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Sample records for altered cellular priorities

  1. Cellular mechanisms for altered learning in aging.

    Science.gov (United States)

    Oh, M Matthew; Disterhoft, John F

    2010-01-01

    Getting gray hair is part of the natural progression of aging. People expect it and they can change their hair color, if they choose. People also expect increases in memory lapses and learning difficulties as they get older. However, unlike hair color, there is no magic cure or option to fix learning and memory difficulties, because the cellular mechanisms of learning and aging in all the different types of neurons throughout the brain have yet to be discovered. This review describes our efforts to identify a cellular biomarker in hippocampal pyramidal neurons that has been demonstrated to reliably change with learning and with aging - the postburst afterhyperpolarization. We propose that this biomarker, which plays a critical role in regulating neuronal excitability, can be used as a benchmark for future studies in order to understand and identify the cellular mechanisms of learning and aging in the hippocampus, as well as in other cortical regions.

  2. Cellular mechanisms for altered learning in aging

    OpenAIRE

    Oh, M Matthew; Disterhoft, John F

    2010-01-01

    Getting gray hair is part of the natural progression of aging. People expect it and they can change their hair color, if they choose. People also expect increases in memory lapses and learning difficulties as they get older. However, unlike hair color, there is no magic cure or option to fix learning and memory difficulties, because the cellular mechanisms of learning and aging in all the different types of neurons throughout the brain have yet to be discovered. This review describes our effo...

  3. Cellular Transplantation Alters the Disease Progression in Becker's Muscular Dystrophy.

    Science.gov (United States)

    Sharma, Alok; Paranjape, Amruta; Sane, Hemangi; Bhagawanani, Khushboo; Gokulchandran, Nandini; Badhe, Prerna

    2013-01-01

    Becker's Muscular Dystrophy (BMD) is a dystrophinopathy manifested as progressive muscle degeneration. Autologous Bone Marrow Mononuclear Cells (BMMNCs) have shown some myogenic potential. The paracrine effects of the BMMNCs reduce the inflammation and are thought to reduce muscle degeneration. We treated a 39 year old dental surgeon suffering from BMD. Muscle strength was reduced when measured using modified Medical Research Council's Manual Muscle Testing (mMRC-MMT). Static sitting balance was poor. He was wheelchair dependent for ambulation and moderately independent in Activities of Daily Living (ADL). Functional Independence Measure (FIM) score was 93. Musculoskeletal Magnetic Resonance Imaging (MRI-MSK) showed moderate fatty infiltration in the muscles. Three cellular transplantations were carried out. Clinical assessment and the investigations were repeated. Progressive increase in the muscle strength was noted. Ambulation was independent using push-knee splints and minimal assistance when weary. Static and dynamic balance in sitting and standing improved. FIM score increased from 93 to 105. There was no increase in the degree of fatty infiltration, as seen on the MRI-MSK. The case study provides evidence for the putative benefits of cellular therapy in altering the disease progression in BMD. It also suggests augmented clinical benefits of combination of cellular therapy and rehabilitation.

  4. 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

  5. Impact of Membrane Phospholipid Alterations in Escherichia coli on Cellular Function and Bacterial Stress Adaptation.

    Science.gov (United States)

    Rowlett, Veronica W; Mallampalli, Venkata K P S; Karlstaedt, Anja; Dowhan, William; Taegtmeyer, Heinrich; Margolin, William; Vitrac, Heidi

    2017-07-01

    Bacteria have evolved multiple strategies to sense and rapidly adapt to challenging and ever-changing environmental conditions. The ability to alter membrane lipid composition, a key component of the cellular envelope, is crucial for bacterial survival and adaptation in response to environmental stress. However, the precise roles played by membrane phospholipids in bacterial physiology and stress adaptation are not fully elucidated. The goal of this study was to define the role of membrane phospholipids in adaptation to stress and maintenance of bacterial cell fitness. By using genetically modified strains in which the membrane phospholipid composition can be systematically manipulated, we show that alterations in major Escherichia coli phospholipids transform these cells globally. We found that alterations in phospholipids impair the cellular envelope structure and function, the ability to form biofilms, and bacterial fitness and cause phospholipid-dependent susceptibility to environmental stresses. This study provides an unprecedented view of the structural, signaling, and metabolic pathways in which bacterial phospholipids participate, allowing the design of new approaches in the investigation of lipid-dependent processes involved in bacterial physiology and adaptation. IMPORTANCE In order to cope with and adapt to a wide range of environmental conditions, bacteria have to sense and quickly respond to fluctuating conditions. In this study, we investigated the effects of systematic and controlled alterations in bacterial phospholipids on cell shape, physiology, and stress adaptation. We provide new evidence that alterations of specific phospholipids in Escherichia coli have detrimental effects on cellular shape, envelope integrity, and cell physiology that impair biofilm formation, cellular envelope remodeling, and adaptability to environmental stresses. These findings hold promise for future antibacterial therapies that target bacterial lipid biosynthesis

  6. Altered Cellular Distribution and Sub-Cellular Sorting of Doppel (Dpl Protein in Human Astrocytoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Elena Sbalchiero

    2008-01-01

    Full Text Available Doppel, a prion-like protein, is a GPI-membrane anchored protein generally not expressed in the Central Nervous System (CNS of different mammalian species, including human. Nevertheless, in astrocytomas, a particular kind of glial tumors, the doppel encoding gene (PRND is over-expressed and the corresponding protein product (Dpl is ectopically localized in the cytoplasm of the tumor cells. In this study we have analysed the sub-cellular localization of Dpl using double-immunofluorescence staining and confocal microscopy examinations in two astrocytoma-derived human cell lines (IPDDC-A2 and D384-MG. Our results confirmed that Dpl is localized in the cytoplasm of the astrocytoma cells and indicated that it is mostly associated with Lamp-1 and Limp-2 positive lysosomal vesicles and, marginally, to the Golgi apparatus and other cellular organelles. Noticeably, none of the examined tumor cells showed a membrane-Dpl localization. The membrane-associated Dpl expression was restored after the transfection of the astrocytoma cells with mutated Dpl-expression vectors in its glycosylation sites. Additionally, Dpl showed altered expression and traffic using the acidotropic agent ammonium chloride, leading to the accumulation of Dpl in nascent exocytic vesicles. Altogether, these results indicated that in the astrocytic tumor cells Dpl has an altered biosynthetic trafficking, likely derived from abnormal post-translational processes: these modifications do not permit the localization of Dpl in correspondence of the plasma membrane and lead to its intracellular accumulation in the lysosomes. In these proteolytic compartments, the astrocytic tumor cells might provide to the degradation of the excess of a potentially cytotoxic Dpl product.

  7. Altered cellular distribution and sub-cellular sorting of doppel (Dpl) protein in human astrocytoma cell lines.

    Science.gov (United States)

    Sbalchiero, Elena; Azzalin, Alberto; Palumbo, Silvia; Barbieri, Giulia; Arias, Agustina; Simonelli, Luca; Ferretti, Luca; Comincini, Sergio

    2008-01-01

    Doppel, a prion-like protein, is a GPI-membrane anchored protein generally not expressed in the Central Nervous System (CNS) of different mammalian species, including human. Nevertheless, in astrocytomas, a particular kind of glial tumors, the doppel encoding gene (PRND) is over-expressed and the corresponding protein product (Dpl) is ectopically localized in the cytoplasm of the tumor cells. In this study we have analysed the sub-cellular localization of Dpl using double-immunofluorescence staining and confocal microscopy examinations in two astrocytoma-derived human cell lines (IPDDC-A2 and D384-MG). Our results confirmed that Dpl is localized in the cytoplasm of the astrocytoma cells and indicated that it is mostly associated with Lamp-1 and Limp-2 positive lysosomal vesicles and, marginally, to the Golgi apparatus and other cellular organelles. Noticeably, none of the examined tumor cells showed a membrane-Dpl localization. The membrane-associated Dpl expression was restored after the transfection of the astrocytoma cells with mutated Dpl-expression vectors in its glycosylation sites. Additionally, Dpl showed altered expression and traffic using the acidotropic agent ammonium chloride, leading to the accumulation of Dpl in nascent exocytic vesicles. Altogether, these results indicated that in the astrocytic tumor cells Dpl has an altered biosynthetic trafficking, likely derived from abnormal post-translational processes: these modifications do not permit the localization of Dpl in correspondence of the plasma membrane and lead to its intracellular accumulation in the lysosomes. In these proteolytic compartments, the astrocytic tumor cells might provide to the degradation of the excess of a potentially cytotoxic Dpl product.

  8. 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

  9. Cellular Transplantation Alters the Disease Progression in Becker’s Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2013-01-01

    Full Text Available Becker’s Muscular Dystrophy (BMD is a dystrophinopathy manifested as progressive muscle degeneration. Autologous Bone Marrow Mononuclear Cells (BMMNCs have shown some myogenic potential. The paracrine effects of the BMMNCs reduce the inflammation and are thought to reduce muscle degeneration. We treated a 39 year old dental surgeon suffering from BMD. Muscle strength was reduced when measured using modified Medical Research Council’s Manual Muscle Testing (mMRC-MMT. Static sitting balance was poor. He was wheelchair dependent for ambulation and moderately independent in Activities of Daily Living (ADL. Functional Independence Measure (FIM score was 93. Musculoskeletal Magnetic Resonance Imaging (MRI-MSK showed moderate fatty infiltration in the muscles. Three cellular transplantations were carried out. Clinical assessment and the investigations were repeated. Progressive increase in the muscle strength was noted. Ambulation was independent using push-knee splints and minimal assistance when weary. Static and dynamic balance in sitting and standing improved. FIM score increased from 93 to 105. There was no increase in the degree of fatty infiltration, as seen on the MRI-MSK. The case study provides evidence for the putative benefits of cellular therapy in altering the disease progression in BMD. It also suggests augmented clinical benefits of combination of cellular therapy and rehabilitation.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Tóth, Renáta; Alonso, Maria F; Bain, Judith M; Vágvölgyi, Csaba; Erwig, Lars-Peter; Gácser, Attila

    2015-01-01

    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 Candida parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response toward 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  16. 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.

  17. 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

  18. HIV-1 transgenic rats display alterations in immunophenotype and cellular responses associated with aging.

    Science.gov (United States)

    Abbondanzo, Susan J; Chang, Sulie L

    2014-01-01

    Advances in anti-retroviral therapy over the last two decades have allowed life expectancy in patients infected with the human immunodeficiency virus to approach that of the general population. The process of aging in mammalian species, including rats, results in immune response changes, alterations in immunological phenotypes, and ultimately increased susceptibility to many infectious diseases. In order to investigate the immunological pathologies associated with chronic HIV-1 disease, particularly in aging individuals, the HIV-1 transgenic (HIV-1Tg) rat model was utilized. HIV-1Tg rats were challenged with lipopolysaccharide (LPS) to determine immunological alterations during the aging process. LPS is known to cause an imbalance in cytokine and chemokine release, and provides a method to identify changes in immune responses to bacterial infection in an HIV animal model. An immune profile and accompanying cellular consequences as well as changes in inflammatory cytokine and chemokine release related to age and genotype were assessed in HIV-1Tg rats. The percentage of T cells decreased with age, particularly T cytotoxic cells, whereas T helper cells increased with age. Neutrophils and monocytes increased in HIV-1Tg rats during maturation compared to age-matched F344 control rats. Aging HIV-1Tg rats displayed a significant increase in the pro-inflammatory cytokines, IL-6 and TNF-α, along with an increase in the chemokine, KC/GRO, in comparison to age-matched controls. Our data indicate that immunophenotype and immune responses can change during aging in HIV-positive individuals. This information could be important in determining the most beneficial age-dependent therapeutic treatment for HIV patients.

  19. HIV-1 transgenic rats display alterations in immunophenotype and cellular responses associated with aging.

    Directory of Open Access Journals (Sweden)

    Susan J Abbondanzo

    Full Text Available Advances in anti-retroviral therapy over the last two decades have allowed life expectancy in patients infected with the human immunodeficiency virus to approach that of the general population. The process of aging in mammalian species, including rats, results in immune response changes, alterations in immunological phenotypes, and ultimately increased susceptibility to many infectious diseases. In order to investigate the immunological pathologies associated with chronic HIV-1 disease, particularly in aging individuals, the HIV-1 transgenic (HIV-1Tg rat model was utilized. HIV-1Tg rats were challenged with lipopolysaccharide (LPS to determine immunological alterations during the aging process. LPS is known to cause an imbalance in cytokine and chemokine release, and provides a method to identify changes in immune responses to bacterial infection in an HIV animal model. An immune profile and accompanying cellular consequences as well as changes in inflammatory cytokine and chemokine release related to age and genotype were assessed in HIV-1Tg rats. The percentage of T cells decreased with age, particularly T cytotoxic cells, whereas T helper cells increased with age. Neutrophils and monocytes increased in HIV-1Tg rats during maturation compared to age-matched F344 control rats. Aging HIV-1Tg rats displayed a significant increase in the pro-inflammatory cytokines, IL-6 and TNF-α, along with an increase in the chemokine, KC/GRO, in comparison to age-matched controls. Our data indicate that immunophenotype and immune responses can change during aging in HIV-positive individuals. This information could be important in determining the most beneficial age-dependent therapeutic treatment for HIV patients.

  20. Morphine alters the circulating proteolytic profile in mice: functional consequences on cellular migration and invasion.

    Science.gov (United States)

    Xie, Nan; Khabbazi, Samira; Nassar, Zeyad D; Gregory, Kye; Vithanage, Tharindu; Anand-Apte, Bela; Cabot, Peter J; Sturgess, David; Shaw, Paul N; Parat, Marie-Odile

    2017-12-01

    Opioids modulate the tumor microenvironment with potential functional consequences for tumor growth and metastasis. We evaluated the effects of morphine administration on the circulating proteolytic profile of tumor-free mice. Serum from morphine-treated (1 or 10 mg/kg, i.p. every 12 h) or saline-treated mice was collected at different time points and tested ex vivo in endothelial, lymphatic endothelial, and breast cancer cell migration assays. Serum from mice that were treated with 10 mg/kg morphine for 3 d displayed reduced chemotactic potential for endothelial and breast cancer cells, and elicited reduced cancer cell invasion through reconstituted basement membrane compared with serum from saline controls. This was associated with decreased circulating matrix metalloproteinase 9 (MMP-9) and increased circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) and TIMP-3/4 as assessed by zymography and reverse zymography. By using quantitative RT-PCR, we confirmed morphine-induced alterations in MMP-9 and TIMP expression and identified organs, including the liver and spleen, in which these changes originated. Pharmacologic inhibition of MMP-9 abrogated the difference in chemotactic attraction between serum from saline-treated and morphine-treated mice, which indicated that reduced proteolytic ability mediated the decreased migration toward serum from morphine-treated mice. This novel mechanism may enable morphine administration to promote an environment that is less conducive to tumor growth, invasion, and metastasis.-Xie, N., Khabbazi, S., Nassar, Z. D., Gregory, K., Vithanage, T., Anand-Apte, B., Cabot, P. J., Sturgess, D., Shaw, P. N., Parat, M.-O. Morphine alters the circulating proteolytic profile in mice: functional consequences on cellular migration and invasion. © FASEB.

  1. Downregulation of SREBP inhibits tumor growth and initiation by altering cellular metabolism in colon cancer.

    Science.gov (United States)

    Wen, Yang-An; Xiong, Xiaopeng; Zaytseva, Yekaterina Y; Napier, Dana L; Vallee, Emma; Li, Austin T; Wang, Chi; Weiss, Heidi L; Evers, B Mark; Gao, Tianyan

    2018-02-15

    Sterol regulatory element-binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression of genes required for the synthesis of fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c, and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are derived from a single gene through the use of alternative transcription start sites. Here we investigated the role of SREBP-mediated lipogenesis in regulating tumor growth and initiation in colon cancer. Knockdown of either SREBP1 or SREBP2 decreased levels of fatty acids as a result of decreased expression of SREBP target genes required for lipid biosynthesis in colon cancer cells. Bioenergetic analysis revealed that silencing SREBP1 or SREBP2 expression reduced the mitochondrial respiration, glycolysis, as well as fatty acid oxidation indicating an alteration in cellular metabolism. Consequently, the rate of cell proliferation and the ability of cancer cells to form tumor spheroids in suspension culture were significantly decreased. Similar results were obtained in colon cancer cells in which the proteolytic activation of SREBP was blocked. Importantly, knockdown of either SREBP1 or SREBP2 inhibited xenograft tumor growth in vivo and decreased the expression of genes associated with cancer stem cells. Taken together, our findings establish the molecular basis of SREBP-dependent metabolic regulation and provide a rationale for targeting lipid biosynthesis as a promising approach in colon cancer treatment.

  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. 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.

  4. 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.

  5. 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.

  6. Cellular effects of fluorodeoxyglucose: Global changes in the lipidome and alteration in intracellular transport.

    Science.gov (United States)

    Kavaliauskiene, Simona; Torgersen, Maria Lyngaas; Lingelem, Anne Berit Dyve; Klokk, Tove Irene; Lintonen, Tuulia; Simolin, Helena; Ekroos, Kim; Skotland, Tore; Sandvig, Kirsten

    2016-11-29

    2-fluoro-2-deoxy-D-glucose (FDG), labeled with 18F radioisotope, is the most common imaging agent used for positron emission tomography (PET) in oncology. However, little is known about the cellular effects of FDG. Another glucose analogue, 2-deoxy-D-glucose (2DG), has been shown to affect many cellular functions, including intracellular transport and lipid metabolism, and has been found to improve the efficacy of cancer chemotherapeutic agents in vivo. Thus, in the present study, we have investigated cellular effects of FDG with the focus on changes in cellular lipids and intracellular transport. By quantifying more than 200 lipids from 17 different lipid classes in HEp-2 cells and by analyzing glycosphingolipids from MCF-7, HT-29 and HBMEC cells, we have discovered that FDG treatment inhibits glucosylceramide synthesis and thus reduces cellular levels of glycosphingolipids. In addition, in HEp-2 cells the levels and/or species composition of other lipid classes, namely diacylglycerols, phosphatidic acids and phosphatidylinositols, were found to change upon treatment with FDG. Furthermore, we show here that FDG inhibits retrograde Shiga toxin transport and is much more efficient in protecting cells against the toxin than 2DG. In summary, our data reveal novel effects of FDG on cellular transport and glycosphingolipid metabolism, which suggest a potential clinical application of FDG as an adjuvant for cancer chemotherapy.

  7. 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.

  8. Methyl jasmonate deficiency alters cellular metabolome including the aminome of tomato (Solanum lycopersicum L.) fruit

    Science.gov (United States)

    Lipoxygenase (LOX) catalyzes oxidation of C-13 atom of C:18 polyunsaturated fatty acids and produces jasmonic acid and other oxylipins that have important biological relevance. However, the role of these important molecules in cellular metabolism is barely understood. We have used a transgenic appro...

  9. Altered Expression of Plasminogen Activator and Plasminogen Activator Inhibitor during Cellular Senescence

    NARCIS (Netherlands)

    West, Michael D.; Shay, Jerry W.; Wright, Woodring E.; Linskens, Maarten H.K.

    1996-01-01

    Fibroblast senescence is associated with a loss of proliferative potential and an alteration in extracellular gene expression. Because the expression of extracellular gene products are frequently growth state dependent, we undertook a comparative study of the regulation of the components of the

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

    Science.gov (United States)

    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.

  11. Opt2 mediates the exposure of phospholipids during cellular adaptation to altered lipid asymmetry.

    Science.gov (United States)

    Yamauchi, Saori; Obara, Keisuke; Uchibori, Kenya; Kamimura, Akiko; Azumi, Kaoru; Kihara, Akio

    2015-01-01

    Plasma membrane lipid asymmetry is important for various membrane-associated functions and is regulated by membrane proteins termed flippases and floppases. The Rim101 pathway senses altered lipid asymmetry in the yeast plasma membrane. The mutant lem3Δ cells, in which lipid asymmetry is disturbed owing to the inactivation of the plasma membrane flippases, showed a severe growth defect when the Rim101 pathway was impaired. To identify factors involved in the Rim101-pathway-dependent adaptation to altered lipid asymmetry, we performed DNA microarray analysis and found that Opt2 induced by the Rim101 pathway plays an important role in the adaptation to altered lipid asymmetry. Biochemical investigation of Opt2 revealed its localization to the plasma membrane and the Golgi, and provided several lines of evidence for the Opt2-mediated exposure of phospholipids. In addition, Opt2 was found to be required for the maintenance of vacuolar morphology and polarized cell growth. These results suggest that Opt2 is a novel factor involved in cell homeostasis by regulating lipid asymmetry. © 2015. Published by The Company of Biologists Ltd.

  12. 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

  13. Metabolomics Reveals that Dietary Xenoestrogens Alter Cellular Metabolism Induced by Palbociclib/Letrozole Combination Cancer Therapy.

    Science.gov (United States)

    Warth, Benedikt; Raffeiner, Philipp; Granados, Ana; Huan, Tao; Fang, Mingliang; Forsberg, Erica M; Benton, H Paul; Goetz, Laura; Johnson, Caroline H; Siuzdak, Gary

    2018-03-15

    Recently, the palbociclib/letrozole combination therapy was granted accelerated US FDA approval for the treatment of estrogen receptor (ER)-positive breast cancer. Since the underlying metabolic effects of these drugs are yet unknown, we investigated their synergism at the metabolome level in MCF-7 cells. As xenoestrogens interact with the ER, we additionally aimed at deciphering the impact of the phytoestrogen genistein and the estrogenic mycotoxin zearalenone. A global metabolomics approach was applied to unravel metabolite and pathway modifications. The results clearly showed that the combined effects of palbociclib and letrozole on cellular metabolism were far more pronounced than that of each agent alone and potently influenced by xenoestrogens. This behavior was confirmed in proliferation experiments and functional assays. Specifically, amino acids and central carbon metabolites were attenuated, while higher abundances were observed for fatty acids and most nucleic acid-related metabolites. Interestingly, exposure to model xenoestrogens appeared to counteract these effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  15. Binding of hepatitis B virus to its cellular receptor alters the expression profile of genes of bile acid metabolism.

    Science.gov (United States)

    Oehler, Nicola; Volz, Tassilo; Bhadra, Oliver D; Kah, Janine; Allweiss, Lena; Giersch, Katja; Bierwolf, Jeanette; Riecken, Kristoffer; Pollok, Jörg M; Lohse, Ansgar W; Fehse, Boris; Petersen, Joerg; Urban, Stephan; Lütgehetmann, Marc; Heeren, Joerg; Dandri, Maura

    2014-11-01

    Chronic hepatitis B virus (HBV) infection has been associated with alterations in lipid metabolism. Moreover, the Na+-taurocholate cotransporting polypeptide (NTCP), responsible for bile acid (BA) uptake into hepatocytes, was identified as the functional cellular receptor mediating HBV entry. The aim of the study was to determine whether HBV alters the liver metabolic profile by employing HBV-infected and uninfected human liver chimeric mice. Humanized urokinase plasminogen activator/severe combined immunodeficiency mice were used to establish chronic HBV infection. Gene expression profiles were determined by real-time polymerase chain reaction using primers specifically recognizing transcripts of either human or murine origin. Liver biopsy samples obtained from HBV-chronic individuals were used to validate changes determined in mice. Besides modest changes in lipid metabolism, HBV-infected mice displayed a significant enhancement of human cholesterol 7α-hydroxylase (human [h]CYP7A1; median 12-fold induction; Pmetabolic alterations. Binding of HBV to NTCP limits its function, thus promoting compensatory BA synthesis and cholesterol provision. The intimate link determined between HBV and liver metabolism underlines the importance to exploit further metabolic pathways, as well as possible NTCP-related viral-drug interactions. © 2014 by the American Association for the Study of Liver Diseases.

  16. Purification of highly active alphavirus replication complexes demonstrates altered fractionation of multiple cellular membranes.

    Science.gov (United States)

    Pietilä, Maija K; van Hemert, Martijn J; Ahola, Tero

    2018-01-24

    Positive-strand RNA viruses replicate their genomes in membrane-associated structures; alphaviruses and many other groups induce membrane invaginations called spherules. Here, we established a protocol to purify these membranous replication complexes (RCs) from cells infected with Semliki Forest virus (SFV). We isolated SFV spherules located on the plasma membrane and further purified them using two consecutive density gradients. This revealed that SFV infection strongly modifies cellular membranes. We removed soluble proteins, the Golgi and most of the mitochondria, but plasma membrane, endoplasmic reticulum (ER) and late endosome markers enriched in the membrane fraction that contained viral RNA synthesizing activity, replicase proteins and minus- and plus-strand RNA. Electron microscopy revealed that the purified membranes displayed spherule-like structures with a narrow neck. This membrane enrichment was specific to viral replication as such a distribution of membrane markers was only observed after infection. Besides the plasma membrane, SFV infection remodeled the ER, and the co-fractionation of the RC-carrying plasma membrane and ER suggests that SFV may recruit ER proteins or membrane to the site of replication. The purified RCs were highly active in synthesizing both genomic and subgenomic RNA. Detergent solubilization destroyed the replication activity demonstrating that the membrane association of the complex is essential. Most of the newly made RNA was in double-stranded replicative molecules but the purified complexes also produced single-stranded RNA as well as released newly made RNA. This indicates that the purification established here maintained the functionality of RCs and thus enables further structural and functional studies of active RCs. IMPORTANCE Similar to all positive-strand RNA viruses, the arthropod-borne alphaviruses induce membranous genome factories but little is known about the arrangement of viral replicase proteins and the

  17. Adaptive endoplasmic reticulum stress alters cellular responses to the extracellular milieu.

    Science.gov (United States)

    Liu, Yiting; Neely, Elizabeth; Simmons, Zachary; Connor, James R

    2015-05-01

    The ability to respond to perturbations in endoplasmic reticulum (ER) function is a critical property for all cells. In the presence of chronic ER stress, the cell must adapt so that cell survival is favored or the stress may promote apoptosis. In some pathological processes, such as neurodengeneration, persistent ER stress can be tolerated for an extended period, but eventually cell death occurs. It is not known how an adaptive response converts from survival into apoptosis. To gain a better understanding of the role of adaptive ER stress in neurodegeneration, in this study, with a neuronal cell line SH-SY5Y and primary motor neuron-glia cell mixed cultures, we induced adaptive ER stress and modified the extracellular environment with physiologically relevant changes that alone did not activate ER stress. Our data demonstrate that an adaptive ER stress favored neuronal cell survival, but when cells were exposed to additional physiological insults the level of ER stress was increased, followed by activation of the caspase pathway. Our results indicate that an adaptive ER stress response could be converted to apoptosis when the external cellular milieu changed, suggesting that the conversion from prosurvival to proapoptotic pathways can be driven by the external milieu. This conversion was due at least partially to an increased level of ER stress. © 2015 Wiley Periodicals, Inc.

  18. BRCA1 haploinsufficiency leads to altered expression of genes involved in cellular proliferation and development.

    Directory of Open Access Journals (Sweden)

    Harriet E Feilotter

    Full Text Available The assessment of BRCA1 and BRCA2 coding sequences to identify pathogenic mutations associated with inherited breast/ovarian cancer syndrome has provided a method to identify high-risk individuals, allowing them to seek preventative treatments and strategies. However, the current test is expensive, and cannot differentiate between pathogenic variants and those that may be benign. Focusing only on one of the two BRCA partners, we have developed a biological assay for haploinsufficiency of BRCA1. Using a series of EBV-transformed cell lines, we explored gene expression patterns in cells that were BRCA1 wildtype compared to those that carried (heterozygous BRCA1 pathogenic mutations. We identified a subset of 43 genes whose combined expression pattern is a sensitive predictor of BRCA1 status. The gene set was disproportionately made up of genes involved in cellular differentiation, lending credence to the hypothesis that single copy loss of BRCA1 function may impact differentiation, rendering cells more susceptible to undergoing malignant processes.

  19. Soluble Fms-Like Tyrosine Kinase-1 Alters Cellular Metabolism and Mitochondrial Bioenergetics in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Lissette C. Sánchez-Aranguren

    2018-03-01

    Full Text Available Preeclampsia is a maternal hypertensive disorder that affects up to 1 out of 12 pregnancies worldwide. It is characterized by proteinuria, endothelial dysfunction, and elevated levels of the soluble form of the vascular endothelial growth factor receptor-1 (VEGFR-1, known as sFlt-1. sFlt-1 effects are mediated in part by decreasing VEGF signaling. The direct effects of sFlt-1 on cellular metabolism and bioenergetics in preeclampsia, have not been established. The goal of this study was to evaluate whether sFlt-1 causes mitochondrial dysfunction leading to disruption of normal functioning in endothelial and placental cells in preeclampsia. Endothelial cells (ECs and first-trimester trophoblast (HTR-8/SVneo were treated with serum from preeclamptic women rich in sFlt-1 or with the recombinant protein. sFlt-1, dose-dependently inhibited ECs respiration and acidification rates indicating a metabolic phenotype switch enhancing glycolytic flux. HTR-8/SVneo displayed a strong basal glycolytic metabolism, remaining less sensitive to sFlt-1-induced mitochondrial impairment. Moreover, results obtained in ECs exposed to serum from preeclamptic subjects demonstrated that increased sFlt-1 leads to metabolic perturbations accountable for mitochondrial dysfunction observed in preeclampsia. sFlt-1 exacerbated mitochondrial reactive oxygen species (ROS formation and mitochondrial membrane potential dissipation in ECs and trophoblasts exposed to serum from preeclamptic women. Forcing oxidative metabolism by culturing cells in galactose media, further sensitized cells to sFlt-1. This approach let us establish that sFlt-1 targets mitochondrial function in ECs. Effects of sFlt-1 on HTR-8/SVneo cells metabolism were amplified in galactose, demonstrating that sFlt-1 only target cells that rely mainly on oxidative metabolism. Together, our results establish the early metabolic perturbations induced by sFlt-1 and the resulting endothelial and mitochondrial dysfunction

  20. Overexpression of plastid terminal oxidase inSynechocystissp. PCC 6803 alters cellular redox state.

    Science.gov (United States)

    Feilke, Kathleen; Ajlani, Ghada; Krieger-Liszkay, Anja

    2017-09-26

    Cyanobacteria are the most ancient organisms performing oxygenic photosynthesis, and they are the ancestors of plant plastids. All plastids contain the plastid terminal oxidase (PTOX), while only certain cyanobacteria contain PTOX. Many putative functions have been discussed for PTOX in higher plants including a photoprotective role during abiotic stresses like high light, salinity and extreme temperatures. Since PTOX oxidizes PQH 2 and reduces oxygen to water, it is thought to protect against photo-oxidative damage by removing excess electrons from the plastoquinone (PQ) pool. To investigate the role of PTOX we overexpressed rice PTOX fused to the maltose-binding protein (MBP-OsPTOX) in Synechocystis sp. PCC 6803, a model cyanobacterium that does not encode PTOX. The fusion was highly expressed and OsPTOX was active, as shown by chlorophyll fluorescence and P 700 absorption measurements. The presence of PTOX led to a highly oxidized state of the NAD(P)H/NAD(P) + pool, as detected by NAD(P)H fluorescence. Moreover, in the PTOX overexpressor the electron transport capacity of PSI relative to PSII was higher, indicating an alteration of the photosystem I (PSI) to photosystem II (PSII) stoichiometry. We suggest that PTOX controls the expression of responsive genes of the photosynthetic apparatus in a different way from the PQ/PQH 2 ratio.This article is part of the themed issue 'Enhancing photosynthesis in crop plants: targets for improvement'. © 2017 The Author(s).

  1. Cellular alterations and enhanced induction of cleft palate after coadministration of retinoic acid and TCDD

    Energy Technology Data Exchange (ETDEWEB)

    Abbott, B.D.; Birnbaum, L.S. (National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA))

    1989-06-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and retinoic acid (RA) are both teratogenic in mice. TCDD is a highly toxic, stable environmental contaminant, while RA is a naturally occurring form of vitamin A. Exposure to TCDD induces hydronephrosis and cleft palate, and exposure to RA induces limb defects and cleft palate. Teratology studies previously have shown that the incidence of clefting is higher after exposure to RA + TCDD than would be observed for the same doses of either compound given alone. This study examines the cellular effects which result in cleft palate, after po administration on gestation Day (GD) 10 or 12 of RA + TCDD in corn oil (10 ml/kg total volume). Exposure on GD 10 to 6 micrograms TCDD + 40 mg RA/kg inhibited early growth of the shelves and clefting was due to a failure of shelves to meet and fuse. This effect on mesenchyme was observed in previous studies to occur after exposure on GD 10 to 40 mg/kg RA alone, but not after TCDD alone. After exposure on GD 12 to 6 micrograms TCDD + 80 mg RA/kg, clefting was due to a failure of shelves to fuse after making contact, because the medial cells differentiated into an oral-like epithelium. This response was observed in previous studies to occur after exposure to TCDD alone, but RA alone on GD 12 resulted in differentiation toward nasal-like cells. The interaction between TCDD and RA results in RA-like clefting after exposure on GD 10 and TCDD-like clefting after exposure on GD 12, and this clefting occurs at higher incidences than would occur after the same levels of either agent alone. After exposure on either GD 10 or 12 to RA + TCDD, the programmed cell death of the medial cells does not occur, and these cells continue to express EGF receptors and to bind 125I-EGF. The effects of RA and TCDD may involve modulation of the cells responses to embryonic growth and differentiation factors.

