    International Nuclear Information System (INIS)

    Oggioni, G.; Murphy, F.H.; Smeers, Y.

    2014-01-01

    This paper compares the impact of the Nodal Pricing and European Market Coupling organizations on different economic agents of the power system under two main wind policies. Under the “priority dispatch” policy, Transmission System Operators (TSOs) must accommodate all wind energy produced, which thus has the priority over energy produced by conventional plants; in the “no priority dispatch” policy, TSOs can decide not to inject all potential wind power in the grid in order to limit congestion problems. The effects of these two wind policies are measured by developing simple stochastic programming models that consider cases with different wind penetration levels, existing capacities and endogenous investments, as well as assumptions on the EU-ETS. Our computational experiments show that, when there is “priority dispatch”, Nodal Pricing and Market Coupling evolve in a similar way as long as wind penetration is not too high. In contrast, a significant increase of wind penetration causes the collapse of the Market Coupling organization while Nodal Pricing continues to perform well. On the other hand, “no priority dispatch” removes most of the problems resulting from Market Coupling, which still exhibits a slightly lower efficiency than Nodal Pricing. These outcomes do not depend on the contextual assumptions (fixed capacities vs. investment; EU-ETS vs. non EU-ETS) that characterize the several cases analyzed. This suggests that our policy conclusions are robust. Furthermore, our models overestimate the flexibility of conventional plants, which means that these conclusions would likely be reinforced with a more detailed model. - Highlights: • We compare “priority dispatch (PD)” and “no priority dispatch (NPD)” policies under EU rules. • We compare Nodal Pricing (NP) and Market Coupling (MC) architectures for power markets. • Both wind priority policies are more efficient in NP than MC. • The PD policy crashes MC when wind penetration is

  18. Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Elizabeth S.; Kawahara, Rebeca [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Kadowaki, Marina K. [Universidade Estadual do Oeste do Parana, Cascavel, PR (Brazil); Amstalden, Hudson G.; Noleto, Guilhermina R.; Cadena, Silvia Maria S.C.; Winnischofer, Sheila M.B. [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Martinez, Glaucia R., E-mail: grmartinez@ufpr.br [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil)

    2012-09-10

    Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of B16-F10 melanoma cells. Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited (by induction of cell cycle arrest in the G1 phase) and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence. Proteomic analysis demonstrated the involvement of proteins from other pathways besides those related to the cell cycle, including protein disulfide isomerase A3, heat-shock protein 70, and fructose biphosphate aldolase A (all up-regulated), and lactate dehydrogenase (down-regulated). In RT-qPCR experiments, the levels of pyruvate kinase M2 mRNA dropped, whereas the levels of ATP synthase (beta-F1) mRNA increased. These data indicate that melanogenesis stimulation of B16-F10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis. -- Highlights: Black-Right-Pointing-Pointer Melanogenesis stimulation by L-tyrosine+NH{sub 4}Cl in B16-F10 melanoma cells increases ROS levels. Black-Right-Pointing-Pointer Melanogenesis inhibits cell proliferation, and induced cell cycle arrest in the G1 phase. Black-Right-Pointing-Pointer Proteomic analysis showed alterations in proteins of the cell cycle and glucose metabolism. Black-Right-Pointing-Pointer RT-qPCR analysis confirmed alterations of metabolic targets after melanogenesis stimulation.

  19. Physiotherapy Research Priorities in Switzerland: Views of the Various Stakeholders.

    Science.gov (United States)

    Nast, Irina; Tal, Amir; Schmid, Stefan; Schoeb, Veronika; Rau, Barbara; Barbero, Marco; Kool, Jan

    2016-09-01

    Research priorities, defined by multiple stakeholders, can proximally facilitate the coordination of research projects and national and international cooperation and distally further improve the quality of physiotherapy practice. The aim of this study was therefore to establish physiotherapy research priorities in Switzerland considering multiple stakeholders' opinions. A mixed methods design was chosen. For a qualitative identification of physiotherapy research topics, 18 focus group discussions and 23 semi-structured interviews/written commentaries were conducted. For the quantitative analysis, 420 participants prioritized research topics using a two-round Delphi questionnaire survey. The following stakeholder groups were surveyed in the German-speaking, French-speaking and Italian-speaking regions of Switzerland: physiotherapy researchers, practitioners and educators, representatives of patient organizations, public health organizations, health insurers, physicians, nurses, occupational therapists and other health professionals, as well as physical educators. The top five overall physiotherapy research priorities identified were as follows: physiotherapy treatment, physiotherapy assessment and diagnosis, prevention, physiotherapist-patient interaction and physiotherapy professional education at the bachelor level. With regard to diagnostic groups, the highest priorities were placed on musculoskeletal disorders, neurology, orthopaedics, geriatrics and ergonomics/occupational health. Consensus was moderate to high, and only few differences between stakeholder groups were revealed. Research directly related to physiotherapy treatment is of highest priority. It should focus on diagnostic groups related to chronicity in anticipation of demographic changes. Multidisciplinary networks for research and practice, alongside sound coordination of research projects, should increase the impact of physiotherapy research. An accurate dissemination of research priorities

  20. An empirical Bayes safety evaluation of tram/streetcar signal and lane priority measures in Melbourne.

    Science.gov (United States)

    Naznin, Farhana; Currie, Graham; Sarvi, Majid; Logan, David

    2016-01-01

    Streetcars/tram systems are growing worldwide, and many are given priority to increase speed and reliability performance in mixed traffic conditions. Research related to the road safety impact of tram priority is limited. This study explores the road safety impacts of tram priority measures including lane and intersection/signal priority measures. A before-after crash study was conducted using the empirical Bayes (EB) method to provide more accurate crash impact estimates by accounting for wider crash trends and regression to the mean effects. Before-after crash data for 29 intersections with tram signal priority and 23 arterials with tram lane priority in Melbourne, Australia, were analyzed to evaluate the road safety impact of tram priority. The EB before-after analysis results indicated a statistically significant adjusted crash reduction rate of 16.4% after implementation of tram priority measures. Signal priority measures were found to reduce crashes by 13.9% and lane priority by 19.4%. A disaggregate level simple before-after analysis indicated reductions in total and serious crashes as well as vehicle-, pedestrian-, and motorcycle-involved crashes. In addition, reductions in on-path crashes, pedestrian-involved crashes, and collisions among vehicles moving in the same and opposite directions and all other specific crash types were found after tram priority implementation. Results suggest that streetcar/tram priority measures result in safety benefits for all road users, including vehicles, pedestrians, and cyclists. Policy implications and areas for future research are discussed.

  1. Model Checking Timed Automata with Priorities using DBM Subtraction

    DEFF Research Database (Denmark)

    David, Alexandre; Larsen, Kim Guldstrand; Pettersson, Paul

    2006-01-01

    In this paper we describe an extension of timed automata with priorities, and efficient algorithms to compute subtraction on DBMs (difference bounded matrices), needed in symbolic model-checking of timed automata with priorities. The subtraction is one of the few operations on DBMs that result...... in a non-convex set needing sets of DBMs for representation. Our subtraction algorithms are efficient in the sense that the number of generated DBMs is significantly reduced compared to a naive algorithm. The overhead in time is compensated by the gain from reducing the number of resulting DBMs since...... this number affects the performance of symbolic model-checking. The uses of the DBM subtraction operation extend beyond timed automata with priorities. It is also useful for allowing guards on transitions with urgent actions, deadlock checking, and timed games....

  2. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Payne CM

    2011-05-01

    Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

  3. Dynamic behavior of cellular materials and cellular structures: Experiments and modeling

    Science.gov (United States)

    Gao, Ziyang

    Cellular solids, including cellular materials and cellular structures (CMS), have attracted people's great interests because of their low densities and novel physical, mechanical, thermal, electrical and acoustic properties. They offer potential for lightweight structures, energy absorption, thermal management, etc. Therefore, the studies of cellular solids have become one of the hottest research fields nowadays. From energy absorption point of view, any plastically deformed structures can be divided into two types (called type I and type II), and the basic cells of the CMS may take the configurations of these two types of structures. Accordingly, separated discussions are presented in this thesis. First, a modified 1-D model is proposed and numerically solved for a typical type II structure. Good agreement is achieved with the previous experimental data, hence is used to simulate the dynamic behavior of a type II chain. Resulted from different load speeds, interesting collapse modes are observed, and the parameters which govern the cell's post-collapse behavior are identified through a comprehensive non-dimensional analysis on general cellular chains. Secondly, the MHS specimens are chosen as an example of type I foam materials because of their good uniformity of the cell geometry. An extensive experimental study was carried out, where more attention was paid to their responses to dynamic loadings. Great enhancement of the stress-strain curve was observed in dynamic cases, and the energy absorption capacity is found to be several times higher than that of the commercial metal foams. Based on the experimental study, finite elemental simulations and theoretical modeling are also conducted, achieving good agreements and demonstrating the validities of those models. It is believed that the experimental, numerical and analytical results obtained in the present study will certainly deepen the understanding of the unsolved fundamental issues on the mechanical behavior of

  4. Setting priorities in primary health care - on whose conditions? A questionnaire study

    Directory of Open Access Journals (Sweden)

    Arvidsson Eva

    2012-11-01

    Full Text Available Abstract Background In Sweden three key criteria are used for priority setting: severity of the health condition; patient benefit; and cost-effectiveness. They are derived from the ethical principles established by the Swedish parliament 1997 but have been used only to a limited extent in primary care. The aim of this study was to describe and analyse: 1 GPs', nurses', and patients' prioritising in routine primary care 2 The association between the three key priority setting criteria and the overall priority assigned by the GPs and nurses to individual patients. Methods Paired questionnaires were distributed to all patients and the GPs or nurses they had contact with during a 2-week period at four health centres in Sweden. The staff registered the health conditions or health problem, and the planned intervention. Then they estimated the severity of the health condition, the expected patient benefit, and the cost-effectiveness of the planned intervention. Both the staff and the patients reported their overall prioritisation of the patient. In total, 1851 paired questionnaires were collected. Results Compared to the medical staff, the patients assigned relatively higher priority to acute/minor conditions than to preventive check-ups for chronic conditions. Severity of the health condition was the priority setting criterion that had the strongest association with the overall priority for the staff as a whole, but for the GPs it was cost-effectiveness. Conclusions The challenge for primary care providers is to balance the patients' demands with medical needs and cost-effectiveness. Transparent priority setting in primary care might contribute to a greater consensus between GPs and nurses on how to use the key priority setting criteria.

  5. Setting research priorities across science, technology, and health sectors: the Tanzania experience.

    Science.gov (United States)

    de Haan, Sylvia; Kingamkono, Rose; Tindamanyire, Neema; Mshinda, Hassan; Makandi, Harun; Tibazarwa, Flora; Kubata, Bruno; Montorzi, Gabriela

    2015-03-12

    Identifying research priorities is key to innovation and economic growth, since it informs decision makers on effectively targeting issues that have the greatest potential public benefit. As such, the process of setting research priorities is of pivotal importance for favouring the science, technology, and innovation (STI)-driven development of low- and middle-income countries. We report herein on a major cross-sectoral nationwide research priority setting effort recently carried out in Tanzania by the Tanzania Commission for Science and Technology (COSTECH) in partnership with the Council on Health Research for Development (COHRED) and the NEPAD Agency. The first of its type in the country, the process brought together stakeholders from 42 sub-sectors in science, technology, and health. The cross-sectoral research priority setting process consisted of a 'training-of-trainers' workshop, a demonstration workshop, and seven priority setting workshops delivered to representatives from public and private research and development institutions, universities, non-governmental organizations, and other agencies affiliated to COSTECH. The workshops resulted in ranked listings of research priorities for each sub-sector, totalling approximately 800 priorities. This large number was significantly reduced by an expert panel in order to build a manageable instrument aligned to national development plans that could be used to guide research investments. The Tanzania experience is an instructive example of the challenges and issues to be faced in when attempting to identify research priority areas and setting an STI research agenda in low- and middle-income countries. As countries increase their investment in research, it is essential to increase investment in research management and governance as well, a key and much needed capacity for countries to make proper use of research investments.

  6. Setting priorities in primary health care--on whose conditions? A questionnaire study.

    Science.gov (United States)

    Arvidsson, Eva; André, Malin; Borgquist, Lars; Andersson, David; Carlsson, Per

    2012-11-26

    In Sweden three key criteria are used for priority setting: severity of the health condition; patient benefit; and cost-effectiveness. They are derived from the ethical principles established by the Swedish parliament 1997 but have been used only to a limited extent in primary care. The aim of this study was to describe and analyse: 1) GPs', nurses', and patients' prioritising in routine primary care 2) The association between the three key priority setting criteria and the overall priority assigned by the GPs and nurses to individual patients. Paired questionnaires were distributed to all patients and the GPs or nurses they had contact with during a 2-week period at four health centres in Sweden. The staff registered the health conditions or health problem, and the planned intervention. Then they estimated the severity of the health condition, the expected patient benefit, and the cost-effectiveness of the planned intervention. Both the staff and the patients reported their overall prioritisation of the patient. In total, 1851 paired questionnaires were collected. Compared to the medical staff, the patients assigned relatively higher priority to acute/minor conditions than to preventive check-ups for chronic conditions. Severity of the health condition was the priority setting criterion that had the strongest association with the overall priority for the staff as a whole, but for the GPs it was cost-effectiveness. The challenge for primary care providers is to balance the patients' demands with medical needs and cost-effectiveness. Transparent priority setting in primary care might contribute to a greater consensus between GPs and nurses on how to use the key priority setting criteria.