  2. Targeted mutation of the MLN64 START domain causes only modest alterations in cellular sterol metabolism.

    Science.gov (United States)

    Kishida, Tatsuro; Kostetskii, Igor; Zhang, Zhibing; Martinez, Federico; Liu, Pei; Walkley, Steven U; Dwyer, Nancy K; Blanchette-Mackie, E Joan; Radice, Glenn L; Strauss, Jerome F

    2004-04-30

    The StAR-related lipid transfer (START) domain, first identified in the steroidogenic acute regulatory protein (StAR), is involved in the intracellular trafficking of lipids. Sixteen mammalian START domain-containing proteins have been identified to date. StAR, a protein targeted to mitochondria, stimulates the movement of cholesterol from the outer to the inner mitochondrial membranes, where it is metabolized into pregnenolone in steroidogenic cells. MLN64, the START domain protein most closely related to StAR, is localized to late endosomes along with other proteins involved in sterol trafficking, including NPC1 and NPC2, where it has been postulated to participate in sterol distribution to intracellular membranes. To investigate the role of MLN64 in sterol metabolism, we created mice with a targeted mutation in the Mln64 START domain, expecting to find a phenotype similar to that in humans and mice lacking NPC1 or NPC2 (progressive neurodegenerative symptoms, free cholesterol accumulation in lysosomes). Unexpectedly, mice homozygous for the Mln64 mutant allele were viable, neurologically intact, and fertile. No significant alterations in plasma lipid levels, liver lipid content and distribution, and expression of genes involved in sterol metabolism were observed, except for an increase in sterol ester storage in mutant mice fed a high fat diet. Embryonic fibroblast cells transfected with the cholesterol side-chain cleavage system and primary cultures of granulosa cells from Mln64 mutant mice showed defects in sterol trafficking as reflected in reduced conversion of endogenous cholesterol to steroid hormones. These observations suggest that the Mln64 START domain is largely dispensable for sterol metabolism in mice.

  3. Myocardial perfusion alterations observed months after radiotherapy are related to the cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Dogan, I.; Sonmez, B. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Nuclear Medicine; Sezen, O.; Zengin, A.Y.; Bahat, Z. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Radiation Oncology; Yenilmez, E.; Yulug, E. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Histology and Embryology; Abidin, I. [Karadeniz Technical Univ., Trabzon (Turkey). Dept. of Biophysics

    2010-07-01

    Myocardial perfusion scintigraphy (MPS) is one of the widely used tools to follow developing radiation-induced heart disease (RIHD). But the clinical significance of MPS defects has not been fully understood. We have investigated the biodistribution alterations related to perfusion defects following radiotherapy (RT) and showed coexisting morphological changes. Animals, methods: A total of 18 Wistar rats were divided into three groups (1 control and 2 irradiated groups). A single cardiac 20 Gy radiation dose was used to induce long term cardiac defects. Biodistribution studies with technetium ({sup 99m}Tc) sestamibi and histological evaluations were performed 4 and 6 months after irradiation. The percent radioactivity (%ID/g) was calculated for each heart. For determination of the myocardial damage, positive apoptotic cardiomyocytes, myocardial cell degeneration, myocardial fibrosis, vascular damage and ultrastructural structures were evaluated. Results: Six months after treatment, a significant drop of myocardial uptake was observed (p < 0.05). Irradiation-induced apoptosis rose within the first 4 months after radiation treatment and were stayed elevated until the end of the observation period (p < 0.05). Also, the irradiation has induced myocardial degeneration, perivascular and interstitial fibrosis in the heart at the end of six and four months (p < 0.01). The severity and extent of myocardial injury has became more evident at the end of six month (p < 0.05). At ultrastructural level, prominent changes have been observed in the capillary endothelial and myocardial cells. Conclusion: Our findings suggest that the reduced rest myocardial perfusion, occuring months after the radiation, indicates a serious myocard tissue damage which is characterized by myocardial degeneration and fibrosis. (orig.)

  4. Methylglyoxal synthase regulates cell elongation via alterations of cellular methylglyoxal and spermidine content in Bacillus subtilis.

    Science.gov (United States)

    Shin, Sang-Min; Song, Sung-Hyun; Lee, Jin-Woo; Kwak, Min-Kyu; Kang, Sa-Ouk

    2017-10-01

    Methylglyoxal regulates cell division and differentiation through its interaction with polyamines. Loss of their biosynthesizing enzyme causes physiological impairment and cell elongation in eukaryotes. However, the reciprocal effects of methylglyoxal and polyamine production and its regulatory metabolic switches on morphological changes in prokaryotes have not been addressed. Here, Bacillus subtilis methylglyoxal synthase (mgsA) and polyamine biosynthesizing genes encoding arginine decarboxylase (SpeA), agmatinase (SpeB), and spermidine synthase (SpeE), were disrupted or overexpressed. Treatment of 0.2mM methylglyoxal and 1mM spermidine led to the elongation and shortening of B. subtilis wild-type cells to 12.38±3.21μm (P<0.05) and 3.24±0.73μm (P<0.01), respectively, compared to untreated cells (5.72±0.68μm). mgsA-deficient (mgsA - ) and -overexpressing (mgsA OE ) mutants also demonstrated cell shortening and elongation, similar to speB- and speE-deficient (speB - and speE - ) and -overexpressing (speB OE and speE OE ) mutants. Importantly, both mgsA-depleted speB OE and speE OE mutants (speB OE /mgsA - and speE OE /mgsA - ) were drastically shortened to 24.5% and 23.8% of parental speB OE and speE OE mutants, respectively. These phenotypes were associated with reciprocal alterations of mgsA and polyamine transcripts governed by the contents of methylglyoxal and spermidine, which are involved in enzymatic or genetic metabolite-control mechanisms. Additionally, biophysically detected methylglyoxal-spermidine Schiff bases did not affect morphogenesis. Taken together, the findings indicate that methylglyoxal triggers cell elongation. Furthermore, cells with methylglyoxal accumulation commonly exhibit an elongated rod-shaped morphology through upregulation of mgsA, polyamine genes, and the global regulator spx, as well as repression of the cell division and shape regulator, FtsZ. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. 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.

  6. Asbestos-Induced Cellular and Molecular Alteration of Immunocompetent Cells and Their Relationship with Chronic Inflammation and Carcinogenesis

    Science.gov (United States)

    Matsuzaki, Hidenori; Maeda, Megumi; Lee, Suni; Nishimura, Yasumitsu; Kumagai-Takei, Naoko; Hayashi, Hiroaki; Yamamoto, Shoko; Hatayama, Tamayo; Kojima, Yoko; Tabata, Rika; Kishimoto, Takumi; Hiratsuka, Junichi; Otsuki, Takemi

    2012-01-01

    Asbestos causes lung fibrosis known as asbestosis as well as cancers such as malignant mesothelioma and lung cancer. Asbestos is a mineral silicate containing iron, magnesium, and calcium with a core of SiO2. The immunological effect of silica, SiO2, involves the dysregulation of autoimmunity because of the complications of autoimmune diseases found in silicosis. Asbestos can therefore cause alteration of immunocompetent cells to result in a decline of tumor immunity. Additionally, due to its physical characteristics, asbestos fibers remain in the lung, regional lymph nodes, and the pleural cavity, particularly at the opening sites of lymphatic vessels. Asbestos can induce chronic inflammation in these areas due to the production of reactive oxygen/nitrogen species. As a consequence, immunocompetent cells can have their cellular and molecular features altered by chronic and recurrent encounters with asbestos fibers, and there may be modification by the surrounding inflammation, all of which eventually lead to decreased tumor immunity. In this paper, the brief results of our investigation regarding reduction of tumor immunity of immunocompetent cells exposed to asbestos in vitro are discussed, as are our findings concerned with an investigation of chronic inflammation and analyses of peripheral blood samples derived from patients with pleural plaque and mesothelioma that have been exposed to asbestos. PMID:22500091

  7. 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

  8. 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

  9. Bovine spongiform encephalopathy induces misfolding of alleged prion-resistant species cellular prion protein without altering its pathobiological features.

    Science.gov (United States)

    Vidal, Enric; Fernández-Borges, Natalia; Pintado, Belén; Ordóñez, Montserrat; Márquez, Mercedes; Fondevila, Dolors; Torres, Juan María; Pumarola, Martí; Castilla, Joaquín

    2013-05-01

    Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrP(c)) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine and human PrP(C). Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species.

  10. Infant avoidance training alters cellular activation patterns in prefronto-limbic circuits during adult avoidance learning: I. Cellular imaging of neurons expressing the synaptic plasticity early growth response protein 1 (Egr1).

    Science.gov (United States)

    Gröger, Nicole; Mannewitz, Anja; Bock, Jörg; de Schultz, Tony Fernando; Guttmann, Katja; Poeggel, Gerd; Braun, Katharina

    2017-11-01

    Both positive feedback learning and negative feedback learning are essential for adapting and optimizing behavioral performance. There is increasing evidence in humans and animals that the ability of negative feedback learning emerges postnatally. Our work in rats, using a two-way active avoidance task (TWA) as an experimental paradigm for negative feedback learning, revealed that medial and lateral prefrontal regions of infant rats undergo dramatic synaptic reorganization during avoidance training, resulting in improved avoidance learning in adulthood. The aim of this study was to identify changes of cellular activation patterns during the course of training and in relation to infant pretraining. We applied a quantitative cellular imaging technique using the immunocytochemical detection of the activity marker early growth response protein 1 (Egr1) as a candidate contributing to learning-induced synaptic plasticity. We found region-specific cellular activity patterns, which indicate that during the acquisition phase, Egr1 expression is specifically elevated in cellular ensembles of the orbitofrontal, dorsal anterior cingulate and hippocampal CA1 region. During memory retrieval Egr1 expression is elevated in cellular ensembles of the dentate gyrus. Moreover, we, for the first time, show here that TWA training during infancy alters adult learning- and memory-related patterns of Egr1 expression in these brain regions. It is tempting to speculate that during infant learning, specific Egr1-expressing cellular ensembles are "tagged" representing long-term memory formation, and that these cell ensembles may be reactivated during adult learning.

  11. Transmissible Gastroenteritis Virus (TGEV) Infection Alters the Expression of Cellular MicroRNA Species That Affect Transcription of TGEV Gene 7

    OpenAIRE

    Song, Xiangjun; Zhao, Xiaomin; Huang, Yong; Xiang, Hailing; Zhang, Wenlong; Tong, Dewen

    2015-01-01

    Transmissible gastroenteritis virus (TGEV) is a member of Coronaviridae family. TGEV infection has emerged as a major cause of severe gastroenteritis and leads to alterations of many cellular processes. Meanwhile, the pathogenic mechanism of TGEV is still unclear. microRNAs (miRNAs) are a novel class of small non-coding RNAs which are involved in the regulation of numerous biological processes such as viral infection and cell apoptosis. Accumulating data show that miRNAs are involved in the p...

  12. 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

    Extracellular superoxide dismutase (EC-SOD) is responsible for the dismutation of the superoxide radical produced in the extracellular space and known to be expressed by inflammatory cells, including macrophages and neutrophils. Here we show that EC-SOD is produced by resting macrophages...... 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...

  13. The effect of oxidant and the non-oxidant alteration of cellular thiol concentration on the formation of protein mixed-disulfides in HEK 293 cells.

    Directory of Open Access Journals (Sweden)

    Jasen Lee Gilge

    Full Text Available Cellular molecules possess various mechanisms in responding to oxidant stress. In terms of protein responses, protein S-glutathionylation is a unique post-translational modification of protein reactive cysteines forming disulfides with glutathione molecules. This modification has been proposed to play roles in antioxidant, regulatory and signaling in cells under oxidant stress. Recently, the increased level of protein S-glutathionylation has been linked with the development of diseases. In this report, specific S-glutathionylated proteins were demonstrated in human embryonic kidney 293 cells treated with two different oxidative reagents: diamide and hydrogen peroxide. Diamide is a chemical oxidizing agent whereas hydrogen peroxide is a physiological oxidant. Under the experimental conditions, these two oxidants decreased glutathione concentration without toxicity. S-glutathionylated proteins were detected by immunoblotting and glutathione concentrations were determined by high performance liquid chromatography. We further show the effect of alteration of the cellular thiol pool on the amount of protein S-glutathionylation in oxidant-treated cells. Cellular thiol concentrations were altered either by a specific way using buthionine sulfoximine, a specific inhibitor of glutathione biosynthesis or by a non-specific way, incubating cells in cystine-methionine deficient media. Cells only treated with either buthionine sulfoximine or cystine-methionine deficient media did not induce protein S-glutathionylation, even though both conditions decreased 65% of cellular glutathione. Moreover, the amount of protein S-glutathionylation under both conditions in the presence of oxidants was not altered when compared to the amount observed in regular media with oxidants present. Protein S-glutathionylation is a dynamic reaction which depends on the rate of adding and removing glutathione. Phenylarsine oxide, which specifically forms a covalent adduct with

  14. Transmissible gastroenteritis virus (TGEV) infection alters the expression of cellular microRNA species that affect transcription of TGEV gene 7.

    Science.gov (United States)

    Song, Xiangjun; Zhao, Xiaomin; Huang, Yong; Xiang, Hailing; Zhang, Wenlong; Tong, Dewen

    2015-01-01

    Transmissible gastroenteritis virus (TGEV) is a member of Coronaviridae family. TGEV infection has emerged as a major cause of severe gastroenteritis and leads to alterations of many cellular processes. Meanwhile, the pathogenic mechanism of TGEV is still unclear. microRNAs (miRNAs) are a novel class of small non-coding RNAs which are involved in the regulation of numerous biological processes such as viral infection and cell apoptosis. Accumulating data show that miRNAs are involved in the process of coronavirus infection such as replication of severe acute respiratory syndrome coronavirus (SARS-CoV). However, the link between miRNAs and TGEV infection is unknown. In this study, we performed microRNA microarray assay and predicted targets of altered miRNAs. The results showed TGEV infection caused the change of miRNAs profile. Then we selected miR-4331 for further analysis and subsequently identified cell division cycle-associated protein 7 (CDCA7) as the target of miR-4331. Moreover, miR-4331 showed the ability to inhibit transcription of TGEV gene 7 (a non-structure gene) via directly targeting CDCA7. In conclusion, differentially expressed miR-4331 that is caused by TGEV infection can suppress transcription of TGEV gene 7 via targeting cellular CDCA7. Our key finding is that TGEV selectively manipulates the expression of some cellular miRNAs to regulate its subgenomic transcription.

  15. A single amino acid substitution in the transmembrane envelope glycoprotein of feline immunodeficiency virus alters cellular tropism

    NARCIS (Netherlands)

    Horzinek, M.C.; Vahlenkamp, T.W.; Verschoor, E.J.; Schuurman, N.M.P.; Vliet, A.L.W. van; Egberink, H.F.; Ronde, A. de

    1997-01-01

    The cellular tropism of the feline immunodeficiency virus (FIV) is affected by changes in variable region 3 (V3) of the surface (SU) envelope glycoprotein (Verschoor, E. J., et al., J. Virol. 69:4752- 4757, 1995). By using high-dose DNA transfection, an FIV molecular clone with a non-CRFK-tropic V3

  16. The anti‑dengue virus properties of statins may be associated with alterations in the cellular antiviral profile expression.

    Science.gov (United States)

    Bryan-Marrugo, Owen Lloyd; Arellanos-Soto, Daniel; Rojas-Martinez, Augusto; Barrera-Saldaña, Hugo; Ramos-Jimenez, Javier; Vidaltamayo, Roman; Rivas-Estilla, Ana María

    2016-09-01

    Dengue virus (DENV) susceptibility to cholesterol depleting treatments has been previously reported. There are numerous questions regarding how DENV seizes cellular machinery and cholesterol to improve viral production and the effect of cholesterol sequestering agents on the cellular antiviral response. The aim of the present study was to evaluate the mechanisms involved in the negative regulation of DENV replication induced by agents that diminish intracellular cholesterol levels. Cholesterol synthesis was pharmacologically (fluvastatin, atorvastatin, lovastatin, pravastatin and simvastatin treatment) and genetically (HMGCR‑RNAi) inhibited, in uninfected and DENV2‑infected hepatoma Huh‑7 cells. The cholesterol levels, DENV titer and cellular antiviral expression profile were evaluated. A reduction in the DENV titer, measured as plaque forming units, was observed in DENV‑infected cells following 48 h treatment with 10 µM fluvastatin, 10 µM atorvastatin, 20 µM lovastatin and 20 µM simvastatin, which achieved 70, 70, 65 and 55% DENV2 inhibition, respectively, compared with the untreated cells. In addition, the cytopathic effect was reduced in the statin‑treated DENV‑infected cells. Statins simultaneously reduced cholesterol levels at 48 h, with the exception of DENV2 infected cells. Genetic inhibition of cholesterol synthesis was performed using RNA interference for 3‑hydroxy‑3‑methylglutaryl‑CoA reductase (HMGCR‑siRNA), which indicated a slight reduction in DENV2 titer at 48 h post‑infection, however, with no significant reduction in cholesterol levels. In addition, DENV2 infection was observed to augment the intracellular cholesterol levels in all experimental conditions. Comparison between the cellular antiviral response triggered by DENV2 infection, statin treatment and HMGCR‑siRNA in infected, uninfected, treated and untreated Huh7 cells, showed different expression profiles for the antiviral genes evaluated. All

  17. Heavy metal tolerance genes alter cellular thermodynamics in Pseudomonas putida and river Pseudomonas spp. and influence amebal predation.

    Science.gov (United States)

    McTee, Michael R; Gibbons, Sean M; Feris, Kevin; Gordon, Nathan S; Gannon, James E; Ramsey, Philip W

    2013-10-01

    Predation rates were measured for two Acanthamoeba castellanii strains feeding on metal-tolerant and metal-sensitive strains of Pseudomonas putida and compared with cellular thermodynamic data. Predation rates by A. castellanii strain ATCC 30010 correlated with cell volume of the prey. To explore whether this observation could be environmentally relevant, pseudomonad species were isolated from a pristine and a metal-contaminated river and were paired based on phylogenetic and physiological relatedness. Then, cellular thermodynamics and predation rates were measured on the most similar pseudomonad pair. Under cadmium stress, the strain from contaminated river sediments, Pseudomonas sp. CF150, exited metabolic dormancy faster than its pair from pristine sediments, Pseudomonas sp. N9, but consumed available resources less efficiently (more energy was lost as heat). Predation rates by both strains of ameba were greater on Pseudomonas sp. CF150 than on Pseudomonas sp. N9 at the highest cadmium concentration. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  18. Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered MicroRNA expression in solid tumors

    DEFF Research Database (Denmark)

    Sempere, Lorenzo F; Preis, Meir; Yezefski, Todd

    2010-01-01

    High-throughput profiling experiments have linked altered expression of microRNAs (miRNA) to different types of cancer. Tumor tissues are a heterogeneous mixture of not only cancer cells, but also supportive and reactive tumor microenvironment elements. To clarify the clinical significance...... of altered miRNA expression in solid tumors, we developed a sensitive fluorescence-based in situ hybridization (ISH) method to visualize miRNA accumulation within individual cells in formalin-fixed, paraffin-embedded tissue specimens. This ISH method was implemented to be compatible with routine clinical...... immunohistochemical (IHC) assays to enable the detection of miRNAs and protein markers in the same tissue section for colocalization and functional studies....

  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. 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

  1. Alterations in macrophage cellular proteome induced by calcium oxalate crystals: the association of HSP90 and F-actin is important for phagosome formation.

    Science.gov (United States)

    Singhto, Nilubon; Sintiprungrat, Kitisak; Thongboonkerd, Visith

    2013-08-02

    The presence of macrophages in renal interstitium is the key feature of progressive renal inflammation in kidney stone disease. However, response of macrophages to calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stone, remained unclear. This study aimed to investigate alterations in the cellular proteome of macrophages induced by COM crystals using a proteomics approach. U937-derived macrophages (by phorbol-12-myristate-13-acetate activation) were incubated without or with 100 μg/mL COM crystals for 24 h. Their cellular proteins were resolved by 2-DE (n = 10 gels; 5 were derived from 5 independent cultures in each group) and visualized with Deep Purple fluorescent dye. Spot matching, quantitative intensity analysis, and statistics revealed 18 differentially expressed protein spots, which were successfully identified by Q-TOF MS and MS/MS analyses. The altered levels of α-tubulin, β-actin and ezrin were validated by Western blot analysis. Protein interaction network analysis using STRING software showed that 90 kDa heat shock protein (HSP90) was associated with β-actin and α-tubulin (all these three proteins were increased in the COM-treated macrophages). Multiple immunofluorescence stainings confirmed the associations of HSP90 with filamentous form of actin (F-actin) and α-tubulin. However, only the association between HSP90 and F-actin was found on the phagosome membrane surrounding COM crystal, indicating that the association of HSP90 with F-actin, but not with α-tubulin, is important for phagosome formation. Silencing of HSP90 (siHSP90) reduced expression of cytoskeletal proteins and phagosome marker (Rab5) and successfully diminished COM crystal-induced phagocytosis and migration of macrophages. Our findings enlightened the significant role of these altered proteins, especially HSP90, in enhanced phagocytic activity of the COM-exposed macrophages.

  2. Altering adsorbed proteins or cellular gene expression in bone-metastatic cancer cells affects PTHrP and Gli2 without altering cell growth

    Directory of Open Access Journals (Sweden)

    Jonathan M. Page

    2015-09-01

    Full Text Available The contents of this data in brief are related to the article titled “Matrix Rigidity Regulates the Transition of Tumor Cells to a Bone-Destructive Phenotype through Integrin β3 and TGF-β Receptor Type II”. In this DIB we will present our supplemental data investigating Integrin expression, attachment of cells to various adhesion molecules, and changes in gene expression in multiple cancer cell lines. Since the interactions of Integrins with adsorbed matrix proteins are thought to affect the ability of cancer cells to interact with their underlying substrates, we examined the expression of Integrin β1, β3, and β5 in response to matrix rigidity. We found that only Iβ3 increased with increasing substrate modulus. While it was shown that fibronectin greatly affects the expression of tumor-produced factors associated with bone destruction (parathyroid hormone-related protein, PTHrP, and Gli2, poly-l-lysine, vitronectin and type I collagen were also analyzed as potential matrix proteins. Each of the proteins was independently adsorbed on both rigid and compliant polyurethane films which were subsequently used to culture cancer cells. Poly-l-lysine, vitronectin and type I collagen all had negligible effects on PTHrP or Gli2 expression, but fibronectin was shown to have a dose dependent effect. Finally, altering the expression of Iβ3 demonstrated that it is required for tumor cells to respond to the rigidity of the matrix, but does not affect other cell growth or viability. Together these data support the data presented in our manuscript to show that the rigidity of bone drives Integrinβ3/TGF-β crosstalk, leading to increased expression of Gli2 and PTHrP.

  3. Alteration of cellular behavior and response to PI3K pathway inhibition by culture in 3D collagen gels.

    Directory of Open Access Journals (Sweden)

    Brian Fallica

    Full Text Available Most investigations into cancer cell drug response are performed with cells cultured on flat (2D tissue culture plastic. Emerging research has shown that the presence of a three-dimensional (3D extracellular matrix (ECM is critical for normal cell behavior including migration, adhesion, signaling, proliferation and apoptosis. In this study we investigate differences between cancer cell signaling in 2D culture and a 3D ECM, employing real-time, live cell tracking to directly observe U2OS human osteosarcoma and MCF7 human breast cancer cells embedded in type 1 collagen gels. The activation of the important PI3K signaling pathway under these different growth conditions is studied, and the response to inhibition of both PI3K and mTOR with PI103 investigated. Cells grown in 3D gels show reduced proliferation and migration as well as reduced PI3K pathway activation when compared to cells grown in 2D. Our results quantitatively demonstrate that a collagen ECM can protect U2OS cells from PI103. Overall, our data suggests that 3D gels may provide a better medium for investigation of anti-cancer drugs than 2D monolayers, therefore allowing better understanding of cellular response and behavior in native like environments.

  4. Modulation of insulin action by vanadate: evidence of a role for phosphotyrosine phosphatase activity to alter cellular signaling.

    Science.gov (United States)

    Fantus, I G; Deragon, G; Lai, R; Tang, S

    A number of vanadium compounds (vanadate, vanadyl sulfate, metavanadate) have insulin-mimicking actions both in vitro and in vivo. They have multiple biological effects in cultured cells and interact directly with various enzymes. The inhibitory action on phosphoprotein tyrosine phosphatases (PTPs) and enhancement of cellular tyrosine phosphorylation appear to be the most relevant to explain the ability to mimic insulin. We demonstrated that in rat adipocytes both acute insulin effects, e.g. stimulation of IGF-II and transferrin binding and a chronic effect, insulin receptor downregulation, were stimulated by vanadate. Vanadate also enhanced insulin binding, particularly at very low insulin concentrations, associated with increased receptor affinity. This resulted in increased adipocyte insulin sensitivity. Finally vanadate augmented the extent of activation of the insulin receptor kinase by submaximal insulin concentrations. This was associated with a prolongation of the insulin biological response, lipogenesis, after removal of hormone. in rat adipocytes vanadate promotes insulin action by three mechanisms, 1) a direct insulin-mimetic action, 2) an enhancement of insulin sensitivity and 3) a prolongation of insulin biological response. These data suggest that PTP inhibitors have potential as useful therapeutic agents in insulin-resistant and relatively insulin-deficient forms of diabetes mellitus.

  5. Defining priorities

    CERN Document Server

    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...

  6. Cellular hyper-excitability caused by mutations that alter the activation process of voltage-gated sodium channels

    Directory of Open Access Journals (Sweden)

    Mohamed-Yassine eAMAROUCH

    2015-02-01

    Full Text Available Voltage-gated sodium channels (Nav are widely expressed as macro-molecular complexes in both excitable and non-excitable tissues. In excitable tissues, the upstroke of the action potential is the result of the passage of a large and rapid influx of sodium ions through these channels. NaV dysfunction has been associated with an increasingly wide range of neurological, muscular and cardiac disorders. The purpose of this review is to summarize the recently identified sodium channel mutations that are linked to hyper-excitability phenotypes and associated with the alteration of the activation process of voltage gated sodium channels. Indeed, several clinical manifestations that demonstrate an alteration of tissue excitability were recently shown to be strongly associated with the presence of mutations that affect the activation process of the voltage-gated sodium channels. These emerging genotype-phenotype correlations have expanded the clinical spectrum of sodium channelopathies to include disorders which feature a hyper-excitability phenotype that may or may not be associated with a cardiomyopathy. The p.I141V mutation in SCN4A and SCN5A, as well as its homologous p.I136V mutation in SCN9A, are interesting examples of mutations that have been linked to inherited hyperexcitability myotonia, exercise-induced polymorphic ventricular arrhythmias and erythromelalgia, respectively. Regardless of which sodium channel isoform is investigated, the substitution of the isoleucine to valine in the locus 141 induces similar modifications in the biophysical properties of the voltage-gated sodium channels by shifting the voltage-dependence of steady state activation towards more negative potentials.

  7. Myofibroblasts electrotonically coupled to cardiomyocytes alter conduction: insights at the cellular level from a detailed in silico tissue structure model

    Directory of Open Access Journals (Sweden)

    Florian Jousset

    2016-10-01

    Full Text Available Fibrotic myocardial remodeling is typically accompanied by the appearance of myofibroblasts (MFBs. In vitro, MFBs were shown to slow conduction and precipitate ectopic activity following gap junctional coupling to cardiomyocytes (CMCs. To gain further mechanistic insights into this arrhythmogenic MFB-CMC crosstalk, we performed numerical simulations in cell-based high-resolution two-dimensional tissue models that replicated experimental conditions. Cell dimensions were determined using confocal microscopy of single and co-cultured neonatal rat ventricular CMCs and MFBs. Conduction was investigated as a function of MFB density in three distinct cellular tissue architectures: CMC strands with endogenous MFBs, CMC strands with coating MFBs of two different sizes, and CMC strands with MFB inserts. Simulations were performed to identify individual contributions of heterocellular gap junctional coupling and of the specific electrical phenotype of MFBs. With increasing MFB density, both endogenous and coating MFBs slowed conduction. At MFB densities of 5-30%, conduction slowing was most pronounced in strands with endogenous MFBs due to the MFB-dependent increase in axial resistance. At MFB densities >40%, very slow conduction and spontaneous activity was primarily due to MFB-induced CMC depolarization. Coating MFBs caused non-uniformities of resting membrane potential, which were more prominent with large than with small MFBs. In simulations of MFB inserts connecting two CMC strands conduction delays increased with increasing insert lengths and block appeared for inserts >1.2 mm. Thus, electrophysiological properties of engineered CMC-MFB co-cultures depend on MFB density, MFB size and their specific positioning in respect to CMCs. These factors may influence conduction characteristics in the heterocellular myocardium.

  8. An antipsychotic drug exerts anti-prion effects by altering the localization of the cellular prion protein.

    Directory of Open Access Journals (Sweden)

    Claudia Stincardini

    Full Text Available Prion diseases are neurodegenerative conditions characterized by the conformational conversion of the cellular prion protein (PrPC, an endogenous membrane glycoprotein of uncertain function, into PrPSc, a pathological isoform that replicates by imposing its abnormal folding onto PrPC molecules. A great deal of evidence supports the notion that PrPC plays at least two roles in prion diseases, by acting as a substrate for PrPSc replication, and as a mediator of its toxicity. This conclusion was recently supported by data suggesting that PrPC may transduce neurotoxic signals elicited by other disease-associated protein aggregates. Thus, PrPC may represent a convenient pharmacological target for prion diseases, and possibly other neurodegenerative conditions. Here, we sought to characterize the activity of chlorpromazine (CPZ, an antipsychotic previously shown to inhibit prion replication by directly binding to PrPC. By employing biochemical and biophysical techniques, we provide direct experimental evidence indicating that CPZ does not bind PrPC at biologically relevant concentrations. Instead, the compound exerts anti-prion effects by inducing the relocalization of PrPC from the plasma membrane. Consistent with these findings, CPZ also inhibits the cytotoxic effects delivered by a PrP mutant. Interestingly, we found that the different pharmacological effects of CPZ could be mimicked by two inhibitors of the GTPase activity of dynamins, a class of proteins involved in the scission of newly formed membrane vesicles, and recently reported as potential pharmacological targets of CPZ. Collectively, our results redefine the mechanism by which CPZ exerts anti-prion effects, and support a primary role for dynamins in the membrane recycling of PrPC, as well as in the propagation of infectious prions.

  9. Absence of PAF receptor alters cellular infiltrate but not rolling and adhesion of leukocytes in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Rodrigues, David Henrique; Lacerda-Queiroz, Norinne; de Miranda, Aline Silva; Fagundes, Caio Tavares; Campos, Roberta Dayrell de Lima; Arantes, Rosa Esteves; Vilela, Márcia de Carvalho; Rachid, Milene Alvarenga; Teixeira, Mauro Martins; Teixeira, Antônio Lúcio

    2011-04-18

    Experimental autoimmune encephalomyelitis (EAE) is a condition induced in some susceptible species to the study of multiple sclerosis (MS). The platelet activating factor (PAF) is an important mediator of immune responses and seems to be involved in MS. However, the participation of PAF in EAE and MS remains controversial. Thus, in this study, we aimed to evaluate the role of PAF receptor in the pathogenesis of EAE. EAE was induced using an emulsion containing MOG(35-55). EAE-induced PAF receptor knock out (PAFR(-/-)) mice presented milder disease when compared to C57BL/6 wild type (WT) animals. PAFR(-/-) animals had lower inflammatory infiltrates in central nervous system (CNS) tissue when compared to WT mice. However, intravital microscopy in cerebral microvasculature revealed similar levels of rolling and adhering leukocytes in both WT and PAFR(-/-) mice. Interleukine (IL)-17 and chemokines C-C motif legends (CCL)2 and CCL5 were significantly lower in PAFR(-/-) mice when compared to WT mice. Brain infiltrating cluster of differentiation (CD)4(+) leukocytes and IL-17(+) leukocytes was diminished in PAFR(-/-) when compared to WT mice. Taken together, our results suggest that PAF receptor is important in the induction and development of EAE, although it has no influence in rolling and adhesion steps of cell recruitment. The absence of PAF receptor results in milder disease by altering the type of inflammatory mediators and cells that are present in CNS tissue. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Cultured fibroblast monolayers secrete a protein that alters the cellular binding of somatomedin-C/insulinlike growth factor I

    International Nuclear Information System (INIS)

    Clemmons, D.R.; Elgin, R.G.; Han, V.K.; Casella, S.J.; D'Ercole, A.J.; Van Wyk, J.J.

    1986-01-01

    We studied somatomedin-C/insulinlike growth factor (Sm-C/IGF-I) binding to human fibroblasts in both adherent monolayers and in suspension cultures. The addition of Sm-C/IGF-I in concentrations between 0.5 and 10 ng/ml to monolayers cultures resulted in a paradoxical increase in 125 I-Sm-C/IGF-I binding and concentrations between 25 and 300 ng/ml were required to displace the labeled peptide. The addition of unlabeled insulin resulted in no displacement of labeled Sm-C/IGF-I from the adherent cells. When fibroblast suspensions were used Sm-C/IGF-I concentrations between 1 and 10 ng/ml caused displacement, the paradoxical increase in 125 I-Sm-C/IGF-I binding was not detected, and insulin displaced 60% of the labeled peptide. Affinity cross-linking to fibroblast monolayers revealed a 43,000-mol wt 125 I-Sm-C-binding-protein complex that was not detected after cross-linking to suspended cells. The 43,000-mol wt complex was not detected after cross-linking to smooth muscle cell monolayers, and binding studies showed that 125 I-Sm-C/IGF-I was displaced greater than 90% by Sm-C/IGF-I using concentrations between 0.5 and 10 ng/ml. Because fibroblast-conditioned medium contains the 43,000-mol wt complex, smooth muscle cells were incubated with conditioned medium for 24 h prior to initiation of the binding studies. 125 I-Sm-C/IGF-I-binding increased 1.6-fold compared to control cultures and after cross-linking the 43,000-mol wt complex could be detected on the smooth muscle cell surface. Human fibroblast monolayers secrete a protein that binds 125 I-Sm-C/IGF-I which can be transferred to the smooth muscle cell surface and alters 125I-Sm-C/IGF-I binding

  11. Tribulus terrestris (Linn.) Attenuates Cellular Alterations Induced by Ischemia in H9c2 Cells Via Antioxidant Potential.

    Science.gov (United States)

    Reshma, P L; Lekshmi, V S; Sankar, Vandana; Raghu, K G

    2015-06-01

    Tribulus terrestris L. was evaluated for its cardioprotective property against myocardial ischemia in a cell line model. Initially, methanolic extract was prepared and subjected to sequential extraction with various solvents. The extract with high phenolic content (T. terrestris L. ethyl acetate extract-TTME) was further characterized for its chemical constituents and taken forward for evaluation against cardiac ischemia. HPLC analysis revealed the presence of phenolic compounds like caffeic acid (12.41 ± 0.22 mg g(-1)), chlorogenic acid (0.52 ± 0.06 mg g(-1)) and 4-hydroxybenzoic acid (0.60 ± 0.08 mg g(-1)). H9c2 cells were pretreated with TTME (10, 25, 50 and 100 µg/ml) for 24 h before the induction of ischemia. Then ischemia was induced by exposing cells to ischemia buffer, in a hypoxic chamber, maintained at 0.1% O2, 95% N2 and 5% CO2, for 1 h. A significant (p ≤ 0.05) increase in reactive oxygen species generation (56%), superoxide production (18%), loss of plasma membrane integrity, dissipation of transmembrane potential, permeability transition pore opening and apoptosis had been observed during ischemia. However, pretreatment with TTME was found to significantly (p ≤ 0.05) attenuate the alterations caused by ischemia. The overall results of this study partially reveal the scientific basis of the use of T. terrestris L. in the traditional system of medicine for heart diseases. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Targeted disruption of the idol gene alters cellular regulation of the low-density lipoprotein receptor by sterols and liver x receptor agonists.

    Science.gov (United States)

    Scotti, Elena; Hong, Cynthia; Yoshinaga, Yuko; Tu, Yiping; Hu, Yan; Zelcer, Noam; Boyadjian, Rima; de Jong, Pieter J; Young, Stephen G; Fong, Loren G; Tontonoz, Peter

    2011-05-01

    Previously, we identified the E3 ubiquitin ligase Idol (inducible degrader of the low-density lipoprotein [LDL] receptor [LDLR]) as a posttranscriptional regulator of the LDLR pathway. Idol stimulates LDLR degradation through ubiquitination of its C-terminal domain, thereby limiting cholesterol uptake. Here we report the generation and characterization of mouse embryonic stem cells homozygous for a null mutation in the Idol gene. Cells lacking Idol exhibit markedly elevated levels of the LDLR protein and increased rates of LDL uptake. Furthermore, despite an intact sterol responsive element-binding protein (SREBP) pathway, Idol-null cells exhibit an altered response to multiple regulators of sterol metabolism, including serum, oxysterols, and synthetic liver X receptor (LXR) agonists. The ability of oxysterols and lipoprotein-containing serum to suppress LDLR protein levels is reduced, and the time course of suppression is delayed, in cells lacking Idol. LXR ligands have no effect on LDLR levels in Idol-null cells, indicating that Idol is required for LXR-dependent inhibition of the LDLR pathway. In line with these results, the half-life of the LDLR protein is prolonged in the absence of Idol. Finally, the ability of statins and PCSK9 to alter LDLR levels is independent of, and additive with, the LXR-Idol pathway. These results demonstrate that the LXR-Idol pathway is an important contributor to feedback inhibition of the LDLR by sterols and a biological determinant of cellular LDL uptake.

  13. Targeted Disruption of the Idol Gene Alters Cellular Regulation of the Low-Density Lipoprotein Receptor by Sterols and Liver X Receptor Agonists ▿ §

    Science.gov (United States)

    Scotti, Elena; Hong, Cynthia; Yoshinaga, Yuko; Tu, Yiping; Hu, Yan; Zelcer, Noam; Boyadjian, Rima; de Jong, Pieter J.; Young, Stephen G.; Fong, Loren G.; Tontonoz, Peter

    2011-01-01

    Previously, we identified the E3 ubiquitin ligase Idol (inducible degrader of the low-density lipoprotein [LDL] receptor [LDLR]) as a posttranscriptional regulator of the LDLR pathway. Idol stimulates LDLR degradation through ubiquitination of its C-terminal domain, thereby limiting cholesterol uptake. Here we report the generation and characterization of mouse embryonic stem cells homozygous for a null mutation in the Idol gene. Cells lacking Idol exhibit markedly elevated levels of the LDLR protein and increased rates of LDL uptake. Furthermore, despite an intact sterol responsive element-binding protein (SREBP) pathway, Idol-null cells exhibit an altered response to multiple regulators of sterol metabolism, including serum, oxysterols, and synthetic liver X receptor (LXR) agonists. The ability of oxysterols and lipoprotein-containing serum to suppress LDLR protein levels is reduced, and the time course of suppression is delayed, in cells lacking Idol. LXR ligands have no effect on LDLR levels in Idol-null cells, indicating that Idol is required for LXR-dependent inhibition of the LDLR pathway. In line with these results, the half-life of the LDLR protein is prolonged in the absence of Idol. Finally, the ability of statins and PCSK9 to alter LDLR levels is independent of, and additive with, the LXR-Idol pathway. These results demonstrate that the LXR-Idol pathway is an important contributor to feedback inhibition of the LDLR by sterols and a biological determinant of cellular LDL uptake. PMID:21343340

  14. Maternal obesity induced by a high fat diet causes altered cellular development in fetal brains suggestive of a predisposition of offspring to neurological disorders in later life.

    Science.gov (United States)

    Stachowiak, Ewa K; Srinivasan, Malathi; Stachowiak, Michal K; Patel, Mulchand S

    2013-12-01

    Fetal development in an obese maternal intrauterine environment has been shown to predispose the offspring for a number of metabolic disorders in later life. The observation that a large percentage of women of child-bearing age in the US are overweight/obese during pregnancy is therefore a source of concern. A high fat (HF) diet-induced obesity in female rats has been used as a model for maternal obesity. The objective of this study was to determine cellular development in brains of term fetuses of obese rats fed a HF diet from the time of weaning. Fetal brains were dissected out on gestational day 21 and processed for immunohistochemical analysis in the hypothalamic as well as extra-hypothalamic regions. The major observation of this study is that fetal development in the obese HF female rat induced several alterations in the HF fetal brain. Marked increases were observed in orexigenic signaling and a significant decrease was observed for anorexigenic signaling in the vicinity of the 3rd ventricle in HF brains. Additionally, our results indicated diminished migration and maturation of stem-like cells in the 3rd ventricular region as well as in the brain cortex. The results from the present study indicate developmental alterations in the hypothalamic and extra-hypothalamic regions in the HF fetal brain suggestive of a predisposition for the development of obesity and possibly neurodevelopmental abnormalities in the offspring.

  15. 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...... 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.......…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...

  16. 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.

  17. Utility of hesperidinase for food function research: enzymatic digestion of botanical extracts alters cellular antioxidant capacities and anti-inflammatory properties.

    Science.gov (United States)

    Yu, Lu; Huang, Haiqiu; Yu, Liangli Lucy; Wang, Thomas T Y

    2014-08-27

    Food-derived phytochemicals, many known for their health beneficial effects, often exist in conjugated forms containing sugar moieties such as glucose or rhamnose in foods. The uptake of these compounds requires colonic bacterial cleavage of sugar moieties. However, most studies involved in screening extracts for biological activities do not take this process into account. This study seeks to determine the utility of commercially available hesperidinase to mimic colonic digestion and to test the effects of this treatment on the biological properties of extracts. Using hesperidinase resulted in efficient hydrolysis of Engelhardia roxburghiana Wall. extract containing rhamnose conjugates. Enzymatic digestion enhanced the extract's cellular antioxidant ability by 2-fold in HepG2/C3A and the anti-inflammatory effect on lipopolysaccharide-induced interleukin (IL)-1β and IL-6 expression in mouse macrophage J774A.1 and human monocyte THP-1 cells. Enzymatic digestion also efficiently processed extracts with mixed rhamnose and glucose conjugates and altered their biological activities. Results of the present study supported the importance of considering enzymatic digestion during the biological activity studies of botanicals.

  18. Whey Protein Concentrate Renders MDA-MB-231 Cells Sensitive to Rapamycin by Altering Cellular Redox State and Activating GSK3β/mTOR Signaling.

    Science.gov (United States)

    Cheng, Shih-Hsuan; Tseng, Yang-Ming; Wu, Szu-Hsien; Tsai, Shih-Meng; Tsai, Li-Yu

    2017-11-21

    Whey protein concentrate (WPC) is an amino acid-rich supplement that has been shown to increase cellular antioxidant capacity. Mammalian target of rapamycin (mTOR) is a crucial regulator of signaling in mammalian cells, and serves as a therapeutic target for triple-negative breast cancer (TNBC). This study was designed to investigate the effect of combining WPC with rapamycin on MDA-MB-231 human breast cancer cells. These cells were found to be insensitive to rapamycin and exhibited higher glutathione (GSH) and reactive oxygen species levels than non-tumorigenic MCF-10A cells. However, for MDA-MB-231 cells, the half maximal inhibitory concentration of rapamycin was lower when this drug was administered in combination with WPC than when used alone. Furthermore, combining WPC with rapamycin depleted GSH levels and reduced Nrf2 nuclear accumulation. In addition, WPC activated GSK3β/mTOR signaling, and GSK3β appeared to be involved in the WPC-mediated Nrf2 reduction and mTOR activation. In conclusion, WPC induced rapamycin sensitivity in MDA-MB-231 cells by altering their redox state and activating GSK3β/mTOR signaling. These results not only suggest a novel therapeutic approach for breast cancer treatment, but also provide insight into the critical pathways affecting the resistance to mTOR inhibition observed in a subgroup of TNBC patients.

  19. Chronic loss of noradrenergic tone produces β-arrestin2-mediated cocaine hypersensitivity and alters cellular D2 responses in the nucleus accumbens.

    Science.gov (United States)

    Gaval-Cruz, Meriem; Goertz, Richard B; Puttick, Daniel J; Bowles, Dawn E; Meyer, Rebecca C; Hall, Randy A; Ko, Daijin; Paladini, Carlos A; Weinshenker, David

    2016-01-01

    Cocaine blocks plasma membrane monoamine transporters and increases extracellular levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT). The addictive properties of cocaine are mediated primarily by DA, while NE and 5-HT play modulatory roles. Chronic inhibition of dopamine β-hydroxylase (DBH), which converts DA to NE, increases the aversive effects of cocaine and reduces cocaine use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism in rodents, but the underlying mechanism is unknown. We found a decrease in β-arrestin2 (βArr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of βArr2 in the NAc normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3 agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from control, but not Dbh -/- animals, where instead there was a trend for an excitatory effect. The Gαi inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the Gαs inhibitor NF449 restored the ability of quinpirole to decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These results suggest that chronic loss of noradrenergic tone alters behavioral responses to cocaine via decreases in βArr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs. © 2014 Society for the Study of Addiction.

  20. Dietary turmeric modulates DMBA-induced p21ras, MAP kinases and AP-1/NF-κB pathway to alter cellular responses during hamster buccal pouch carcinogenesis

    International Nuclear Information System (INIS)

    Garg, Rachana; Ingle, Arvind; Maru, Girish

    2008-01-01

    The chemopreventive efficacy of turmeric has been established in experimental systems. However, its mechanism(s) of action are not fully elucidated in vivo. The present study investigates the mechanism of turmeric-mediated chemoprevention in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis at 2, 4, 6, 10 and 12 weeks. Dietary turmeric (1%) led to decrease in DMBA-induced tumor burden and multiplicity, and enhanced the latency period in parallel, to its modulatory effects on oncogene products and various cellular responses during HBP tumorigenesis. DMBA-induced expression of ras oncogene product, p21 and downstream target, the mitogen-activated protein kinases were significantly decreased by turmeric during HBP carcinogenesis. Turmeric also diminished the DMBA-induced mRNA expression of proto-oncogenes (c-jun, c-fos) and NF-κB, leading to decreased protein levels and in further attenuation of DMBA-induced AP-1/NF-κB DNA-binding in the buccal pouch nuclear extracts. Besides, buccal pouch of hamsters receiving turmeric diet showed significant alterations in DMBA-induced effects: (a) decrease in cell proliferation (diminished PCNA and Bcl2 expression), (b) enhanced apoptosis (increased expression of Bax, caspase-3 and apoptotic index), (c) decrease in inflammation (levels of Cox-2, the downstream target of AP-1/NF-κB, and PGE2) and (d) aberrant expression of differentiation markers, the cytokeratins (1, 5, 8, and 18). Together, the protective effects of dietary turmeric converge on augmenting apoptosis of the initiated cells and decreasing cell proliferation in DMBA-treated animals, which in turn, is reflected in decreased tumor burden, multiplicity and enhanced latency period. Some of these biomarkers are likely to be helpful in monitoring clinical trials and evaluating drug effect measurements

  1. 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

  2. Intrinsic cellular and molecular properties of in vivo hippocampal synaptic plasticity are altered in the absence of key synaptic matrix molecules.

    Science.gov (United States)

    Jansen, Stephan; Gottschling, Christine; Faissner, Andreas; Manahan-Vaughan, Denise

    2017-08-01

    Hippocampal synaptic plasticity comprises a key cellular mechanism for information storage. In the hippocampus, both long-term potentiation (LTP) and long-term depression (LTD) are triggered by synaptic Ca 2+ -elevations that are typically mediated by the opening of voltage-gated cation channels, such as N-methyl-d-aspartate receptors (NMDAR), in the postsynaptic density. The integrity of the post-synaptic density is ensured by the extracellular matrix (ECM). Here, we explored whether synaptic plasticity is affected in adult behaving mice that lack the ECM proteins brevican, neurocan, tenascin-C, and tenascin-R (KO). We observed that the profiles of synaptic potentiation and depression in the dentate gyrus (DG) were profoundly altered compared to plasticity profiles in wild-type littermates (WT). Specifically, synaptic depression was amplified in a frequency-dependent manner and although late-LTP (>24 hr) was expressed following strong afferent tetanization, the early component of LTP (4 hr) elicited by weaker tetanization was equivalent in WT and KO animals. Furthermore, this latter form of LTP was NMDAR-dependent in WT but not KO mice. Scrutiny of DG receptor expression revealed significantly lower levels of both the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor, of the metabotropic glutamate receptor, mGlu5 and of the L-type calcium channel, Ca v 1.3 in KO compared to WT animals. Homer 1a and of the P/Q-type calcium channel, Ca v 1.2 were unchanged in KO mice. Taken together, findings suggest that in mice that lack multiple ECM proteins, synaptic plasticity is intact, but is fundamentally different. © 2017 Wiley Periodicals, Inc.

  3. Infant avoidance training alters cellular activation patterns in prefronto-limbic circuits during adult avoidance learning: II. Cellular imaging of neurons expressing the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1).

    Science.gov (United States)

    Gröger, Nicole; Mannewitz, Anja; Bock, Jörg; Becker, Susann; Guttmann, Katja; Poeggel, Gerd; Braun, Katharina

    2018-03-01

    Positive and negative feedback learning is essential to optimize behavioral performance. We used the two-way active avoidance (TWA) task as an experimental paradigm for negative feedback learning with the aim to test the hypothesis that neuronal ensembles activate the activity-regulated cytoskeletal (Arc/Arg3.1) protein during different phases of avoidance learning and during retrieval. A variety of studies in humans and other animals revealed that the ability of aversive feedback learning emerges postnatally. Our previous findings demonstrated that rats, which as infants are not capable to learn an active avoidance strategy, show improved avoidance learning as adults. Based on these findings, we further tested the hypothesis that specific neuronal ensembles are "tagged" during infant TWA training and then reactivated during adult re-exposure to the same learning task. Using cellular imaging by immunocytochemical detection of Arc/Arg3.1, we observed that, compared to the untrained control group, (1) only in the dentate gyrus the density of Arc/Arg3.1-expressing neurons was elevated during the acquisition phase of TWA learning, and (2) this increase in Arc/Arg3.1-expressing neurons was not specific for the TWA learning task. With respect to the effects of infant TWA training we found that compared to the naïve non-pretrained group (a) the infant pretraining group displayed a higher density of Arc/Arg3.1-expressing neurons in the anterior cingulate cortex during acquisition on training day 1, and (b) the infant pretraining group displayed elevated density of Arc/Arg3.1-expressing neurons in the dentate gyrus during retrieval on test day 5. Correlation analysis for the acquisition phase revealed for the ACd that the animals which showed the highest number of avoidances and the fastest escape latencies displayed the highest density of Arc/Arg3.1-expressing neurons. Taken together, we are the first to use the synaptic plasticity protein Arc/Arg3.1 to label neuronal

  4. Priority arbitration mechanism

    Science.gov (United States)

    Garmire, Derrick L [Kingston, NY; Herring, Jay R [Poughkeepsie, NY; Stunkel, Craig B [Bethel, CT

    2007-03-06

    A method is provided for selecting a data source for transmission on one of several logical (virtual) lanes embodied in a single physical connection. Lanes are assigned to either a high priority class or to a low priority class. One of six conditions is employed to determine when re-arbitration of lane priorities is desired. When this occurs a next source for transmission is selected based on a the specification of the maximum number of high priority packets that can be sent after a lower priority transmission has been interrupted. Alternatively, a next source for transmission is selected based on a the specification of the maximum number of high priority packets that can be sent while a lower priority packet is waiting. If initialized correctly, the arbiter keeps all of the packets of a high priority packet contiguous, while allowing lower priority packets to be interrupted by the higher priority packets, but not to the point of starvation of the lower priority packets.

  5. Growth Hormone Receptor Antagonist Transgenic Mice Have Increased Subcutaneous Adipose Tissue Mass, Altered Glucose Homeostasis and No Change in White Adipose Tissue Cellular Senescence.

    Science.gov (United States)

    Comisford, Ross; Lubbers, Ellen R; Householder, Lara A; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L; List, Edward O; Kopchick, John J; Berryman, Darlene E

    2016-01-01

    Growth hormone (GH)-resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests that long-lived GH-resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. The objective of this study was to examine WAT senescence, WAT distribution and glucose homeostasis in dwarf GH receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. 18-month-old female GHA mice and wild-type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose as well as glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase staining to quantify the senescent cell burden, and real-time qPCR to quantify gene expression of senescence markers p16 and IL-6. GHA mice had a 22% reduction in total body weight, a 33% reduction in lean mass and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p < 0.05) and a 1.7-fold increase in extra-/intraperitoneal WAT ratio compared to controls (p < 0.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin sensitivity, but no change in cellular senescence. The similar abundance of

  6. Growth hormone receptor antagonist (GHA) transgenic mice have increased subcutaneous adipose tissue mass, altered glucose homeostasis, and no change in white adipose tissue cellular senescence

    Science.gov (United States)

    Comisford, Ross; Lubbers, Ellen R.; Householder, Lara; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L.; List, Edward O.; Kopchick, John J.; Berryman, Darlene E.

    2015-01-01

    Background Growth hormone (GH) resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests long-lived GH resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. OBJECTIVE The objective of this study was to examine white adipose tissue (WAT) senescence, WAT distribution, and glucose homeostasis in dwarf growth hormone receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. METHODS 18mo old female GHA mice and wild type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose, and glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase (SA-β-gal) staining to quantify the senescent cell burden and real time qPCR to quantify gene expression of senescence markers p16 and IL-6. RESULTS GHA mice had a 22% reduction in total body weight, 33% reduction in lean mass, and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p<.05) and a 1.7 fold increase in extra-/intraperitoneal WAT ratio compared to controls (p<.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. CONCLUSIONS Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin

  7. MicroRNA Expression Is Altered in an Ovalbumin-Induced Asthma Model and Targeting miR-155 with Antagomirs Reveals Cellular Specificity.

    Directory of Open Access Journals (Sweden)

    Maximilian W Plank

    Full Text Available MicroRNAs are post-transcriptional regulators of gene expression that are differentially regulated during development and in inflammatory diseases. A role for miRNAs in allergic asthma is emerging and further investigation is required to determine whether they may serve as potential therapeutic targets. We profiled miRNA expression in murine lungs from an ovalbumin-induced allergic airways disease model, and compared expression to animals receiving dexamethasone treatment and non-allergic controls. Our analysis identified 29 miRNAs that were significantly altered during allergic inflammation. Target prediction analysis revealed novel genes with altered expression in allergic airways disease and suggests synergistic miRNA regulation of target mRNAs. To assess the impacts of one induced miRNA on pathology, we targeted miR-155-5p using a specific antagomir. Antagomir administration successfully reduced miR-155-5p expression with high specificity, but failed to alter the disease phenotype. Interestingly, further investigation revealed that antagomir delivery has variable efficacy across different immune cell types, effectively targeting myeloid cell populations, but exhibiting poor uptake in lymphocytes. Our findings demonstrate that antagomir-based targeting of miRNA function in the lung is highly specific, but highlights cell-specificity as a key limitation to be considered for antagomir-based strategies as therapeutics.

  8. Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation.

    Directory of Open Access Journals (Sweden)

    Yu Wang

    Full Text Available Radiotherapy with heavy ions is considered advantageous compared to irradiation with photons due to the characteristics of the Braggs peak and the high linear energy transfer (LET value. To understand the mechanisms of cellular responses to different LET values and dosages of heavy ion radiation, we analyzed the proteomic profiles of mouse embryo fibroblast MEF cells exposed to two doses from different LET values of heavy ion 12C. Total proteins were extracted from these cells and examined by Q Exactive with Liquid Chromatography (LC-Electrospray Ionization (ESI Tandem MS (MS/MS. Using bioinformatics approaches, differentially expressed proteins with 1.5 or 2.0-fold changes between different dosages of exposure were compared. With the higher the dosage and/or LET of ion irradiation, the worse response the cells were in terms of protein expression. For instance, compared to the control (0 Gy, 771 (20.2% proteins in cells irradiated at 0.2 Gy of carbon-ion radiation with 12.6 keV/μm, 313 proteins (8.2% in cells irradiated at 2 Gy of carbon-ion radiation with 12.6 keV/μm, and 243 proteins (6.4% in cells irradiated at 2 Gy of carbon-ion radiation with 31.5 keV/μm exhibited changes of 1.5-fold or greater. Gene ontology (GO analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG analysis, Munich Information Center for Protein Sequences (MIPS analysis, and BioCarta analysis all indicated that RNA metabolic processes (RNA splicing, destabilization and deadenylation and proteasome pathways may play key roles in the cellular response to heavy-ion irradiation. Proteasome pathways ranked highest among all biological processes associated with heavy carbon-ion irradiation. In addition, network analysis revealed that cellular pathways involving proteins such as Col1a1 and Fn1 continued to respond to high dosages of heavy-ion irradiation, suggesting that these pathways still protect cells against damage. However, pathways such as those involving Ikbkg1

  9. Small molecule inhibitors of Staphylococcus aureus RnpA alter cellular mRNA turnover, exhibit antimicrobial activity, and attenuate pathogenesis.

    Directory of Open Access Journals (Sweden)

    Patrick D Olson

    2011-02-01

    Full Text Available Methicillin-resistant Staphylococcus aureus is estimated to cause more U.S. deaths annually than HIV/AIDS. The emergence of hypervirulent and multidrug-resistant strains has further amplified public health concern and accentuated the need for new classes of antibiotics. RNA degradation is a required cellular process that could be exploited for novel antimicrobial drug development. However, such discovery efforts have been hindered because components of the Gram-positive RNA turnover machinery are incompletely defined. In the current study we found that the essential S. aureus protein, RnpA, catalyzes rRNA and mRNA digestion in vitro. Exploiting this activity, high through-put and secondary screening assays identified a small molecule inhibitor of RnpA-mediated in vitro RNA degradation. This agent was shown to limit cellular mRNA degradation and exhibited antimicrobial activity against predominant methicillin-resistant S. aureus (MRSA lineages circulating throughout the U.S., vancomycin intermediate susceptible S. aureus (VISA, vancomycin resistant S. aureus (VRSA and other Gram-positive bacterial pathogens with high RnpA amino acid conservation. We also found that this RnpA-inhibitor ameliorates disease in a systemic mouse infection model and has antimicrobial activity against biofilm-associated S. aureus. Taken together, these findings indicate that RnpA, either alone, as a component of the RNase P holoenzyme, and/or as a member of a more elaborate complex, may play a role in S. aureus RNA degradation and provide proof of principle for RNA catabolism-based antimicrobial therapy.

  10. 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…

  11. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  12. Myofibroblasts Electrotonically Coupled to Cardiomyocytes Alter Conduction: Insights at the Cellular Level from a DetailedIn silicoTissue Structure Model.

    Science.gov (United States)

    Jousset, Florian; Maguy, Ange; Rohr, Stephan; Kucera, Jan P

    2016-01-01

    Fibrotic myocardial remodeling is typically accompanied by the appearance of myofibroblasts (MFBs). In vitro , MFBs were shown to slow conduction and precipitate ectopic activity following gap junctional coupling to cardiomyocytes (CMCs). To gain further mechanistic insights into this arrhythmogenic MFB-CMC crosstalk, we performed numerical simulations in cell-based high-resolution two-dimensional tissue models that replicated experimental conditions. Cell dimensions were determined using confocal microscopy of single and co-cultured neonatal rat ventricular CMCs and MFBs. Conduction was investigated as a function of MFB density in three distinct cellular tissue architectures: CMC strands with endogenous MFBs, CMC strands with coating MFBs of two different sizes, and CMC strands with MFB inserts. Simulations were performed to identify individual contributions of heterocellular gap junctional coupling and of the specific electrical phenotype of MFBs. With increasing MFB density, both endogenous and coating MFBs slowed conduction. At MFB densities of 5-30%, conduction slowing was most pronounced in strands with endogenous MFBs due to the MFB-dependent increase in axial resistance. At MFB densities >40%, very slow conduction and spontaneous activity was primarily due to MFB-induced CMC depolarization. Coating MFBs caused non-uniformities of resting membrane potential, which were more prominent with large than with small MFBs. In simulations of MFB inserts connecting two CMC strands, conduction delays increased with increasing insert lengths and block appeared for inserts >1.2 mm. Thus, electrophysiological properties of engineered CMC-MFB co-cultures depend on MFB density, MFB size and their specific positioning in respect to CMCs. These factors may influence conduction characteristics in the heterocellular myocardium.

  13. Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways.

    Science.gov (United States)

    Déziel, Bob A; Patel, Kunal; Neto, Catherine; Gottschall-Pass, Katherine; Hurta, Robert A R

    2010-10-15

    Prostate cancer is one of the most common cancers in the Western world, and it is believed that an individual's diet affects his risk of developing cancer. There has been an interest in examining phytochemicals, the secondary metabolites of plants, in order to determine their potential anti-cancer activities in vitro and in vivo. In this study we document the effects of proanthocyanidins (PACs) from the American Cranberry (Vaccinium macrocarpon) on matrix metalloproteinase (MMP) activity in DU145 human prostate cancer cells. Cranberry PACs decreased cellular viability of DU145 cells at a concentration of 25 µg/ml by 30% after 6 h of treatment. Treatment of DU145 cells with PACs resulted in an inhibition of both MMPs 2 and 9 activity. PACs increased the expression of TIMP-2, a known inhibitor of MMP activity, and decreased the expression of EMMPRIN, an inducer of MMP expression. PACs decreased the expression of PI-3 kinase and AKT proteins, and increased the phosphorylation of both p38 and ERK1/2. Cranberry PACs also decreased the translocation of the NF-κB p65 protein to the nucleus. Cranberry PACs increased c-jun and decreased c-fos protein levels. These results suggest that cranberry PACs decreases MMP activity through the induction and/or inhibition of specific temporal MMP regulators, and by affecting either the phosphorylation status and/or expression of MAP kinase, PI-3 kinase, NF-κB and AP-1 pathway proteins. This study further demonstrates that cranberry PACs are a strong candidate for further research as novel anti-cancer agents. © 2010 Wiley-Liss, Inc.

  14. Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver.

    Science.gov (United States)

    Cavin, C; Marin-Kuan, M; Langouët, S; Bezençon, C; Guignard, G; Verguet, C; Piguet, D; Holzhäuser, D; Cornaz, R; Schilter, B

    2008-04-01

    Coffee consumption has been associated with a significant decrease in the risk of developing chronic diseases such as Parkinson disease, diabetes type-2 and several types of cancers (e.g. colon, liver). In the present study, a coffee-dependent induction of enzymes involved in xenobiotic detoxification processes was observed in rat liver and primary hepatocytes. In addition, coffee was found to induce the mRNA and protein expression of enzymes involved in cellular antioxidant defenses. These inductions were correlated with the activation of the Nrf2 transcription factor as shown using an ARE-reporter luciferase assay. The induction of detoxifying enzymes GSTs and AKR is compatible with a protection against both genotoxicity and cytotoxicity of aflatoxin B1 (AFB1). This hypothesis was confirmed in in vitro and ex vivo test systems, where coffee reduced both AFB1-DNA and protein adducts. Interestingly, coffee was also found to inhibit cytochrome CYP1A1/2, indicating that other mechanisms different from a stimulation of detoxification may also play a significant role in the chemoprotective effects of coffee. Further investigations in either human liver cell line and primary hepatocytes indicated that the chemoprotective effects of coffee against AFB1 genotoxicity are likely to be of relevance for humans. These data strongly suggest that coffee may protect against the adverse effects of AFB1. In addition, the coffee-mediated stimulation of the Nrf2-ARE pathway resulting in increased endogenous defense mechanisms against electrophilic but also oxidative insults further support that coffee may be associated with a protection against various types of chemical stresses.

  15. Relaxation of cellular K+gradients by valinomycin induces diatoxanthin accumulation in Cyclotella meneghiniana cells and alters FCPa fluorescence yield in vitro.

    Science.gov (United States)

    Ahmad, Rana A; Dietzel, Lars

    2017-09-01

    Regulation of photosynthetic light harvesting involves all major thylakoid membrane complexes. One important factor is the proton motive force (pmf) driving ATP production. Its proton gradient (ΔpH) component regulates the high energy quenching. Potassium ions largely contribute to the formation of the electric field (ΔΨ). ΔΨ and ΔpH partially compensate each other to form pmf. Whilst in plants considerable progress has been made in analyzing the interplay of H + and K + gradients, in diatoms knowledge in this field is still scarce. We relaxed cellular K + gradients by valinomycin in Cyclotella meneghiniana. We observed a slow decrease of PSII maximum quantum yield in the dark upon valinomycin addition correlating with diatoxanthin accumulation which we attribute to the breakdown of organellar K + gradients (either plastid or mitochondria) which might compensate for the loss of the K + gradient by adjustment of the thylakoid pH in a secondary step. This response is reversible when ΔpH is relaxed. Similarly, we found higher non-photochemical quenching (NPQ) caused by higher DT accumulation in the steady state in valinomycin-treated cells. In vitro fucoxanthin chlorophyll a (FCPa) antenna complexes in liposomes with natural lipid composition showed a decrease in fluorescence yield if a K + gradient is built up. The effect reversed by relaxing the gradient. We interpret these fluorescence changes with surface charge dynamics and FCPa organization in the membrane rather than a direct influence of K + gradients on FCPa complexes. Both experiments reveal that K + gradients might contribute to fine tuning of light harvesting capacity in relation to pmf in diatoms. © 2017 Scandinavian Plant Physiology Society.

  16. Altered poly(ADP-ribose) metabolism impairs cellular responses to genotoxic stress in a hypomorphic mutant of poly(ADP-ribose) glycohydrolase

    International Nuclear Information System (INIS)

    Gao Hong; Coyle, Donna L.; Meyer-Ficca, Mirella L.; Meyer, Ralph G.; Jacobson, Elaine L.; Wang, Zhao-Qi; Jacobson, Myron K.

    2007-01-01

    Genotoxic stress activates nuclear poly(ADP-ribose) (PAR) metabolism leading to PAR synthesis catalyzed by DNA damage activated poly(ADP-ribose) polymerases (PARPs) and rapid PAR turnover by action of nuclear poly(ADP-ribose) glycohydrolase (PARG). The involvement of PARP-1 and PARP-2 in responses to DNA damage has been well studied but the involvement of nuclear PARG is less well understood. To gain insights into the function of nuclear PARG in DNA damage responses, we have quantitatively studied PAR metabolism in cells derived from a hypomorphic mutant mouse model in which exons 2 and 3 of the PARG gene have been deleted (PARG-Δ2,3 cells), resulting in a nuclear PARG containing a catalytic domain but lacking the N-terminal region (A domain) of the protein. Following DNA damage induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), we found that the activity of both PARG and PARPs in intact cells is increased in PARG-Δ2,3 cells. The increased PARG activity leads to decreased PARP-1 automodification with resulting increased PARP activity. The degree of PARG activation is greater than PARP, resulting in decreased PAR accumulation. Following MNNG treatment, PARG-Δ2,3 cells show reduced formation of XRCC1 foci, delayed H2AX phosphorylation, decreased DNA break intermediates during repair, and increased cell death. Our results show that a precise coordination of PARPs and PARG activities is important for normal cellular responses to DNA damage and that this coordination is defective in the absence of the PARG A domain

  17. Microglial inhibitory mechanism of Coenzyme Q10 against Aβ (1-42 induced cognitive dysfunctions: possible behavioral, biochemical, cellular and histopathological alterations

    Directory of Open Access Journals (Sweden)

    Arti eSingh

    2015-11-01

    Full Text Available Rationale: Alzheimer’s disease (AD is a debilitating disease with complex pathophysiology. Amyloid beta (Aβ (1-42 is a reliable model of AD that recapitulates many aspects of human AD. Objective: The present study has been designed to investigate the neuroprotective potential of Coenzyme Q10 (CoQ10 and its modulation with minocycline (microglial inhibitor against Aβ (1-42 induced cognitive dysfunction in rats. Method: Intrahippocampal (i.h. Aβ (1-42 (1µg/µl; 4µl/site were administered followed by drug treatment with galantamine (2 mg/kg, CoQ10 (20 and 40 mg/kg, minocycline (50 and 100 mg/kg and their combinations for a period of 21 days. Various neurobehavioral parameters followed by biochemical, acetylcholinesterase (AChE level, proinflammatory markers (TNF-α, mitochondrial respiratory enzyme complexes (I-IV and histopathological examinations were assessed.Results: Aβ (1-42 administration significantly impaired cognitive performance in Morris water maze (MWM performance test, causes oxidative stress, raised AChE level, caused neuroinflammation, mitochondrial dysfunction and histopathological alterations as compared to sham treatment. Treatment with CoQ10 (20 and 40 mg/kg and minocycline (50 and 100 mg/kg alone for 21days significantly improved cognitive performance as evidenced by reduced transfer latency and increased time spent in target quadrant (TSTQ, reduced AChE activity, oxidative damage (reduced LPO, nitrite level and restored SOD, catalase and GHS levels, TNF-α level, restored mitochondrial respiratory enzyme complex (I, II, III, IV activities and histopathological alterations as compared to control (Aβ (1-42 treated animals group. Further, combination of minocycline (50 and 100 mg/kg with CoQ10 (20 and 40 mg/kg significantly modulate the protective effect of CoQ10 as compared to their effect alone. Conclusion: The present study suggests that the neuroprotective effect of CoQ10 could be due to its microglia inhibitory

  18. Altered composition of bone as triggered by irradiation facilitates the rapid erosion of the matrix by both cellular and physicochemical processes.