  7. M/M/1 RETRIAL QUEUEING SYSTEM WITH VACATION INTERRUPTIONS UNDER PRE-EMPTIVE PRIORITY SERVICE

    Directory of Open Access Journals (Sweden)

    Muthu Ganapathi Subramanian Annasamy

    2010-10-01

    Full Text Available Consider a single server retrial queueing system with pre-emptive priority service and vacation interruptions in which customers arrive in a Poisson process with arrival rate λ1 for low priority customers and λ2 for high priority customers. Further it is assume that the service times follow an exponential distribution with parameters μ1 and μ2 for low and high priority customers respectively. The retrial is introduced for low priority customers only. The server goes for vacation after exhaustively completing the service to both types of customers.  The vacation rate follows an exponential distribution with parameter α. The concept of vacation interruption is used in this paper that is the server comes from the vacation into normal working condition without completing his vacation period subject to some conditions. Let k be the maximum number of waiting spaces for high priority customers in front of the service station. The high priority customers will be governed by the pre-emptive priority service. We assume that the access from orbit to the service facility is governed by the classical retrial policy. This model is solved by using Matrix geometric Technique. Numerical  study  have been done for Analysis of Mean number of low priority customers in the orbit (MNCO, Mean number of high priority customers in the queue(MPQL,Truncation level (OCUT,Probability of server free and Probabilities  of server busy with low and high priority customers and probability of server in vacation for various values of λ1 , λ2 , μ1 , μ2, α and σ  in elaborate manner and also various particular cases of  this model have been discussed.

  8. Research priorities by professional background - A detailed analysis of the James Lind Alliance Priority Setting Partnership.

    Science.gov (United States)

    Arulkumaran, Nishkantha; Reay, Hannah; Brett, Stephen J

    2016-05-01

    The Intensive Care Foundation, in partnership with the James Lind Alliance, has supported a national project to identify and prioritise unanswered questions about adult intensive care that are important to people who have been critically ill, their families, and the health professionals who care for them. We conducted a secondary analysis to explore differences in priorities determined by different respondent groups in order to identify different groups' perceptions of gaps in knowledge. There were two surveys conducted as part of the original project. Survey 1 comprised a single open question to identify important research topics; survey 2 aimed to prioritise these topics using a 10-point Likert scale. In survey 1, despite clear differences in suggestions amongst the respondent groups, themes of comfort/communication and post-ICU rehabilitation were the within the top 2 suggestions across all groups. Patients and relatives suggested research topics to which they could easily relate, whereas there was a greater breadth of suggestions from clinicians. In survey 2, the number of research priorities that received a mode score of 10 varied from 1 to 36. Patients scored 36 out of the 37 topics with a mode score of 10. All other groups scored topics with more discrimination, with the number of topics with a mode score of 10 ranging from 1 to 20. Differences in the proportions of the representative groups are therefore unlikely to have translated to an impartial conclusion. Clinicians, patients, and family members have jointly identified the research priorities for UK ICM practice.

  9. A checklist for health research priority setting: nine common themes of good practice.

    Science.gov (United States)

    Viergever, Roderik F; Olifson, Sylvie; Ghaffar, Abdul; Terry, Robert F

    2010-12-15

    Health research priority setting processes assist researchers and policymakers in effectively targeting research that has the greatest potential public health benefit. Many different approaches to health research prioritization exist, but there is no agreement on what might constitute best practice. Moreover, because of the many different contexts for which priorities can be set, attempting to produce one best practice is in fact not appropriate, as the optimal approach varies per exercise. Therefore, following a literature review and an analysis of health research priority setting exercises that were organized or coordinated by the World Health Organization since 2005, we propose a checklist for health research priority setting that allows for informed choices on different approaches and outlines nine common themes of good practice. It is intended to provide generic assistance for planning health research prioritization processes. The checklist explains what needs to be clarified in order to establish the context for which priorities are set; it reviews available approaches to health research priority setting; it offers discussions on stakeholder participation and information gathering; it sets out options for use of criteria and different methods for deciding upon priorities; and it emphasizes the importance of well-planned implementation, evaluation and transparency.

  10. 78 FR 5330 - Proposed Priorities and Definitions-NIDRR DRRP-Community Living and Participation, Health and...

    Science.gov (United States)

    2013-01-25

    ... outcomes for transition-aged youth with disabilities. (vii) Vocational rehabilitation (VR) practices that... priorities, we designate the type of each priority as absolute, competitive preference, or invitational...)). Competitive preference priority: Under a competitive preference priority, we give competitive preference to an...

  11. Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation.

    Science.gov (United States)

    Manzoni, Claudia; Mamais, Adamantios; Dihanich, Sybille; McGoldrick, Phillip; Devine, Michael J; Zerle, Julia; Kara, Eleanna; Taanman, Jan-Willem; Healy, Daniel G; Marti-Masso, Jose-Felix; Schapira, Anthony H; Plun-Favreau, Helene; Tooze, Sharon; Hardy, John; Bandopadhyay, Rina; Lewis, Patrick A

    2013-11-29

    LRRK2 is one of the most important genetic contributors to Parkinson's disease (PD). Point mutations in this gene cause an autosomal dominant form of PD, but to date no cellular phenotype has been consistently linked with mutations in each of the functional domains (ROC, COR and Kinase) of the protein product of this gene. In this study, primary fibroblasts from individuals carrying pathogenic mutations in the three central domains of LRRK2 were assessed for alterations in the autophagy/lysosomal pathway using a combination of biochemical and cellular approaches. Mutations in all three domains resulted in alterations in markers for autophagy/lysosomal function compared to wild type cells. These data highlight the autophagy and lysosomal pathways as read outs for pathogenic LRRK2 function and as a marker for disease, and provide insight into the mechanisms linking LRRK2 function and mutations. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Statistical mechanics of cellular automata

    International Nuclear Information System (INIS)

    Wolfram, S.

    1983-01-01

    Cellular automata are used as simple mathematical models to investigate self-organization in statistical mechanics. A detailed analysis is given of ''elementary'' cellular automata consisting of a sequence of sites with values 0 or 1 on a line, with each site evolving deterministically in discrete time steps according to p definite rules involving the values of its nearest neighbors. With simple initial configurations, the cellular automata either tend to homogeneous states, or generate self-similar patterns with fractal dimensions approx. =1.59 or approx. =1.69. With ''random'' initial configurations, the irreversible character of the cellular automaton evolution leads to several self-organization phenomena. Statistical properties of the structures generated are found to lie in two universality classes, independent of the details of the initial state or the cellular automaton rules. More complicated cellular automata are briefly considered, and connections with dynamical systems theory and the formal theory of computation are discussed

  13. Strategies for implementing transit priority

    International Nuclear Information System (INIS)

    2005-11-01

    Increased urbanization in Canada has placed pressure on an eroding, ageing infrastructure and raised concerns about declining air quality. In addition to reducing emissions, well-designed transit systems can reduce traffic and improve road safety. This paper presented a set of transit best practices which addressed the need to improve supply, influence demand, and make operational improvements with the least environmental impact. The objective of this paper was to gather the best implementation strategies for urban roads from municipalities across Canada, and to focus on solutions that can be applied to bus and streetcar systems to make better use of shared facilities. Bus bulbs, signal priority, queue jumps and green waves were recommended, as well as dedicated lanes and exclusive transit facilities. Advances in technology were reviewed, as well as the use of intelligent transportation systems to improve transit with little or no impact on other road users. Case studies were presented from various municipalities across Canada. Various stages of project development, design and construction, operations and maintenance strategies for the various projects were reviewed. The most successful installations were found to be in cities that have established a clear policy on transit improvements. It was suggested that defining the need for priority and determining where it can be implemented is central to the development of a strategic program. Dedicated programs looking at transit priority were recommended, and risks arising from integrating new infrastructure were reviewed. It was suggested that the range of stakeholders involved, and the internal organization of the implementing authority bore a significant impact on overall cost and schedule of transit projects. It was concluded that appropriate planning is needed to control risks. 20 refs., 3 figs

  14. Montessori Early Childhood Teacher Perceptions of Family Priorities and Stressors

    Directory of Open Access Journals (Sweden)

    Ann Epstein

    2015-11-01

    Full Text Available Teachers of young children work closely with families. One component of teacher-family partnerships is teachers’ understanding of family priorities and stressors. This study examines Montessori early childhood (ages three through six teacher perceptions of family priorities and stressors through an analysis of responses to two parallel surveys.  Eighty teachers (37% of those who received the survey and forty-nine family members (representing a 55% response rate completed the survey.  Significant differences were found between teachers’ perceptions of four (of seven family priorities and families’ actual responses. Teachers ranked “making academic progress” as the most important of seven possible family priorities. However, families stated that “developing kindness” is the most important priority for their young children. No significant differences were found when comparing teacher rankings of family stressors with actual family responses. Montessori early childhood teachers ranked “not having enough time” as the most stressful of six possible stressors. Families confirmed that time pressures cause them the most stress. Maria Montessori’s recommendations for teachers and families are summarized. Recommendations for building stronger family partnerships in the context of Montessori’s philosophy, for example on-going self-reflection, are provided.             Keywords: Montessori, teacher-family partnerships, early childhood teacher perceptions

  15. Wireless Cellular Mobile Communications

    OpenAIRE

    Zalud, V.

    2002-01-01

    In this article is briefly reviewed the history of wireless cellular mobile communications, examined the progress in current second generation (2G) cellular standards and discussed their migration to the third generation (3G). The European 2G cellular standard GSM and its evolution phases GPRS and EDGE are described somewhat in detail. The third generation standard UMTS taking up on GSM/GPRS core network and equipped with a new advanced access network on the basis of code division multiple ac...

  16. Occupational health research priorities in Malaysia: a Delphi study

    OpenAIRE

    Sadhra, S; Beach, J; Aw, T; Sheikh-Ahmed, K

    2001-01-01

    OBJECTIVES—As part of a consultancy project on occupational health, the Delphi method was used to identify research priorities in occupational health in Malaysia.
METHODS—Participation was sought from government ministries, industry, and professional organisations, and university departments with an interest in occupational and public health. Two rounds of questionnaires resulted in a final list of priorities, with noticeable differences between participants depending on whether they worked i...

  17. Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis

    Science.gov (United States)

    Watanabe, Miki; Muraleedharan, Ranjithmenon; Lambert, Paul F.; Lane, Andrew N.; Romick-Rosendale, Lindsey E.; Wells, Susanne I.

    2017-01-01

    The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos). To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA) that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth. PMID:28558019

  18. Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis.

    Directory of Open Access Journals (Sweden)

    Marie C Matrka

    Full Text Available The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos. To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth.

  19. Web server for priority ordered multimedia services

    Science.gov (United States)

    Celenk, Mehmet; Godavari, Rakesh K.; Vetnes, Vermund

    2001-10-01

    In this work, our aim is to provide finer priority levels in the design of a general-purpose Web multimedia server with provisions of the CM services. The type of services provided include reading/writing a web page, downloading/uploading an audio/video stream, navigating the Web through browsing, and interactive video teleconferencing. The selected priority encoding levels for such operations follow the order of admin read/write, hot page CM and Web multicasting, CM read, Web read, CM write and Web write. Hot pages are the most requested CM streams (e.g., the newest movies, video clips, and HDTV channels) and Web pages (e.g., portal pages of the commercial Internet search engines). Maintaining a list of these hot Web pages and CM streams in a content addressable buffer enables a server to multicast hot streams with lower latency and higher system throughput. Cold Web pages and CM streams are treated as regular Web and CM requests. Interactive CM operations such as pause (P), resume (R), fast-forward (FF), and rewind (RW) have to be executed without allocation of extra resources. The proposed multimedia server model is a part of the distributed network with load balancing schedulers. The SM is connected to an integrated disk scheduler (IDS), which supervises an allocated disk manager. The IDS follows the same priority handling as the SM, and implements a SCAN disk-scheduling method for an improved disk access and a higher throughput. Different disks are used for the Web and CM services in order to meet the QoS requirements of CM services. The IDS ouput is forwarded to an Integrated Transmission Scheduler (ITS). The ITS creates a priority ordered buffering of the retrieved Web pages and CM data streams that are fed into an auto regressive moving average (ARMA) based traffic shaping circuitry before being transmitted through the network.

  20. MSAT and cellular hybrid networking

    Science.gov (United States)

    Baranowsky, Patrick W., II

    Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

  1. Research Priorities for the Intersection of Alcohol and HIV/AIDS in Low and Middle Income Countries: A Priority Setting Exercise.