    Directory of Open Access Journals (Sweden)

    Danielle E Green

    Full Text Available Radiation rapidly undermines trabecular architecture, a destructive process which proceeds despite a devastated cell population. In addition to the 'biologically orchestrated' resorption of the matrix by osteoclasts, physicochemical processes enabled by a damaged matrix may contribute to the rapid erosion of bone quality. 8w male C57BL/6 mice exposed to 5 Gy of Cs(137 γ-irradiation were compared to age-matched control at 2d, 10d, or 8w following exposure. By 10d, irradiation had led to significant loss of trabecular bone volume fraction. Assessed by reflection-based Fourier transform infrared imaging (FTIRI, chemical composition of the irradiated matrix indicated that mineralization had diminished at 2d by -4.3±4.8%, and at 10d by -5.8±3.2%. These data suggest that irradiation facilitates the dissolution of the matrix through a change in the material itself, a conclusion supported by a 13.7±4.5% increase in the elastic modulus as measured by nanoindentation. The decline in viable cells within the marrow of irradiated mice at 2d implies that the immediate collapse of bone quality and inherent increased risk of fracture is not solely a result of an overly-active biologic process, but one fostered by alterations in the material matrix that predisposes the material to erosion.

  19. Data Priority List

    Data.gov (United States)

    City of Jackson, Mississippi — This data shows the priority ranking given to each City of Jackson data-set by the Data Governance Committee. The goal is to upload each set of data within the next...

  20. Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells: a potential cellular interaction relevant to AMD.

    Directory of Open Access Journals (Sweden)

    Wenxin Ma

    2009-11-01

    Full Text Available Age-related macular degeneration (AMD is a leading cause of legal blindness in the elderly in the industrialized word. While the immune system in the retina is likely to be important in AMD pathogenesis, the cell biology underlying the disease is incompletely understood. Clinical and basic science studies have implicated alterations in the retinal pigment epithelium (RPE layer as a locus of early change. Also, retinal microglia, the resident immune cells of the retina, have been observed to translocate from their normal position in the inner retina to accumulate in the subretinal space close to the RPE layer in AMD eyes and in animal models of AMD.In this study, we examined the effects of retinal microglia on RPE cells using 1 an in vitro model where activated retinal microglia are co-cultured with primary RPE cells, and 2 an in vivo mouse model where retinal microglia are transplanted into the subretinal space. We found that retinal microglia induced in RPE cells 1 changes in RPE structure and distribution, 2 increased expression and secretion of pro-inflammatory, chemotactic, and pro-angiogenic molecules, and 3 increased extent of in vivo choroidal neovascularization in the subretinal space.These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD.

  1. 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

  2. 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

  3. 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...... where Meld takes worst case time o(n). To our knowledge this is the first priority queue implementation that supports Meld in worst case constant time and DeleteMin in logarithmic time....

  4. 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.

  5. Faculty Internationalization Priorities

    Science.gov (United States)

    Criswell, John R., II; Zhu, Hao

    2015-01-01

    The internationalization of higher education has been the subject of a substantial body of research. However, few studies have examined how faculty members, significant implementers of internationalization, think about internationalization priorities. This article presents the results of a questionnaire which was sent to faculty members at three…

  6. Millennial Perspectives and Priorities

    Science.gov (United States)

    Therrell, James A.; Dunneback, Staci K.

    2015-01-01

    Through prioritizing student voice, this study investigated the perspectives of millennial students in relation to their preferences and priorities for how they desired to experience teaching and learning. While not experts, our assumption was that undergraduate students, because of their relatively long experience as students, would be closely in…

  7. 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...

  8. Future research priorities for morbidity control of lymphedema

    Directory of Open Access Journals (Sweden)

    S R Narahari

    2017-01-01

    Full Text Available Background: Innovation in the treatment of lower extremity lymphedema has received low priority from the governments and pharmaceutical industry. Advancing lymphedema is irreversible and initiates fibrosis in the dermis, reactive changes in the epidermis and subcutis. Most medical treatments offered for lymphedema are either too demanding with a less than satisfactory response or patients have low concordance due to complex schedules. A priority setting partnership (PSP was established to decide on the future priorities in lymphedema research. Methods: A table of abstracts following a literature search was published in workshop website. Stake holders were requested to upload their priorities. Their questions were listed, randomized, and sent to lymphologists for ranking. High ranked ten research priorities, obtained through median score, were presented in final prioritization work shop attended by invited stake holders. A free medical camp was organized during workshop to understand patients' priorities. Results: One hundred research priorities were selected from priorities uploaded to website. Ten priorities were short listed through a peer review process involving 12 lymphologists, for final discussion. They were related to simplification of integrative treatment for lymphedema, cellular changes in lymphedema and mechanisms of its reversal, eliminating bacterial entry lesions to reduce cellulitis episodes, exploring evidence for therapies in traditional medicine, improving patient concordance to compression therapy, epidemiology of lymphatic filariasis (LF, and economic benefit of integrative treatments of lymphedema. Conclusion: A robust research priority setting process, organized as described in James Lind Alliance guidebook, identified seven priority areas to achieve effective morbidity control of lymphedema including LF. All stake holders including Department of Health Research, Government of India, participated in the PSP.

  9. Priorities Without Priorities: Representing Preemption in Psi-Calculi

    Directory of Open Access Journals (Sweden)

    Johannes Åman Pohjola

    2014-08-01

    Full Text Available Psi-calculi is a parametric framework for extensions of the pi-calculus with data terms and arbitrary logics. In this framework there is no direct way to represent action priorities, where an action can execute only if all other enabled actions have lower priority. We here demonstrate that the psi-calculi parameters can be chosen such that the effect of action priorities can be encoded. To accomplish this we define an extension of psi-calculi with action priorities, and show that for every calculus in the extended framework there is a corresponding ordinary psi-calculus, without priorities, and a translation between them that satisfies strong operational correspondence. This is a significantly stronger result than for most encodings between process calculi in the literature. We also formally prove in Nominal Isabelle that the standard congruence and structural laws about strong bisimulation hold in psi-calculi extended with priorities.

  10. Social Priorities as Data

    Science.gov (United States)

    Grubert, E.

    2015-12-01

    Decision makers' responses to local risks and expected changes to a community from circumstances like natural hazards, human developments, and demographic changes can greatly affect social and environmental outcomes in a community. Translating physical data based in disciplines like engineering and geosciences into positive outcomes for communities can be challenging and often results in conflict that appears to pit "science" against "the public." Scientists can be reluctant to offer recommendations for action based on their work, often (and often correctly) noting that their role is not to make value judgments for a community - particularly for a community that is not their own. Conversely, decision makers can be frustrated by the lack of guidance they receive to help translate data into effective and acceptable action. The solution posed by this submission, given the goal of co-production of knowledge by scientists and decision makers to foster better community outcomes, is to involve the community directly by integrating social scientific methods that address decision making and community engagement to the scientist-decision maker interaction. Specifically, the missing dataset in many scientist-decision maker interactions is the nature of community priorities. Using scientifically valid methods to rigorously collect and characterize community priorities to help recommend tradeoffs between different outcomes indicated by the work of physical and natural scientists can bridge the gap between science and action by involving the community in the process. This submission presents early work on US preferences for different types of social and environmental outcomes designed to integrate directly with engineering and physical science frameworks like Life Cycle Assessment and Environmental Impact Statements. Cardinal preference data are based on surveys of US adults using tools like the Analytical Hierarchy Process, budget allocation, and ranking.

  11. 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.

  12. Our top priority

    CERN Multimedia

    2012-01-01

    After three years of LHC running, we are still at the beginning of a long research programme with our flagship facility, and hopefully 4 July 2012 will go down in history as the date of one of many landmark discoveries spanning several years. CERN’s top priority for the next decade and more is the full exploitation of the LHC. With speculation about potential future facilities mounting in the light of the discovery of a new Higgs-like particle, it’s important to state that most clearly. Of course, this will rely on continued global collaboration, and it’s important that CERN engage constructively with other regions.   It is important to plan ahead, particularly since the lead times for new projects in particle physics are long, and our field is increasingly global in nature. That’s why the European particle physics community is currently engaged in updating its long-term strategy. Planning ahead allowed us to be ready technologically to build the LHC whe...

  13. Cellular dosimetry

    International Nuclear Information System (INIS)

    Humm, J.L.; Chin, L.M.

    1989-01-01

    Radiation dose is a useful predictive parameter for describing radiation toxicity in conventional radiotherapy. Traditionally, in vitro radiation biology dose-effect relations are expressed in the form of cell survival curves, a semilog plot of cell survival versus dose. However, the characteristic linear or linear quadratic survival curve shape, for high- and low-LET radiations respectively, is only strictly valid when the radiation dose is uniform across the entire target population. With an external beam of 60 Co gamma rays or x-rays, a uniform field may be readily achievable. When radionuclides are incorporated into a cell milieu, several new problems emerge which can result in a departure from uniformity in energy deposition throughout a cell population. This nonuniformity can have very important consequences for the shape of the survival curve. Cases in which perturbations of source uniformity may arise include: 1. Elemental sources may equilibrate in the cell medium with partition coefficients between the extracellular, cytosol, and nuclear compartments. The effect of preferential cell internalization or binding to cell membrane of some radionuclides can increase or decrease the slope of the survival curve. 2. Radionuclides bound to antibodies, hormones, metabolite precursors, etc., may result in a source localization pattern characteristic of the carrier agent, i.e., the sources may bind to cell surface receptors or antigens, be internalized, bind to secreted antigen concentrated around a fraction of the cell population, or become directly incorporated into the cell DNA. We propose to relate the distribution of energy deposition in cell nuclei to biological correlates of cellular inactivation. The probability of each cell's survival is weighted by its individual radiation burden, and the summation of these probabilities for the cell population can be used to predict the number or fraction of cell survivors

  14. Healthcare priority setting in Kenya

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

  15. Highest priority in Pakistan.

    Science.gov (United States)

    Adil, E

    1968-01-01

    Responding to the challenge posed by its population problem, Pakistan's national leadership gave the highest priority to family planning in its socioeconomic development plan. In Pakistan, as elsewhere in the world, the first family planning effort originated in the private sector. The Family Planning Association of Pakistan made a tentative beginning in popularizing family planning in the country. Some clinics were opened and some publicity and education were undertaken to emphasize the need for family limitation. It was recognized soon that the government needed to assume the primarily responsibility if family planning efforts were to be successful. For the 1st plan period, 1955-60, about $10 million was allocated by the central government in the social welfare sector for voluntary family planning. The level of support continued on the same basis during the 2nd plan, 1960-65, but has been raised 4-fold in the 1965-70 scheme of family planning. Pakistan's Family Planning Association continues to play vital collaborative roles in designing and pretesting of prototype publicity material, involvement of voluntary social workers, and functional research in the clinical and public relations fields. The real breakthrough in the program came with the 3rd 5-year plan, 1965-70. High priority assigned to family planning is reflected by the total initial budget of Rs.284 million (about $60,000,000) for the 5-year period. Current policy is postulated on 6 basic assumptions: family planning efforts need to be public relations-oriented; operations should be conducted through autonomous bodies with decentralized authority at all tiers down to the grassroots level, for expeditious decision making; monetary incentives play an important role; interpersonal motivation in terms of life experience of the clientele through various contacts, coupled with mass media for publicity, can produce a sociological breakthrough; supplies and services in all related disciplines should be

  16. Female contraception: changing priorities.

    Science.gov (United States)

    Johansson, E D

    1993-04-01

    Late marriage, withdrawal, and induced abortion were the methods that achieved the demographic transition from high to low birth and death rates in Europe and North America. The demographic transition in France was early and significant, possibly because it was the most populous country in Europe. Induced abortion caused high morbidity and mortality, especially among working-class women. In countries where abortions are still illegal, women die, mainly due to bleeding and infections. Women who survive often suffer infertility. Modern surgical techniques and the availability of hormonal interruption of early pregnancy make abortions safe. Today, Europe has very low fertility. In Europe, Ireland has the highest total fertility rate (TFR) (2.1) followed by Sweden (2). All the other European countries have TFRs much less than 2 (1.3-1.8). The populations of these countries will decline if massive immigration does not occur. Very effective contraceptives have contributed to this low fertility. Women in Europe use contraceptives during most of their reproductive years. Thus, contraceptive safety and efficacy are extremely important. Another important consideration is the effect of contraceptives on sexually transmitted diseases. A very rapid fall in death rates has occurred in developing countries without a concomitant fall in birth rates, resulting in very high population growth. Safe and effective contraceptive methods and the revolution in information technology exist today but did not when Europe and North America went through their demographic transition. These 2 conditions may help speed up the demographic transition in developing countries. Many developing countries must reevaluate their priorities to achieve safe motherhood and a subsequent reduction in fertility. Many African governments spend more money on the safety of their Heads of State than on maternal health. Improvements in contraceptive counseling, distribution, and promotion are needed to bring about

  17. 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

  18. 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,...

  19. 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...

  20. 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...

  1. Cellular: Toward personal communications

    Science.gov (United States)

    Heffernan, Stuart

    1991-09-01

    The cellular industry is one of the fastest growing segment of the telecommunications industry. With an estimated penetration rate of 20 percent in the near future, cellular is becoming an ubiquitous telecommunications service in the U.S. In this paper we will examine the major advancements in the cellular industry: customer equipment, cellular networks, engineering tools, customer support, and nationwide seamless service.

  2. 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.

  3. Perturbations of Amino Acid Metabolism Associated with Glyphosate-Dependent Inhibition of Shikimic Acid Metabolism Affect Cellular Redox Homeostasis and Alter the Abundance of Proteins Involved in Photosynthesis and Photorespiration1[W][OA

    Science.gov (United States)

    Vivancos, Pedro Diaz; Driscoll, Simon P.; Bulman, Christopher A.; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H.

    2011-01-01

    The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway. PMID:21757634

  4. Perturbations of amino acid metabolism associated with glyphosate-dependent inhibition of shikimic acid metabolism affect cellular redox homeostasis and alter the abundance of proteins involved in photosynthesis and photorespiration.

    Science.gov (United States)

    Vivancos, Pedro Diaz; Driscoll, Simon P; Bulman, Christopher A; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H

    2011-09-01

    The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway.

  5. Priority-queue framework: Programs

    DEFF Research Database (Denmark)

    Katajainen, Jyrki

    2009-01-01

    This is an electronic appendix to the article "Generic-programming framework for benchmarking weak queues and its relatives". The report contains the programs related to our priority-queue framework. Look at the CPH STL reports 2009-3 and 2009-4 to see examples of other component frameworks....

  6. Autism Research: Prospects and Priorities.

    Science.gov (United States)

    Rutter, Michael

    1996-01-01

    Research prospects and priorities in autism are discussed with respect to: (1) diagnosis, classification, and epidemiology; (2) clinical research; (3) neuropsychological research; (4) genetics; (5) structural and functional brain imaging; (6) postmortem studies; (7) other biological research; and (8) treatment research. Application of research…

  7. 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.

  8. Flat Cellular (UMTS) Networks

    NARCIS (Netherlands)

    Bosch, H.G.P.; Samuel, L.G.; Mullender, Sape J.; Polakos, P.; Rittenhouse, G.

    Traditionally, cellular systems have been built in a hierarchical manner: many specialized cellular access network elements that collectively form a hierarchical cellular system. When 2G and later 3G systems were designed there was a good reason to make system hierarchical: from a cost-perspective

  9. Priority order and consumer behavior

    OpenAIRE

    浜田, 文雅

    2014-01-01

    This paper attempts to propose an alternative microeconomic theory of consumer behavior in terms of distributional approach. A model determining the optimal priority order of and demand for consumer goods not only of the homogeneous type but also of the heterogeneous type under the budget constraint of a consumer and the market conditions is presented. Utility of a commodity is decomposed into the value in use and the value in quality. The latter is assumed to depend on personal income level....

  10. Differential cellular metabolite alterations in HaCaT cells caused by exposure to the aryl hydrocarbon receptor-binding polycyclic aromatic hydrocarbons chrysene, benzo[a]pyrene and dibenzo[a,l]pyrene

    Directory of Open Access Journals (Sweden)

    Sarah Potratz

    Full Text Available Polycyclic aromatic hydrocarbons (PAHs are ubiquitous in the human environment. Since they are present in crude oilfractions used for the production of rubber and plastics, consumers may come into direct dermal contacts with these compounds (e.g., via tool handles on a daily basis. Some individual PAHs are identified as genotoxic mutagens thereby prompting particular toxicological and environmental concern. Among this group, benzo[a]pyrene (BAP constitutes a model carcinogen which is also used as reference compound for risk assessment purposes. It acts as a strong agonist of the aryl hydrocarbon receptor (AHR and becomes metabolically activated toward mutagenic and carcinogenic intermediates by cytochrome P450-dependent monooxygenases (CYPs. While BAP has been exhaustively characterized with regard to its toxicological properties, there is much less information available for other PAHs. We treated an AHR-proficient immortal human keratinocyte cell line (i.e., HaCaT with three selected PAHs: BAP, chrysene (CRY and dibenzo[a,l]pyrene (DALP. Compound-mediated alterations of endogenous metabolites were investigated by an LC–MS/MS-based targeted approach. To examine AHR-dependent changes of the measured metabolites, AHR-deficient HaCaT knockdown cells (AHR-KD were used for comparison. Our results reveal that 24 metabolites are sufficient to separate the PAH-exposed cells from untreated controls by application of a multivariate model. Alterations in the metabolomics profiles caused by each PAH show influences on the energy and lipid metabolism of the cells indicating reduced tricarboxylic acid (TCA cycle activity and β-oxidation. Up-regulation of sphingomyelin levels after exposure to BAP and DALP point to pro-apoptotic processes caused by these two potent PAHs. Our results suggest that in vitro metabolomics can serve as tool to develop bioassays for application in hazard assessment. Keywords: Polycyclic aromatic hydrocarbons, Metabolomics, Aryl

  11. IDRC Thematic Priorities | IDRC - International Development ...

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

    IDRC Doctoral Research Awards support research aligned with IDRC's mandate and thematic priorities. Proposed research must fit within the priorities of the Agriculture and Environment, Inclusive Economies, or Technology and Innovation program areas as set out in this document.

  12. 78 FR 29785 - Priority Mail Pricing

    Science.gov (United States)

    2013-05-21

    ... Priority Mail pieces, the Postal Service hopes to improve the competitiveness of Priority Mail and... be 3.619. Id. \\4\\ This is based on the Consumer Price Index-All Urban Consumers, U.S. All Items (the...

  13. 77 FR 65912 - Priority Mail Contract

    Science.gov (United States)

    2012-10-31

    ... POSTAL REGULATORY COMMISSION [Docket Nos. CP2010-1; Order No. 1517] Priority Mail Contract AGENCY... filing concerning an amendment to Priority Mail Contract 19. This notice informs the public of the filing... Service filed notice that it has agreed to an amendment to the existing Priority Mail Contract 19 subject...

  14. 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...

  15. 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

  16. 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.

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

    Science.gov (United States)

    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.

  18. Increasing the availability of threonine, isoleucine, valine, and leucine relative to lysine while maintaining an ideal ratio of lysine:methionine alters mammary cellular metabolites, mammalian target of rapamycin signaling, and gene transcription.

    Science.gov (United States)

    Dong, X; Zhou, Z; Wang, L; Saremi, B; Helmbrecht, A; Wang, Z; Loor, J J

    2018-03-14

    in mTORC1 phosphorylation status, it resulted in the lowest phosphorylation of Akt and eEF2 and mRNA abundance of CSN2 and various AA transporters (SLC7A5, SLC36A1, SLC38A2, SLC38A9, SLC43A1). Overall, data indicate that an increase in Val at an ideal ratio of Lys:Met could further enhance milk protein synthesis by altering intracellular concentrations of essential AA and metabolites that could play a regulatory role, increasing phosphorylation status of mTORC1 and key signaling proteins, and upregulation of AA transporters. The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

  19. 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

  20. 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

  1. 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.

  2. Plasmonic Nanostructured Cellular Automata

    Science.gov (United States)

    Alkhazraji, Emad; Ghalib, A.; Manzoor, K.; Alsunaidi, M. A.

    2017-03-01

    In this work, we have investigated the scattering plasmonic resonance characteristics of silver nanospheres with a geometrical distribution that is modelled by Cellular Automata using time-domain numerical analysis. Cellular Automata are discrete mathematical structures that model different natural phenomena. Two binary one-dimensional Cellular Automata rules are considered to model the nanostructure, namely rule 30 and rule 33. The analysis produces three-dimensional scattering profiles of the entire plasmonic nanostructure. For the Cellular Automaton rule 33, the introduction of more Cellular Automata generations resulted only in slight red and blue shifts in the plasmonic modes with respect to the first generation. On the other hand, while rule 30 introduced significant red shifts in the resonance peaks at early generations, at later generations however, a peculiar effect is witnessed in the scattering profile as new peaks emerge as a feature of the overall Cellular Automata structure rather than the sum of the smaller parts that compose it. We strongly believe that these features that emerge as a result adopting the different 256 Cellular Automata rules as configuration models of nanostructures in different applications and systems might possess a great potential in enhancing their capability, sensitivity, efficiency, and power utilization.

  3. 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)

  4. 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

  5. Recent advances in cellular glycomic analyses.

    Science.gov (United States)

    Furukawa, Jun-Ichi; Fujitani, Naoki; Shinohara, Yasuro

    2013-02-21

    A large variety of glycans is intricately located on the cell surface, and the overall profile (the glycome, given the entire repertoire of glycoconjugate-associated sugars in cells and tissues) is believed to be crucial for the diverse roles of glycans, which are mediated by specific interactions that control cell-cell adhesion, immune response, microbial pathogenesis and other cellular events. The glycomic profile also reflects cellular alterations, such as development, differentiation and cancerous change. A glycoconjugate-based approach would therefore be expected to streamline discovery of novel cellular biomarkers. Development of such an approach has proven challenging, due to the technical difficulties associated with the analysis of various types of cellular glycomes; however, recent progress in the development of analytical methodologies and strategies has begun to clarify the cellular glycomics of various classes of glycoconjugates. This review focuses on recent advances in the technical aspects of cellular glycomic analyses of major classes of glycoconjugates, including N- and O-linked glycans, derived from glycoproteins, proteoglycans and glycosphingolipids. Articles that unveil the glycomics of various biologically important cells, including embryonic and somatic stem cells, induced pluripotent stem (iPS) cells and cancer cells, are discussed.

  6. 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.

  7. Cellular MR Imaging

    OpenAIRE

    Michel Modo; Mathias Hoehn; Jeff W.M. Bulte

    2005-01-01

    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 [(U)SPIO] 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, ...

  8. 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)

  9. Research priorities: women in Africa.

    Science.gov (United States)

    Okeyo, A P

    1979-01-01

    In December 1979, an Expert Meeting on Research and Data Collection on Women and Development was convened in Nairobi for the purpose of defining research priorities and methodological approaches for studying the role of African women in development. After reviewing current literature relevant to the subject matter, the participants developed a number of hypotheses regarding the impact of development activities on the role and status of women, and recommended that these hypotheses be tested in future reserach. In general, agrarian reform, mechanization of agriculture, the introduction of cash cropping, and modernization were hypothesized as having a negative impact on the role, status, productive activities, and nutritional standards of women. Other hypotheses stated that development programs and agricultural extension services tended to neglect women. Recommended research methodologies include: 1) efforts to involve the community members in the development and implementation of research projects undertaken in their communities; 2) increased use of local experts and community members in data collection; and 3) interdisciplinary collaboration. The participants also recommended that each country compile a statistical profile on the women in their countries. The profiles should include comparable information on: 1) fertility; 2) educational levels, employment status, and income levels for women; 3) household composition; and 4) types of services available to women.

  10. The 50 Constellation Priority Sites

    Science.gov (United States)

    Noble, S.; Joosten, K.; Eppler, D.; Gruener, J.; Mendell, W.; French, R.; Plescia, J.; Spudis, P.; Wargo, M.; Robinson, M.; hide

    2009-01-01

    The Constellation program (CxP) has developed a list of 50 sites of interest on the Moon which will be targeted by the LRO narrow angle camera. The list has also been provided to the M team to supplement their targeting list. This list does not represent a "site selection" process; rather the goal was to find "representative" sites and terrains to understand the range of possible surface conditions for human lunar exploration to aid engineering design and operational planning. The list compilers leveraged heavily on past site selection work (e.g. Geoscience and a Lunar Base Workshop - 1988, Site Selection Strategy for a Lunar Outpost - 1990, Exploration Systems Architecture Study (ESAS) - 2005). Considerations included scientific, resource utilization, and operational merits, and a desire to span lunar terrain types. The targets have been organized into two "tiers" of 25 sites each to provide a relative priority ranking in the event of mutual interference. A LEAG SAT (special action team) was established to validate and recommend modifications to the list. This SAT was chaired by Dr. Paul Lucey. They provided their final results to CxP in May. Dr. Wendell Mendell will organize an on-going analysis of the data as they come down to ensure data quality and determine if and when a site has sufficient data to be retired from the list. The list was compiled using the best available data, however, it is understood that with the flood of new lunar data, minor modifications or adjustments may be required.

  11. Cellular Transplantation Alters the Disease Progression in Becker's Muscular Dystrophy

    OpenAIRE

    Sharma, Alok; Paranjape, Amruta; Sane, Hemangi; Bhagawanani, Khushboo; Gokulchandran, Nandini; Badhe, Prerna

    2013-01-01

    Becker’s Muscular Dystrophy (BMD) is a dystrophinopathy manifested as progressive muscle degeneration. Autologous Bone Marrow Mononuclear Cells (BMMNCs) have shown some myogenic potential. The paracrine effects of the BMMNCs reduce the inflammation and are thought to reduce muscle degeneration. We treated a 39 year old dental surgeon suffering from BMD. Muscle strength was reduced when measured using modified Medical Research Council’s Manual Muscle Testing (mMRC-MMT). Static sitting balance ...

  12. Environmental effect indicators for priority pollutants

    NARCIS (Netherlands)

    Zwart D de; Hollander HA den; Geelen L; Huijbregts MAJ; Vakgroep Milieukunde, Radboud; LER

    2006-01-01

    Here a method is described for estimating public health and ecosystem effects due to the emission of priority pollutants in the Netherlands. Priority pollutants are subject to measures of emission reduction because of their immediate threat to the environment. The method proposed calculates

  13. MODEL OF PRIORITY SERVICE FOR AIRDROME'S OPERATIONS

    Directory of Open Access Journals (Sweden)

    A. K. Mitrofanov

    2015-01-01

    Full Text Available The model of process of priority service of departure and arrival operations is discussed. Priorities are operatively appointed by the controllers personnel according to requirements of documents of the civil aviation authorities and a situation developing on the earth and in air around airfield. Expressions for an assessment of properties of service of flights are received.

  14. 7 CFR 3431.14 - Priority.

    Science.gov (United States)

    2010-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.14 Priority. Pursuant to NVMSA, the Secretary will give priority to agreements with veterinarians for the practice of food animal medicine in veterinarian shortage...

  15. 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...

  16. 76 FR 54244 - Telecommunications Service Priority System

    Science.gov (United States)

    2011-08-31

    ... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2011-0043] Telecommunications Service Priority... concerning Extension, without change, of a currently approved collection: 1670-0005, Telecommunications... TSP System is to provide a legal basis for telecommunications vendors to provide priority provisioning...

  17. 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...

  18. SPECIATION AND DETERMINATION OF PRIORITY METALS IN ...

    African Journals Online (AJOL)

    ABSTRACT. 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,.

  19. Cellular basis of memory for addiction.

    Science.gov (United States)

    Nestler, Eric J

    2013-12-01

    DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. Here, we review the types of molecular and cellular adaptations that occur in specific brain regions to mediate addiction-associated behavioral abnormalities. These include alterations in gene expression achieved in part via epigenetic mechanisms, plasticity in the neurophysiological functioning of neurons and synapses, and associated plasticity in neuronal and synaptic morphology mediated in part by altered neurotrophic factor signaling. Each of these types of drug-induced modifications can be viewed as a form of "cellular or molecular memory." Moreover, it is striking that most addiction-related forms of plasticity are very similar to the types of plasticity that have been associated with more classic forms of "behavioral memory," perhaps reflecting the finite repertoire of adaptive mechanisms available to neurons when faced with environmental challenges. Finally, addiction-related molecular and cellular adaptations involve most of the same brain regions that mediate more classic forms of memory, consistent with the view that abnormal memories are important drivers of addiction syndromes. The goal of these studies which aim to explicate the molecular and cellular basis of drug addiction is to eventually develop biologically based diagnostic tests, as well as more effective treatments for addiction disorders.

  20. Epigenetics and Cellular Metabolism

    Directory of Open Access Journals (Sweden)

    Wenyi Xu

    2016-01-01

    Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  1. Architected Cellular Materials

    Science.gov (United States)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  2. 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.

  3. Cairo conference affirms CEDPA priorities.

    Science.gov (United States)

    1995-01-01

    The International Conference on Population and Development (ICPD) that was held in Cairo during September adopted a 20-year Programme of Action endorsing the empowerment of women as the foundation of sustainable development. 178 countries and more than a 1000 nongovernmental organizations (NGOs), including the Centre for Development and Population Activities (CEDPA), from 100 countries attended the conference and the parallel NGO forum. The final document sets out specific steps for achievement of universal access to a full range of voluntary, quality family planning and reproductive health services for women and men; provision of services for the special needs of adolescents; closure of the gender gap in education; and empowerment of women via education, health care, and economic options. The CEDPA network of alumnae from 30 countries had worked over the 3 years prior to the conference for the inclusion of women's priorities in policies and to achieve consensus among the government and NGO caucuses. 14 alumnae, including Peggy Curlin (CEDPA President and US delegate), were appointed to their countries' delegations and directly influenced the Programme of Action. The NGO Forum provided a place to exchange experiences and expertise; CEDPA mounted an exhibit, "Empowering Women." The network's theme was "Access, Choice, and Participation." With support from the United Nations Population Fund, CEDPA developed a manual, "After Cairo: A Handbook on Advocacy for Women Leaders," which has been distributed at training sessions and workshops and was translated into French (with support from the US Agency for International Development in Mali) for distribution at the Dakar conference in November in preparation for the World Conference on Women. CEDPA and The Global Committee for Cairo honored the secretary-general of the conference, Dr. Nafis Sadik, for her leadership of the ICPD and UNFPA, and Aziza Hussein, co-chair of the NGO steering committee, at a luncheon; Dr. Sadik

  4. 37 CFR 1.452 - Restoration of right of priority.

    Science.gov (United States)

    2010-07-01

    ... § 1.452 Restoration of right of priority. (a) If the international application has an international... within two months from the expiration of the priority period, the right of priority in the international... priority period was unintentional. (b) A request to restore the right of priority in an international...

  5. New directions in research priority-setting

    DEFF Research Database (Denmark)

    Nielsen, Morten Velsing

    2017-01-01

    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......, the case of RESEARCH2015 shows that mutual responsiveness is a relevant perspective for understanding social impacts in research priority-setting....

  6. 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....

  7. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  8. 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.

  9. Ethics and Research Priorities in Academic Administration.

    Science.gov (United States)

    Yeaworth, Rosalee C.

    1997-01-01

    Reviews macro and micro issues in determining research priorities for nursing education. Illustrates how decisions can be shaped by such ethical principles as caring, utility, justice, and faithfulness. Considers distributive justice as a guide for resource allocation. (SK)

  10. 42 CFR 57.1506 - Priority.

    Science.gov (United States)

    2010-10-01

    ... to Assist in Construction of Teaching Facilities for Health Profession Personnel § 57.1506 Priority... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS GRANTS FOR CONSTRUCTION OF TEACHING... will begin its teaching program. ...

  11. Smectite alteration

    International Nuclear Information System (INIS)

    Anderson, D.M.

    1984-11-01

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  12. 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

  13. Research priorities for zoonoses and marginalized infections.

    Science.gov (United States)

    2012-01-01

    This report provides a review and analysis of the research landscape for zoonoses and marginalized infections which affect poor populations, and a list of research priorities to support disease control. The work is the output of the Disease Reference Group on Zoonoses and Marginalized Infectious Diseases of Poverty (DRG6), which is part of an independent think tank of international experts, established and funded by the Special Programme for Research and Training in Tropical Diseases (TDR), to identify key research priorities through review of research evidence and input from stakeholder consultations. The report covers a diverse range of diseases, including zoonotic helminth, protozoan, viral and bacterial infections considered to be neglected and associated with poverty. Disease-specific research issues are elaborated under individual disease sections and many common priorities are identified among the diseases such as the need for new and/or improved drugs and regimens, diagnostics and, where appropriate, vaccines. The disease-specific priorities are described as micro priorities compared with the macro level priorities which will drive policy-making for: improved surveillance; interaction between the health, livestock, agriculture, natural resources and wildlife sectors in tackling zoonotic diseases; and true assessment of the burden of zoonoses. This is one often disease and thematic reference group reports that have come out of the TDR Think Tank, all of which have contributed to the development of the Global Report search on Infectious Diseases of Poverty, available at: w.who.int/tdr/stewardship/global_report/en/index.html.

  14. Design of Modified HRRN Scheduling Algorithm for Priority Systems Using Hybrid Priority Scheme

    OpenAIRE

    Varma, P. Surendra

    2013-01-01

    The basic aim of this paper is to design a scheduling algorithm which is suitable for priority systems and it should not suffer with starvation or indefinite postponement. Highest Response Ratio Next (HRRN) scheduling is a non-preemptive discipline, in which the priority of each job is dependent on its estimated run time, and also the amount of time it has spent waiting. Jobs gain higher priority the longer they wait, which prevents indefinite postponement (process starvation). In fact, the j...

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Sibbald Shannon L

    2009-03-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  17. Community-based decision making and priority setting using the R software: the community priority index.