    Science.gov (United States)

    Gordon, Sara; Rotheram-Borus, Mary Jane; Skeen, Sarah; Perry, Charles; Bryant, Kendall; Tomlinson, Mark

    2017-11-01

    The harmful use of alcohol is a component cause for more than 200 diseases. The association between alcohol consumption, risk taking behavior and a range of infectious diseases such as HIV/AIDS is well established. The prevalence of HIV/AIDS as well as harmful alcohol use in low and middle income countries is high. Alcohol has been identified as a modifiable risk factor in the prevention and treatment of HIV/AIDS. The objective of this paper is to define research priorities for the interaction of alcohol and HIV/AIDS in low and middle income countries. The Child Health and Nutrition Research Initiative (CHNRI) priority setting methodology was applied in order to assess research priorities of the interaction of alcohol and HIV/AIDS. A group of 171 global and local experts in the field of alcohol and or HIV/AIDS related research were identified and invited to generate research questions. This resulted in 205 research questions which have been categorized and refined by senior researchers into 48 research questions to be evaluated using five criteria: answerability, effectiveness, feasibility, applicability and impact, as well as equity. A total of 59 experts participated independently in the voluntary scoring exercise (a 34% response rate). There was substantial consensus among experts on priorities for research on alcohol and HIV. These tended to break down into two categories, those focusing on better understanding the nexus between alcohol and HIV and those directed towards informing practical interventions to reduce the impact of alcohol use on HIV treatment outcomes, which replicates what Bryant (Subst Use Misuse 41:1465-1507, 2006) and Parry et al. (Addiction 108:1-2, 2012) found. Responses from experts were stratified by location in order to determine any differences between groups. On average experts in the LMIC gave higher scores than the HIC experts. Recent research has shown the causal link between alcohol consumption and the incidence of HIV

  2. 76 FR 17808 - Final Vehicle Safety Rulemaking and Research Priority Plan 2011-2013

    Science.gov (United States)

    2011-03-31

    ... [Docket No. NHTSA-2009-0108] Final Vehicle Safety Rulemaking and Research Priority Plan 2011- 2013 AGENCY... availability. SUMMARY: This document announces the availability of the Final NHTSA Vehicle Safety and Fuel.... This Priority Plan is an update to the Final Vehicle Safety Rulemaking and Research Priority Plan 2009...

  3. Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients

    Science.gov (United States)

    Sauer, Aisha V.; Hernandez, Raisa Jofra; Fumagalli, Francesca; Bianchi, Veronica; Poliani, Pietro L.; Dallatomasina, Chiara; Riboni, Elisa; Politi, Letterio S.; Tabucchi, Antonella; Carlucci, Filippo; Casiraghi, Miriam; Carriglio, Nicola; Cominelli, Manuela; Forcellini, Carlo Alberto; Barzaghi, Federica; Ferrua, Francesca; Minicucci, Fabio; Medaglini, Stefania; Leocani, Letizia; la Marca, Giancarlo; Notarangelo, Lucia D.; Azzari, Chiara; Comi, Giancarlo; Baldoli, Cristina; Canale, Sabrina; Sessa, Maria; D’Adamo, Patrizia; Aiuti, Alessandro

    2017-01-01

    Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency. PMID:28074903

  4. Identifying priority areas for ecosystem service management in South African grasslands.

    Science.gov (United States)

    Egoh, Benis N; Reyers, Belinda; Rouget, Mathieu; Richardson, David M

    2011-06-01

    Grasslands provide many ecosystem services required to support human well-being and are home to a diverse fauna and flora. Degradation of grasslands due to agriculture and other forms of land use threaten biodiversity and ecosystem services. Various efforts are underway around the world to stem these declines. The Grassland Programme in South Africa is one such initiative and is aimed at safeguarding both biodiversity and ecosystem services. As part of this developing programme, we identified spatial priority areas for ecosystem services, tested the effect of different target levels of ecosystem services used to identify priority areas, and evaluated whether biodiversity priority areas can be aligned with those for ecosystem services. We mapped five ecosystem services (below ground carbon storage, surface water supply, water flow regulation, soil accumulation and soil retention) and identified priority areas for individual ecosystem services and for all five services at the scale of quaternary catchments. Planning for individual ecosystem services showed that, depending on the ecosystem service of interest, between 4% and 13% of the grassland biome was required to conserve at least 40% of the soil and water services. Thirty-four percent of the biome was needed to conserve 40% of the carbon service in the grassland. Priority areas identified for five ecosystem services under three target levels (20%, 40%, 60% of the total amount) showed that between 17% and 56% of the grassland biome was needed to conserve these ecosystem services. There was moderate to high overlap between priority areas selected for ecosystem services and already-identified terrestrial and freshwater biodiversity priority areas. This level of overlap coupled with low irreplaceability values obtained when planning for individual ecosystem services makes it possible to combine biodiversity and ecosystem services in one plan using systematic conservation planning. Copyright © 2011 Elsevier Ltd. All

  5. DRD4 long allele carriers show heightened attention to high-priority items relative to low-priority items.

    Science.gov (United States)

    Gorlick, Marissa A; Worthy, Darrell A; Knopik, Valerie S; McGeary, John E; Beevers, Christopher G; Maddox, W Todd

    2015-03-01

    Humans with seven or more repeats in exon III of the DRD4 gene (long DRD4 carriers) sometimes demonstrate impaired attention, as seen in attention-deficit hyperactivity disorder, and at other times demonstrate heightened attention, as seen in addictive behavior. Although the clinical effects of DRD4 are the focus of much work, this gene may not necessarily serve as a "risk" gene for attentional deficits, but as a plasticity gene where attention is heightened for priority items in the environment and impaired for minor items. Here we examine the role of DRD4 in two tasks that benefit from selective attention to high-priority information. We examine a category learning task where performance is supported by focusing on features and updating verbal rules. Here, selective attention to the most salient features is associated with good performance. In addition, we examine the Operation Span (OSPAN) task, a working memory capacity task that relies on selective attention to update and maintain items in memory while also performing a secondary task. Long DRD4 carriers show superior performance relative to short DRD4 homozygotes (six or less tandem repeats) in both the category learning and OSPAN tasks. These results suggest that DRD4 may serve as a "plasticity" gene where individuals with the long allele show heightened selective attention to high-priority items in the environment, which can be beneficial in the appropriate context.

  6. Cross-Layer Design and Analysis of Downlink Communications in Cellular CDMA Systems

    Directory of Open Access Journals (Sweden)

    Sun Jin Yuan

    2006-01-01

    Full Text Available A cellular CDMA network with voice and data communications is considered. Focusing on the downlink direction, we seek for the overall performance improvement which can be achieved by cross-layer analysis and design, taking physical layer, link layer, network layer, and transport layer into account. We are concerned with the role of each single layer as well as the interaction among layers, and propose algorithms/schemes accordingly to improve the system performance. These proposals include adaptive scheduling for link layer, priority-based handoff strategy for network admission control, and an algorithm for the avoidance of TCP spurious timeouts at the transport layer. Numerical results show the performance gain of each proposed scheme over independent performance of an individual layer in the wireless mobile network. We conclude that the system performance in terms of capacity, throughput, dropping probability, outage, power efficiency, delay, and fairness can be enhanced by jointly considering the interactions across layers.

  7. Cellular oxido-reductive proteins of Chlamydomonas reinhardtii control the biosynthesis of silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Barwal Indu

    2011-12-01

    Full Text Available Abstract Background Elucidation of molecular mechanism of silver nanoparticles (SNPs biosynthesis is important to control its size, shape and monodispersity. The evaluation of molecular mechanism of biosynthesis of SNPs is of prime importance for the commercialization and methodology development for controlling the shape and size (uniform distribution of SNPs. The unicellular algae Chlamydomonas reinhardtii was exploited as a model system to elucidate the role of cellular proteins in SNPs biosynthesis. Results The C. reinhardtii cell free extract (in vitro and in vivo cells mediated synthesis of silver nanoparticles reveals SNPs of size range 5 ± 1 to 15 ± 2 nm and 5 ± 1 to 35 ± 5 nm respectively. In vivo biosynthesized SNPs were localized in the peripheral cytoplasm and at one side of flagella root, the site of pathway of ATP transport and its synthesis related enzymes. This provides an evidence for the involvement of oxidoreductive proteins in biosynthesis and stabilization of SNPs. Alteration in size distribution and decrease of synthesis rate of SNPs in protein-depleted fractions confirmed the involvement of cellular proteins in SNPs biosynthesis. Spectroscopic and SDS-PAGE analysis indicate the association of various proteins on C. reinhardtii mediated in vivo and in vitro biosynthesized SNPs. We have identified various cellular proteins associated with biosynthesized (in vivo and in vitro SNPs by using MALDI-MS-MS, like ATP synthase, superoxide dismutase, carbonic anhydrase, ferredoxin-NADP+ reductase, histone etc. However, these proteins were not associated on the incubation of pre-synthesized silver nanoparticles in vitro. Conclusion Present study provides the indication of involvement of molecular machinery and various cellular proteins in the biosynthesis of silver nanoparticles. In this report, the study is mainly focused towards understanding the role of diverse cellular protein in the synthesis and capping of silver

  8. Information and shared decision-making are top patients' priorities

    Directory of Open Access Journals (Sweden)

    Bronstein Alexander

    2006-02-01

    Full Text Available Abstract Background The profound changes in medical care and the recent stress on a patient-centered approach mandate evaluation of current patient priorities. Methods Hospitalized and ambulatory patients at an academic medical center in central Israel were investigated. Consecutive patients (n = 274 indicated their first and second priority for a change or improvement in their medical care out of a mixed shortlist of 6 issues, 3 related to patient-physician relationship (being better informed and taking part in decisions; being seen by the same doctor each time; a longer consultation time and 3 issues related to the organizational aspect of care (easier access to specialists/hospital; shorter queue for tests; less charges for drugs. Results Getting more information from the physician and taking part in decisions was the most desirable patient choice, selected by 27.4% as their first priority. The next choices – access and queue – also relate to more patient autonomy and control over that of managed care regulations. Patients studied were least interested in continuity of care, consultation time or cost of drugs. Demographic or clinical variables were not significantly related to patients' choices. Conclusion Beyond its many benefits, being informed by their doctor and shared decision making is a top patient priority.

  9. Top-down cellular pyramids

    Energy Technology Data Exchange (ETDEWEB)

    Wu, A Y; Rosenfeld, A

    1983-10-01

    A cellular pyramid is an exponentially tapering stack of arrays of processors (cells), where each cell is connected to its neighbors (siblings) on its own level, to a parent on the level above, and to its children on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case. 23 references.

  10. Cellular decomposition in vikalloys

    International Nuclear Information System (INIS)

    Belyatskaya, I.S.; Vintajkin, E.Z.; Georgieva, I.Ya.; Golikov, V.A.; Udovenko, V.A.

    1981-01-01

    Austenite decomposition in Fe-Co-V and Fe-Co-V-Ni alloys at 475-600 deg C is investigated. The cellular decomposition in ternary alloys results in the formation of bcc (ordered) and fcc structures, and in quaternary alloys - bcc (ordered) and 12R structures. The cellular 12R structure results from the emergence of stacking faults in the fcc lattice with irregular spacing in four layers. The cellular decomposition results in a high-dispersion structure and magnetic properties approaching the level of well-known vikalloys [ru

  11. Toxicity potentials from waste cellular phones, and a waste management policy integrating consumer, corporate, and government responsibilities

    International Nuclear Information System (INIS)

    Lim, Seong-Rin; Schoenung, Julie M.

    2010-01-01

    Cellular phones have high environmental impact potentials because of their heavy metal content and current consumer attitudes toward purchasing new phones with higher functionality and neglecting to return waste phones into proper take-back systems. This study evaluates human health and ecological toxicity potentials from waste cellular phones; highlights consumer, corporate, and government responsibilities for effective waste management; and identifies key elements needed for an effective waste management strategy. The toxicity potentials are evaluated by using heavy metal content, respective characterization factors, and a pathway and impact model for heavy metals that considers end-of-life disposal in landfills or by incineration. Cancer potentials derive primarily from Pb and As; non-cancer potentials primarily from Cu and Pb; and ecotoxicity potentials primarily from Cu and Hg. These results are not completely in agreement with previous work in which leachability thresholds were the metric used to establish priority, thereby indicating the need for multiple or revised metrics. The triple bottom line of consumer, corporate, and government responsibilities is emphasized in terms of consumer attitudes, design for environment (DfE), and establishment and implementation of waste management systems including recycling streams, respectively. The key strategic elements for effective waste management include environmental taxation and a deposit-refund system to motivate consumer responsibility, which is linked and integrated with corporate and government responsibilities. The results of this study can contribute to DfE and waste management policy for cellular phones.

  12. Toxicity potentials from waste cellular phones, and a waste management policy integrating consumer, corporate, and government responsibilities.

    Science.gov (United States)

    Lim, Seong-Rin; Schoenung, Julie M

    2010-01-01

    Cellular phones have high environmental impact potentials because of their heavy metal content and current consumer attitudes toward purchasing new phones with higher functionality and neglecting to return waste phones into proper take-back systems. This study evaluates human health and ecological toxicity potentials from waste cellular phones; highlights consumer, corporate, and government responsibilities for effective waste management; and identifies key elements needed for an effective waste management strategy. The toxicity potentials are evaluated by using heavy metal content, respective characterization factors, and a pathway and impact model for heavy metals that considers end-of-life disposal in landfills or by incineration. Cancer potentials derive primarily from Pb and As; non-cancer potentials primarily from Cu and Pb; and ecotoxicity potentials primarily from Cu and Hg. These results are not completely in agreement with previous work in which leachability thresholds were the metric used to establish priority, thereby indicating the need for multiple or revised metrics. The triple bottom line of consumer, corporate, and government responsibilities is emphasized in terms of consumer attitudes, design for environment (DfE), and establishment and implementation of waste management systems including recycling streams, respectively. The key strategic elements for effective waste management include environmental taxation and a deposit-refund system to motivate consumer responsibility, which is linked and integrated with corporate and government responsibilities. The results of this study can contribute to DfE and waste management policy for cellular phones. 2010 Elsevier Ltd. All rights reserved.

  13. Perioperative leadership: managing change with insights, priorities, and tools.

    Science.gov (United States)

    Taylor, David L

    2014-07-01

    The personal leadership of the perioperative director is a critical factor in the success of any change management initiative. This article presents an approach to perioperative nursing leadership that addresses obstacles that prevent surgical departments from achieving high performance in clinical and financial outcomes. This leadership approach consists of specific insights, priorities, and tools: key insights include self-understanding of personal barriers to leadership and accuracy at understanding economic and strategic considerations related to the OR environment; key priorities include creating a customer-centered organization, focusing on process improvement, and concentrating on culture change; and key tools include using techniques (e.g., direct engagement, collaborative leadership) to align surgical organizations with leadership priorities and mitigate specific perioperative management risks. Included in this article is a leadership development plan for perioperative directors. Copyright © 2014 AORN, Inc. Published by Elsevier Inc. All rights reserved.

  14. Final priority; technical assistance to improve state data capacity--National Technical Assistance Center to improve state capacity to accurately collect and report IDEA data. Final priority.

    Science.gov (United States)

    2013-05-20

    The Assistant Secretary for Special Education and Rehabilitative Services announces a priority under the Technical Assistance to Improve State Data Capacity program. The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2013 and later years. We take this action to focus attention on an identified national need to provide technical assistance (TA) to States to improve their capacity to meet the data collection and reporting requirements of the Individuals with Disabilities Education Act (IDEA). We intend this priority to establish a TA center to improve State capacity to accurately collect and report IDEA data (Data Center).

  15. Setting practical conservation priorities for birds in the Western Andes of Colombia.

    Science.gov (United States)

    Ocampo-Peñuela, Natalia; Pimm, Stuart L

    2014-10-01

    We aspired to set conservation priorities in ways that lead to direct conservation actions. Very large-scale strategic mapping leads to familiar conservation priorities exemplified by biodiversity hotspots. In contrast, tactical conservation actions unfold on much smaller geographical extents and they need to reflect the habitat loss and fragmentation that have sharply restricted where species now live. Our aspirations for direct, practical actions were demanding. First, we identified the global, strategic conservation priorities and then downscaled to practical local actions within the selected priorities. In doing this, we recognized the limitations of incomplete information. We started such a process in Colombia and used the results presented here to implement reforestation of degraded land to prevent the isolation of a large area of cloud forest. We used existing range maps of 171 bird species to identify priority conservation areas that would conserve the greatest number of species at risk in Colombia. By at risk species, we mean those that are endemic and have small ranges. The Western Andes had the highest concentrations of such species-100 in total-but the lowest densities of national parks. We then adjusted the priorities for this region by refining these species ranges by selecting only areas of suitable elevation and remaining habitat. The estimated ranges of these species shrank by 18-100% after accounting for habitat and suitable elevation. Setting conservation priorities on the basis of currently available range maps excluded priority areas in the Western Andes and, by extension, likely elsewhere and for other taxa. By incorporating detailed maps of remaining natural habitats, we made practical recommendations for conservation actions. One recommendation was to restore forest connections to a patch of cloud forest about to become isolated from the main Andes. © 2014 Society for Conservation Biology.

  16. Priority image transmission in wireless sensor networks

    International Nuclear Information System (INIS)

    Nasri, M.; Helali, A.; Sghaier, H.; Maaref, H.

    2011-01-01

    The emerging technology during the last years allowed the development of new sensors equipped with wireless communication which can be organized into a cooperative autonomous network. Some application areas for wireless sensor networks (WSNs) are home automations, health care services, military domain, and environment monitoring. The required constraints are limited capacity of processing, limited storage capability, and especially these nodes are limited in energy. In addition, such networks are tiny battery powered which their lifetime is very limited. During image processing and transmission to the destination, the lifetime of sensor network is decreased quickly due to battery and processing power constraints. Therefore, digital image transmissions are a significant challenge for image sensor based Wireless Sensor Networks (WSNs). Based on a wavelet image compression, we propose a novel, robust and energy-efficient scheme, called Priority Image Transmission (PIT) in WSN by providing various priority levels during image transmissions. Different priorities in the compressed image are considered. The information for the significant wavelet coeffcients are transmitted with higher quality assurance, whereas relatively less important coefficients are transmitted with lower overhead. Simulation results show that the proposed scheme prolongs the system lifetime and achieves higher energy efficiency in WSN with an acceptable compromise on the image quality.

  17. Multiserver Queue with Guard Channel for Priority and Retrial Customers

    Directory of Open Access Journals (Sweden)

    Kazuki Kajiwara

    2016-01-01

    Full Text Available This paper considers a retrial queueing model where a group of guard channels is reserved for priority and retrial customers. Priority and normal customers arrive at the system according to two distinct Poisson processes. Priority customers are accepted if there is an idle channel upon arrival while normal customers are accepted if and only if the number of idle channels is larger than the number of guard channels. Blocked customers (priority or normal join a virtual orbit and repeat their attempts in a later time. Customers from the orbit (retrial customers are accepted if there is an idle channel available upon arrival. We formulate the queueing system using a level dependent quasi-birth-and-death (QBD process. We obtain a Taylor series expansion for the nonzero elements of the rate matrices of the level dependent QBD process. Using the expansion results, we obtain an asymptotic upper bound for the joint stationary distribution of the number of busy channels and that of customers in the orbit. Furthermore, we develop an efficient numerical algorithm to calculate the joint stationary distribution.

  18. A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev

    International Nuclear Information System (INIS)

    Fang Jianhua; Kubota, Satoshi; Yang Bin; Zhou Naiming; Zhang Hui; Godbout, Roseline; Pomerantz, Roger J.

    2004-01-01

    HIV-1 Rev escorts unspliced viral mRNAs out of the nucleus of infected cells, which allows formation of infectious HIV-1 virions. We have identified a putative DEAD box (Asp-Glu-Ala-Asp) RNA helicase, DDX1, as a cellular co-factor of Rev, through yeast and mammalian two-hybrid systems using the N-terminal motif of Rev as 'bait'. DDX1 is not a functional homolog of HIV-1 Rev, but down-regulation of DDX1 resulted in an alternative splicing pattern of Rev-responsive element (RRE)-containing mRNA, and attenuation of Gag p24 antigen production from HLfb rev(-) cells rescued by exogenous Rev. Co-transfection of a DDX1 expression vector with HIV-1 significantly increased viral production. DDX1 binding to Rev, as well as to the RRE, strongly suggest that DDX1 affects Rev function through the Rev-RRE axis. Moreover, down-regulation of DDX1 altered the steady state subcellular distribution of Rev, from nuclear/nucleolar to cytoplasmic dominance. These findings indicate that DDX1 is a critical cellular co-factor for Rev function, which maintains the proper subcellular distribution of this lentiviral regulatory protein. Therefore, alterations in DDX1-Rev interactions could induce HIV-1 persistence and targeting DDX1 may lead to rationally designed and novel anti-HIV-1 strategies and therapeutics

  19. Energy secretary's priorities include San Francisco area research projects

    CERN Multimedia

    Widener, A

    2003-01-01

    "Bay Area research labs got a big boost Monday when the Secretary of Energy unveiled his priorities for major research projects his agency hopes to fund over the next two decades. Among the agency's 28 top priorities are a major computer expansion and an experiment examining the expanding universe that could be housed at Lawrence Berkeley Lab and a powerful X-ray laser planned for the Stanford Linear Accelerator Center" (1 page).

  20. Adaptive Priority-Based Downlink Scheduling for WiMAX Networks

    OpenAIRE

    Wu, Shih-Jung; Huang, Shih-Yi; Huang, Kuo-Feng

    2012-01-01

    Supporting quality of service (QoS) guarantees for diverse multimedia services are the primary concerns for WiMAX (IEEE 802.16) networks. A scheduling scheme that satisfies QoS requirements has become more important for wireless communications. We propose a downlink scheduling scheme called adaptive priority-based downlink scheduling (APDS) for providing QoS guarantees in IEEE 802.16 networks. APDS comprises two major components: priority assignment and resource allocation. Different service-...

  1. A checklist for health research priority setting: nine common themes of good practice

    Directory of Open Access Journals (Sweden)

    Terry Robert F

    2010-12-01

    Full Text Available Abstract Health research priority setting processes assist researchers and policymakers in effectively targeting research that has the greatest potential public health benefit. Many different approaches to health research prioritization exist, but there is no agreement on what might constitute best practice. Moreover, because of the many different contexts for which priorities can be set, attempting to produce one best practice is in fact not appropriate, as the optimal approach varies per exercise. Therefore, following a literature review and an analysis of health research priority setting exercises that were organized or coordinated by the World Health Organization since 2005, we propose a checklist for health research priority setting that allows for informed choices on different approaches and outlines nine common themes of good practice. It is intended to provide generic assistance for planning health research prioritization processes. The checklist explains what needs to be clarified in order to establish the context for which priorities are set; it reviews available approaches to health research priority setting; it offers discussions on stakeholder participation and information gathering; it sets out options for use of criteria and different methods for deciding upon priorities; and it emphasizes the importance of well-planned implementation, evaluation and transparency.

  2. Functional Task Test: 1. Sensorimotor changes Associated with Postflight Alterations in Astronaut Functional Task Performance

    Science.gov (United States)

    Bloomberg, J. J.; Arzeno, N. H.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Miller, C. A.; Mulavara, A. P.; Platts, S. H.; Peters, B. T.; hide

    2011-01-01

    Space flight is known to cause alterations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These changes may affect a crewmember s ability to perform critical mission tasks immediately after landing on a planetary surface. The overall goal of this project is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. This presentation will focus on the sensorimotor contributions to postflight functional performance.

  3. Heat Shock Protein 47: A Novel Biomarker of Phenotypically Altered Collagen-Producing Cells

    International Nuclear Information System (INIS)

    Taguchi, Takashi; Nazneen, Arifa; Al-Shihri, Abdulmonem A.; Turkistani, Khadijah A.; Razzaque, Mohammed S.

    2011-01-01

    Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that helps the molecular maturation of various types of collagens. A close association between increased expression of HSP47 and the excessive accumulation of collagens is found in various human and experimental fibrotic diseases. Increased levels of HSP47 in fibrotic diseases are thought to assist in the increased assembly of procollagen, and thereby contribute to the excessive deposition of collagens in fibrotic areas. Currently, there is not a good universal histological marker to identify collagen-producing cells. Identifying phenotypically altered collagen-producing cells is essential for the development of cell-based therapies to reduce the progression of fibrotic diseases. Since HSP47 has a single substrate, which is collagen, the HSP47 cellular expression provides a novel universal biomarker to identify phenotypically altered collagen-producing cells during wound healing and fibrosis. In this brief article, we explained why HSP47 could be used as a universal marker for identifying phenotypically altered collagen-producing cells

  4. Publishing priorities of biomedical research funders

    Science.gov (United States)

    Collins, Ellen

    2013-01-01

    Objectives To understand the publishing priorities, especially in relation to open access, of 10 UK biomedical research funders. Design Semistructured interviews. Setting 10 UK biomedical research funders. Participants 12 employees with responsibility for research management at 10 UK biomedical research funders; a purposive sample to represent a range of backgrounds and organisation types. Conclusions Publicly funded and large biomedical research funders are committed to open access publishing and are pleased with recent developments which have stimulated growth in this area. Smaller charitable funders are supportive of the aims of open access, but are concerned about the practical implications for their budgets and their funded researchers. Across the board, biomedical research funders are turning their attention to other priorities for sharing research outputs, including data, protocols and negative results. Further work is required to understand how smaller funders, including charitable funders, can support open access. PMID:24154520

  5. Strategic priorities of Iranian companies: an application of mission statement content analysis

    OpenAIRE

    Shahriar AZIZI; Vahid MAKIZADEH

    2014-01-01

    The mission statement describes the strategic priorities of a company. It determines the roadmap for strategic decision in the corporation. Research on mission statement elements is an interesting field because it clarifies the strategic priorities of the company. This paper aims to analyze these priorities among 48 large Iranian companies active in four selected industries based on David’s (1989) nine-element model. These components include customer, market, general image, product, technolog...

  6. Priority effects are weakened by a short, but not long, history of sympatric evolution.

    Science.gov (United States)

    Zee, Peter C; Fukami, Tadashi

    2018-01-31

    Priority effects, or the effects of species arrival history on local species abundances, have been documented in a range of taxa. However, factors determining the extent to which priority effects affect community assembly remain unclear. Using laboratory populations of the bacterium Pseudomonas fluorescens , we examined whether shared evolutionary history affected the strength of priority effects. We hypothesized that sympatric evolution of populations belonging to the same guild would lead to niche differentiation, resulting in phenotypic complementarity that weakens priority effects. Consistent with this hypothesis, we found that priority effects tended to be weaker in sympatrically evolved pairs of immigrating populations than in allopatrically evolved pairs. Furthermore, priority effects were weaker under higher phenotypic complementarity. However, these patterns were observed only in populations with a relatively short history of sympatric evolution, and disappeared when populations had evolved together for a long time. Together, our results suggest that the evolutionary history of organismal traits may dictate the strength of priority effects and, consequently, the extent of historical contingency in the assembly of ecological communities. © 2018 The Author(s).