    Science.gov (United States)

    Salihu, Hamisu M; Salinas-Miranda, Abraham A; Paothong, Arnut; Wang, Wei; King, Lindsey M

    2015-01-01

    This paper outlines how to compute community priority indices in the context of multicriteria decision making in community settings. A simple R function was developed and validated with community needs assessment data. Particularly, the first part of this paper briefly overviews the existing methods for priority setting and reviews the utility of a multicriteria decision-making approach for community-based prioritization. The second part illustrates how community priority indices can be calculated using the freely available R program to handle community data by showing the computational and mathematical steps of CPI (Community Priority Index) with bootstrapped 95% confidence intervals.

  18. Radiopharmaceutical cellular uptake mechanisms

    International Nuclear Information System (INIS)

    Stefanescu, Cipriana; Rusu, V.

    1996-01-01

    Cellular radiopharmaceutical specificity depends mainly of the uptake mechanisms. Usually, this can be one of the classical membrane transport type (a passive or active transport, a receptor mediated one or a combination of them). It can also be an electrochemical gradient dependent membrane transport in relation with Nernst equation, as in case of 99m Tc MIBI, the representative molecule of a widely studied family tracers, with applications in cardiac and oncological scintigraphy. Another mechanism can be an ATP dependent active transport, that results in the most important 201 Tl inflow. 201 Tl inflow is also an example of multiple mechanisms involved in cellular ionic inflow. Over 30% of 201 Tl transport imply other ways, like Na + - K + - Cl - co-transport. For a given tracer, the mechanism may depend also on the cell type. In conclusion, knowledge of the radiotracer uptake mechanisms allows finding the 'ideal' radiotracer with high specificity for the tissue to be visualized. (authors)

  19. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  20. Nested cellular automata

    International Nuclear Information System (INIS)

    Quasthoff, U.

    1985-07-01

    Cellular automata by definition consist of a finite or infinite number of cells, say of unit length, with each cell having the same transition function. These cells are usually considered as the smallest elements and so the space filled with these cells becomes discrete. Nevertheless, large pictures created by such cellular automata look very fractal. So we try to replace each cell by a couple of smaller cells, which have the same transition functions as the large ones. There are automata where this replacement does not destroy the macroscopic structure. In these cases this nesting process can be iterated. The paper contains large classes of automata with the above properties. In the case of one dimensional automata with two states and next neighbour interaction and a nesting function of the same type a complete classification is given. (author)

  1. Radiolabeled cellular blood elements

    International Nuclear Information System (INIS)

    Thakur, M.L.; Ezikowitz, M.D.; Hardeman, M.R.

    1985-01-01

    This book contains papers delivered by guest lectures and participants at the Advanced Study Institute's colloquium on Radiolabeled Cellular Blood Elements at Maratea, Italy on August 29, to September 9, 1982. The book includes chapters on basic cell physiology and critical reviews of data and experience in the preparation and use of radiolabeled cells, as well as reports on very recent developments, from a faculty that included experts on cell physiology in health and disease and on the technology of in vivo labeling

  2. 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

  3. Wavefront cellular learning automata

    Science.gov (United States)

    Moradabadi, Behnaz; Meybodi, Mohammad Reza

    2018-02-01

    This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure for the WCLA is necessary in many dynamic areas such as social networks, computer networks, grid computing, and web mining. In this paper, we introduce the WCLA framework as an optimization tool with diffusion capability, study its behavior over time using ordinary differential equation solutions, and present its accuracy using expediency analysis. To show the superiority of the proposed WCLA, we compare the proposed method with some other types of cellular learning automata using two benchmark problems.

  4. Global Conservation Priorities for Marine Turtles

    Science.gov (United States)

    Wallace, Bryan P.; DiMatteo, Andrew D.; Bolten, Alan B.; Chaloupka, Milani Y.; Hutchinson, Brian J.; Abreu-Grobois, F. Alberto; Mortimer, Jeanne A.; Seminoff, Jeffrey A.; Amorocho, Diego; Bjorndal, Karen A.; Bourjea, Jérôme; Bowen, Brian W.; Briseño Dueñas, Raquel; Casale, Paolo; Choudhury, B. C.; Costa, Alice; Dutton, Peter H.; Fallabrino, Alejandro; Finkbeiner, Elena M.; Girard, Alexandre; Girondot, Marc; Hamann, Mark; Hurley, Brendan J.; López-Mendilaharsu, Milagros; Marcovaldi, Maria Angela; Musick, John A.; Nel, Ronel; Pilcher, Nicolas J.; Troëng, Sebastian; Witherington, Blair; Mast, Roderic B.

    2011-01-01

    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-setting for

  5. 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

  6. Environment Aware Cellular Networks

    KAUST Repository

    Ghazzai, Hakim

    2015-02-01

    The unprecedented rise of mobile user demand over the years have led to an enormous growth of the energy consumption of wireless networks as well as the greenhouse gas emissions which are estimated currently to be around 70 million tons per year. This significant growth of energy consumption impels network companies to pay huge bills which represent around half of their operating expenditures. Therefore, many service providers, including mobile operators, are looking for new and modern green solutions to help reduce their expenses as well as the level of their CO2 emissions. Base stations are the most power greedy element in cellular networks: they drain around 80% of the total network energy consumption even during low traffic periods. Thus, there is a growing need to develop more energy-efficient techniques to enhance the green performance of future 4G/5G cellular networks. Due to the problem of traffic load fluctuations in cellular networks during different periods of the day and between different areas (shopping or business districts and residential areas), the base station sleeping strategy has been one of the main popular research topics in green communications. In this presentation, we present several practical green techniques that provide significant gains for mobile operators. Indeed, combined with the base station sleeping strategy, these techniques achieve not only a minimization of the fossil fuel consumption but also an enhancement of mobile operator profits. We start with an optimized cell planning method that considers varying spatial and temporal user densities. We then use the optimal transport theory in order to define the cell boundaries such that the network total transmit power is reduced. Afterwards, we exploit the features of the modern electrical grid, the smart grid, as a new tool of power management for cellular networks and we optimize the energy procurement from multiple energy retailers characterized by different prices and pollutant

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

    Directory of Open Access Journals (Sweden)

    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

  8. The Causal Priority of Form in Aristotle

    Directory of Open Access Journals (Sweden)

    Kathrin Koslicki

    2014-12-01

    Full Text Available In various texts (e.g., Met. Z.17, Aristotle assigns priority to form, in its role as a principle and cause, over matter and the matter-form compound. Given the central role played by this claim in Aristotle's search for primary substance in the Metaphysics, it is important to understand what motivates him in locating the primary causal responsibility for a thing's being what it is with the form, rather than the matter. According to Met. Theta.8, actuality [energeia/entelecheia] in general is prior to potentiality [dunamis] in three ways, viz., in definition, time and substance. I propose an explicitly causal reading of this general priority claim, as it pertains to the matter-form relationship. The priority of form over matter in definition, time and substance, in my view, is best explained by appeal to the role of form as the formal, efficient and final cause of the matter-form compound, respectively, while the posteriority of matter to form according to all three notions of priority is most plausibly accounted for by the fact that the causal contribution of matter is limited to its role as material cause. When approached from this angle, the work of Met. Theta.8 can be seen to lend direct support to the more specific and explicitly causal priority claim we encounter in Met. Z.17, viz., that form is prior to matter in its role as the principle and primary cause of a matter-form compound's being what it is.

  9. Overview of molecular, cellular, and genetic neurotoxicology.

    Science.gov (United States)

    Wallace, David R

    2005-05-01

    It has become increasingly evident that the field of neurotoxicology is not only rapidly growing but also rapidly evolving, especially over the last 20 years. As the number of drugs and environmental and bacterial/viral agents with potential neurotoxic properties has grown, the need for additional testing has increased. Only recently has the technology advanced to a level that neurotoxicologic studies can be performed without operating in a "black box." Examination of the effects of agents that are suspected of being toxic can occur on the molecular (protein-protein), cellular (biomarkers, neuronal function), and genetic (polymorphisms) level. Together, these areas help to elucidate the potential toxic profiles of unknown (and in some cases, known) agents. The area of proteomics is one of the fastest growing areas in science and particularly applicable to neurotoxicology. Lubec et al, provide a review of the potential and limitations of proteomics. Proteomics focuses on a more comprehensive view of cellular proteins and provides considerably more information about the effects of toxins on the CNS. Proteomics can be classified into three different focuses: post-translational modification, protein-expression profiling, and protein-network mapping. Together, these methods represent a more complete and powerful image of protein modifications following potential toxin exposure. Cellular neurotoxicology involves many cellular processes including alterations in cellular energy homeostasis, ion homeostasis, intracellular signaling function, and neurotransmitter release, uptake, and storage. The greatest hurdle in cellular neurotoxicology has been the discovery of appropriate biomarkers that are reliable, reproducible, and easy to obtain. There are biomarkers of exposure effect, and susceptibility. Finding the appropriate biomarker for a particular toxin is a daunting task. The appropriate biomarker for a particular toxin is a daunting task. The advantage to biomarker

  10. Evaluation of Structural Cellular Glass

    Science.gov (United States)

    Adams, M. A.; Zwissler, J. G.

    1984-01-01

    Preliminary design information presented. First report discusses state of structural-cellular-glass programs as of June 1979. Second report gives further details of program to develop improved cellular glasses and to characterize properties of glasses and commercially available materials.

  11. 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.

  12. Cellular communication through light.

    Directory of Open Access Journals (Sweden)

    Daniel Fels

    Full Text Available Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry.

  13. Cellular communication through light.

    Science.gov (United States)

    Fels, Daniel

    2009-01-01

    Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source) as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials) allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more) frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry.

  14. Design of Modified HRRN Scheduling Algorithm for priority systems Using Hybrid Priority scheme

    Directory of Open Access Journals (Sweden)

    P. Surendra Varma

    2013-01-01

    Full Text Available The basic aim of this paper is to design a scheduling algorithm which is suitable for priority systems and it should not suffer with starvation or indefinite postponement. Highest Response Ratio Next (HRRN scheduling is a non-preemptive discipline, in which the priority of each job is dependent on its estimated run time, and also the amount of time it has spent waiting. Jobs gain higher priority the longer they wait, which prevents indefinite postponement (process starvation. In fact, the jobs that have spent a long time waiting compete against those estimated to have short run times. HRRN prevents indefinite postponements but does not suitable for priority systems. So, modifying HRRN in such a way that it will be suitable for priority based systems.

  15. Review of cellular mechanotransduction

    Science.gov (United States)

    Wang, Ning

    2017-06-01

    Living cells and tissues experience physical forces and chemical stimuli in the human body. The process of converting mechanical forces into biochemical activities and gene expression is mechanochemical transduction or mechanotransduction. Significant advances have been made in understanding mechanotransduction at the cellular and molecular levels over the last two decades. However, major challenges remain in elucidating how a living cell integrates signals from mechanotransduction with chemical signals to regulate gene expression and to generate coherent biological responses in living tissues in physiological conditions and diseases.

  16. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  17. Cellular mechanics and motility

    Science.gov (United States)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  18. 18 CFR 281.206 - Priority 1 reclassification.

    Science.gov (United States)

    2010-04-01

    ....206 Priority 1 reclassification. (a) Definitions. For purposes of this section “high-priority... pipeline purchaser is entitled to receive from an interstate pipeline supplier for the high-priority... interstate pipeline suppliers to reclassify its high-priority entitlements in its currently effective...

  19. Elliptical Particle Clustering in Cellular Flows

    Science.gov (United States)

    Atis, Severine; Sapsis, Themistoklis; Peacock, Thomas

    2015-11-01

    The transport of finite-sized objects by fluid flows is relevant to a wide variety of phenomena, such as debris transport on the ocean surface or bacteria advection in fluid environment. The shape of the advected objects can strongly alter their coupling with the surrounding flow field, and hence, greatly affecting their dispersion by the flow. We present the results of investigations of the behavior of neutrally buoyant, elliptical particles in two-dimensional cellular flows. We find that their trajectories, and overall organization, are markedly different than for spherical particles, with clear clustering for the elliptical particles associated with vortices.

  20. Chronic Allium sativum administration alters spontaneous ...

    African Journals Online (AJOL)

    This study was conducted to investigate the effects of Allium sativum extract on the medial prefrontal cortex and neurobehaviour of adult Wistar rats. ... altered spontaneous alternation, while cellular pathologic changes were observed in the medial prefrontal cortex of these test groups in a dose dependent sequence.

  1. 7 CFR 4279.155 - Loan priorities.

    Science.gov (United States)

    2010-01-01

    ... lenders, will consider Agency priorities when choosing projects for guarantee. The lender will provide... natural disaster or experiencing fundamental structural changes in its economic base (5 points). (iv... or economic emergency conditions, or area economic development strategies. An explanation of the...

  2. Climate policy: Uncovering ocean-related priorities

    Science.gov (United States)

    Barkemeyer, Ralf

    2017-11-01

    Given the complexity and multi-faceted nature of policy processes, national-level policy preferences are notoriously difficult to capture. Now, research applying an automated text mining approach helps to shed light on country-level differences and priorities in the context of marine climate issues.

  3. Institutional Priority for Diversity at Christian Institutions

    Science.gov (United States)

    Paredes-Collins, Kristin

    2009-01-01

    This evaluative study explored the relationship between institutional priority for diversity and minority enrollment at four schools within the Council for Christian Colleges and Universities, a consortium of Christian institutions. This institutional evaluation utilized public resources in order to gather descriptive data on minority enrollment…

  4. Public Opinion Poll on Community Priorities: Sacramento

    Science.gov (United States)

    Sierra Health Foundation, 2009

    2009-01-01

    The primary goal of this study was to measure public perceptions, opinions and priorities as they pertain to youth issues in Sacramento for the purposes of further developing public and private youth programming and public policy in the Sacramento region. By presenting a "statistically reliable" profile of public opinion on youth issues,…

  5. 15 CFR 700.11 - Priority ratings.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Priority ratings. 700.11 Section 700.11 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS...

  6. The Top Training Priorities for 2003.

    Science.gov (United States)

    Hall, Brandon

    2003-01-01

    A survey of 222 training professionals identified current training priorities: soft skills training; technical training; enhancing the quality of training; business skills; business alignment, business impact, and return on investment; online learning; sales training; safety and compliance training; performance management; and human…

  7. Packet models revisited: tandem and priority systems

    NARCIS (Netherlands)

    M.R.H. Mandjes (Michel)

    2004-01-01

    textabstractWe examine two extensions of traditional single-node packet-scale queueing models: tandem networks and (strict) priority systems. Two generic input processes are considered: periodic and Poisson arrivals. For the two-node tandem, an exact expression is derived for the joint distribution

  8. Establishing and agreeing on research priorities

    Science.gov (United States)

    Ian de Ia Roche

    1999-01-01

    The organizers asked me to share with you my experiences in developing and implementing a process for establishing and agreeing on research priorities in a multi-stakeholder research institute such as Forintek. The mechanism we have in place has been well received by Forintek's membership and certain aspects have been adopted by other research organizations. While...

  9. 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...

  10. 12 CFR 360.3 - Priorities.

    Science.gov (United States)

    2010-01-01

    ... taxes, other than Federal income taxes, except to the extent subordinated pursuant to applicable law; but no other claim of a governmental unit shall have a priority higher than that of a general creditor... taxes; (9) Claims that have been subordinated in whole or in part to general creditor claims, which...

  11. Clinical research priorities in emergency medicine.

    Science.gov (United States)

    Keijzers, Gerben; Thom, Ogilvie; Taylor, David; Knott, Jonathan; Taylor, David McD

    2014-02-01

    To determine the clinical research priorities of Fellows of the Australasian College for Emergency Medicine (ACEM) in order to inform the strategic research agenda specific to multicentre clinical research. An anonymous survey of all ACEM Fellows (FACEMs) listed on the ACEM researcher database was conducted between January and March 2013. Of 108 FACEMs invited to participate, 54 (50%) responded. Over half of respondents (61%) had a higher research degree but only a minority (24%) had funded research positions. The top research categories identified as priorities were resuscitation, trauma, cardiology, ED ultrasound, acute behavioural disturbance and geriatrics. The most common specific sub-categories included anterior chest pain, fluid resuscitation in trauma, and drug therapy for both atrial fibrillation and acute behavioural disturbance. Several specific research questions related to chest pain, resuscitation/sepsis, stroke, paediatrics and pulmonary embolus. The findings provide guidance and support for research areas amenable to collaborative multicentre clinical research within emergency medicine. Discussion rounds are planned to translate these perceived research priorities to actual priorities. © 2013 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  12. 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.

  13. 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.

  14. Mitigation assessment results and priorities in China

    Energy Technology Data Exchange (ETDEWEB)

    Wu Zongxin; Wei Zhihong [Tsinghua Univ., Beijing (China)

    1996-12-31

    In this paper energy related CO2 emission projections of China by 2030 are given. CO2 mitigation potential and technology options in main fields of energy conservation and energy substitution are analyzed. CO2 reduction costs of main mitigation technologies are estimated and the AHP approach is used for helping assessment of priority technologies.

  15. 7 CFR 632.12 - Funding priorities.

    Science.gov (United States)

    2010-01-01

    ... danger of adverse effects of coal-mining practices. Extreme danger means a condition that could be..., and general welfare from the adverse effects of coal-mining practices that do not constitute an extreme danger. (3) Priority 3. Restoration of the land and water resources and the environment where...

  16. Priority environmental investment programme: Development and implementation

    Directory of Open Access Journals (Sweden)

    Njegovan Zoran M.

    2004-01-01

    Full Text Available This paper is created to serve as a methodological base and possible work plan for Assistance in Priority Environmental Investment Programme Development and Implementation in the Republic of Serbia. It will contribute to improved mechanisms for selection of priority environmental investments. Also, the paper should outline a scope of work for technical assistance for Republic of Serbia in developing mechanisms for identifying and selecting priority environmental investments. The main feature of the long-term environmental policy in the Republic of Serbia is absence of integrated approach, which goes hand by hand with the international environmental standards, and lack of efficient economic instruments and regulations. It causes an inadequate technology policy and location of the polluters. Besides that there has been a lack of appropriate environmental monitoring system good enough to provide efficient ex-ante and ex-post protection. It has caused a lot of environmental damages so that a completely new approach in the field of environment is expected to be created out of which the Priority Environmental Investment Programme (PEIP should be a main tool for experience of good environmental governance in the Republic of Serbia as well as in the region of SEE.

  17. Patient involvement in research priorities (PIRE)

    DEFF Research Database (Denmark)

    Piil, Karin; Jarden, Mary

    2016-01-01

    Introduction: Patient involvement in healthcare has expanded from the clinical practice setting to include collaboration during the research process. There has been a growing international interest in patient and public involvement in setting research priorities to reduce the risk of discrepancy ...

  18. 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. PMID:22952807

  19. 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

  20. 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

  1. 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

  2. Middle Urals` pollution prevention priorities assessment project

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, M.; Ott, R.L. [Lawrence Livermore National Lab., CA (United States); Chukanov, V. [Institute of Industrial Ecology, Ekaterinburg (Russian Federation)] [and others

    1995-09-13

    The Middle Urals is an important Russian industrial region. The key industries are also the most environmentally damaging: mining, metallurgical and chemical industries. There are some 600 large-sized and medium-sized enterprises located within the Middle Urals` region. Their annual solid and gaseous chemical releases have led to exceeding some maximum permissible contaminant concentrations by factors of tens and hundreds. The environmental problems of the Middle Urals are of such magnitude, seriousness, and urgency that the limited available resources can be applied only to the problems of the highest priority in the most cost-effective way. By the combined efforts of scientists from Lawrence Livermore National Laboratory (USA), Institute of Industrial Ecology (Ekaterinburg, Russia) and Russian Federal Nuclear Center (Snezhinsk, Russia) the project on Environmental Priorities Assessment was initiated in 1993. Because the project will cut across a spectrum of Russian environmental, social, and political issues, it has been established as a genuine Russian effort led by Russian principals. Russian participants are the prime movers and decision-makers, and LLNL participants are advisors. A preliminary project has been completed to gather relevant environmental data and to develop a formal proposal for the full priorities assessment project for submittal to the International Science and Technology Center. The proposed priorities assessment methodology will be described in this paper. The specific objectives of this project are to develop and to implement a methodology to establish Russian priorities for future pollution prevention efforts in a limited geographic region of the Middle Urals (a part of Chelyabinsk and Sverdlovsk Oblasts). This methodology will be developed on two geographic levels: local (town scale) and regional (region scale). Detailed environmental analysis will be performed on a local scale and extrapolated to the regional scale.

  3. Cellular image classification

    CERN Document Server

    Xu, Xiang; Lin, Feng

    2017-01-01

    This book introduces new techniques for cellular image feature extraction, pattern recognition and classification. The authors use the antinuclear antibodies (ANAs) in patient serum as the subjects and the Indirect Immunofluorescence (IIF) technique as the imaging protocol to illustrate the applications of the described methods. Throughout the book, the authors provide evaluations for the proposed methods on two publicly available human epithelial (HEp-2) cell datasets: ICPR2012 dataset from the ICPR'12 HEp-2 cell classification contest and ICIP2013 training dataset from the ICIP'13 Competition on cells classification by fluorescent image analysis. First, the reading of imaging results is significantly influenced by one’s qualification and reading systems, causing high intra- and inter-laboratory variance. The authors present a low-order LP21 fiber mode for optical single cell manipulation and imaging staining patterns of HEp-2 cells. A focused four-lobed mode distribution is stable and effective in optical...

  4. Cellular-scale hydrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Abkarian, Manouk [Laboratoire des Colloides, Verres et Nanomateriaux, Universite de Montpellier, Montpellier Cedex 5 (France); Faivre, Magalie [CEA-LETI, Division of Technology for Biology and Health, 17, Avenue des Martyrs, 38054 Grenoble (France); Horton, Renita; Stone, Howard A [School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138 (United States); Smistrup, Kristian [MIC, Department of Micro and Nanotechnology, Technical University of Denmark, DK-2800, Kongens Lyngby (Denmark); Best-Popescu, Catherine A [Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, IL 61801 (United States)

    2008-09-01

    Microfluidic tools are providing many new insights into the chemical, physical and physicochemical responses of cells. Both suspension-level and single-cell measurements have been studied. We review our studies of these kinds of problems for red blood cells with particular focus on the shapes of individual cells in confined geometries, the development and use of a 'differential manometer' for evaluating the mechanical response of individual cells or other objects flowing in confined geometries, and the cross-streamline drift of cells that pass through a constriction. In particular, we show how fluid mechanical effects on suspended cells can be studied systematically in small devices, and how these features can be exploited to develop methods for characterizing physicochemical responses and possibly for the diagnosis of cellular-scale changes to environmental factors.

  5. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, M; Met, Ö; Svane, I M

    2012-01-01

    -associated antigens introduced to dendritic cells (DCs) generated in vitro. This may in part result from suboptimal maturation of DCs leading to insufficient production of IL-12, a key driver of cellular immunity. Therefore, tremendous efforts have been put into the design of maturation cocktails that are able...... of tolerogenic molecules and activation-induced dendritic cell death should be avoided. Thus, compounds such as IFN-γ may initially induce immunity but later on tolerance. Maturation with PGE(2) obviously promotes migration via expression of CCR7 but on the down side PGE(2) limits the production of IL-12...... to transiently affect in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  6. 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

  7. 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

  8. 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.

  9. 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

  10. Quality improvement and emerging global health priorities

    Science.gov (United States)

    Mensah Abrampah, Nana; Syed, Shamsuzzoha Babar; Hirschhorn, Lisa R; Nambiar, Bejoy; Iqbal, Usman; Garcia-Elorrio, Ezequiel; Chattu, Vijay Kumar; Devnani, Mahesh; Kelley, Edward

    2018-01-01

    Abstract Quality improvement approaches can strengthen action on a range of global health priorities. Quality improvement efforts are uniquely placed to reorient care delivery systems towards integrated people-centred health services and strengthen health systems to achieve Universal Health Coverage (UHC). This article makes the case for addressing shortfalls of previous agendas by articulating the critical role of quality improvement in the Sustainable Development Goal era. Quality improvement can stimulate convergence between health security and health systems; address global health security priorities through participatory quality improvement approaches; and improve health outcomes at all levels of the health system. Entry points for action include the linkage with antimicrobial resistance and the contentious issue of the health of migrants. The work required includes focussed attention on the continuum of national quality policy formulation, implementation and learning; alongside strengthening the measurement-improvement linkage. Quality improvement plays a key role in strengthening health systems to achieve UHC.

  11. Reappraising cancer: life priorities and growth.

    Science.gov (United States)

    Strack, Juliane; Lopes, Paulo; Gaspar, Manfred

    2010-01-01

    People who have undergone traumatic life experiences such as cancer often report a new meaning and greater appreciation of life. These subjectively experienced positive changes are referred to as posttraumatic growth (PTG). The present study investigated correlates of PTG in cancer patients. 128 cancer patients at a rehabilitation clinic in Germany completed self-report questionnaires. Cognitive reappraisal of emotion, gratitude finding, and openness to experience correlated with PTG. Patients also reported different priorities in life after cancer, reflecting more present-oriented and intrinsic concerns. Our findings suggest that reappraising emotions and adjusting life priorities may help cancer patients to experience PTG by facilitating emotion-focused coping and reframing an apparently adverse situation as a positive experience. Copyright 2010 S. Karger AG, Basel.

  12. Results of the staff survey: your priorities

    CERN Multimedia

    Staff Association

    2014-01-01

    This is the first in a series of articles which will give some details about the results of the Staff Association staff survey To know your priorities and the evolution of your concerns over the last decade we study how, in each of our latest three surveys, you chose from a list of 15 items the five most important and classified them by assigning them a priority, from the most important to the fifth most important. The list of fifteen items, and a short description, follows. Career evolution (classification, level of recruitment, advancement, promotion) Salary level Family policy (recognition of partners, allowances, school fees, kindergarten, nursery, crèche, parental leave) Health insurance Non-residence and international indemnity Annual salary adjustment (cost variation index) Contract policy (duration, recruitment, award of IC, conditions of the beginning and ending of the contract) Motivation at work (interest, team, supervision, mobility, reward scheme) Pensions (retirement, disability, o...

  13. Health priorities in an Australian mining town

    DEFF Research Database (Denmark)

    Ellis, I. K.; Skinner, T. C.; Bhana, A.

    2014-01-01

    needs attention and Indigenous men need particular attention. Men's health-seeking behaviour has been suggested as one of the causes of poor outcomes. This study aimed to identify differences in health concerns between men and women, and Indigenous and non-Indigenous people in an Australian mining town...... recorded gender, age, Aboriginal or Torres Strait Islander self-identification status, whether people worked in the mining industry or not and in what capacity and occupation. Participants were asked a series of questions about health issues of concern from a list of 13 issues which included national...... and local health priorities. They were then asked to prioritise their choices. Results: Three hundred and eighty participants completed the survey, 48% were male; 18.4% identified as an Indigenous person and 21% worked in the local mining industry. Men's and women's health priorities were generally similar...

  14. Identifying national freshwater ecosystem priority areas

    CSIR Research Space (South Africa)

    Nel, JL

    2012-10-01

    Full Text Available on the brink of extinction. ? An implementation manual that provides relatively detailed guidance on how to effect the implementation of these priority areas in different policy contexts was also developed (Driver et al., 2011). FURTHER INFORMATION... (http://bgis.sanbi.org/nfepa/project.asp). ACKNOWLEDGEMENTS This study was co-funded by the CSIR, SANBI, Water Research Commission, Department of Environmental Affairs, Department of Water Affairs, Worldwide Fund for Nature, South African Institute...

  15. 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.

  16. The priority intervention group in action

    International Nuclear Information System (INIS)

    2001-01-01

    After the storm of december 1999 in France, RTE defined and implemented a GIP, Group of Priority Intervention to manage such crisis and intervene more rapidly. A crisis drill has been organised the first of February 2001 to repair high voltage electric lines. The document presents the drill and analyses the results. Some information on the RTE missions and management facing the electric power market deregulation are also provided. (A.L.B.)

  17. European research priorities for intracerebral haemorrhage

    DEFF Research Database (Denmark)

    Steiner, Thorsten; Petersson, Jesper; Al-Shahi Salman, Rustam

    2011-01-01

    Over 2 million people are affected by intracerebral haemorrhage (ICH) worldwide every year, one third of them dying within 1 month, and many survivors being left with permanent disability. Unlike most other stroke types, the incidence, morbidity and mortality of ICH have not declined over time...... and disability. The European Research Network on Intracerebral Haemorrhage EURONICH is a multidisciplinary academic research collaboration that has been established to define current research priorities and to conduct large clinical studies on all aspects of ICH....

  18. Priority of areas for agricultural radiovulnerability mapping

    International Nuclear Information System (INIS)

    Rochedo, Elaine R.R.; Igreja, Eduardo; Perez, Daniel V.; Rochedo, Pedro R.R.; Silva, Diogo N.G.

    2013-01-01

    The methodology for classifying areas according to soil properties for the vulnerability to a 137 Cs contamination is of high importance to the preparedness related to nuclear and/or radiological accidents that lead to release of radionuclides to the environment with the consequent contamination of agricultural areas. The priority of research for agricultural areas should then focus on the surrounding areas of nuclear power plant that have higher probability of public exposure through the ingestion pathway. The objective of this work was to create a rank order for priority of areas to be mapped based on EMBRAPA database on soil properties. The 16 municipalities previously selected to define parameters for dose assessment simulations related to the Brazilian Nuclear Power Plants, located in the district of Angra dos Reis, Rio de Janeiro, have been investigated in order to create this rank order to direct the research on radio vulnerability mapping, considering their relevance to public exposure based on their agricultural productivity. The two aspects selected in this study account for the maximum loss of income and to the collective doses that can be averted due to the banning of agricultural products. These quantities are inputs to optimization analysis. The priority defined shall then guide research on both the adequate values for the transfer factors and on the agricultural countermeasures suitable to each area according to the cause(s) of their vulnerability and their typical agricultural crops. (author)

  19. 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.

  20. 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.

  1. Priority of areas for agricultural radiovulnerability mapping

    Energy Technology Data Exchange (ETDEWEB)

    Rochedo, Elaine R.R.; Igreja, Eduardo, E-mail: elainerochedo@gmail.com, E-mail: eduigreja@gmail.com [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear; Wasserman, Maria Angelica V., E-mail: mwasserman@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Perez, Daniel V., E-mail: chpd@cnps.embrapa.br [Empresa Brasileira de Pesquisa Agropecuaria (EMBRAPA), Rio de Janeiro, RJ (Brazil). Centro Nacional de Pesquisa de Solos; Rochedo, Pedro R.R., E-mail: rochedopedro@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Programa de Planejamento Energetico; Silva, Diogo N.G., E-mail: diogongs@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Instituto de Biofisica Carlos Chagas Filho

    2013-07-01

    The methodology for classifying areas according to soil properties for the vulnerability to a {sup 137}Cs contamination is of high importance to the preparedness related to nuclear and/or radiological accidents that lead to release of radionuclides to the environment with the consequent contamination of agricultural areas. The priority of research for agricultural areas should then focus on the surrounding areas of nuclear power plant that have higher probability of public exposure through the ingestion pathway. The objective of this work was to create a rank order for priority of areas to be mapped based on EMBRAPA database on soil properties. The 16 municipalities previously selected to define parameters for dose assessment simulations related to the Brazilian Nuclear Power Plants, located in the district of Angra dos Reis, Rio de Janeiro, have been investigated in order to create this rank order to direct the research on radio vulnerability mapping, considering their relevance to public exposure based on their agricultural productivity. The two aspects selected in this study account for the maximum loss of income and to the collective doses that can be averted due to the banning of agricultural products. These quantities are inputs to optimization analysis. The priority defined shall then guide research on both the adequate values for the transfer factors and on the agricultural countermeasures suitable to each area according to the cause(s) of their vulnerability and their typical agricultural crops. (author)

  2. 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.

  3. 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.

  4. 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

  5. 1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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,...

  8. AMPK-sensitive cellular transport.

    Science.gov (United States)

    Dërmaku-Sopjani, Miribane; Abazi, Sokol; Faggio, Caterina; Kolgeci, Jehona; Sopjani, Mentor

    2014-03-01

    The energy sensing AMP-activated protein kinase (AMPK) regulates cellular and whole-body energy balance through stimulating catabolic ATP-generating and suppressing anabolic ATP-consuming pathways thereby helping cells survive during energy depletion. The kinase has previously been reported to be either directly or indirectly involved in the regulation of several carriers, channels and pumps of high significance in cellular physiology. Thus AMPK provides a necessary link between cellular energy metabolism and cellular transport activity. Better understanding of the AMPK role in cellular transport offers a potential for improved therapies in various human diseases and disorders. In this review, we discuss recent advances in understanding the role and function of AMPK in transport regulation under physiological and pathological states.

  9. 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...

  10. 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...

  11. 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

  12. 78 FR 12368 - Priority Mail Contract; Negotiated Service Agreement

    Science.gov (United States)

    2013-02-22

    ... POSTAL REGULATORY COMMISSION [Docket No. CP2013-7; Order No. 1660] Priority Mail Contract... noticing a recent Postal Service filing concerning an amendment to the existing Priority Mail Contract 47... that it has agreed to an amendment to existing Priority Mail Contract 47, which was added to the...

  13. 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…

  14. 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...

  15. 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...

  16. 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.

  17. European research priorities for intracerebral haemorrhage

    DEFF Research Database (Denmark)

    Steiner, Thorsten; Petersson, Jesper; Al-Shahi Salman, Rustam

    2011-01-01

    . No standardised diagnostic workup for the detection of the various underlying causes of ICH currently exists, and the evidence for medical or surgical therapeutic interventions remains limited. A dedicated European research programme for ICH is needed to identify ways to reduce the burden of ICH-related death...... and disability. The European Research Network on Intracerebral Haemorrhage EURONICH is a multidisciplinary academic research collaboration that has been established to define current research priorities and to conduct large clinical studies on all aspects of ICH....