  7. Research priorities in mental health occupational therapy: A study of clinician perspectives.

    Science.gov (United States)

    Hitch, Danielle; Lhuede, Kate

    2015-10-01

    The evidence to support mental health occupational therapy has proliferated in the early years of this century, but this growth has tended to be organic rather than targeted. Previous efforts to identify research priorities in this area of practice are either out dated, or encompass discrete areas of practice. The aim of this study was to identify priority areas for research in mental health occupational therapy from clinician's perspectives. A Policy Delphi method was used to enable occupational therapists to define and differentiate their perspectives on research priorities. Forty-two occupational therapists took part in the first two rounds of this method, with 69% (n = 29) going on to complete the third and final round of data collection. A Likert scale was used to rate the importance of each priority, and descriptive quantitative analysis undertaken to identify those most consistently identified as being highly important. Four research priorities were identified as being highly important in this study: (i) working in an occupationally focussed way; (ii) consumer experience of therapy groups; (iii) identifying factors which increase consumer engagement in occupation; and (iv) engaging patients on the inpatient unit in meaningful and positive occupation. Two of the priority areas are already the subject of substantial evidence bases, but there has been far less research into consumer experiences of groups and occupational engagement in acute settings. Collaboration between research teams and greater consumer inclusion are recommended for the future. This study provides an updated indication of research priorities for mental health occupational therapy in Australia. © 2015 Occupational Therapy Australia.

  8. Cellular automata analysis and applications

    CERN Document Server

    Hadeler, Karl-Peter

    2017-01-01

    This book focuses on a coherent representation of the main approaches to analyze the dynamics of cellular automata. Cellular automata are an inevitable tool in mathematical modeling. In contrast to classical modeling approaches as partial differential equations, cellular automata are straightforward to simulate but hard to analyze. In this book we present a review of approaches and theories that allow the reader to understand the behavior of cellular automata beyond simulations. The first part consists of an introduction of cellular automata on Cayley graphs, and their characterization via the fundamental Cutis-Hedlund-Lyndon theorems in the context of different topological concepts (Cantor, Besicovitch and Weyl topology). The second part focuses on classification results: What classification follows from topological concepts (Hurley classification), Lyapunov stability (Gilman classification), and the theory of formal languages and grammars (Kůrka classification). These classifications suggest to cluster cel...

  9. Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Janel E. Le Belle

    2014-11-01

    Full Text Available A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  10. Evaluating priority setting success in healthcare: a pilot study

    Directory of Open Access Journals (Sweden)

    Upshur Ross

    2010-05-01

    Full Text Available Abstract Background In healthcare today, decisions are made in the face of serious resource constraints. Healthcare managers are struggling to provide high quality care, manage resources effectively, and meet changing patient needs. Healthcare managers who are constantly making difficult resource decisions desire a way to improve their priority setting processes. Despite the wealth of existing priority setting literature (for example, program budgeting and marginal analysis, accountability for reasonableness, the 'describe-evaluate-improve' strategy there are still no tools to evaluate how healthcare resources are prioritised. This paper describes the development and piloting of a process to evaluate priority setting in health institutions. The evaluation process was designed to examine the procedural and substantive dimensions of priority setting using a multi-methods approach, including a staff survey, decision-maker interviews, and document analysis. Methods The evaluation process was piloted in a mid-size community hospital in Ontario, Canada while its leaders worked through their annual budgeting process. Both qualitative and quantitative methods were used to analyze the data. Results The evaluation process was both applicable to the context and it captured the budgeting process. In general, the pilot test provided support for our evaluation process and our definition of success, (i.e., our conceptual framework. Conclusions The purpose of the evaluation process is to provide a simple, practical way for an organization to better understand what it means to achieve success in its priority setting activities and identify areas for improvement. In order for the process to be used by healthcare managers today, modification and contextualization of the process are anticipated. As the evaluation process is applied in more health care organizations or applied repeatedly in an organization, it may become more streamlined.

  11. 78 FR 29785 - Priority Mail Pricing

    Science.gov (United States)

    2013-05-21

    ... POSTAL REGULATORY COMMISSION [Docket No. R2013-7; Order No. 1714] Priority Mail Pricing AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal... that after the price change, the unused pricing authority available for the Special Services class will...

  12. Global health trials methodological research agenda:results from a priority setting exercise

    OpenAIRE

    Blazeby, Jane; Nasser, Mona; Soares-Weiser, Karla; Sydes, Matthew R.; Zhang, Junhua; Williamson, Paula R

    2018-01-01

    BackgroundMethodological research into the design, conduct, analysis and reporting of trials is essential to optimise the process. UK specialists in the field have established a set of top priorities in aid of this research. These priorities however may not be reflected in the needs of similar research in low to middle income countries (LMICs) with different healthcare provision, resources and research infrastructure. The aim of the study was to identify the top priorities for methodological ...

  13. Social welfare in one-sided matchings: Random priority and beyond

    DEFF Research Database (Denmark)

    Filos-Ratsikas, Aris; Frederiksen, Søren Kristoffer Stiil; Zhang, Jie

    2014-01-01

    We study the problem of approximate social welfare maximization (without money) in one-sided matching problems when agents have unrestricted cardinal preferences over a finite set of items. Random priority is a very well-known truthful-in-expectation mechanism for the problem. We prove...... that the approximation ratio of random priority is Theta(n^{-1/2}) while no truthful-in-expectation mechanism can achieve an approximation ratio better than O(n^{-1/2}), where n is the number of agents and items. Furthermore, we prove that the approximation ratio of all ordinal (not necessarily truthful......-in-expectation) mechanisms is upper bounded by O(n^{-1/2}), indicating that random priority is asymptotically the best truthful-in-expectation mechanism and the best ordinal mechanism for the problem....

  14. Incorporating public priorities in the Ocean Health Index: Canada as a case study.

    Directory of Open Access Journals (Sweden)

    Rémi M Daigle

    Full Text Available The Ocean Health Index (OHI is a framework to assess ocean health by considering many benefits (called 'goals' provided by the ocean provides to humans, such as food provision, tourism opportunities, and coastal protection. The OHI framework can be used to assess marine areas at global or regional scales, but how various OHI goals should be weighted to reflect priorities at those scales remains unclear. In this study, we adapted the framework in two ways for application to Canada as a case study. First, we customized the OHI goals to create a national Canadian Ocean Health Index (COHI. In particular, we altered the list of iconic species assessed, added methane clathrates and subsea permafrost as carbon storage habitats, and developed a new goal, 'Aboriginal Needs', to measure access of Aboriginal people to traditional marine hunting and fishing grounds. Second, we evaluated various goal weighting schemes based on preferences elicited from the general public in online surveys. We quantified these public preferences in three ways: using Likert scores, simple ranks from a best-worst choice experiment, and model coefficients from the analysis of elicited choice experiment. The latter provided the clearest statistical discrimination among goals, and we recommend their use because they can more accurately reflect both public opinion and the trade-offs faced by policy-makers. This initial iteration of the COHI can be used as a baseline against which future COHI scores can be compared, and could potentially be used as a management tool to prioritise actions on a national scale and predict public support for these actions given that the goal weights are based on public priorities.

  15. Evaluating healthcare priority setting at the meso level: A thematic review of empirical literature

    Science.gov (United States)

    Waithaka, Dennis; Tsofa, Benjamin; Barasa, Edwine

    2018-01-01

    Background: Decentralization of health systems has made sub-national/regional healthcare systems the backbone of healthcare delivery. These regions are tasked with the difficult responsibility of determining healthcare priorities and resource allocation amidst scarce resources. We aimed to review empirical literature that evaluated priority setting practice at the meso (sub-national) level of health systems. Methods: We systematically searched PubMed, ScienceDirect and Google scholar databases and supplemented these with manual searching for relevant studies, based on the reference list of selected papers. We only included empirical studies that described and evaluated, or those that only evaluated priority setting practice at the meso-level. A total of 16 papers were identified from LMICs and HICs. We analyzed data from the selected papers by thematic review. Results: Few studies used systematic priority setting processes, and all but one were from HICs. Both formal and informal criteria are used in priority-setting, however, informal criteria appear to be more perverse in LMICs compared to HICs. The priority setting process at the meso-level is a top-down approach with minimal involvement of the community. Accountability for reasonableness was the most common evaluative framework as it was used in 12 of the 16 studies. Efficiency, reallocation of resources and options for service delivery redesign were the most common outcome measures used to evaluate priority setting. Limitations: Our study was limited by the fact that there are very few empirical studies that have evaluated priority setting at the meso-level and there is likelihood that we did not capture all the studies. Conclusions: Improving priority setting practices at the meso level is crucial to strengthening health systems. This can be achieved through incorporating and adapting systematic priority setting processes and frameworks to the context where used, and making considerations of both process

  16. Comparative study of cell alterations in oral lichen planus and epidermoid carcinoma of the mouth mucosa.

    Science.gov (United States)

    Sousa, Fernando Augusto Cervantes Garcia de; Paradella, Thaís Cachuté; Brandão, Adriana Aigotti Haberbeck; Rosa, Luiz Eduardo Blumer

    2009-01-01

    Currently, much is discussed regarding the pre-malignant nature of mouth mucosa lichen planus. The present study aims at analyzing the alterations found in the epithelial cells present in the oral cavity lichen planus, comparing them to those found in epidermoid carcinoma. Histological cross-sections of oral lichen planus and epidermoid carcinoma, dyed by hematoxylineosin, were analyzed through light microscopy. The most frequently found alterations in oral lichen planus were: an increase in the nucleus/cytoplasm relation (93.33%), nucleus membrane thickness (86.67%) and bi-nucleus or multinucleous (86.67%). The Student t test (alpha=5%) revealed a statistically significant difference between the average number of cell alterations in oral lichen planus (5.87+/-1.57) and in epidermoid carcinoma (7.60+/-1.81). As to the types of alterations, the chi-squared test also revealed statistically significant differences among the lesions assessed in relation to the following cell alterations: nuclear excess chromatism, atypical mitoses, cellular pleomorphism and abnormal cell differentiation (poral lichen planus, the results obtained in this study show that the alterations present in oral lichen planus differ considerably from those seen in epidermoid carcinoma, thus showing how distinct these two diseases are.

  17. An Active Queue Management for QoS Guarantee of the High Priority Service Class

    Science.gov (United States)

    Kim, Hyun Jong; Shim, Jae Chan; Kim, Hwa-Suk; Cho, Kee Seong; Choi, Seong Gon

    In this paper, we propose the active queue management mechanism (Active-WRED) for guaranteeing the quality of the high priority service class (VoIP or IPTV) in the multi-class traffic service environment. In the congestion situation, this mechanism increases the drop probability of the low priority traffic and reduces the drop probability of the high priority traffic; therefore it can guarantee the quality of the high priority service class from the poor quality by the packet loss.

  18. Isogenic Cellular Systems Model the Impact of Genetic Risk Variants in the Pathogenesis of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Mark A. Wallet

    2017-10-01

    Full Text Available At least 57 independent loci within the human genome confer varying degrees of risk for the development of type 1 diabetes (T1D. The majority of these variants are thought to contribute to overall genetic risk by modulating host innate and adaptive immune responses, ultimately resulting in a loss of immunological tolerance to β cell antigens. Early efforts to link specific risk variants with functional alterations in host immune responses have employed animal models or genotype-selected individuals from clinical bioresource banks. While some notable genotype:phenotype associations have been described, there remains an urgent need to accelerate the discovery of causal variants and elucidate the molecular mechanisms by which susceptible alleles alter immune functions. One significant limitation has been the inability to study human T1D risk loci on an isogenic background. The advent of induced pluripotent stem cells (iPSCs and genome-editing technologies have made it possible to address a number of these outstanding questions. Specifically, the ability to drive multiple cell fates from iPSC under isogenic conditions now facilitates the analysis of causal variants in multiple cellular lineages. Bioinformatic analyses have revealed that T1D risk genes cluster within a limited number of immune signaling pathways, yet the relevant immune cell subsets and cellular activation states in which candidate risk genes impact cellular activities remain largely unknown. In this review, we summarize the functional impact of several candidate risk variants on host immunity in T1D and present an isogenic disease-in-a-dish model system for interrogating risk variants, with the goal of expediting precision therapeutics in T1D.

  19. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

    As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

  20. Identification of circular RNAs from the parental genes involved in multiple aspects of cellular metabolism in barley

    DEFF Research Database (Denmark)

    Shirvanehdeh, Behrooz Darbani; Noeparvar, Shahin; Borg, Søren

    2016-01-01

    circular RNAs as novel interactors in the regulation of gene expression in plants and imply the comprehensiveness of this regulatory pathway by identifying circular RNAs for a diverse set of genes. These genes are involved in several aspects of cellular metabolism as hormonal signaling, intracellular...... protein sorting, carbohydrate metabolism and cell-wall biogenesis, respiration, amino acid biosynthesis, transcription and translation, and protein ubiquitination. Additionally, these parental loci of circular RNAs, from both nuclear and mitochondrial genomes, encode for different transcript classes...... and elucidate their cellular-level alterations across tissues and in response to micronutrients iron and zinc. In further support of circular RNAs’ functional roles in plants, we report several cases where fluctuations of circRNAs do not correlate with the levels of their parental-loci encoded linear...

  1. Clinical Findings Documenting Cellular and Molecular Abnormalities of Glia in Depressive Disorders

    Directory of Open Access Journals (Sweden)

    Boldizsár Czéh

    2018-02-01

    Full Text Available Depressive disorders are complex, multifactorial mental disorders with unknown neurobiology. Numerous theories aim to explain the pathophysiology. According to the “gliocentric theory”, glial abnormalities are responsible for the development of the disease. The aim of this review article is to summarize the rapidly growing number of cellular and molecular evidences indicating disturbed glial functioning in depressive disorders. We focus here exclusively on the clinical studies and present the in vivo neuroimaging findings together with the postmortem molecular and histopathological data. Postmortem studies demonstrate glial cell loss while the in vivo imaging data reveal disturbed glial functioning and altered white matter microstructure. Molecular studies report on altered gene expression of glial specific genes. In sum, the clinical findings provide ample evidences on glial pathology and demonstrate that all major glial cell types are affected. However, we still lack convincing theories explaining how the glial abnormalities develop and how exactly contribute to the emotional and cognitive disturbances. Abnormal astrocytic functioning may lead to disturbed metabolism affecting ion homeostasis and glutamate clearance, which in turn, affect synaptic communication. Abnormal oligodendrocyte functioning may disrupt the connectivity of neuronal networks, while microglial activation indicates neuroinflammatory processes. These cellular changes may relate to each other or they may indicate different endophenotypes. A theory has been put forward that the stress-induced inflammation—mediated by microglial activation—triggers a cascade of events leading to damaged astrocytes and oligodendroglia and consequently to their dysfunctions. The clinical data support the “gliocentric” theory, but future research should clarify whether these glial changes are truly the cause or simply the consequences of this devastating disorder.

  2. 7 CFR 1710.119 - Loan processing priorities.

    Science.gov (United States)

    2010-01-01

    ... and Basic Policies § 1710.119 Loan processing priorities. (a) Generally loans are processed in... in effect at the time the facilities were originally constructed; (3) To finance the capital needs of...

  3. Research priorities for coordinating management of food safety and water quality.

    Science.gov (United States)

    Crohn, David M; Bianchi, Mary L

    2008-01-01

    Efforts to exclude disease organisms from farms growing irrigated lettuce and leafy vegetables on California's central coast are conflicting with traditionally accepted strategies to protect surface water quality. To begin resolving this dilemma, over 100 officials, researchers, and industry representatives gathered in April 2007 to set research priorities that could lead to effective co-management of both food safety and water quality. Following the meeting, research priorities were refined and ordered by way of a Delphi process completed by 35 meeting participants. Although water quality and food safety experts conceptualized the issues differently, there were no deep disagreements with respect to research needs. Top priority was given to investigating the fate of pathogens potentially present on farms. Intermediate priorities included characterizing the influence of specific farm management practices on food safety and improving our understanding of vector processes. A scientific subdiscipline focusing on competing risks is needed to characterize and resolve conflicts between human and environmental health.

  4. Stimulation of Cellular Proliferation by Hepatitis B Virus X Protein

    Directory of Open Access Journals (Sweden)

    Charles R. Madden

    2001-01-01

    Full Text Available Chronic infection with the hepatitis B virus (HBV is a known risk factor in the development of human hepatocellular carcinoma (HCC. The HBV-encoded X protein, HBx, has been investigated for properties that may explain its cancer cofactor role in transgenic mouse lines. We discuss here recent data showing that HBx is able to induce hepatocellular proliferation in vitro and in vivo. This property of HBx is predicted to sensitize hepatocytes to other HCC cofactors, including exposure to carcinogens and to other hepatitis viruses. Cellular proliferation is intimately linked to the mechanism(s by which most tumor-associated viruses transform virus-infected cells. The HBx alteration of the cell cycle provides an additional mechanism by which chronic HBV infection may contribute to HCC.

  5. PRIORITIES OF REGIONAL ENVIRONMENTAL POLICY: THE ISSUES OF DIAGNOSTICS

    Directory of Open Access Journals (Sweden)

    T. I. Kudryavtseva

    2010-03-01

    Full Text Available Methods of eliciting priority ecological problems are analyzed in the article. The problem of air pollution is considered to be the foreground issue for both the Ural Federal District and Russia; that was due substantiated. An extended technique of setting priorities for air pollutants and techniques for integral ecological and social assessment of air pollution acuteness extent in the region have been offered; calculations for the Ural Federal District have been made according to the techniques mentioned.

  6. Pharmacists' perceptions of advancing public health priorities through medication therapy management

    Directory of Open Access Journals (Sweden)

    Casserlie LM

    2016-09-01

    Full Text Available Background: Public health priorities can be addressed by pharmacists through channels such as medication therapy management (MTM to optimize patient and population outcomes. However, no studies have specifically assessed pharmacists’ perceptions of addressing public health priorities through MTM. Objective: The objective of this study was to assess pharmacists’ opinions regarding the feasibility and appropriateness of addressing seven areas of public health priority through MTM services to impact public health in direct patient care settings. Methods: An anonymous 37-question electronic survey was conducted to evaluate Ohio pharmacists’ opinions of advancing seven public health priorities identified from Healthy People 2020 (family planning, preconception care, smoking cessation, immunizations, nutrition/biometric wellness assessments, point-of-care testing, fall prevention through MTM activities; to identify potential barriers; and to collect demographic information. The cross-sectional survey was sent to a random sample of 500 pharmacists registered with the Ohio State Board of Pharmacy. Results: Seventy-six pharmacists responded to the survey, resulting in a 16% response rate. On average, it took respondents 5-10 minutes to complete the survey. The majority of respondents thought that each of the seven public health priorities were “important” or “very important” to patient health; the most commonly identified areas included smoking cessation, immunizations, and fall prevention (97.5%. When asked to indicate which of the seven areas they thought they could potentially have a role to provide services through MTM, on average pharmacists picked 4 of the priority areas. Only 6.6% indicated there was no role for pharmacists to provide MTM services for any of the listed categories. Staffing, time, and reimbursement represented the most commonly perceived barriers for pharmacists in providing MTM services. Fifty-seven percent indicated

  7. 5. Interrelationships, functional packages and priorities.

    Science.gov (United States)

    2014-05-01

    The basic societal functions (BSFs) do not exist in isolation. Many of the functions are dependent and/or interdependent on one another and/or on the components that comprise the BSFs. Dependency occurs when goods and/or services are required for a function, subfunction, or a component of a function. Interdependency occurs when the same component (commodity, service, or process) is required by more than one BSF or component(s) of a BSF. Insufficiencies of functions that are interdependent are more likely to render a society dysfunctional than are those that are not interdependent. Combinations of functions from different BSF form functional packages. In times of disaster and limited resources, subfunctions, elements, and subelements, etc. must be prioritised in terms of their relative importance for the continuation of the most essential services. Priorities must be established so that when resources are scarce, nonessential services may be temporarily discontinued and similarly, priorities must be determined for re-establishment of services as needed resources become available.

  8. 9-cis-retinoic Acid and troglitazone impacts cellular adhesion, proliferation, and integrin expression in K562 cells.

    Science.gov (United States)

    Hanson, Amanda M; Gambill, Jessica; Phomakay, Venusa; Staten, C Tyler; Kelley, Melissa D

    2014-01-01

    Retinoids are established pleiotropic regulators of both adaptive and innate immune responses. Recently, troglitazone, a PPAR gamma agonist, has been demonstrated to have anti-inflammatory effects. Separately, retinoids and troglitazone are implicated in immune related processes; however, their combinatory role in cellular adhesion and proliferation has not been well established. In this study, the effect of 9-cis-retinoic acid (9-cis-RA) and troglitazone on K562 cellular adhesion and proliferation was investigated. Troglitazone exposure decreased K562 cellular adhesion to RGD containing extracellular matrix proteins fibronectin, FN-120, and vitronectin in a concentration and time-dependent manner. In the presence of troglitazone, 9-cis-retinoic acid restores cellular adhesion to levels comparable to vehicle treatment alone on fibronectin, FN-120, and vitronectin substrates within 72 hours. Due to the prominent role of integrins in attachment to extracellular matrix proteins, we evaluated the level of integrin α5 subunit expression. Troglitazone treatment results in decrease in α5 subunit expression on the cell surface. In the presence of both agonists, cell surface α5 subunit expression was restored to levels comparable to vehicle treatment alone. Additionally, troglitazone and 9-cis-RA mediated cell adhesion was decreased in the presence of a function blocking integrin alpha 5 inhibitor. Further, through retinoid metabolic profiling and HPLC analysis, our study demonstrates that troglitazone augments retinoid availability in K562 cells. Finally, we demonstrate that troglitazone and 9-cis-retinoic acid synergistically dampen cellular proliferation in K562 cells. Our study is the first to report that the combination of troglitazone and 9-cis-retinoic acid restores cellular adhesion, alters retinoid availability, impacts integrin expression, and dampens cellular proliferation in K562 cells.

  9. Alpha-ketoglutarate and N-acetyl cysteine protect PC12 cells from cyanide-induced cytotoxicity and altered energy metabolism.

    Science.gov (United States)

    Satpute, R M; Hariharakrishnan, J; Bhattacharya, R

    2008-01-01

    Cyanide is a rapidly acting neurotoxin that inhibits cellular respiration and energy metabolism leading to histotoxic hypoxia. This results in the dissipation of mitochondrial membrane potential (MMP) accompanied by decreased cellular ATP content which in turn is responsible for increased levels of intracellular calcium ions ([Ca(2+)](i)) and total lactic acid content of the cells. Rat pheochromocytoma (PC12) cells possess much of the biochemical machinery associated with synaptic neurons. In the present study, we evaluated the cytoprotective effects of alpha-ketoglutarate (A-KG) and N-acetylcysteine (NAC) against cyanide-induced cytotoxicity and altered energy metabolism in PC12 cells. Cyanide-antagonism by A-KG is attributed to cyanohydrin formation whereas NAC is known for its antioxidant properties. Data on leakage of intracellular lactate dehydrogenase and mitochondrial function (MTT assay) revealed that simultaneous treatment of A-KG (0.5 mM) and NAC (0.25 mM) significantly prevented the cytotoxicity of cyanide. Also, cellular ATP content was found to improve, followed by restoration of MMP, intracellular calcium [Ca(2+)](i) and lactic acid levels. Treatment with A-KG and NAC also attenuated the levels of peroxides generated by cyanide. The study indicates that combined administration of A-KG and NAC protected the cyanide-challenged PC12 cells by resolving the altered energy metabolism. The results have implications in the development of new treatment regimen for cyanide poisoning.

  10. Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy.

    Science.gov (United States)

    Li, Mi; Liu, LianQing; Xi, Ning; Wang, YueChao; Xiao, XiuBin; Zhang, WeiJing

    2015-09-01

    Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature-controllable atomic force microscopy (AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells.

  11. Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator and Drugs: Insights from Cellular Trafficking.

    Science.gov (United States)

    Bridges, Robert J; Bradbury, Neil A

    2018-01-01

    The eukaryotic cell is organized into membrane-delineated compartments that are characterized by specific cadres of proteins sustaining biochemically distinct cellular processes. The appropriate subcellular localization of proteins is key to proper organelle function and provides a physiological context for cellular processes. Disruption of normal trafficking pathways for proteins is seen in several genetic diseases, where a protein's absence for a specific subcellular compartment leads to organelle disruption, and in the context of an individual, a disruption of normal physiology. Importantly, several drug therapies can also alter protein trafficking, causing unwanted side effects. Thus, a deeper understanding of trafficking pathways needs to be appreciated as novel therapeutic modalities are proposed. Despite the promising efficacy of novel therapeutic agents, the intracellular bioavailability of these compounds has proved to be a potential barrier, leading to failures in treatments for various diseases and disorders. While endocytosis of drug moieties provides an efficient means of getting material into cells, the subsequent release and endosomal escape of materials into the cytosol where they need to act has been a barrier. An understanding of cellular protein/lipid trafficking pathways has opened up strategies for increasing drug bioavailability. Approaches to enhance endosomal exit have greatly increased the cytosolic bioavailability of drugs and will provide a means of investigating previous drugs that may have been shelved due to their low cytosolic concentration.

  12. Cellular communications a comprehensive and practical guide

    CERN Document Server

    Tripathi, Nishith

    2014-01-01

    Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

  13. Setting Priorities for Space Research: Opportunities and Imperatives

    Science.gov (United States)

    Dutton, John A.; Abelson, Philip H.; Beckwith, Steven V. W.; Bishop, William P.; Byerly, Radford, Jr.; Crowe, Lawson; Dews, Peter; Garriott, Owen K.; Lunine, Jonathan; Macauley, Molly K.