  18. Value-Based Care and Strategic Priorities.

    Science.gov (United States)

    Gross, Wendy L; Cooper, Lebron; Boggs, Steven; Gold, Barbara

    2017-12-01

    The anesthesia market continues to undergo disruption. Financial margins are shrinking, and buyers are demanding that anesthesia services be provided in an efficient, low-cost manner. To help anesthesiologists analyze their market, Drucker and Porter's framework of buyers, suppliers, quality, barriers to entry, substitution, and strategic priorities allows for a structured analysis. Once this analysis is completed, anesthesiologists must articulate their value to other medical professionals and to hospitals. Anesthesiologists can survive and thrive in a value-based health care environment if they are capable of providing services differently and able to deliver cost-effective care. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Absolute Priority for a Vehicle in VANET

    Science.gov (United States)

    Shirani, Rostam; Hendessi, Faramarz; Montazeri, Mohammad Ali; Sheikh Zefreh, Mohammad

    In today's world, traffic jams waste hundreds of hours of our life. This causes many researchers try to resolve the problem with the idea of Intelligent Transportation System. For some applications like a travelling ambulance, it is important to reduce delay even for a second. In this paper, we propose a completely infrastructure-less approach for finding shortest path and controlling traffic light to provide absolute priority for an emergency vehicle. We use the idea of vehicular ad-hoc networking to reduce the imposed travelling time. Then, we simulate our proposed protocol and compare it with a centrally controlled traffic light system.

  20. [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.

  1. Research priorities for public mental health in Europe

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  2. The role of actin networks in cellular mechanosensing

    Science.gov (United States)

    Azatov, Mikheil

    Physical processes play an important role in many biological phenomena, such as wound healing, organ development, and tumor metastasis. During these processes, cells constantly interact with and adapt to their environment by exerting forces to mechanically probe the features of their surroundings and generating appropriate biochemical responses. The mechanisms underlying how cells sense the physical properties of their environment are not well understood. In this thesis, I present my studies to investigate cellular responses to the stiffness and topography of the environment. In order to sense the physical properties of their environment, cells dynamically reorganize the structure of their actin cytoskeleton, a dynamic network of biopolymers, altering the shape and spatial distribution of protein assemblies. Several observations suggest that proteins that crosslink actin filaments may play an important role in cellular mechanosensitivity. Palladin is an actin-crosslinking protein that is found in the lamellar actin network, stress fibers and focal adhesions, cellular structures that are critical for mechanosensing of the physical environment. By virtue of its close interactions with these structures in the cell, palladin may play an important role in cell mechanics. However, the role of actin crosslinkers in general, and palladin in particular, in cellular force generation and mechanosensing is not well known. I have investigated the role of palladin in regulating the plasticity of the actin cytoskeleton and cellular force generation in response to alterations in substrate stiffness. I have shown that the expression levels of palladin modulate the forces exerted by cells and their ability to sense substrate stiffness. Perturbation experiments also suggest that palladin levels in cells altered myosin motor activity. These results suggest that the actin crosslinkers, such as palladin, and myosin motors coordinate for optimal cell function and to prevent aberrant

  3. 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.

  4. Conservative parallel simulation of priority class queueing networks

    Science.gov (United States)

    Nicol, David

    1992-01-01

    A conservative synchronization protocol is described for the parallel simulation of queueing networks having C job priority classes, where a job's class is fixed. This problem has long vexed designers of conservative synchronization protocols because of its seemingly poor ability to compute lookahead: the time of the next departure. For, a job in service having low priority can be preempted at any time by an arrival having higher priority and an arbitrarily small service time. The solution is to skew the event generation activity so that the events for higher priority jobs are generated farther ahead in simulated time than lower priority jobs. Thus, when a lower priority job enters service for the first time, all the higher priority jobs that may preempt it are already known and the job's departure time can be exactly predicted. Finally, the protocol was analyzed and it was demonstrated that good performance can be expected on the simulation of large queueing networks.

  5. Priorities for research in soil ecology.

    Science.gov (United States)

    Eisenhauer, Nico; Antunes, Pedro M; Bennett, Alison E; Birkhofer, Klaus; Bissett, Andrew; Bowker, Matthew A; Caruso, Tancredi; Chen, Baodong; Coleman, David C; de Boer, Wietse; de Ruiter, Peter; DeLuca, Thomas H; Frati, Francesco; Griffiths, Bryan S; Hart, Miranda M; Hättenschwiler, Stephan; Haimi, Jari; Heethoff, Michael; Kaneko, Nobuhiro; Kelly, Laura C; Leinaas, Hans Petter; Lindo, Zoë; Macdonald, Catriona; Rillig, Matthias C; Ruess, Liliane; Scheu, Stefan; Schmidt, Olaf; Seastedt, Timothy R; van Straalen, Nico M; Tiunov, Alexei V; Zimmer, Martin; Powell, Jeff R

    2017-07-01

    The ecological interactions that occur in and with soil are of consequence in many ecosystems on the planet. These interactions provide numerous essential ecosystem services, and the sustainable management of soils has attracted increasing scientific and public attention. Although soil ecology emerged as an independent field of research many decades ago, and we have gained important insights into the functioning of soils, there still are fundamental aspects that need to be better understood to ensure that the ecosystem services that soils provide are not lost and that soils can be used in a sustainable way. In this perspectives paper, we highlight some of the major knowledge gaps that should be prioritized in soil ecological research. These research priorities were compiled based on an online survey of 32 editors of Pedobiologia - Journal of Soil Ecology. These editors work at universities and research centers in Europe, North America, Asia, and Australia.The questions were categorized into four themes: (1) soil biodiversity and biogeography, (2) interactions and the functioning of ecosystems, (3) global change and soil management, and (4) new directions. The respondents identified priorities that may be achievable in the near future, as well as several that are currently achievable but remain open. While some of the identified barriers to progress were technological in nature, many respondents cited a need for substantial leadership and goodwill among members of the soil ecology research community, including the need for multi-institutional partnerships, and had substantial concerns regarding the loss of taxonomic expertise.

  6. TB and HIV Therapeutics: Pharmacology Research Priorities

    Directory of Open Access Journals (Sweden)

    Kelly E. Dooley

    2012-01-01

    Full Text Available An unprecedented number of investigational drugs are in the development pipeline for the treatment of tuberculosis. Among patients with tuberculosis, co-infection with HIV is common, and concurrent treatment of tuberculosis and HIV is now the standard of care. To ensure that combinations of anti-tuberculosis drugs and antiretrovirals are safe and are tested at doses most likely to be effective, selected pharmacokinetic studies based on knowledge of their metabolic pathways and their capacity to induce or inhibit metabolizing enzymes of companion drugs must be conducted. Drug interaction studies should be followed up by evaluations in larger populations to evaluate safety and pharmacodynamics more fully. Involving patients with HIV in trials of TB drugs early in development enhances the knowledge gained from the trials and will ensure that promising new tuberculosis treatments are available to patients with HIV as early as possible. In this review, we summarize current and planned pharmacokinetic and drug interaction studies involving investigational and licensed tuberculosis drugs and antiretrovirals and suggest priorities for tuberculosis-HIV pharmacokinetic, pharmacodynamic, and drug-drug interaction studies for the future. Priority studies for children and pregnant women with HIV and tuberculosis co-infection are briefly discussed.

  7. Priorities for research in soil ecology

    Science.gov (United States)

    Eisenhauer, Nico; Antunes, Pedro M.; Bennett, Alison E.; Birkhofer, Klaus; Bissett, Andrew; Bowker, Matthew A.; Caruso, Tancredi; Chen, Baodong; Coleman, David C.; de Boer, Wietse; de Ruiter, Peter; DeLuca, Thomas H.; Frati, Francesco; Griffiths, Bryan S.; Hart, Miranda M.; Hättenschwiler, Stephan; Haimi, Jari; Heethoff, Michael; Kaneko, Nobuhiro; Kelly, Laura C.; Leinaas, Hans Petter; Lindo, Zoë; Macdonald, Catriona; Rillig, Matthias C.; Ruess, Liliane; Scheu, Stefan; Schmidt, Olaf; Seastedt, Timothy R.; van Straalen, Nico M.; Tiunov, Alexei V.; Zimmer, Martin; Powell, Jeff R.

    2017-01-01

    The ecological interactions that occur in and with soil are of consequence in many ecosystems on the planet. These interactions provide numerous essential ecosystem services, and the sustainable management of soils has attracted increasing scientific and public attention. Although soil ecology emerged as an independent field of research many decades ago, and we have gained important insights into the functioning of soils, there still are fundamental aspects that need to be better understood to ensure that the ecosystem services that soils provide are not lost and that soils can be used in a sustainable way. In this perspectives paper, we highlight some of the major knowledge gaps that should be prioritized in soil ecological research. These research priorities were compiled based on an online survey of 32 editors of Pedobiologia – Journal of Soil Ecology. These editors work at universities and research centers in Europe, North America, Asia, and Australia.The questions were categorized into four themes: (1) soil biodiversity and biogeography, (2) interactions and the functioning of ecosystems, (3) global change and soil management, and (4) new directions. The respondents identified priorities that may be achievable in the near future, as well as several that are currently achievable but remain open. While some of the identified barriers to progress were technological in nature, many respondents cited a need for substantial leadership and goodwill among members of the soil ecology research community, including the need for multi-institutional partnerships, and had substantial concerns regarding the loss of taxonomic expertise. PMID:29129942

  8. Priority of areas for agricultural countermeasure assessment

    International Nuclear Information System (INIS)

    Rochedo, E.R.R.; Barboza, A.E.; Igreja, E.; Silva, D.N.G. da; Wasserman, A.E.

    2015-01-01

    Within the overall preparedness related to nuclear and/or radiological accidents that lead to the release of radionuclides to the environment with the consequent contamination of agricultural areas, the priority of research for agricultural areas should then focus on the surrounding areas of nuclear power plants that have higher probability of public exposure through the ingestion pathway. The objective of this work was to create a rank order of priority of agricultural products to be considered in assessing the effects of countermeasures, based on both economic value and doses to the public. Additionally, the study describes relevant needs of radioecological studies to improve short and long-terms dose assessments. . Sixteen municipalities surrounding the Brazilian Nuclear Power Central were analyzed for a contamination with 137 Cs, considering seasonal aspects related to agricultural practices in the Southeastern Brazil. Rank order provided by considering economical aspects shows that there is a need for radioecological research for some high value products, such as palmetto and sugar cane, and the need to include in the current model more detailed description for some food items, such as eggs. Combined rank criteria shows that main product within the considered area is milk. As so, the study of countermeasures for the ingestion of milk should be prioritized. (authors)

  9. Priorities for professionalism: what do surgeons think?

    Science.gov (United States)

    Hillis, David J; Gorton, Michael W; Barraclough, Bruce H; Beckett, David

    2015-05-04

    To gain an understanding of the relative importance of the nine surgical competencies and their 27 attributes defined by the Royal Australasian College of Surgeons (RACS), which together provide the curriculum framework for today's surgeons. Between 9 August and 30 September 2010, trainees and Fellows of the RACS across Australia and New Zealand actively involved in educational activities rated, via questionnaire, the importance of the RACS competencies (technical expertise, communication, professionalism, medical expertise, judgement and decision making, scholarship and teaching, collaboration and teamwork, management and leadership, and health advocacy) and associated attributes. Importance ranking of competencies and their attributes for surgical education and training. Of 3054 questionnaires distributed, 1834 (60%) were returned. We identified clear priorities in the perceived relative importance of the nine competencies and 27 attributes. The most important attributes were competence, insight, and recognising conditions amenable to surgery; least important were responding to community and cultural needs, supporting others, and maintaining personal health and wellbeing. Key differences were noted for the competency of collaboration and teamwork, which was ranked as more important by trainees than by Fellows. Female trainees and Fellows regarded all attributes as more important than did male trainees and Fellows. In a complex environment with multiple pressures, the priorities of the competencies are important. Trainees and Fellows had a very similar approach to the prioritisation of the attributes. Of concern is the lesser importance given to attributes beyond individual expertise.

  10. Delineation of nursing administration research priorities.

    Science.gov (United States)

    Henry, B; Moody, L E; Pendergast, J F; O'Donnell, J; Hutchinson, S A; Scully, G

    1987-01-01

    The purposes of this national study were to determine: (a) a definition of nursing administration research and (b) priority nursing administration research questions. Brainstorming was used initially with Council on Graduate Education for Administration in Nursing (CGEAN) members in 1984, to delineate concepts for definitions. Definitions and research questions were generated and rated in a three-round Delphi survey by 129 experts from nursing and health administration. According to the most widely supported definition, nursing administration research is concerned with establishing costs of nursing care, examining the relationships between nursing services and quality patient care, and viewing problems of nursing service delivery within the broader context of policy analysis and delivery of health services. The research question of most importance was: What are the cost-effective components of clinical nursing care that yield high patient satisfaction, decrease the number of complications, and shorten hospital stay for identified groups of patients? In a scenario exercise at the 1985 CGEAN meeting, additional priorities identified were vulnerable populations and equity.

  11. Method ranks competing projects by priorities, risk

    International Nuclear Information System (INIS)

    Moeckel, D.R.

    1993-01-01

    A practical, objective guide for ranking projects based on risk-based priorities has been developed by Sun Pipe Line Co. The deliberately simple system guides decisions on how to allocate scarce company resources because all managers employ the same criteria in weighing potential risks to the company versus benefits. Managers at all levels are continuously having to comply with an ever growing amount of legislative and regulatory requirements while at the same time trying to run their businesses effectively. The system primarily is designed for use as a compliance oversight and tracking process to document, categorize, and follow-up on work concerning various issues or projects. That is, the system consists of an electronic database which is updated periodically, and is used by various levels of management to monitor progress of health, safety, environmental and compliance-related projects. Criteria used in determining a risk factor and assigning a priority also have been adapted and found useful for evaluating other types of projects. The process enables management to better define potential risks and/or loss of benefits that are being accepted when a project is rejected from an immediate work plan or budget. In times of financial austerity, it is extremely important that the right decisions are made at the right time

  12. Roles of Apoptosis and Cellular Senescence in Cancer and Aging.

    Science.gov (United States)

    Cerella, Claudia; Grandjenette, Cindy; Dicato, Mario; Diederich, Marc

    2016-01-01

    Cancer and aging are two similar processes representing the final outcome of timedependent accumulation of various irreversible dysfunctions, mainly caused by stress-induced DNA and cellular damages. Apoptosis and senescence are two types of cellular response to damages that are altered in both cancer and aging, albeit through different mechanisms. Carcinogenesis is associated with a progressive reduction in the ability of the cells to trigger apoptosis and senescence. In contrast, in aging tissues, there is an increased accumulation of senescent cells, and the nature of apoptosis deregulation varies depending on the tissue. Thus, the prevailing model suggests that apoptosis and cellular senescence function as two essential tumor-suppressor mechanisms, ensuring the health of the individual during early and reproductive stages of life, but become detrimental and promote aging later in life. The recent discovery that various anticancer agents, including canonical inducers of apoptosis, act also as inducers of cellular senescence indicates that pro-senescence strategies may have applications in cancer prevention therapy. Therefore, dissection of the mechanisms mediating the delicate balance between apoptosis and cellular senescence will be beneficial in the therapeutic exploitation of both processes in the development of future anticancer and anti-aging strategies, including minimizing the side effects of such strategies. Here, we provide an overview of the roles of apoptosis and cellular senescence in cancer and aging.

  13. Priorities for modeling biological processes in climates altered by nuclear war

    International Nuclear Information System (INIS)

    Detling, J.K.; Kercher, J.R.; Post, W.M.; Cowles, S.W.; Harwell, M.A.

    1987-01-01

    This document describes research that has been accomplished or currently models the effects of reduced light and temperature on terrestrial systems. We shall divide the systems to be studied into cultivated lands and uncultivated lands. The cultivated class consists of monoculture systems in which the individual plants belong to the same age and size class. The systems in the uncultivated class consist of uneven age, multi-species assemblies of interacting plants and animals. The uncultivated class ranges from minimally managed systems, e.g., rangelands and some forests, to completely unmanaged wildlands. For the cultivated case, the variable of concern is the annual yield of the crop under consideration. The models should be able to estimate percent yield loss as a function of reductions of light and temperature. The models should be accurate for the range of environments predicted for the growing season immediately following or during which the hypothetical nuclear exchange occurs. The models should be able to estimate yield loss in any subsequent year for which climatic conditions still differ significantly from normal. For the uncultivated case, the modelling program needs to be able to predict the effects on individual plants much the same as in the cultivated case; but in addition, the modelling program will have the task of estimating the effect that these changes in individual organisms will have at higher levels of organization, i.e., on populations, communities, and regional distributions of species. 25 refs., 1 tab

  14. 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.

  15. Novel Materials for Cellular Nanosensors

    DEFF Research Database (Denmark)

    Sasso, Luigi

    The monitoring of cellular behavior is useful for the advancement of biomedical diagnostics, drug development and the understanding of a cell as the main unit of the human body. Micro- and nanotechnology allow for the creation of functional devices that enhance the study of cellular dynamics...... by providing platforms that offer biocompatible surfaces for the cell culturing in lab-on-chip devices integrated with optimized nanosensors with high specificities and sensitivities towards cellular analytes. In this project, novel materials were investigated with a focus on providing suitable surface...... modifications for electrochemical nanosensors for the detection of analytes released from cells. Two type of materials were investigated, each pertaining to the two different aspects of such devices: peptide nanostructures were studied for the creation of cellular sensing substrates that mimic in vivo surfaces...

  16. Systems biology of cellular rhythms.

    Science.gov (United States)

    Goldbeter, A; Gérard, C; Gonze, D; Leloup, J-C; Dupont, G

    2012-08-31

    Rhythms abound in biological systems, particularly at the cellular level where they originate from the feedback loops present in regulatory networks. Cellular rhythms can be investigated both by experimental and modeling approaches, and thus represent a prototypic field of research for systems biology. They have also become a major topic in synthetic biology. We review advances in the study of cellular rhythms of biochemical rather than electrical origin by considering a variety of oscillatory processes such as Ca++ oscillations, circadian rhythms, the segmentation clock, oscillations in p53 and NF-κB, synthetic oscillators, and the oscillatory dynamics of cyclin-dependent kinases driving the cell cycle. Finally we discuss the coupling between cellular rhythms and their robustness with respect to molecular noise.

  17. A Course in Cellular Bioengineering.

    Science.gov (United States)

    Lauffenburger, Douglas A.

    1989-01-01

    Gives an overview of a course in chemical engineering entitled "Cellular Bioengineering," dealing with how chemical engineering principles can be applied to molecular cell biology. Topics used are listed and some key references are discussed. Listed are 85 references. (YP)

  18. Origami interleaved tube cellular materials

    International Nuclear Information System (INIS)

    Cheung, Kenneth C; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

    2014-01-01

    A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis. (paper)

  19. Priority Services Design and Forecasting Project: Priority services methods at Commonwealth Edison

    Energy Technology Data Exchange (ETDEWEB)

    Hamm, G.L.; Wood, R.O.; Buchanan, J.B. (Applied Decision Analysis, Inc., Menlo Park, CA (United States)); Glyer, J.D.; Quinn, J.A.; Caves, D.W. (Christensen (Laurits R.) Associates, Inc., Madison, WI (United States))

    1992-12-01

    Priority services are programs such as interruptible service that allow a utility to share control of electricity use with customers. This study of Commonwealth Edison customers tested the validity of previously developed models of customer response to controlled energy services; developed a more cost-effective, computerized survey technique; and estimated customer acceptance of various controlled energy services.

  20. 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.

  1. Conformational sampling of peptides in cellular environments.

    Science.gov (United States)

    Tanizaki, Seiichiro; Clifford, Jacob; Connelly, Brian D; Feig, Michael

    2008-02-01

    Biological systems provide a complex environment that can be understood in terms of its dielectric properties. High concentrations of macromolecules and cosolvents effectively reduce the dielectric constant of cellular environments, thereby affecting the conformational sampling of biomolecules. To examine this effect in more detail, the conformational preference of alanine dipeptide, poly-alanine, and melittin in different dielectric environments is studied with computer simulations based on recently developed generalized Born methodology. Results from these simulations suggest that extended conformations are favored over alpha-helical conformations at the dipeptide level at and below dielectric constants of 5-10. Furthermore, lower-dielectric environments begin to significantly stabilize helical structures in poly-alanine at epsilon = 20. In the more complex peptide melittin, different dielectric environments shift the equilibrium between two main conformations: a nearly fully extended helix that is most stable in low dielectrics and a compact, V-shaped conformation consisting of two helices that is preferred in higher dielectric environments. An additional conformation is only found to be significantly populated at intermediate dielectric constants. Good agreement with previous studies of different peptides in specific, less-polar solvent environments, suggest that helix stabilization and shifts in conformational preferences in such environments are primarily due to a reduced dielectric environment rather than specific molecular details. The findings presented here make predictions of how peptide sampling may be altered in dense cellular environments with reduced dielectric response.

  2. Conformational Sampling of Peptides in Cellular Environments☆

    Science.gov (United States)

    Tanizaki, Seiichiro; Clifford, Jacob; Connelly, Brian D.; Feig, Michael

    2008-01-01

    Abstract Biological systems provide a complex environment that can be understood in terms of its dielectric properties. High concentrations of macromolecules and cosolvents effectively reduce the dielectric constant of cellular environments, thereby affecting the conformational sampling of biomolecules. To examine this effect in more detail, the conformational preference of alanine dipeptide, poly-alanine, and melittin in different dielectric environments is studied with computer simulations based on recently developed generalized Born methodology. Results from these simulations suggest that extended conformations are favored over α-helical conformations at the dipeptide level at and below dielectric constants of 5–10. Furthermore, lower-dielectric environments begin to significantly stabilize helical structures in poly-alanine at ɛ = 20. In the more complex peptide melittin, different dielectric environments shift the equilibrium between two main conformations: a nearly fully extended helix that is most stable in low dielectrics and a compact, V-shaped conformation consisting of two helices that is preferred in higher dielectric environments. An additional conformation is only found to be significantly populated at intermediate dielectric constants. Good agreement with previous studies of different peptides in specific, less-polar solvent environments, suggest that helix stabilization and shifts in conformational preferences in such environments are primarily due to a reduced dielectric environment rather than specific molecular details. The findings presented here make predictions of how peptide sampling may be altered in dense cellular environments with reduced dielectric response. PMID:17905846

  3. Rhabdomyosarcoma: Advances in Molecular and Cellular Biology.

    Science.gov (United States)

    Sun, Xin; Guo, Wei; Shen, Jacson K; Mankin, Henry J; Hornicek, Francis J; Duan, Zhenfeng

    2015-01-01

    Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and adolescence. The two major histological subtypes of RMS are alveolar RMS, driven by the fusion protein PAX3-FKHR or PAX7-FKHR, and embryonic RMS, which is usually genetically heterogeneous. The prognosis of RMS has improved in the past several decades due to multidisciplinary care. However, in recent years, the treatment of patients with metastatic or refractory RMS has reached a plateau. Thus, to improve the survival rate of RMS patients and their overall well-being, further understanding of the molecular and cellular biology of RMS and identification of novel therapeutic targets are imperative. In this review, we describe the most recent discoveries in the molecular and cellular biology of RMS, including alterations in oncogenic pathways, miRNA (miR), in vivo models, stem cells, and important signal transduction cascades implicated in the development and progression of RMS. Furthermore, we discuss novel potential targeted therapies that may improve the current treatment of RMS.

  4. Cellular redox, cancer and human papillomavirus.

    Science.gov (United States)

    Cruz-Gregorio, Alfredo; Manzo-Merino, Joaquín; Lizano, Marcela

    2018-02-15

    High-risk Human Papillomavirus (HR-HPV) is the causative agent of different human cancers. A persistent HR-HPV infection alters several cellular processes involved in cell proliferation, apoptosis, immune evasion, genomic instability and transformation. Cumulative evidence from past studies indicates that HR-HPV proteins are associated with oxidative stress (OS) and has been proposed as a risk factor for cancer development. Reactive oxygen and nitrogen species (RONS) regulate a plethora of processes inducing cellular proliferation, differentiation and death. Oxidative stress (OS) is generated when an imbalance in the redox state occurs due to deregulation of the oxidant and antioxidant systems, which, in turn, promotes the damage of DNA, proteins and lipids, allowing the accumulation of mutations and genome instability. OS has been associated with the establishment and development of different cancers, and it has recently been proposed as a co-factor in cervical cancer development. This review is focused on evidence regarding the association of OS with HR-HPV proteins, and the interplay of the viral proteins with different elements of the antioxidant and DNA damage response (DDR) systems, emphasizing the processes that might be required for the viral life cycle and viral DNA integration into the host genome, which is a key element in the carcinogenic process induced by HR-HPV. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Cellular and molecular perspectives in rheumatoid arthritis.

    Science.gov (United States)

    Veale, Douglas J; Orr, Carl; Fearon, Ursula

    2017-06-01

    Synovial immunopathology in rheumatoid arthritis is complex involving both resident and infiltrating cells. The synovial tissue undergoes significant neovascularization, facilitating an influx of lymphocytes and monocytes that transform a typically acellular loose areolar membrane into an invasive tumour-like pannus. The microvasculature proliferates to form straight regularly-branching vessels; however, they are highly dysfunctional resulting in reduced oxygen supply and a hypoxic microenvironment. Autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are found at an early stage, often before arthritis has developed, and they have been implicated in the pathogenesis of RA. Abnormal cellular metabolism and mitochondrial dysfunction thus ensue and, in turn, through the increased production of reactive oxygen species actively induce inflammation. Key pro-inflammatory cytokines, chemokines and growth factors and their signalling pathways, including nuclear factor κB, Janus kinase-signal transducer, are highly activated when immune cells are exposed to hypoxia in the inflamed rheumatoid joint show adaptive survival reactions by activating. This review attempts to highlight those aberrations in the innate and adaptive immune systems including the role of genetic and environmental factors, autoantibodies, cellular alterations, signalling pathways and metabolism that are implicated in the pathogenesis of RA and may therefore provide an opportunity for therapeutic intervention.

  6. 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.

  7. 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.

  8. The economics of priority review vouchers.

    Science.gov (United States)

    Dimitri, Nicola

    2010-11-01

    Priority review vouchers (PRVs) were introduced in 2007 by the US Congress as an incentive mechanism to spur pharmaceutical firms' R&D efforts for neglected diseases (NDs). A voucher, which a firm can obtain upon approval of a new treatment for NDs, entitles the holder to prioritize the FDA review for any drug. The proposal generated much controversy regarding its ability to effectively stimulate R&D for NDs. Here, after reviewing the main issues of the debate, i use a stylized economic model to discuss the strength of PRVs as an economic incentive to invest in research. My findings suggest that R&D investments might be higher when the developer could prioritize a valuable compound. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. First thoughts on MD priorities for 2012

    CERN Document Server

    Zimmermann, F; Assmann, R

    2012-01-01

    In 2012, 22 days of beam time will be allocated for LHC MDs. In this paper, after recalling the 2011 LHC MD experience, the MD rrequests for 2012 are reviewed. Three primary MD themes for 2012 can be identified: 1)pushing performance in 2012, 2)preparing for 2014/15, and 3)towards maximum luminosity. Example topics include emittance growth in collision or enhanced satellites for theme 1), 25 ns operation for 2), and ATS optics for 3). Structures lists of MD requests and topics for each theme as well as some initial thoughts on the MD priorities are presented. For certain topics, "start-of-fill MDs" are proposed in order to most efficiently use of the available beam time.

  10. Sustainable development: four post-2015 priorities

    International Nuclear Information System (INIS)

    Demailly, Damien; Spinazze, Lena; Treyer, Sebastien

    2016-06-01

    This Policy Brief provides a political agenda for actors engaged in the transformation. It identifies four priority drivers of action to build on the successes of 2015 and to support the progress towards sustainable development: adapting and implementing international commitments in countries; organizing the monitoring of commitments at the international level; encouraging the convergence of signals to bring about a massive investment shift; anticipating social impacts and placing social justice at the center of the transition. This brief is based on analytical work carried out over several months by a committee of practitioners and sustainable development experts, and on discussions involving 150 participants at the international conference 'Sustainable Development: it's time' organized in Paris by IDDRI on May 10-11, 2016

  11. BULGARIAN EMPLOYMENT POLICY: PRIORITIES AND DIRECTIONS 2017

    Directory of Open Access Journals (Sweden)

    Ekaterina Arabska

    2017-04-01

    Full Text Available Development of labor market and employment policy in Bulgaria in contemporary dynamic conditions of social and economic life is in close relation to the European policies and programs and the needs of creating conditions for raising the level of employability of some special target groups on the labor market determined as the most vulnerable and needing particular measures of support. Current study makes analyses of priorities and directions in Bulgarian national employment policy for 2017 as set into the National action plan on employment considering a number of strategic and legislative documents on both national and European level. The general conclusions are focused on the systematization of actions and the importance of social dialogue.

  12. Trends and priorities in internal audit

    Directory of Open Access Journals (Sweden)

    Victoria STANCIU

    2016-09-01

    Full Text Available The status of the internal audit as an important pillar for corporate governance is recognized unanimously; however, this status is gained through a continuous and joined effort of all internal auditors and by a clear and solid vision of the internal audit function’s development, designed by the chief of internal audit. This status recognizes the internal audit’s support for the achievement of company objectives and the improvement of risk management and it also requires continuous quantitative accumulations in the work of internal auditors. From this perspective, the author’s attention focused on the main risks and priorities that the internal audit is facing as they are reflected by international studies and surveys. The conclusions emphasized by the author’s research may be considered important milestones for the improvement of the internal audit function in Romania and for its solid connection to the realities and problems the companies are confronting with.

  13. Stimulus-Responsive Prochelators for Manipulating Cellular Metals

    OpenAIRE

    WANG, QIN; FRANZ, KATHERINE J.

    2016-01-01

    Metal ions are essential for a wide range of physiological processes, but they can also be toxic if not appropriately regulated by a complex network of metal trafficking proteins. Intervention in cellular metal distribution with small molecule or peptide chelating agents has promising therapeutic potential to harness metals to fight disease. Molecular outcomes associated with forming metal-chelate interactions in situ include altering concentration and subcellular metal distribution, inhibiti...

  14. AIRPORTS CLASSIFICATION AND PRIORITY OF THEIR RECONSTRUCTION

    Directory of Open Access Journals (Sweden)

    K. V. Marintseva

    2014-03-01

    Full Text Available Purpose. It is important for Ukraine to have a network of airports, which would promote the current and long-term implementation of air transportation needs of the population and the economics. This study aims to establish criteria of airports classification to determine their role in the development of the air transport system of Ukraine. Methodology. The methods of statistical analysis were used for the processing of data according to categories of airport productivity and geographic information system for data visualization. Findings. It is established that the existing division of Ukrainian airports into international and domestic, as well as into coordinated and non-coordinated ones is not relevant for determining the role of airport in the development of air transport system of the country and accordingly for the priority in financing of their modernization. The approach to the determination of airports classifications using analysis of performance categories was developed. Originality. Classification criterions of the airports in Ukraine are proposed: by type of activity and by the maintenance of scheduled route network. It is proposed to classify the airports by the type of activity to the primary commercial, commercial, cargo primary commercial, cargo commercial and general aviation. According to the scheduled route network maintenane it is proposed to classify the airports as the primary, non-primary and auxiliary hubs. An example of classification by the given criteria is submitted. Practical value. The value of the obtained results is in the possibility of using the proposed classification in the task of determining the priorities for financing the country's airports. As opposed to the practice of directed funding procedure in the framework of the state program of airports development, it is proposed to take into account the fact that the resumption of the functioning of the airport and/or its modernization should be as a response to

  15. Research priorities for occupational radiation protection

    International Nuclear Information System (INIS)

    1994-02-01

    The Subpanel on Occupational Radiation Protection Research concludes that the most urgently needed research is that leading to the resolution of the potential effects of low-level ionizing radiation. This is the primary driving force in setting appropriate radiation protection standards and in directing the emphasis of radiation protection efforts. Much has already been done in collecting data that represents a compendium of knowledge that should be fully reviewed and understood. It is imperative that health physics researchers more effectively use that data and apply the findings to enhance understanding of the potential health effects of low-level ionizing radiation and improve the risk estimates upon which current occupational radiation protection procedures and requirements depend. Research must be focused to best serve needs in the immediate years ahead. Only then will we get the most out of what is accomplished. Beyond the above fundamental need, a number of applied research areas also have been identified as national priority issues. If effective governmental focus is achieved on several of the most important national priority issues, important occupational radiation protection research will be enhanced, more effectively coordinated, and more quickly applied to the work environment. Response in the near term will be enhanced and costs will be reduced by: developing microprocessor-aided open-quotes smartclose quotes instruments to simplify the use and processing of radiation data; developing more sensitive, energy-independent, and tissue-equivalent dosimeters to more accurately quantify personnel dose; and developing an improved risk assessment technology base. This can lead to savings of millions of dollars in current efforts needed to ensure personnel safety and to meet new, more stringent occupational guidelines

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

    Directory of Open Access Journals (Sweden)

    Simon R Knight

    Full Text Available 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

  17. Continuum representations of cellular solids

    Energy Technology Data Exchange (ETDEWEB)

    Neilsen, M.K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  18. PRIORITY BASED PACKET SCHEDULING APPROACH FOR WIRELESS SENSOR NETWORKS

    OpenAIRE

    K. K. Kannan

    2017-01-01

    A priority based packet scheduling scheme is proposed which aims at scheduling different types of data packets, such as real time and non-real-time data packets at sensor nodes with resource constraints in Wireless Sensor Networks. Most of the existing packet-scheduling mechanisms of Wireless Sensor Networks use First Come First Served (FCFS), non-preemptive priority and preemptive priority scheduling algorithms. These algorithms results in long end-to-end data transmission delay, high energy...

  19. 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...

  20. Aging, Cellular Senescence, and Cancer

    Science.gov (United States)

    Campisi, Judith

    2014-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyper-plastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  1. Research priorities for children's nursing in Ireland: a Delphi study.

    Science.gov (United States)

    Brenner, Maria; Hilliard, Carol; Regan, Geraldine; Coughlan, Barbara; Hayden, Sharon; Drennan, Jonathan; Kelleher, Deirdre

    2014-01-01

    This paper is a report of a study which identified research priorities for children's nursing in an acute care setting in Ireland. A limited number of studies have examined research priorities for children's nursing. This study was undertaken against the backdrop of significant proposed changes to the delivery of children's healthcare. A three round Delphi survey design was used to identify and rate the importance of research priorities for children's nursing. In round I participants were asked to identify five of the most important research priorities for children's nursing. Participants in round II were asked to rate the importance of each research priority on a 7-point Likert scale. In round III participants were presented with the mean score of each research priority from the second questionnaire, and again asked to consider the importance of each topic on a 7-point Likert scale. The aim was to reach consensus on the priorities. The top three priorities identified were recognition and care of the deteriorating child, safe transfer of the critically ill child between acute health care facilities, and the child and family's perceptions of care at end-of life. The wide variation of priorities reflects the scope of care delivery of children's nurses and mirrors many global care concerns in caring for children. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. 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....

  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. Cellular structures with interconnected microchannels

    Energy Technology Data Exchange (ETDEWEB)

    Shaefer, Robert Shahram; Ghoniem, Nasr M.; Williams, Brian

    2018-01-30

    A method for fabricating a cellular tritium breeder component includes obtaining a reticulated carbon foam skeleton comprising a network of interconnected ligaments. The foam skeleton is then melt-infiltrated with a tritium breeder material, for example, lithium zirconate or lithium titanate. The foam skeleton is then removed to define a cellular breeder component having a network of interconnected tritium purge channels. In an embodiment the ligaments of the foam skeleton are enlarged by adding carbon using chemical vapor infiltration (CVI) prior to melt-infiltration. In an embodiment the foam skeleton is coated with a refractory material, for example, tungsten, prior to melt infiltration.

  5. Global properties of cellular automata

    International Nuclear Information System (INIS)

    Jen, E.

    1986-01-01

    Cellular automata are discrete mathematical systems that generate diverse, often complicated, behavior using simple deterministic rules. Analysis of the local structure of these rules makes possible a description of the global properties of the associated automata. A class of cellular automata that generate infinitely many aperoidic temporal sequences is defined,a s is the set of rules for which inverses exist. Necessary and sufficient conditions are derived characterizing the classes of ''nearest-neighbor'' rules for which arbitrary finite initial conditions (i) evolve to a homogeneous state; (ii) generate at least one constant temporal sequence

  6. Determination of the priority indexes for the oil refinery wastewater treatment process

    Science.gov (United States)

    Chesnokova, M. G.; Myshlyavtsev, A. V.; Kriga, A. S.; Shaporenko, A. P.; Markelov, V. V.

    2017-08-01

    The wastewater biological treatment intensity and effectiveness are influenced by many factors: temperature, pH, presence and concentration of toxic substances, the biomass concentration et al. Regulation of them allows controlling the biological treatment process. Using the Bayesian theorem the link between changes was determined and the wastewater indexes normative limits exceeding influence for activated sludge characteristics alteration probability was evaluated. The estimation of total, or aposterioric, priority index presence probability, which characterizes the wastewater treatment level, is an important way to use the Bayesian theorem in activated sludge swelling prediction at the oil refinery biological treatment unit.

  7. Give first priority to publicity and education.

    Science.gov (United States)

    1991-12-01

    Commentary is provided on the implementation of China's Three Priorities in strengthening family planning (FP) for population control. The Three Priorities issued by the Party Central Committee of China and the State Council refers to the emphasis on 1) "publicity and education rather than economic disincentives," 2) contraception rather than induced abortion," and 3) "day to day management work rather than irregular campaigns." The expectations are that leaders at all levels should be active, steadfast, patient, and down to earth. Improvements in management lead to more constant, scientific, and systematic FP. Family planning should be voluntary. The achievement is not just population control but better relations with the Party and cadres, which leads to social stability and unity. The directives have been well thought out and are to be resolutely carried out. It was stressed in April 1991 by the General-Secretary and the Premier that coercion would not be tolerated in FP work. The confidence of the masses must be relied upon. The success of FP is guaranteed with the practice of these directives. Constancy of education and publicity is the key work. There should be a strong population awareness and the awareness of available resources/capita, and also an understanding and firm command of the principles and methods of better implementation. FP has an effect both on the fundamental interests of the country and immediate personal interests. The task is expected to be difficult because traditional ideas are still strong. The country is just at the beginning stages of socialism. A social security system is not a reality and farmer's educational attainment is not high. Productivity in the rural areas is underdeveloped. There is a contradiction between childbearing intentions of some farmers and the government requirements of FP. In order for the people to understand government FP policy, painstaking and meticulous education must be carried out to explain why FP is

  8. Active debris removal of multiple priority targets

    Science.gov (United States)

    Braun, Vitali; Lüpken, A.; Flegel, S.; Gelhaus, J.; Möckel, M.; Kebschull, C.; Wiedemann, C.; Vörsmann, P.

    2013-05-01

    Today's space debris environment shows major concentrations of objects within distinct orbital regions for nearly all size regimes. The most critical region is found at orbital altitudes near 800 km with high declinations. Within this region many satellites are operated in so called sun-synchronous orbits (SSO). Among those, there are Earth observation, communication and weather satellites. Due to the orbital geometry in SSO, head-on encounters with relative velocities of about 15 km/s are most probable and would thus result in highly energetic collisions, which are often referred to as catastrophic collisions, leading to the complete fragmentation of the participating objects. So called feedback collisions can then be triggered by the newly generated fragments, thus leading to a further population increase in the affected orbital region. This effect is known as the Kessler syndrome.Current studies show that catastrophic collisions are not a major problem today, but will become the main process for debris generation within the SSO region in the near future, even without any further launches. In order to avoid this effect, objects with a major impact on collisional cascading have to be actively removed from the critical region after their end of life. Not having the capability to perform an end-of-life maneuver in order to transfer to a graveyard orbit or to de-orbit, many satellites and rocket bodies would have to be de-orbited within a dedicated mission. In such a mission, a service satellite would perform a de-orbit maneuver, after having docked to a specific target.In this paper, chemical and electric propulsion systems were analysed with the main focus on removing multiple targets within one single mission. The targets were chosen from a previously defined priority list in order to enhance the mission efficiency. Total mission time, ΔV and system mass were identified as key parameters to allow for an evaluation of the different concepts. It was shown that it

  9. Auxin and Cellular Elongation1

    Science.gov (United States)

    Velasquez, Silvia Melina; Barbez, Elke

    2016-01-01

    Auxin is a crucial growth regulator in plants. However, a comprehensive understanding of how auxin induces cell expansion is perplexing, because auxin acts in a concentration- and cell type-dependent manner. Consequently, it is desirable to focus on certain cell types to exemplify the underlying growth mechanisms. On the other hand, plant tissues display supracellular growth (beyond the level of single cells); hence, other cell types might compromise the growth of a certain tissue. Tip-growing cells do not display neighbor-induced growth constraints and, therefore, are a valuable source of information for growth-controlling mechanisms. Here, we focus on auxin-induced cellular elongation in root hairs, exposing a mechanistic view of plant growth regulation. We highlight a complex interplay between auxin metabolism and transport, steering root hair development in response to internal and external triggers. Auxin signaling modules and downstream cascades of transcription factors define a developmental program that appears rate limiting for cellular growth. With this knowledge in mind, the root hair cell is a very suitable model system in which to dissect cellular effectors required for cellular expansion. PMID:26787325

  10. CELLULAR COMPARTMENTALIZATION AND HEAVY METAL ...

    African Journals Online (AJOL)

    CELLULAR COMPARTMENTALIZATION AND HEAVY METAL LOAD IN THE MOSS. Barbula lambarenensis AROUND A MEGA CEMENT FACTORY IN SOUTHWEST NIGERIA. *. Ogunkunle, C. O. and Fatoba, P. O.. Department of Plant Biology, University of Ilorin .... the free transport of Zn across the cell wall as it.

  11. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN...

  12. Analysis of cellular manufacturing systems

    NARCIS (Netherlands)

    Heragu, Sunderesh; Zijm, Willem H.M.; Meng, Gang; Heragu, S.S.; van Ommeren, Jan C.W.; van Houtum, Geert-Jan

    2001-01-01

    In this paper, we present an open queuing network modeling approach to estimate performance measures of a cellular manufacturing layout. It is assumed a layout and production data for a planning period of specified length are available. The production data takes into account, processing and handling

  13. Cellular Automata and the Humanities.

    Science.gov (United States)

    Gallo, Ernest

    1994-01-01

    The use of cellular automata to analyze several pre-Socratic hypotheses about the evolution of the physical world is discussed. These hypotheses combine characteristics of both rigorous and metaphoric language. Since the computer demands explicit instructions for each step in the evolution of the automaton, such models can reveal conceptual…

  14. Repaglinide at a cellular level

    DEFF Research Database (Denmark)

    Krogsgaard Thomsen, M; Bokvist, K; Høy, M

    2002-01-01

    To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in ra...

  15. Conservation Priority Index for Estuarine Fish (COPIEF)

    Science.gov (United States)

    Branco, Paulo; Costa, José Lino; Raposo de Almeida, Pedro

    2008-12-01

    Public awareness regarding environmental issues has increased in recent decades. The increasing number of impact assessment studies, management and conservation plans, as well as ecological monitoring studies, demand new and more efficient techniques. Indices are an important tool to aid biologists in these studies and should allow an easier comprehension of the data by managers, decision-makers and the general public. This study presents the first multi-metrical index able to establish a hierarchical ordination of the conservation priority of the estuarine fish species using 72 species from 16 estuarine systems (W and S coasts of Portugal). The index is composed of 10 metrics, comprising species life traits, distribution and population trends. The information needed to score each metric was gathered from the published literature and the index validation was done by external means. This methodology allowed the definition of those fish species most in need of conservation planning, and those less prone to extinction in Portuguese estuarine systems. The proposed index fills a gap in our knowledge and provides a useful tool to the scientific community and to the decision-makers, being a breakthrough in the field of conservation planning of estuarine fish species.

  16. Defining Conservation Priorities Using Fragmentation Forecasts

    Directory of Open Access Journals (Sweden)

    David Wear

    2004-12-01

    Full Text Available Methods are developed for forecasting the effects of population and economic growth on the distribution of interior forest habitat. An application to the southeastern United States shows that models provide significant explanatory power with regard to the observed distribution of interior forest. Estimates for economic and biophysical variables are significant and consistent with theory. Forecasts of interior forest based on the population and economic growth projected for the region are displayed by ecological section and province and by metropolitan statistical area (MSA. Loss of interior forests is expected to be especially high in certain ecological sections, including the southern Appalachian Piedmont in North and South Carolina, the Gulf prairies and marshes in Texas, and the Florida coastal lowlands. Sixty-six percent of loss of interior forests will be in urban counties, which highlights the conservation importance of the urbanizing fringe of several cities. Among the ten MSAs that will lose the most interior forest, seven are found in Florida. These forecasts provide a mechanism for assigning priorities and targeting areas for more detailed study and for conservation efforts.

  17. Reducing violent injuries: priorities for pediatrician advocacy.

    Science.gov (United States)

    Dolins, J C; Christoffel, K K

    1994-10-01

    A basic framework for developing an advocacy plan must systematically break down the large task of policy development implementation into manageable components. The basic framework described in detail in this paper includes three steps: Setting policy objectives by narrowing the scope of policy, by reviewing policy options, and by examining options against selected criteria. Developing strategies for educating the public and for approaching legislative/regulatory bodies. Evaluating the effectiveness of the advocacy action plan as a process and as an agent for change. To illustrate the variety of ways in which pediatricians can be involved in the policy process to reduce violent injuries among children and adolescents, we apply this systematic approach to three priority areas. Prohibiting the use of corporal punishment in schools is intended to curb the institutionalized legitimacy of violence that has been associated with future use of violence. Efforts to remove handguns from the environments of children and adolescents are aimed at reducing the numbers of firearm injuries inflicted upon and by minors. Comprehensive treatment of adolescent victims of assault is intended to decrease the reoccurrence of violent injuries.

  18. Making chicken pox prevention a priority.

    Science.gov (United States)

    Domachowske, Joseph B

    2004-01-01

    School nurses are the IDEAL professionals to catch those kids without a history of chicken pox (varicella illness) who have not been immunized, thereby falling into the susceptible range. We handle charts daily. We have both illness history (if it was provided) and immunization dates. We can call parents. We can talk to kids. Wouldn't it be easy if we could do that and then call (or email) the primary care provider? But there is no longer an "easy" way to communicate health information. Doing things the easy way could be perceived by some as "tattling" and by others as "reporting without permission." Instead, the school nurse must take the time-consuming (and better long range) path of education ... of the student, and the parent. And the priority can slip down below other school nurse requirements such as getting kids their required immunizations, first aid and illness care, individualized health care plans for students with medical problems, parent and teacher phone calls, and endless conversations. It takes a village to raise a child though, and the school nurse is a village resident. The following information is vital to the knowledge base of today's school nurse. Please read it, store it and consider it when planning and intervening with your students in the day-to-day interaction that promotes optimal health and wellness.

  19. Life priorities of underachievers in secondary school

    Directory of Open Access Journals (Sweden)

    Gutvajn Nikoleta

    2010-01-01

    Full Text Available There is a predominant belief in literature and school practice that high school achievement is an important precondition for optimal professional development and success in life, as well as that school failure is a problem that should be dealt with preventively. The goal of this paper is to shed light on the problem of school underachievement from the perspective of students who are positioned as underachievers in educational discourse. The following questions are especially important: whether underachievers recognize the importance of high school achievement for success in life, as well as which constructs are the core and which the peripheral ones in their construct system. Research participants were 60 students from the third grade of secondary school who failed three or more subjects during the school year or at the end of classification periods. Interview and Implications Grid were applied in the research. The results indicate that the most important life priorities of students are the following: acceptance by friends, school completion, school success, love and happiness. It was established that the construct acceptance by friends as opposed to rejection by friends is the core construct for success in life in the construct system of underachievers. The paper points out to the importance of appreciation of personal meanings of school achievement and initiation of dialogue between teachers and students in preventing and overcoming school underachievement.

  20. Hydropower development priority using MCDM method

    International Nuclear Information System (INIS)

    Supriyasilp, Thanaporn; Pongput, Kobkiat; Boonyasirikul, Thana

    2009-01-01

    Hydropower is recognized as a renewable and clean energy sources and its potential should be realized in an environmentally sustainable and socially equitable manner. Traditionally, the decision criteria when analyzing hydropower projects, have been mostly a technical and economical analysis which focused on the production of electricity. However, environmental awareness and sensitivity to locally affected people should also be considered. Multi-criteria decision analysis has been applied to study the potential to develop hydropower projects with electric power greater than 100 kW in the Ping River Basin, Thailand, and to determine the advantages and disadvantages of the projects in five main criteria: electricity generation, engineering and economics, socio-economics, environment, and stakeholder involvement. There are 64 potential sites in the study area. Criteria weights have been discussed and assigned by expert groups for each main criteria and subcriteria. As a consequence of weight assignment, the environmental aspect is the most important aspect in the view of the experts. Two scenarios using expert weight and fair weight have been studied to determine the priority for development of each project. This study has been done to assist policy making for hydropower development in the Ping River Basin.

  1. Which PUB objectives in Africa? Which priorities?

    Science.gov (United States)

    Karambiri, H.

    2003-04-01

    Today, the international co-operation in Africa is in crisis. A crisis due first to the deep world socio-economic upheavals which led to a reduction in public aid to development in the poor countries, and secondly to the revision of cooperation politics of developed countries which resulted in a progressive withdrawal of foreign institutions of research in many LDC. National governments no longer have means, nor necessary competences to ensure the follow-up and the maintenance of measurements networks; in addition, they are more and more withdrawing from research projects in Hydrology, to give priority to more sensitive sectors such as education, health, fight against hunger, etc…In this situation, what can be the role of PUB? We heard much speaking about LDC throughout PUB mission statement. Is this a lobbying to acquire financings from international institutions or a real willpower to solve crucial water problems of these countries and help them to wake up from their deep scientific sleep? PUB must promote a harmonious, a constant and a sustainable development of LDC populations, especially in Africa. This development must be done by the "bottom". It must be based on the expression of endogenous needs and a participative concerted approach. It is only in this way that PUB will be able to distinguish itself from other existing programs. The concept of "capacity building" has not to be the tree hiding the forest. It has to become a reality, which is daily lived and thought.

  2. Hydropower development priority using MCDM method

    Energy Technology Data Exchange (ETDEWEB)

    Supriyasilp, Thanaporn [Department of Civil Engineering, Chiang Mai University, Chiang Mai 50200 (Thailand); Pongput, Kobkiat [Department of Water Resource Engineering, Kasetsart University, Bangkhen Campus, Bangkok 10900 (Thailand); Boonyasirikul, Thana [Electricity Generating Authority of Thailand, Bang Kruai, Nonthaburi 11130 (Thailand)

    2009-05-15

    Hydropower is recognized as a renewable and clean energy sources and its potential should be realized in an environmentally sustainable and socially equitable manner. Traditionally, the decision criteria when analyzing hydropower projects, have been mostly a technical and economical analysis which focused on the production of electricity. However, environmental awareness and sensitivity to locally affected people should also be considered. Multi-criteria decision analysis has been applied to study the potential to develop hydropower projects with electric power greater than 100 kW in the Ping River Basin, Thailand, and to determine the advantages and disadvantages of the projects in five main criteria: electricity generation, engineering and economics, socio-economics, environment, and stakeholder involvement. There are 64 potential sites in the study area. Criteria weights have been discussed and assigned by expert groups for each main criteria and subcriteria. As a consequence of weight assignment, the environmental aspect is the most important aspect in the view of the experts. Two scenarios using expert weight and fair weight have been studied to determine the priority for development of each project. This study has been done to assist policy making for hydropower development in the Ping River Basin. (author)

  3. Cardinal priority ranking based decision making for economic ...

    African Journals Online (AJOL)

    To access the indifference band, interaction with the decision maker is obtained via cardinal priority ranking (CPR) of the objectives. The cardinal priority ranking is ... The validity of the proposed method is demonstrated on IEEE 11-bus system which comprises 3-generators. Keywords: Economic emission dispatch; fuzzy ...

  4. Beyond Dead Reckoning: Research Priorities for Redirecting American Higher Education.

    Science.gov (United States)

    Wegner, Gregory R., Ed.

    This essay identifies a set of research priorities that will enable those most responsible for U.S. higher education to shape the enterprise in more purposeful ways. The present discrepancy between ideals and realities makes it evident that higher education is less than it should be. The essay identifies three broad research priorities: (1)…

  5. 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.…

  6. 12 CFR 709.5 - Payout priorities in involuntary liquidation.

    Science.gov (United States)

    2010-01-01

    .... 709.5 Section 709.5 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING..., severance, and sick leave pay; (3) Taxes legally due and owing to the United States or any state or... or class with higher priority, make such distributions to claimants in priority categories described...

  7. 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.)

  8. 76 FR 32980 - Telecommunications Service Priority (TSP) System

    Science.gov (United States)

    2011-06-07

    ... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2011-0043] Telecommunications Service Priority... INFORMATION: The purpose of the TSP System is to provide a legal basis for telecommunications vendors to provide priority provisioning and restoration of telecommunications services supporting national security...

  9. 47 CFR 80.91 - Order of priority of communications.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Order of priority of communications. 80.91 Section 80.91 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO...-General § 80.91 Order of priority of communications. (a) All stations in the maritime mobile service and...

  10. 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 ...

  11. 49 CFR 38.75 - Priority seating signs.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Priority seating signs. 38.75 Section 38.75 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES Light Rail Vehicles and Systems § 38.75 Priority seating signs. (a) Each vehicle shall contain sign(s)...

  12. Effects of threat management interactions on conservation priorities.

    Science.gov (United States)

    Auerbach, Nancy A; Wilson, Kerrie A; Tulloch, Ayesha I T; Rhodes, Jonathan R; Hanson, Jeffrey O; Possingham, Hugh P

    2015-12-01

    Decisions need to be made about which biodiversity management actions are undertaken to mitigate threats and about where these actions are implemented. However, management actions can interact; that is, the cost, benefit, and feasibility of one action can change when another action is undertaken. There is little guidance on how to explicitly and efficiently prioritize management for multiple threats, including deciding where to act. Integrated management could focus on one management action to abate a dominant threat or on a strategy comprising multiple actions to abate multiple threats. Furthermore management could be undertaken at sites that are in close proximity to reduce costs. We used cost-effectiveness analysis to prioritize investments in fire management, controlling invasive predators, and reducing grazing pressure in a bio-diverse region of southeastern Queensland, Australia. We compared outcomes of 5 management approaches based on different assumptions about interactions and quantified how investment needed, benefits expected, and the locations prioritized for implementation differed when interactions were taken into account. Managing for interactions altered decisions about where to invest and in which actions to invest and had the potential to deliver increased investment efficiency. Differences in high priority locations and actions were greatest between the approaches when we made different assumptions about how management actions deliver benefits through threat abatement: either all threats must be managed to conserve species or only one management action may be required. Threatened species management that does not consider interactions between actions may result in misplaced investments or misguided expectations of the effort required to mitigate threats to species. © 2015 The Authors. Conservation Biology published by Wiley Periodicals, Inc., on behalf of Society for Conservation Biology.

  13. 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...... 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.......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...

  14. 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.

  15. Decentralized health care priority-setting in Tanzania

    DEFF Research Database (Denmark)

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

    2010-01-01

    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......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...... not satisfy all four conditions of Accountability for Reasonableness; namely relevance, publicity, appeals and revision, and enforcement. This paper aims to make two important contributions to this problematic situation. First, it provides empirical analysis of priority-setting at the district level...

  16. 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

  17. Short communication: high cellular iron levels are associated with increased HIV infection and replication.

    Science.gov (United States)

    Chang, Hsiang-Chun; Bayeva, Marina; Taiwo, Babafemi; Palella, Frank J; Hope, Thomas J; Ardehali, Hossein

    2015-03-01

    HIV is a pandemic disease, and many cellular and systemic factors are known to alter its infectivity and replication. Earlier studies had suggested that anemia is common in HIV-infected patients; however, higher iron was also observed in AIDS patients prior to the introduction of antiretroviral therapy (ART). Therefore, the relationship between iron and viral infection is not well delineated. To address this issue, we altered the levels of cellular iron in primary CD4(+) T cells and showed that higher iron is associated with increased HIV infection and replication. In addition, HIV infection alone leads to increased cellular iron, and several ART drugs increase cellular iron independent of HIV infection. Finally, HIV infection is associated with increased serum iron in HIV-positive patients regardless of treatment with ART. These results establish a relationship between iron and HIV infection and suggest that iron homeostasis may be a viable therapeutic target for HIV.

  18. Safe Motherhood Initiative: getting our priorities straight.

    Science.gov (United States)

    Sai, F T; Measham, D M

    1992-02-22

    Developing countries, nongovernmental organizations, and the international development community support the Safe Motherhood Initiative. These partners know why they need to take action to assure safe motherhood, but do not agree on how to make motherhood safe. The dominant view is that the 1st priority is to provide and/or improve needed obstetric care at the 1st referral level and manage complications once they occur. It is based on the fact that the medical community cannot yet identify most women with pregnancy complications in time to prevent their occurrence. 2 safe motherhood advocates challenge this view. They point out that it only centers on reducing maternal mortality. 2nd they believe that prenatal care and health education do play a strategic role in making motherhood safe because they can inform, motivate, and empower women to use formal emergency care services. 3rd health workers should not dismiss prenatal care since some interventions are indeed effective, e.g., prevention, detection, and investigation of anemia and hypertensive disease of pregnancy and prevention and treatment of sexually transmitted diseases. Finally some areas in developing countries do not have the resources to establish or upgrade referral level health facilities so they must maximize existing resources to intervene and treat complications such as training midwives, nurses, and traditional birth attendants. The advocates propose 3 tired strategies to bring about safe motherhood. The provision of prenatal care, trained attendance at delivery, accessible emergency services, and family planning and abortion services comprise the 1st tier. The 2nd tier of activities targets youth. These activities include sexual and reproductive health programs, education, female employment opportunities, and legislation on age of marriage. The 3rd tier embraces all factors that influence women's health and status: sexual and reproductive health, education, income, social and cultural practices

  19. [Determination of priority unfavorable environmental factors].

    Science.gov (United States)

    Zaikova, Z A; Burdukovskaya, A V; Belykh, A I

    In the Irkutsk region there are recorded high indices of rates of morbidity, disability, mortality rate of the working-age population and low levels of life expectancy of the population, that is confirmed by ranking position levels among the all subjects of the Russian Federation. According to all mentioned indices of health the region is inside the top ten unfavorable regions of Russia. In relation to the problem in the state of health of the adult population the estimation of the causal relationships between environmental factors and certain health indices is actual. The list of studiedfactors included health indices that characterize the harmful working conditions of the working population and basic socioeconomic indices in the region. Estimation of causal-relationship relationships was performed with the use of methods of multivariate analysis - correlation and multiple linear regression. In the selection offactors for the construction of mathematical models of multiple regression there were used methods of the analysis of variables variability, pair correlation coefficients matrix and sequential switching covariates to eliminate the problems of multicollinearity, pre-standardization of indices for the elevation of the numerical stability of regression analysis algorithm. As a result of the execution of the analysis there were constructed statistical models for the dependence in the system variables “environment - public health”, which allowed to identify the most informative regression models for the adult population health according to indices of primary disability of the population, the mortality rate and life expectancy of the working age population. According to results of the analysis there were identified priority factors affecting on the health of the adult population of the Irkutsk region. To these factors there are referred the proportion of workplaces failing to meet sanitary standards for vibration and 8 socio-economic indices of living

  20. 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

  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

    In the effort to address the persistent organ shortage it is sometimes suggested that we should incentivize people to sign up as organ donors. One way of doing so is to give priority in the allocation of organs to those who are themselves registered as donors. Israel introduced such a scheme...... 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...

  2. Reduced cellular immune reactivity in healthy individuals during the malaria transmission season

    DEFF Research Database (Denmark)

    Theander, T G; Hviid, L; Abu-Zeid, Y A

    1990-01-01

    Antigen-induced cellular immune responses are suppressed during acute malaria. The present study engages the possibility that malaria-induced alterations in cellular immune reactivity extend beyond the clinical disease. Thus, lymphoproliferative responses of healthy individuals were diminished du...... during the malaria transmission period in individuals living in an area of highly seasonal, unstable malaria transmission. This finding may have important implications for the design of studies of stimulatory properties of antigens using lymphocytes of endemic origin....

  3. Universal map for cellular automata

    International Nuclear Information System (INIS)

    García-Morales, V.

    2012-01-01

    A universal map is derived for all deterministic 1D cellular automata (CAs) containing no freely adjustable parameters and valid for any alphabet size and any neighborhood range (including non-symmetrical neighborhoods). The map can be extended to an arbitrary number of dimensions and topologies and to arbitrary order in time. Specific CA maps for the famous Conway's Game of Life and Wolfram's 256 elementary CAs are given. An induction method for CAs, based in the universal map, allows mathematical expressions for the orbits of a wide variety of elementary CAs to be systematically derived. -- Highlights: ► A universal map is derived for all deterministic 1D cellular automata (CA). ► The map is generalized to 2D for Von Neumann, Moore and hexagonal neighborhoods. ► A map for all Wolfram's 256 elementary CAs is derived. ► A map for Conway's “Game of Life” is obtained.

  4. 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.

  5. Cellular Adhesion and Adhesion Molecules

    OpenAIRE

    SELLER, Zerrin

    2014-01-01

    In recent years, cell adhesion and cell adhesion molecules have been shown to be important for many normal biological processes, including embryonic cell migration, immune system functions and wound healing. It has also been shown that they contribute to the pathogenesis of a large number of common human disorders, such as rheumatoid arthritis and tumor cell metastasis in cancer. In this review, the basic mechanisms of cellular adhesion and the structural and functional features of adhes...

  6. Aging, Cellular Senescence, and Cancer

    OpenAIRE

    Campisi, Judith

    2012-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses ...

  7. Cellular automata with voting rule

    International Nuclear Information System (INIS)

    Makowiec, D.

    1996-01-01

    The chosen local interaction - the voting (majority) rule applied to the square lattice is known to cause the non ergodic cellular automata behaviour. Presented computer simulation results verify two cases of non ergodicity. The first one is implicated by the noise introduced to the local interactions and the second one follows properties of the initial lattice configuration selected at random. For the simplified voting rule - non symmetric voting, the critical behaviour has been explained rigorously. (author)

  8. 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.

  9. Global priorities for conservation across multiple dimensions of mammalian diversity.

    Science.gov (United States)

    Brum, Fernanda T; Graham, Catherine H; Costa, Gabriel C; Hedges, S Blair; Penone, Caterina; Radeloff, Volker C; Rondinini, Carlo; Loyola, Rafael; Davidson, Ana D

    2017-07-18

    Conservation priorities that are based on species distribution, endemism, and vulnerability may underrepresent biologically unique species as well as their functional roles and evolutionary histories. To ensure that priorities are biologically comprehensive, multiple dimensions of diversity must be considered. Further, understanding how the different dimensions relate to one another spatially is important for conservation prioritization, but the relationship remains poorly understood. Here, we use spatial conservation planning to ( i ) identify and compare priority regions for global mammal conservation across three key dimensions of biodiversity-taxonomic, phylogenetic, and traits-and ( ii ) determine the overlap of these regions with the locations of threatened species and existing protected areas. We show that priority areas for mammal conservation exhibit low overlap across the three dimensions, highlighting the need for an integrative approach for biodiversity conservation. Additionally, currently protected areas poorly represent the three dimensions of mammalian biodiversity. We identify areas of high conservation priority among and across the dimensions that should receive special attention for expanding the global protected area network. These high-priority areas, combined with areas of high priority for other taxonomic groups and with social, economic, and political considerations, provide a biological foundation for future conservation planning efforts.

  10. 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

  11. 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

  12. 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.

  13. Democracy and environment: Rethinking our educational priorities

    Science.gov (United States)

    Goodlad, Stephen John

    Two groups of scholars have recently pined prominence. Both are concerned about what is taught in America's schools and how it is taught. One group is focused on the need to strengthen a democracy they see as weakening and under attack. A second is concerned about an impending ecological catastrophe. These two concerns are often regarded as separate, unrelated, even conflicting. This paper argues that democracy and environmental issues actually have much in common; that both are fundamentally concerned with relationships and both are threatened in similar ways, for similar reasons. Moreover, if fully and property understood, these two crises can be recognized as mere symptoms of a much deeper crisis of modern, industrialized cultures, which are defined as vast, paradigmatic "super-cultures" that share enough in common that they can be seen as unique in their own right. To address this cultural crisis will require deliberate, widespread intervention. This intervention should begin in our public schools: first, because a major purpose of public education is enculturation. Second, educators have moral and ethical obligations that suggest that such intervention is justified, perhaps even imperative. If public education is to play a proactive role in our cultural evolution, sweeping curricular and pedagogical reforms will be necessary. Cultural issues cannot be separated from other aspects of a curriculum, or set aside as a separate discipline. Therefore fundamental curricular and pedagogical changes will need to be made throughout the entire educational system. Democracy (how we interact with one another) and environment (how we interact with the world around us) ought to form the foundational priorities on which all such reforms rest. An undertaking of this magnitude will encounter a great many obstacles. Some of the most prominent of those obstacles are assessed and serve as broad indicators of certain key areas in which reform efforts might be initiated. Finally

  14. 78 FR 7439 - Proposed Alterations to Pawtucket Dam on the Merrimack River in Lowell, MA; Public Meeting

    Science.gov (United States)

    2013-02-01

    ... PRESERVATION Proposed Alterations to Pawtucket Dam on the Merrimack River in Lowell, MA; Public Meeting AGENCY..., regarding proposed alterations to Pawtucket Dam on the Merrimack River in Lowell, MA. SUMMARY: The Federal... consulting parties, and notifying the public. Priority for speaking at the public meeting will be given to...

  15. An International Perspective on Real Estate Research Priorities

    OpenAIRE

    Newell, Graeme; Worzala, Elaine; McAllister, Patrick; Schulte, Karl-Werner

    2004-01-01

    Surveys of real estate research priorities for real estate fund managers in the United States, United Kingdom, Australia and Germany over 2000–03 are examined. Thirty-nine real estate research priorities are assessed, with much closer alignment forreal estate research priorities in the U.K., Germany and Australia than seen for the U.S. The role of real estate in a mixed-asset portfolio and real estate and portfolio risk management figure prominently amongst the general real estate research pr...

  16. 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.

  17. Bacterial Cellular Engineering by Genome Editing and Gene Silencing

    Directory of Open Access Journals (Sweden)

    Nobutaka Nakashima

    2014-02-01

    Full Text Available Genome editing is an important technology for bacterial cellular engineering, which is commonly conducted by homologous recombination-based procedures, including gene knockout (disruption, knock-in (insertion, and allelic exchange. In addition, some new recombination-independent approaches have emerged that utilize catalytic RNAs, artificial nucleases, nucleic acid analogs, and peptide nucleic acids. Apart from these methods, which directly modify the genomic structure, an alternative approach is to conditionally modify the gene expression profile at the posttranscriptional level without altering the genomes. This is performed by expressing antisense RNAs to knock down (silence target mRNAs in vivo. This review describes the features and recent advances on methods used in genomic engineering and silencing technologies that are advantageously used for bacterial cellular engineering.

  18. 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.

  19. Cellular-based sea level gauge

    Digital Repository Service at National Institute of Oceanography (India)

    Desai, R.G.P.; Joseph, A.

    -speed data transfer and near real-time data reporting. While satellite communication is expensive, wireless communication infrastructure and the ubiquity of cellular phones have made cellular communication affordable. Low initial and recurring costs...

  20. [Cellular subcutaneous tissue. Anatomic observations].

    Science.gov (United States)

    Marquart-Elbaz, C; Varnaison, E; Sick, H; Grosshans, E; Cribier, B

    2001-11-01

    We showed in a companion paper that the definition of the French "subcutaneous cellular tissue" considerably varied from the 18th to the end of the 20th centuries and has not yet reached a consensus. To address the anatomic reality of this "subcutaneous cellular tissue", we investigated the anatomic structures underlying the fat tissue in normal human skin. Sixty specimens were excised from the surface to the deep structures (bone, muscle, cartilage) on different body sites of 3 cadavers from the Institut d'Anatomie Normale de Strasbourg. Samples were paraffin-embedded, stained and analysed with a binocular microscope taking x 1 photographs. Specimens were also excised and fixed after subcutaneous injection of Indian ink, after mechanic tissue splitting and after performing artificial skin folds. The aspects of the deep parts of the skin greatly varied according to their anatomic localisation. Below the adipose tissue, we often found a lamellar fibrous layer which extended from the interlobular septa and contained horizontally distributed fat cells. No specific tissue below the hypodermis was observed. Artificial skin folds concerned either exclusively the dermis, when they were superficial or included the hypodermis, but no specific structure was apparent in the center of the fold. India ink diffused to the adipose tissue, mainly along the septa, but did not localise in a specific subcutaneous compartment. This study shows that the histologic aspects of the deep part of the skin depend mainly on the anatomic localisation. Skin is composed of epidermis, dermis and hypodermis and thus the hypodermis can not be considered as being "subcutaneous". A difficult to individualise, fibrous lamellar structure in continuity with the interlobular septa is often found under the fat lobules. This structure is a cleavage line, as is always the case with loose connective tissues, but belongs to the hypodermis (i.e. fat tissue). No specific tissue nor any virtual space was

  1. 76 FR 29083 - Agriculture Priorities and Allocations System

    Science.gov (United States)

    2011-05-19

    ... or earthquake. In most cases, there is likely to be no economic impact in filling priority orders...; Develop awareness and early warning capabilities to recognize threats; Mitigate vulnerabilities at...