    1992-01-01

    This report represents the first phase of a study by a task group convened by the Space Studies Board to ascertain whether it should attempt to develop a methodology for recommending priorities among the various initiatives in space research (that is, scientific activities concerned with phenomena in space or utilizing observations from space). The report argues that such priority statements by the space research community are both necessary and desirable and would contribute to the formulation and implementation of public policy. The report advocates the establishment of priorities to enhance effective management of the nation's scientific research program in space. It argues that scientific objectives and purposes should determine how and under what circumstances scientific research should be done. The report does not take a position on the controversy between advocates of manned space exploration and those who favor the exclusive use of unmanned space vehicles. Nor does the report address questions about the value or appropriateness of Space Station Freedom or proposals to establish a permanent manned Moon base or to undertake a manned mission to Mars. These issues lie beyond the charge to the task group.

  14. Lipid composition of microdomains is altered in neuronopathic Gaucher disease sheep brain and spleen.

    Science.gov (United States)

    Hein, Leanne K; Rozaklis, Tina; Adams, Melissa K; Hopwood, John J; Karageorgos, Litsa

    2017-07-01

    Gaucher disease is a lysosomal storage disorder caused by a deficiency in glucocerebrosidase activity that leads to accumulation of glucosylceramide and glucosylsphingosine. Membrane raft microdomains are discrete, highly organized microdomains with a unique lipid composition that provide the necessary environment for specific protein-lipid and protein-protein interactions to take place. In this study we purified detergent resistant membranes (DRM; membrane rafts) from the occipital cortex and spleen from sheep affected with acute neuronopathic Gaucher disease and wild-type controls. We observed significant increases in the concentrations of glucosylceramide, hexosylsphingosine, BMP and gangliosides and decreases in the percentage of cholesterol and phosphatidylcholine leading to an altered DRM composition. Altered sphingolipid/cholesterol homeostasis would dramatically disrupt DRM architecture making them less ordered and more fluid. In addition, significant changes in the length and degree of lipid saturation within the DRM microdomains in the Gaucher brain were also observed. As these DRM microdomains are involved in many cellular events, an imbalance or disruption of the cell membrane homeostasis may impair normal cell function. This disruption of membrane raft microdomains and imbalance within the environment of cellular membranes of neuronal cells may be a key factor in initiating a cascade process leading to neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Magnetohydrodynamics cellular automata

    International Nuclear Information System (INIS)

    Hatori, Tadatsugu.

    1990-02-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

  16. Magnetohydrodynamic cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Hatori, Tadatsugu [National Inst. for Fusion Science, Nagoya (Japan)

    1990-03-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author).

  17. Magnetohydrodynamic cellular automata

    International Nuclear Information System (INIS)

    Hatori, Tadatsugu

    1990-01-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

  18. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  19. Effects of cellular non-protein sulfhydryl depletion in radiation induced oncogenic transformation and genotoxicity in mouse C3H 10T1/2 cells

    International Nuclear Information System (INIS)

    Hei, T.K.; Geard, C.R.; Hall, E.J.

    1984-01-01

    A study was made of the effects of cellular non-protein sulfhydryl (NPSH) depletion on cytotoxicity, cell cycle kinetics, oncogenic transformation and sister chromatid exchange (SCE) in C 3 H 10T1/2 cells. Using DL-Buthionine S-R-Sulfoximine (BSO) to deplete thiols, it was found spectrophotometrically that less than 5% of control NPSH level remained in the cells after 24-hour treatment under aerated conditions. Such NPSH depleted cells, when subject to a 3 Gy γ-ray treatment, were found to have no radiosensitizing response either in terms of cell survival or oncogenic transformation. In addition, decreased levels of NPSH had no effect on spontaneous or radiation-induced SCE nor were cell cycle kinetics additionally altered. Therefore, the inability of NPSH depletion to alter γ-ray induced cellular transformation was unrelated to any possible effect of BSO on the cell cycle. These results suggest that such depletion may result in little or no additional oncogenic or genotoxic effects on aerated normal tissues

  20. 45 CFR 1620.3 - Establishing priorities.

    Science.gov (United States)

    2010-10-01

    ... should address the need for outreach, training of the recipient's employees, and support services. (c... IN USE OF RESOURCES § 1620.3 Establishing priorities. (a) The governing body of a recipient must... the cases and matters which may be undertaken by the recipient. (b) The procedures adopted must...

  1. Cellular injury evidenced by impedance technology and infrared microspectroscopy

    Science.gov (United States)

    le Roux, K.; Prinsloo, L. C.; Meyer, D.

    2015-03-01

    Fourier Transform Infrared (FTIR) spectroscopy is finding increasing biological application, for example in the analysis of diseased tissues and cells, cell cycle studies and investigating the mechanisms of action of anticancer drugs. Cancer treatment studies routinely define the types of cell-drug responses as either total cell destruction by the drug (all cells die), moderate damage (cell deterioration where some cells survive) or reversible cell cycle arrest (cytostasis). In this study the loss of viability and related chemical stress experienced by cells treated with the medicinal plant, Plectranthus ciliatus, was investigated using real time cell electronic sensing (RT-CES) technology and FTIR microspectroscopy. The use of plants as medicines is well established and ethnobotany has proven that crude extracts can serve as treatments against various ailments. The aim of this study was to determine whether FTIR microspectroscopy would successfully distinguish between different types of cellular injury induced by a potentially anticancerous plant extract. Cervical adenocarcinoma (HeLa) cells were treated with a crude extract of Pciliatus and cells monitored using RT-CES to characterize the type of cellular responses induced. Cell populations were then investigated using FTIR microspectroscopy and statistically analysed using One-way Analysis of Variance (ANOVA) and Principal Component Analysis (PCA). The plant extract and a cancer drug control (actinomycin D) induced concentration dependent cellular responses ranging from nontoxic, cytostatic or cytotoxic. Thirteen spectral peaks (915 cm-1, 933 cm-1, 989 cm-1, 1192 cm-1, 1369 cm-1, 1437 cm-1, 1450 cm-1, 1546 cm-1, 1634 cm-1, 1679 cm-1 1772 cm-1, 2874 cm-1 and 2962 cm-1) associated with cytotoxicity were significantly (p value < 0.05, one way ANOVA, Tukey test, Bonferroni) altered, while two of the bands were also indicative of early stress related responses. In PCA, poor separation between nontoxic and cytostatic

  2. Cellular Angiofibroma of the Nasopharynx.

    Science.gov (United States)

    Erdur, Zülküf Burak; Yener, Haydar Murat; Yilmaz, Mehmet; Karaaltin, Ayşegül Batioğlu; Inan, Hakki Caner; Alaskarov, Elvin; Gozen, Emine Deniz

    2017-11-01

    Angiofibroma is a common tumor of the nasopharynx region but cellular type is extremely rare in head and neck. A 13-year-old boy presented with frequent epistaxis and nasal obstruction persisting for 6 months. According to the clinical symptoms and imaging studies juvenile angiofibroma was suspected. Following angiographic embolization total excision of the lesion by midfacial degloving approach was performed. Histological examination revealed that the tumor consisted of staghorn blood vessels and irregular fibrous stroma. Stellate fibroblasts with small pyknotic to large vesicular nuclei were seen in a highly cellular stroma. These findings identified cellular angiofibroma mimicking juvenile angiofibroma. This article is about a very rare patient of cellular angiofibroma of nasopharynx.

  3. Tracking SMME research in South Africa’s priority sectors

    Directory of Open Access Journals (Sweden)

    Christian Rogerson

    2012-05-01

    Full Text Available The National Industrial Policy Framework and the Accelerated and Shared Growth Initiative for South Africa emphasize the importance of promoting select ‘priority sectors’. This paper provides a review of existing research concerning SMME development in the three priority sectors of tourism, business process outsourcing and offshoring (BPO & O and, creative industries. The paper argues for the importance of undertaking sector-differentiated research on SMME development in South Africa in order to complement other research which is focussed on sector development as a whole.

  4. Top 10 research priorities in head and neck cancer: Results of an Alberta priority setting partnership of patients, caregivers, family members, and clinicians.

    Science.gov (United States)

    Lechelt, Leah A; Rieger, Jana M; Cowan, Katherine; Debenham, Brock J; Krewski, Bernie; Nayar, Suresh; Regunathan, Akhila; Seikaly, Hadi; Singh, Ameeta E; Laupacis, Andreas

    2018-03-01

    The epidemiology, etiology, and management of head and neck cancer are evolving. Understanding the perspectives and priorities of nonresearchers regarding treatment uncertainties is important to inform future research. Using the James Lind Alliance approach, patients, caregivers, and clinicians responded to a survey regarding their unanswered questions about treating and managing head and neck cancer. Distinct uncertainties were extracted from responses and sorted into themes. Uncertainties already answered in the literature were removed. Those remaining were ranked by patients and clinicians to develop a short list of priorities, which were discussed at a workshop and reduced to the top 10. One hundred sixty-one respondents posed 818 uncertainties, culminating in 77 for interim ranking and 27 for discussion at a workshop. Participants reached consensus on the top 10, which included questions on prevention, screening, treatment, and quality of life. Nonresearchers can effectively collaborate to establish priorities for future research in head and neck cancer. © 2017 Wiley Periodicals, Inc.

  5. Mammals on the EDGE: conservation priorities based on threat and phylogeny.

    Directory of Open Access Journals (Sweden)

    Nick J B Isaac

    2007-03-01

    Full Text Available Conservation priority setting based on phylogenetic diversity has frequently been proposed but rarely implemented. Here, we define a simple index that measures the contribution made by different species to phylogenetic diversity and show how the index might contribute towards species-based conservation priorities. We describe procedures to control for missing species, incomplete phylogenetic resolution and uncertainty in node ages that make it possible to apply the method in poorly known clades. We also show that the index is independent of clade size in phylogenies of more than 100 species, indicating that scores from unrelated taxonomic groups are likely to be comparable. Similar scores are returned under two different species concepts, suggesting that the index is robust to taxonomic changes. The approach is applied to a near-complete species-level phylogeny of the Mammalia to generate a global priority list incorporating both phylogenetic diversity and extinction risk. The 100 highest-ranking species represent a high proportion of total mammalian diversity and include many species not usually recognised as conservation priorities. Many species that are both evolutionarily distinct and globally endangered (EDGE species do not benefit from existing conservation projects or protected areas. The results suggest that global conservation priorities may have to be reassessed in order to prevent a disproportionately large amount of mammalian evolutionary history becoming extinct in the near future.

  6. SARS and hospital priority setting: a qualitative case study and evaluation

    Directory of Open Access Journals (Sweden)

    Upshur Ross EG

    2004-12-01

    Full Text Available Abstract Background Priority setting is one of the most difficult issues facing hospitals because of funding restrictions and changing patient need. A deadly communicable disease outbreak, such as the Severe Acute Respiratory Syndrome (SARS in Toronto in 2003, amplifies the difficulties of hospital priority setting. The purpose of this study is to describe and evaluate priority setting in a hospital in response to SARS using the ethical framework 'accountability for reasonableness'. Methods This study was conducted at a large tertiary hospital in Toronto, Canada. There were two data sources: 1 over 200 key documents (e.g. emails, bulletins, and 2 35 interviews with key informants. Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation. Results Participants described the types of priority setting decisions, the decision making process and the reasoning used. Although the hospital leadership made an effort to meet the conditions of 'accountability for reasonableness', they acknowledged that the decision making was not ideal. We described good practices and opportunities for improvement. Conclusions 'Accountability for reasonableness' is a framework that can be used to guide fair priority setting in health care organizations, such as hospitals. In the midst of a crisis such as SARS where guidance is incomplete, consequences uncertain, and information constantly changing, where hour-by-hour decisions involve life and death, fairness is more important rather than less.

  7. SARS and hospital priority setting: a qualitative case study and evaluation.

    Science.gov (United States)

    Bell, Jennifer A H; Hyland, Sylvia; DePellegrin, Tania; Upshur, Ross E G; Bernstein, Mark; Martin, Douglas K

    2004-12-19

    Priority setting is one of the most difficult issues facing hospitals because of funding restrictions and changing patient need. A deadly communicable disease outbreak, such as the Severe Acute Respiratory Syndrome (SARS) in Toronto in 2003, amplifies the difficulties of hospital priority setting. The purpose of this study is to describe and evaluate priority setting in a hospital in response to SARS using the ethical framework 'accountability for reasonableness'. This study was conducted at a large tertiary hospital in Toronto, Canada. There were two data sources: 1) over 200 key documents (e.g. emails, bulletins), and 2) 35 interviews with key informants. Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation. Participants described the types of priority setting decisions, the decision making process and the reasoning used. Although the hospital leadership made an effort to meet the conditions of 'accountability for reasonableness', they acknowledged that the decision making was not ideal. We described good practices and opportunities for improvement. 'Accountability for reasonableness' is a framework that can be used to guide fair priority setting in health care organizations, such as hospitals. In the midst of a crisis such as SARS where guidance is incomplete, consequences uncertain, and information constantly changing, where hour-by-hour decisions involve life and death, fairness is more important rather than less.

  8. New Approach in Translational Medicine: Effects of Electrolyzed Reduced Water (ERW on NF-κB/iNOS Pathway in U937 Cell Line under Altered Redox State

    Directory of Open Access Journals (Sweden)

    Sara Franceschelli

    2016-09-01

    Full Text Available It is known that increased levels of reactive oxygen species (ROS and reactive nitrogen species (RNS can exert harmful effects, altering the cellular redox state. Electrolyzed Reduced Water (ERW produced near the cathode during water electrolysis exhibits high pH, high concentration of dissolved hydrogen and an extremely negative redox potential. Several findings indicate that ERW had the ability of a scavenger free radical, which results from hydrogen molecules with a high reducing ability and may participate in the redox regulation of cellular function. We investigated the effect of ERW on H2O2-induced U937 damage by evaluating the modulation of redox cellular state. Western blotting and spectrophotometrical analysis showed that ERW inhibited oxidative stress by restoring the antioxidant capacity of superoxide dismutase, catalase and glutathione peroxidase. Consequently, ERW restores the ability of the glutathione reductase to supply the cell of an important endogenous antioxidant, such as GSH, reversing the inhibitory effect of H2O2 on redox balance of U937 cells. Therefore, this means a reduction of cytotoxicity induced by peroxynitrite via a downregulation of the NF-κB/iNOS pathway and could be used as an antioxidant for preventive and therapeutic application. In conclusion, ERW can protect the cellular redox balance, reducing the risk of several diseases with altered cellular homeostasis such as inflammation.

  9. Alterations of sirtuins in mitochondrial cytochrome c-oxidase deficiency.

    Directory of Open Access Journals (Sweden)

    Arne Björn Potthast

    Full Text Available Sirtuins are NAD+ dependent deacetylases, which regulate mitochondrial energy metabolism as well as cellular response to stress. The NAD/NADH-system plays a crucial role in oxidative phosphorylation linking sirtuins and the mitochondrial respiratory chain. Furthermore, sirtuins are able to directly deacetylate and activate different complexes of the respiratory chain. This prompted us to analyse sirtuin levels in skin fibroblasts from patients with cytochrome c-oxidase (COX deficiency and to test the impact of different pharmaceutical activators of sirtuins (SRT1720, paeonol to modulate sirtuins and possibly respiratory chain enzymes in patient cells in vitro.We assayed intracellular levels of sirtuin 1 and the mitochondrial sirtuins SIRT3 and SIRT4 in human fibroblasts from patients with COX- deficiency. Furthermore, sirtuins were measured after inhibiting complex IV in healthy control fibroblasts by cyanide and after incubation with activators SRT1720 and paeonol. To determine the effect of sirtuin inhibition at the cellular level we measured total cellular acetylation (control and patient cells, with and without treatment by Western blot.We observed a significant decrease in cellular levels of all three sirtuins at the activity, protein and transcriptional level (by 15% to 50% in COX-deficient cells. Additionally, the intracellular concentration of NAD+ was reduced in patient cells. We mimicked the biochemical phenotype of COX- deficiency by incubating healthy fibroblasts with cyanide and observed reduced sirtuin levels. A pharmacological activation of sirtuins resulted in normalized sirtuin levels in patient cells. Hyper acetylation was also reversible after treatment with sirtuin activators. Pharmacological modulation of sirtuins resulted in altered respiratory chain complex activities.We found inhibition of situins 1, 3 and 4 at activity, protein and transcriptional levels in fibroblasts from patient with COX-deficiency. Pharmacological

  10. 47 CFR 22.923 - Cellular system configuration.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular system configuration. 22.923 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.923 Cellular system configuration. Mobile stations... directly or through cellular repeaters. Auxiliary test stations may communicate with base or mobile...

  11. Systematic reviews addressing identified health policy priorities in Eastern Mediterranean countries: a situational analysis.

    Science.gov (United States)

    El-Jardali, Fadi; Akl, Elie A; Karroum, Lama Bou; Kdouh, Ola; Akik, Chaza; Fadlallah, Racha; Hammoud, Rawan

    2014-08-20

    Systematic reviews can offer policymakers and stakeholders concise, transparent, and relevant evidence pertaining to pressing policy priorities to help inform the decision-making process. The production and the use of systematic reviews are specifically limited in the Eastern Mediterranean region. The extent to which published systematic reviews address policy priorities in the region is still unknown. This situational analysis exercise aims at assessing the extent to which published systematic reviews address policy priorities identified by policymakers and stakeholders in Eastern Mediterranean region countries. It also provides an overview about the state of systematic review production in the region and identifies knowledge gaps. We conducted a systematic search of the Health System Evidence database to identify published systematic reviews on policy-relevant priorities pertaining to the following themes: human resources for health, health financing, the role of the non-state sector, and access to medicine. Priorities were identified from two priority-setting exercises conducted in the region. We described the distribution of these systematic reviews across themes, sub-themes, authors' affiliations, and countries where included primary studies were conducted. Out of the 1,045 systematic reviews identified in Health System Evidence on selected themes, a total of 200 systematic reviews (19.1%) addressed the priorities from the Eastern Mediterranean region. The theme with the largest number of systematic reviews included was human resources for health (115) followed by health financing (33), access to medicine (27), and role of the non-state sector (25). Authors based in the region produced only three systematic reviews addressing regional priorities (1.5%). Furthermore, no systematic review focused on the Eastern Mediterranean region. Primary studies from the region had limited contribution to systematic reviews; 17 systematic reviews (8.5%) included primary

  12. Systematic reviews addressing identified health policy priorities in Eastern Mediterranean countries: a situational analysis

    Science.gov (United States)

    2014-01-01

    Background Systematic reviews can offer policymakers and stakeholders concise, transparent, and relevant evidence pertaining to pressing policy priorities to help inform the decision-making process. The production and the use of systematic reviews are specifically limited in the Eastern Mediterranean region. The extent to which published systematic reviews address policy priorities in the region is still unknown. This situational analysis exercise aims at assessing the extent to which published systematic reviews address policy priorities identified by policymakers and stakeholders in Eastern Mediterranean region countries. It also provides an overview about the state of systematic review production in the region and identifies knowledge gaps. Methods We conducted a systematic search of the Health System Evidence database to identify published systematic reviews on policy-relevant priorities pertaining to the following themes: human resources for health, health financing, the role of the non-state sector, and access to medicine. Priorities were identified from two priority-setting exercises conducted in the region. We described the distribution of these systematic reviews across themes, sub-themes, authors’ affiliations, and countries where included primary studies were conducted. Results Out of the 1,045 systematic reviews identified in Health System Evidence on selected themes, a total of 200 systematic reviews (19.1%) addressed the priorities from the Eastern Mediterranean region. The theme with the largest number of systematic reviews included was human resources for health (115) followed by health financing (33), access to medicine (27), and role of the non-state sector (25). Authors based in the region produced only three systematic reviews addressing regional priorities (1.5%). Furthermore, no systematic review focused on the Eastern Mediterranean region. Primary studies from the region had limited contribution to systematic reviews; 17 systematic reviews

  13. Protecting Our Priorities: 2010 Annual Report

    Science.gov (United States)

    Western Interstate Commission for Higher Education, 2010

    2010-01-01

    What does "protecting our priorities" mean in an era when economic realities require that institutions of higher education trim their budgets while also providing critical education and training to more and more students--those "human resources" whose skills will be the key to any economic turnaround? This is a question WICHE…

  14. Alterations in cellular energy metabolism associated with the antiproliferative effects of the ATM inhibitor KU-55933 and with metformin.

    Directory of Open Access Journals (Sweden)

    Mahvash Zakikhani

    Full Text Available KU-55933 is a specific inhibitor of the kinase activity of the protein encoded by Ataxia telangiectasia mutated (ATM, an important tumor suppressor gene with key roles in DNA repair. Unexpectedly for an inhibitor of a tumor suppressor gene, KU-55933 reduces proliferation. In view of prior preliminary evidence suggesting defective mitochondrial function in cells of patients with Ataxia Telangiectasia (AT, we examined energy metabolism of cells treated with KU-55933. The compound increased AMPK activation, glucose uptake and lactate production while reducing mitochondrial membrane potential and coupled respiration. The stimulation of glycolysis by KU-55933 did not fully compensate for the reduction in mitochondrial functions, leading to decreased cellular ATP levels and energy stress. These actions are similar to those previously described for the biguanide metformin, a partial inhibitor of respiratory complex I. Both compounds decreased mitochondrial coupled respiration and reduced cellular concentrations of fumarate, malate, citrate, and alpha-ketogluterate. Succinate levels were increased by KU-55933 levels and decreased by metformin, indicating that the effects of ATM inhibition and metformin are not identical. These observations suggest a role for ATM in mitochondrial function and show that both KU-55933 and metformin perturb the TCA cycle as well as oxidative phosphorylation.

  15. Recursive definition of global cellular-automata mappings

    International Nuclear Information System (INIS)

    Feldberg, R.; Knudsen, C.; Rasmussen, S.

    1994-01-01

    A method for a recursive definition of global cellular-automata mappings is presented. The method is based on a graphical representation of global cellular-automata mappings. For a given cellular-automaton rule the recursive algorithm defines the change of the global cellular-automaton mapping as the number of lattice sites is incremented. A proof of lattice size invariance of global cellular-automata mappings is derived from an approximation to the exact recursive definition. The recursive definitions are applied to calculate the fractal dimension of the set of reachable states and of the set of fixed points of cellular automata on an infinite lattice

  16. An Analysis of QoS in ZigBee Network Based on Deviated Node Priority

    Directory of Open Access Journals (Sweden)

    Md. Jaminul Haque Biddut

    2016-01-01

    Full Text Available ZigBee is an IEEE 802.15.4 standardized communication protocol. It forms a flawless Wireless Sensor Network (WSN standard for interoperability at all levels of the network, particularly the application level which most closely touches the user. A large number of devices from different vendors can work seamlessly. These devices act as a network and send huge data traffic to the Coordinator. End devices at different zones have different roles in communication with each other. There has been a lack in executing their requests in a synchronized way based on task priority. This lack leads to massive data traffic loss and degrades the Quality of Service (QoS. One of the challenges is to analyze the QoS parameters in ZigBee network that help to detect the overall network performance. The contribution of this paper is twofold; first, a ZigBee Network is implemented based on node priority. It demonstrates a method to generate a new priority of devices with respect to their existing priority and zones’ priority as well. Second, the QoS is analyzed based on the new priority status for tasks preference purposes. The outcome of this paper shows that the QoS of the network is more conspicuous than non-priority based network.

  17. 15 CFR 700.16 - Changes or cancellations of priority ratings and rated orders.

    Science.gov (United States)

    2010-01-01

    ... Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700...

  18. Cellular senescence and organismal aging.

    Science.gov (United States)

    Jeyapalan, Jessie C; Sedivy, John M

    2008-01-01

    Cellular senescence, first observed and defined using in vitro cell culture studies, is an irreversible cell cycle arrest which can be triggered by a variety of factors. Emerging evidence suggests that cellular senescence acts as an in vivo tumor suppression mechanism by limiting aberrant proliferation. It has also been postulated that cellular senescence can occur independently of cancer and contribute to the physiological processes of normal organismal aging. Recent data have demonstrated the in vivo accumulation of senescent cells with advancing age. Some characteristics of senescent cells, such as the ability to modify their extracellular environment, could play a role in aging and age-related pathology. In this review, we examine current evidence that links cellular senescence and organismal aging.

  19. DecreaseKeys are Expensive for External Memory Priority Queues

    OpenAIRE

    Eenberg, Kasper; Larsen, Kasper Green; Yu, Huacheng

    2016-01-01

    One of the biggest open problems in external memory data structures is the priority queue problem with DecreaseKey operations. If only Insert and ExtractMin operations need to be supported, one can design a comparison-based priority queue performing $O((N/B)\\lg_{M/B} N)$ I/Os over a sequence of $N$ operations, where $B$ is the disk block size in number of words and $M$ is the main memory size in number of words. This matches the lower bound for comparison-based sorting and is hence optimal fo...

  20. Public engagement in setting healthcare priorities: a ranking exercise in Cyprus.

    Science.gov (United States)

    Farmakas, Antonis; Theodorou, Mamas; Galanis, Petros; Karayiannis, Georgios; Ghobrial, Stefanos; Polyzos, Nikos; Papastavrou, Evridiki; Agapidaki, Eirini; Souliotis, Kyriakos

    2017-01-01

    In countries such as Cyprus the financial crisis and the recession have severely affected the funding and priority setting of the health care system. There is evidence highlighting the importance of population' preferences in designing priorities for health care settings. Although public preferences have been thorough analysed in many countries, there is a research gap in terms of simultaneously investigating the relative importance and the weight of differing and competing criteria for determining healthcare priority settings. The main objective of the study was tο investigate public preferences for the relative utility and weight of differing and competing criteria for health care priority setting in Cyprus. The 'conjoint analysis' technique was applied to develop a ranking exercise. The aim of the study was to identify the preferences of the participants for alternative options. Participants were asked to grade in a priority order 16 hypothetical case scenarios of patients with different disease and of diverse socio-economic characteristics awaiting treatment. The sample was purposive and consisted of 100 Cypriots, selected from public locations all over the country. It was revealed that the "severity of the disease" and the " age of the patient" were the key prioritization criteria. Participants assigned the smallest relative value to the criterion " healthy lifestyle" . More precisely, participants older than 35 years old assigned higher relative importance to " age" , while younger participants to the " severity of the disease". The " healthy lifestyle" criterion was assigned to the lowest relative importance to by all participants. In Cyprus, public participation in health care priority setting is almost inexistent. Nonetheless, it seems that the public's participation in this process could lead to a wider acceptance of the healthcare system especially as a result of the financial crisis and the upcoming reforms implemented such as the establishment of the