  2. Health Resources Priority and Allocations System (HRPAS). Interim final rule.

    Science.gov (United States)

    2015-07-17

    This interim final rule establishes standards and procedures by which the U.S. Department of Health and Human Services (HHS) may require that certain contracts or orders that promote the national defense be given priority over other contracts or orders. This rule also sets new standards and procedures by which HHS may allocate materials, services, and facilities to promote the national defense. This rule will implement HHS's administration of priorities and allocations actions, and establish the Health Resources Priorities and Allocation System (HRPAS). The HRPAS will cover health resources pursuant to the authority under Section 101(c) of the Defense Production Act as delegated to HHS by Executive Order 13603. Priorities authorities (and other authorities delegated to the Secretary in E.O. 13603, but not covered by this regulation) may be re-delegated by the Secretary. The Secretary retains the authority for allocations.

  3. Coordination of IVI and transit signal priority on transit evacuations.

    Science.gov (United States)

    2011-02-01

    During an emergency evacuation, execution time is always critical to the evacuees who are : transit dependent. Transit Signal Priority (TSP) can speed up the transit services by prioritizing : the approaching bus at a signalized intersection. With th...

  4. Reconciling food security and bioenergy : Priorities for action

    NARCIS (Netherlands)

    Kline, Keith L.; Msangi, Siwa; Dale, Virginia H.; Woods, Jeremy; Souza, Glaucia m.; Osseweijer, P.; Clancy, Joy S.; Hilbert, Jorge A.; Johnson, Francis X.; Mcdonnell, Patrick C.; Mugera, Harriet K.

    Understanding the complex interactions among food security, bioenergy sustainability, and resource management requires a focus on specific contextual problems and opportunities. The United Nations' 2030 Sustainable Development Goals place a high priority on food and energy security; bioenergy

  5. China Dimensions Data Collection: Priority Programme for China's Agenda 21

    Data.gov (United States)

    National Aeronautics and Space Administration — Priority Programme for China's Agenda 21 consists of full-text program descriptions supporting China's economic and social development. The descriptions represent 69...

  6. 40 CFR 300.425 - Establishing remedial priorities.

    Science.gov (United States)

    2010-07-01

    ... CONTINGENCY PLAN Hazardous Substance Response § 300.425 Establishing remedial priorities. (a) General. The... Ranking System described in appendix A to this part. (2) A state (not including Indian tribes) has...

  7. 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...... cancer treatment, where patients are transitioning to survivorship, might be a vulnerable time. Uncertainty about health status, physical- and emotional symptoms from cancer disease and treatment, and perhaps uncertainty about which doctor to consult, might influence patients’ priorities and attention...... 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...

  8. Global climate change adaptation priorities for biodiversity and food security.

    Directory of Open Access Journals (Sweden)

    Lee Hannah

    Full Text Available International policy is placing increasing emphasis on adaptation to climate change, including the allocation of new funds to assist adaptation efforts. Climate change adaptation funding may be most effective where it meets integrated goals, but global geographic priorities based on multiple development and ecological criteria are not well characterized. Here we show that human and natural adaptation needs related to maintaining agricultural productivity and ecosystem integrity intersect in ten major areas globally, providing a coherent set of international priorities for adaptation funding. An additional seven regional areas are identified as worthy of additional study. The priority areas are locations where changes in crop suitability affecting impoverished farmers intersect with changes in ranges of restricted-range species. Agreement among multiple climate models and emissions scenarios suggests that these priorities are robust. Adaptation funding directed to these areas could simultaneously address multiple international policy goals, including poverty reduction, protecting agricultural production and safeguarding ecosystem services.

  9. Global climate change adaptation priorities for biodiversity and food security.

    Science.gov (United States)

    Hannah, Lee; Ikegami, Makihiko; Hole, David G; Seo, Changwan; Butchart, Stuart H M; Peterson, A Townsend; Roehrdanz, Patrick R

    2013-01-01

    International policy is placing increasing emphasis on adaptation to climate change, including the allocation of new funds to assist adaptation efforts. Climate change adaptation funding may be most effective where it meets integrated goals, but global geographic priorities based on multiple development and ecological criteria are not well characterized. Here we show that human and natural adaptation needs related to maintaining agricultural productivity and ecosystem integrity intersect in ten major areas globally, providing a coherent set of international priorities for adaptation funding. An additional seven regional areas are identified as worthy of additional study. The priority areas are locations where changes in crop suitability affecting impoverished farmers intersect with changes in ranges of restricted-range species. Agreement among multiple climate models and emissions scenarios suggests that these priorities are robust. Adaptation funding directed to these areas could simultaneously address multiple international policy goals, including poverty reduction, protecting agricultural production and safeguarding ecosystem services.

  10. Translating international HIV treatment guidelines into local priorities in Indonesia

    NARCIS (Netherlands)

    N. Tromp; Prawiranegara, R. (Rozar); Siregar, A. (Adiatma); R. Wisaksana (Rudi); Pinxten, L. (Lucas); Pinxten, J. (Juul); Lesmana Putra, A. (Arry); Kurnia Sunjaya, D. (Deni); Jansen, M. (Maarten); J.A.C. Hontelez (Jan); Maurits, S. (Scott); Maharani, F. (Febrina); Bijlmakers, L. (Leon); R. Baltussen (R.)

    2018-01-01

    textabstractObjective: International guidelines recommend countries to expand antiretroviral therapy (ART) to all HIV-infected individuals and establish local-level priorities in relation to other treatment, prevention and mitigation interventions through fair processes. However, no practical

  11. Science and Technology Policies and Priorities: A Comparative Analysis.

    Science.gov (United States)

    Lederman, Leonard L.

    1987-01-01

    Compares the science and technology strategies and priorities of France, Germany, Japan, Sweden, the United Kingdom, and the United States. Analyzes the similarities and differences, historical settings, research and development allocations, coordinating mechanisms, outputs, dissatisfactions, and recent changes. (TW)

  12. Probabilistic inversion in priority setting of emerging zoonoses.

    NARCIS (Netherlands)

    Kurowicka, D.; Bucura, C.; Cooke, R.; Havelaar, A.H.

    2010-01-01

    This article presents methodology of applying probabilistic inversion in combination with expert judgment in priority setting problem. Experts rank scenarios according to severity. A linear multi-criteria analysis model underlying the expert preferences is posited. Using probabilistic inversion, a

  13. Book Review: Putting People First: African Priorities for the UN ...

    African Journals Online (AJOL)

    Abstract. Book Title: Putting People First: African Priorities for the UN Millennium Assembly (2000). Authors: Pandelani Mathoma, Greg Mills, John Stremlau (eds.) Johannesburg: South African Institute of International Affairs, 129 pp.

  14. Cellular automata a parallel model

    CERN Document Server

    Mazoyer, J

    1999-01-01

    Cellular automata can be viewed both as computational models and modelling systems of real processes. This volume emphasises the first aspect. In articles written by leading researchers, sophisticated massive parallel algorithms (firing squad, life, Fischer's primes recognition) are treated. Their computational power and the specific complexity classes they determine are surveyed, while some recent results in relation to chaos from a new dynamic systems point of view are also presented. Audience: This book will be of interest to specialists of theoretical computer science and the parallelism challenge.

  15. Early assembly of cellular life.

    Science.gov (United States)

    Trevors, J T

    2003-04-01

    Popular hypotheses that attempt to explain the origin of prebiotic molecules and cellular life capable of growth and division are not always agreed upon. In this manuscript, information on early bacterial life on Earth is examined using information from several disciplines. For example, knowledge can be integrated from physics, thermodynamics, planetary sciences, geology, biogeochemistry, lipid chemistry, primordial cell structures, cell and molecular biology, microbiology, metabolism and genetics. The origin of life also required a combination of elements, compounds and environmental physical-chemical conditions that allowed cells to assemble in less than a billion years. This may have been widespread in the subsurface of the early Earth located at microscopic physical domains.

  16. 'Biomoleculas': cellular metabolism didactic software

    International Nuclear Information System (INIS)

    Menghi, M L; Novella, L P; Siebenlist, M R

    2007-01-01

    'Biomoleculas' is a software that deals with topics such as the digestion, cellular metabolism and excretion of nutrients. It is a pleasant, simple and didactic guide, made by and for students. In this program, each biomolecule (carbohydrates, lipids and proteins) is accompanied until its degradation and assimilation by crossing and interrelating the different metabolic channels to finally show the destination of the different metabolites formed and the way in which these are excreted. It is used at present as a teaching-learning process tool by the chair of Physiology and Biophysics at the Facultad de Ingenieria - Universidad Nacional de Entre Rios

  17. Game of Life Cellular Automata

    CERN Document Server

    Adamatzky, Andrew

    2010-01-01

    In the late 1960s, British mathematician John Conway invented a virtual mathematical machine that operates on a two-dimensional array of square cell. Each cell takes two states, live and dead. The cells' states are updated simultaneously and in discrete time. A dead cell comes to life if it has exactly three live neighbours. A live cell remains alive if two or three of its neighbours are alive, otherwise the cell dies. Conway's Game of Life became the most programmed solitary game and the most known cellular automaton. The book brings together results of forty years of study into computational

  18. Symmetry analysis of cellular automata

    International Nuclear Information System (INIS)

    García-Morales, V.

    2013-01-01

    By means of B-calculus [V. García-Morales, Phys. Lett. A 376 (2012) 2645] a universal map for deterministic cellular automata (CAs) has been derived. The latter is shown here to be invariant upon certain transformations (global complementation, reflection and shift). When constructing CA rules in terms of rules of lower range a new symmetry, “invariance under construction” is uncovered. Modular arithmetic is also reformulated within B-calculus and a new symmetry of certain totalistic CA rules, which calculate the Pascal simplices modulo an integer number p, is then also uncovered.

  19. 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.

  20. Protein accounting in the cellular economy.

    Science.gov (United States)

    Vázquez-Laslop, Nora; Mankin, Alexander S

    2014-04-24

    Knowing the copy number of cellular proteins is critical for understanding cell physiology. By being able to measure the absolute synthesis rates of the majority of cellular proteins, Li et al. gain insights into key aspects of translation regulation and fundamental principles of cellular strategies to adjust protein synthesis according to the functional needs. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Zeno's paradox in quantum cellular automata

    International Nuclear Information System (INIS)

    Groessing, G.; Zeilinger, A.

    1991-01-01

    The effect of Zeno's paradox in quantum theory is demonstrated with the aid of quantum mechanical cellular automata. It is shown that the degree of non-unitarity of the cellular automaton evolution and the frequency of consecutive measurements of cellular automaton states are operationally indistinguishable. (orig.)

  2. Social values in health priority setting: a conceptual framework.

    Science.gov (United States)

    Clark, Sarah; Weale, Albert

    2012-01-01

    It is commonly recognized that the setting of health priorities requires value judgements and that these judgements are social. Justifying social value judgements is an important element in any public justification of how priorities are set. The purpose of this paper is to review a number of social values relating both to the process and content of priority-setting decisions. A set of key process and content values basic to health priority setting is outlined, and normative analysis applied to those values to identify their key features, possible interpretations in different cultural and institutional contexts, and interactions with other values. Process values are found to be closely linked, such that success in increasing, for example, transparency may depend on increasing participation or accountability, and "content" values are found often to be hidden in technical criteria. There is a complex interplay between value and technical components of priority setting, and between process and content values. Levels of economic development, culture and need will all play a part in determining how different systems balance the values in their decisions. Technical analyses of health priority setting are commonplace, but approaching the issues from the perspective of social values is a more recent approach and one which this paper seeks to refine and develop.

  3. 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.

  4. 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.

  5. 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.

  6. Radiation protection philosophy alters

    International Nuclear Information System (INIS)

    Firmin, G.

    1977-01-01

    Two significant events that have taken place this year in the field of radiation protection are reported. New SI units have been proposed (and effectively adopted), and the ICRP has revised its recommendations. Changes of emphasis in the latest recommendations (ICRP Publication 26) imply an altered radiation protection philosophy, in particular the relation of dose limits to estimates of average risk, an altered view of the critical organ approach and a new attitude to genetic dose to the population. (author)

  7. 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.

  8. 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.

  9. Functional and cellular adaptations of rodent skeletal muscle to weightlessness

    Science.gov (United States)

    Caiozzo, Vincent J.; Haddad, Fadia; Baker, Michael J.; Baldwin, Kenneth M.

    1995-01-01

    This paper describes the affects of microgravity upon three key cellular levels (functional, protein, and mRNA) that are linked to one another. It is clear that at each of these levels, microgravity produces rapid and substantial alterations. One of the key challenges facing the life science community is the development of effective countermeasures that prevent the loss of muscle function as described in this paper. The development of optimal countermeasures, however, awaits a clearer understanding of events occurring at the levels of transcription, translation, and degradation.

  10. Cellular monosaccharide patterns of Neisseriaceae.

    Science.gov (United States)

    Jantzen, E; Bryn, K; Bovre, K

    1976-08-01

    Sixty-four strains of Neisseria, Moraxella, and Acinetobacter were screened for cellular monosaccharides by gas-liquid chromatography and other chromatographic techniques. The four sugars ribose, glucose, glucosamine, and 2-keto-3-deoxyoctonate (KDO) were detected in all strains. Heptose was detected only in "true neisseriae" (Neisseria gonorrhoeae, N. meningitidis, N. sicca, N. cinerea, N. flavescens, and N. elongata) and in the tentaively named species Moraxella urethralis. Some marked interspecies dissimilarities within groups were revealed. Thus, N. ovis and M. atlantae were characterized by the presence of mannose. Intraspecies differences were also encountered. N. meningitidis strains of serogroups B and C were distinguished from strains of serogroup A by their sialic acid content. This sugar was also detected in two out of three examined strains of M. nonliquefaciens. In Acinetobacter, heterogeneity of monosaccharide patterns was rather pronounced. The results show the applicability of gas chromatographic "monosaccharide" profiles fo whole cells or extracted carbohydrate in bacterial classification and identification, including differentiation at the subspecies level. In addition, such profiles may be useful for monitoring during purification of cellular polysaccharides.

  11. Melanoma screening with cellular phones.

    Directory of Open Access Journals (Sweden)

    Cesare Massone

    Full Text Available BACKGROUND: Mobile teledermatology has recently been shown to be suitable for teledermatology despite limitations in image definition in preliminary studies. The unique aspect of mobile teledermatology is that this system represents a filtering or triage system, allowing a sensitive approach for the management of patients with emergent skin diseases. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the feasibility of teleconsultation using a new generation of cellular phones in pigmented skin lesions. 18 patients were selected consecutively in the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, Graz (Austria. Clinical and dermoscopic images were acquired using a Sony Ericsson with a built-in two-megapixel camera. Two teleconsultants reviewed the images on a specific web application (http://www.dermahandy.net/default.asp where images had been uploaded in JPEG format. Compared to the face-to-face diagnoses, the two teleconsultants obtained a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and dermoscopic images, respectively. CONCLUSIONS/SIGNIFICANCE: The present work is the first study performing mobile teledermoscopy using cellular phones. Mobile teledermatology has the potential to become an easy applicable tool for everyone and a new approach for enhanced self-monitoring for skin cancer screening in the spirit of the eHealth program of the European Commission Information for Society and Media.

  12. National Priority List Site Boundaries in Louisiana, Geographic NAD83, EPA (2007) [national_priority_list_bdry_LA_EPA_2007

    Data.gov (United States)

    Louisiana Geographic Information Center — This dataset includes boundaries for most Louisiana sites on the EPA Region 6 National Priority List (NPL) as of 12/01/2006. The boundaries may represent a general...

  13. National Priority List Site Locations in Louisiana, Geographic NAD83, EPA (2006) [national_priority_list_pt_EPA_2006

    Data.gov (United States)

    Louisiana Geographic Information Center — This dataset includes point locations for Louisiana sites on the EPA's National Priority List (NPL) as of 12/01/2006. The field "Status" provides a description of...

  14. 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

  15. 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

  16. 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.

  17. Roles and responsibilities of clinical ethics committees in priority setting.

    Science.gov (United States)

    Magelssen, Morten; Miljeteig, Ingrid; Pedersen, Reidar; Førde, Reidun

    2017-12-01

    Fair prioritization of healthcare resources has been on the agenda for decades, but resource allocation dilemmas in clinical practice remain challenging. Can clinical ethics committees (CECs) be of help? The aim of the study was to explore whether and how CECs handle priority setting dilemmas and contribute to raising awareness of fairness concerns. Descriptions of activities involving priority setting in annual reports from Norwegian CECs (2003-2015) were studied and categorized through qualitative content analysis. Three hundred thirty-nine reports from 38 CECs were studied. We found 78 activities where resource use or priority setting were explicitly highlighted as main topics. Of these, 29 were seminars or other educational activities, 21 were deliberations on individual patient cases, whereas 28 were discussions of principled or general cases. Individual patient cases concerned various distributional dilemmas where values were at stake. Six main topics and seven roles for the CEC were identified. CECs handle issues concerning the introduction of new costly drugs, extraordinarily costly established treatment, the application of priority setting criteria, resource use for vulnerable groups, resource constraints compromising practice, and futility of care. The CEC can act as an analyst, advisor, moderator, disseminator, facilitator, watch dog, and guardian of values and laws. In order to fulfil their responsibilities in handling priority setting cases, CECs need knowledge of both the ethics and the institutionalized systems of priority setting. There is potential for developing this aspect of the CECs' work further. The Norwegian CECs are involved in priority setting decisions where they can play multiple constructive roles. In particular, they advise and raise awareness of ethical aspects in resource allocations; bridge clinical practice with higher-level decisions; and promote fair resource allocation and stakeholder rights and interests.

  18. 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.

  19. Pressure-actuated cellular structures

    International Nuclear Information System (INIS)

    Pagitz, M; Hol, J M A M; Lamacchia, E

    2012-01-01

    Shape changing structures will play an important role in future engineering designs since rigid structures are usually only optimal for a small range of service conditions. Hence, a concept for reliable and energy-efficient morphing structures that possess a large strength to self-weight ratio would be widely applicable. We propose a novel concept for morphing structures that is inspired by the nastic movement of plants. The idea is to connect prismatic cells with tailored pentagonal and/or hexagonal cross sections such that the resulting cellular structure morphs into given target shapes for certain cell pressures. An efficient algorithm for computing equilibrium shapes as well as cross-sectional geometries is presented. The potential of this novel concept is demonstrated by several examples that range from a flagellum like propulsion device to a morphing aircraft wing.

  20. Pressure-actuated cellular structures.

    Science.gov (United States)

    Pagitz, M; Lamacchia, E; Hol, J M A M

    2012-03-01

    Shape changing structures will play an important role in future engineering designs since rigid structures are usually only optimal for a small range of service conditions. Hence, a concept for reliable and energy-efficient morphing structures that possess a large strength to self-weight ratio would be widely applicable. We propose a novel concept for morphing structures that is inspired by the nastic movement of plants. The idea is to connect prismatic cells with tailored pentagonal and/or hexagonal cross sections such that the resulting cellular structure morphs into given target shapes for certain cell pressures. An efficient algorithm for computing equilibrium shapes as well as cross-sectional geometries is presented. The potential of this novel concept is demonstrated by several examples that range from a flagellum like propulsion device to a morphing aircraft wing.

  1. Molecular, cellular, and tissue engineering

    CERN Document Server

    Bronzino, Joseph D

    2015-01-01

    Known as the bible of biomedical engineering, The Biomedical Engineering Handbook, Fourth Edition, sets the standard against which all other references of this nature are measured. As such, it has served as a major resource for both skilled professionals and novices to biomedical engineering. Molecular, Cellular, and Tissue Engineering, the fourth volume of the handbook, presents material from respected scientists with diverse backgrounds in molecular biology, transport phenomena, physiological modeling, tissue engineering, stem cells, drug delivery systems, artificial organs, and personalized medicine. More than three dozen specific topics are examined, including DNA vaccines, biomimetic systems, cardiovascular dynamics, biomaterial scaffolds, cell mechanobiology, synthetic biomaterials, pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, nanobiomaterials for tissue engineering, biomedical imaging of engineered tissues, gene therapy, noninvasive targeted protein and peptide drug deliver...

  2. Cellular compartmentalization of secondary metabolism

    Directory of Open Access Journals (Sweden)

    H. Corby eKistler

    2015-02-01

    Full Text Available Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g. amino acids, acetyl CoA, NADPH, enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.

  3. 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

  4. Cellular Events in Nicotine Addiction

    OpenAIRE

    Penton, Rachel E.; Lester, Robin A.J.

    2009-01-01

    In the twenty-five years since the observation that chronic exposure to nicotine could regulate the number and function of high affinity nicotine binding sites in the brain there has been a major effort to link alterations in nicotinic acetylcholine receptors (nAChRs) to nicotine-induced behaviors that drive the addiction to tobacco products. Here we review the proposed roles of various nAChR subtypes in the addiction process, with emphasis on how they are regulated by nicotine and the implic...

  5. 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.

  6. 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

  7. Music and Alterity Processes

    Directory of Open Access Journals (Sweden)

    Josep Martí

    2014-10-01

    Full Text Available The concept of alterity constitutes an important issue in anthropological research and, therefore, in the study of musical practices, as well. Without it, we could hardly understand other kinds of music situated in different spaces and time from the observer. In order to effectively approach these musical practices, we have to develop strategies to help us reduce as much as possible that which distorts the vision of the other. However, beyond the strictly epistemological and methodological issues, the study of music cannot ignore the ethical question related to the manner in which Western thought has understood and treated the other: through a hierarchical and stereotypical type of thinking based on the condition of otherness. Throughout the article, different alterity procedures are presented and discussed, such as synecdochization, exoticization, undervaluation, overvaluation, misunderstanding and exclusion. Taking these different alterity strategies into account may help us to better understand how the musical other is constructed, used and ultimately instrumentalized.

  8. Mental and neurological health research priorities setting in developing countries.

    Science.gov (United States)

    Khandelwal, Sudhir; Avodé, Gilbert; Baingana, Florence; Conde, Bernado; Cruz, Marcelo; Deva, Parameshvara; Dumas, Michel; Gulbinat, Walter; Lopez, Carmen; Mayeya, John; Mubbashar, Malik H; Mohit, Ahmad; Ndeti, David; Puras, Dainius; Saeed, Khalid; Schilder, Klaas; Silberberg, Donald; Tomov, Toma; Townsend, Clare; Iemmi, Valentina; Jenkins, Rachel

    2010-04-01

    A multi-region consultation process designed to generate locally produced regional and global research priorities on mental and neurological health in low- and middle-income countries. Between 2003 and 2005, priority setting exercises on MNH research, using the systematic combined approach matrix (CAM) were held in the six regions of the developing world. One regional meeting per region was convened, and a global meeting was organized before and after the regional exercises. During regional meetings, regional agendas were created listing both research priorities and local problems in MNH. During global meetings, a global research agenda was established and four crucial areas of research priorities were identified: awareness and advocacy, enhancement of research capacity, training for service delivery, and development of evidence based policy. The combined matrix approach enabled the development of regional and global MNH research agendas, derived from bottom up consultations within and between low- and middle-income countries. Collaboration between regions with similar priorities was instituted. Such research agendas are designed to assist policy-makers and donors in the allocation of scarce resources, but they require regular review to reflect changing needs.

  9. 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

  10. 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…

  11. Priority Services Design and Forecasting Project: Priority service methods at Union Electric Co

    Energy Technology Data Exchange (ETDEWEB)

    Hamm, G.L.; Manzella, A.J. (Applied Decision Analysis, Inc., Menlo Park, CA (United States)); Glyer, D.; Caves, D. (Christensen (Laurits R.) Associates, Inc., Madison, WI (United States))

    1992-12-01

    This report describes a market analysis conducted for Union Electric and the Electric Power Research Institute during the spring and summer of 1991. The subject of this analysis was customer preferences regarding Controlled Energy Services, which are also known as Priority Services, interruptible programs, and curtailable programs. The analysis team developed mathematical models of customers' choices and behavior, collected survey and other data from which to calibrate these models, and then forecast participation in alternative Controlled Energy Service designs. The team also delivered a forecasting model to UE that can be used for further program analyses. This report discusses the logic behind the logit choice and econometric simulation models used in the analysis. The report also describes in detail the conjoint survey instrument used to collect data from which these models could be calibrated and the analysis of this data. The results portion of the report discusses market segmentation and the relative importance of different program attributes in determining customers' choices. Finally, the report presents customers' responses to several specific programs.

  12. Adaptive call admission control and resource allocation in multi server wireless/cellular network

    Science.gov (United States)

    Jain, Madhu; Mittal, Ragini

    2016-11-01

    The ever increasing demand of the subscribers has put pressure on the capacity of wireless networks around the world. To utilize the scare resources, in the present paper we propose an optimal allocation scheme for an integrated wireless/cellular model with handoff priority and handoff guarantee services. The suggested algorithm optimally allocates the resources in each cell and dynamically adjust threshold to control the admission. To give the priority to handoff calls over the new calls, the provision of guard channels and subrating scheme is taken into consideration. The handoff voice call may balk and renege from the system while waiting in the buffer. An iterative algorithm is implemented to generate the arrival rate of the handoff calls in each cell. Various performance indices are established in term of steady state probabilities. The sensitivity analysis has also been carried out to examine the tractability of algorithms and to explore the effects of system descriptors on the performance indices.

  13. 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.

  14. 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.

  15. 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.

  16. Resveratrol Attenuates Copper-Induced Senescence by Improving Cellular Proteostasis

    Directory of Open Access Journals (Sweden)

    Liliana Matos

    2017-01-01

    Full Text Available Copper sulfate-induced premature senescence (CuSO4-SIPS consistently mimetized molecular mechanisms of replicative senescence, particularly at the endoplasmic reticulum proteostasis level. In fact, disruption of protein homeostasis has been associated to age-related cell/tissue dysfunction and human disorders susceptibility. Resveratrol is a polyphenolic compound with proved antiaging properties under particular conditions. In this setting, we aimed to evaluate resveratrol ability to attenuate cellular senescence induction and to unravel related molecular mechanisms. Using CuSO4-SIPS WI-38 fibroblasts, resveratrol is shown to attenuate typical senescence alterations on cell morphology, senescence-associated beta-galactosidase activity, and cell proliferation. The mechanisms implicated in this antisenescence effect seem to be independent of senescence-associated genes and proteins regulation but are reliant on cellular proteostasis improvement. In fact, resveratrol supplementation restores copper-induced increased protein content, attenuates BiP level, and reduces carbonylated and polyubiquitinated proteins by autophagy induction. Our data provide compelling evidence for the beneficial effects of resveratrol by mitigating CuSO4-SIPS stressful consequences by the modulation of protein quality control systems. These findings highlight the importance of a balanced cellular proteostasis and add further knowledge on molecular mechanisms mediating resveratrol antisenescence effects. Moreover, they contribute to identifying specific molecular targets whose modulation will prevent age-associated cell dysfunction and improve human healthspan.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. ABS-SmartPriority: An Agent-Based Simulator of Strategies for Managing Self-Reported Priorities in Smart Cities

    Directory of Open Access Journals (Sweden)

    Iván García-Magariño

    2017-01-01

    Full Text Available Smart cities still need the appropriate tools for allowing researchers to contribute in this growing field that will change the comfort and qualities of live of citizens. Smart cities can provide services such as informing of the less overcrowded tourist routes, path-finding for avoiding traffic jams, search services for parking, collecting tree branches from streets, and the finding of the nearest available public electric bicycles or cars. The levels of urgencies differ from some situations to others. Examples of urgent matters are the fast transportation critical patients and the removal of obstacles in main roads. Since smart cities are meant to manage huge amounts of requests, priorities should be automated and managed in a flexible way for new scenarios. Smart cities may need citizens to report the service priorities. However, citizens may have different criteria and could abuse the highest priority levels hindering the service performance for really urgent matters. A novel agent-based simulation open-source framework is proposed for testing different policies for normalizing and controlling self-reported priorities, with its simulator called ABS-SmartPriority. This approach is illustrated by simulating two different policies, in which the smart policy outperformed the one used as the control mechanism.

  4. Radiation, nitric oxide and cellular death

    International Nuclear Information System (INIS)

    Dubner, D.; Perez, M.R. Del; Michelin, S.C.; Gisone, P.A.

    1997-01-01

    The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

  5. Outer-totalistic cellular automata on graphs

    International Nuclear Information System (INIS)

    Marr, Carsten; Huett, Marc-Thorsten

    2009-01-01

    We present an intuitive formalism for implementing cellular automata on arbitrary topologies. By that means, we identify a symmetry operation in the class of elementary cellular automata. Moreover, we determine the subset of topologically sensitive elementary cellular automata and find that the overall number of complex patterns decreases under increasing neighborhood size in regular graphs. As exemplary applications, we apply the formalism to complex networks and compare the potential of scale-free graphs and metabolic networks to generate complex dynamics

  6. 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.

  7. 77 FR 24646 - Open Access and Priority Rights on Interconnection Facilities

    Science.gov (United States)

    2012-04-25

    ... and AD11-11-000] Open Access and Priority Rights on Interconnection Facilities AGENCY: Federal Energy... seeks comment on open access and priority rights for capacity on interconnection facilities. DATES... ] 61,051 Docket Nos. Open Access and Priority Rights on Interconnection AD12-14-000 Facilities Priority...

  8. 78 FR 42868 - Final Priority; National Institute on Disability and Rehabilitation Research-Rehabilitation...

    Science.gov (United States)

    2013-07-18

    ... each proposal. Changes: None. Comment: As a means of encouraging innovation and competitive pricing in... one or more priorities, we designate the type of each priority as absolute, competitive preference, or...)(3)). Competitive preference priority: Under a competitive preference priority, we give competitive...

  9. 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

  10. Misplaced priorities in the Union Health Budget 2015

    Directory of Open Access Journals (Sweden)

    Soumyadeep Bhaumik

    2015-01-01

    Full Text Available The Union Budget presented on 28 February 2015 in the Indian parliament has allocated only INR 33,000 crores for health. It allocates more funds for building newer tertiary care hospitals and increases income tax exemptions for buying health insurance. The article explains that model that is being followed, as indicated by these measures, will create havoc to the lives of Indians and make them sicker and healthcare costlier. The budget is not in line with the actual priorities of India′s health system and nor paves the road map for Universal Health Coverage. The Government of India needs to gets its priorities right.

  11. Misplaced priorities in the Union Health Budget 2015.

    Science.gov (United States)

    Bhaumik, Soumyadeep

    2015-01-01

    The Union Budget presented on 28 February 2015 in the Indian parliament has allocated only INR 33,000 crores for health. It allocates more funds for building newer tertiary care hospitals and increases income tax exemptions for buying health insurance. The article explains that model that is being followed, as indicated by these measures, will create havoc to the lives of Indians and make them sicker and healthcare costlier. The budget is not in line with the actual priorities of India's health system and nor paves the road map for Universal Health Coverage. The Government of India needs to gets its priorities right.

  12. Priority Selection Within National Innovation Strategy in Global Context

    Directory of Open Access Journals (Sweden)

    Prokopenko Olha

    2017-08-01

    Full Text Available The article deals with global experience in analysing the priorities based on their importance for country development and on national and international criteria using algorithm for the selection process. The main aspects of the process of development and implementation of international technology strategies were considered. The authors prove that through the analysis of innovation systems at macro level decision about the priorities in optimization with the aim to improve regulations in science, technology and innovation is provided. The main techniques and decisions were considered based on foresight-studies. Authors propose to create informative and analytical system for the foresight aims.

  13. The effect of congruence in policy priorities on electoral participation

    DEFF Research Database (Denmark)

    Reher, Stefanie

    2014-01-01

    This paper proposes that voters are more likely to turn out at elections if candidates and parties address their issue concerns in the election campaign. Voters with high levels of congruence in policy priorities should perceive the campaign as more interesting and the election as more relevant....... In addition, the costs associated with the vote choice should be lower if voters' policy priorities are salient. The effect should be weakened by party identification, which acts both as a mobilising force and as a heuristic to the vote choice, making information costs less detrimental to turnout...

  14. Six priorities proposed for marine biotechnology in Denmark

    DEFF Research Database (Denmark)

    Børresen, Torger

    2012-01-01

    A survey initiated by the Ministry of Food, Agriculture and Fisheries in 2010 resulted in six priorities for the development of marine biotechnology in Denmark. Business opportunities were suggested and some elements for a successful strategy were proposed. The six priorities are the following......: - Increased exploitation of marine biomass. In addition to traditional fisheries, full utilisation of all catches and improved utilisation of by-products are suggested. Further, new species of fish and macro algae should be harvested. - New farming operations. Aquaculture should be applied in its widest sense...

  15. Cellular Targets of Dietary Polyphenol Resveratrol

    National Research Council Canada - National Science Library

    Wu, Joseph M

    2006-01-01

    To test the hypothesis that resveratrol, a grape derived polyphenol, exerts its chemopreventive properties against prostate cancer by interacting with specific cellular targets, denoted resveratrol targeting proteins (RTPs...

  16. The cellular memory disc of reprogrammed cells.

    Science.gov (United States)

    Anjamrooz, Seyed Hadi

    2013-04-01

    The crucial facts underlying the low efficiency of cellular reprogramming are poorly understood. Cellular reprogramming occurs in nuclear transfer, induced pluripotent stem cell (iPSC) formation, cell fusion, and lineage-switching experiments. Despite these advances, there are three fundamental problems to be addressed: (1) the majority of cells cannot be reprogrammed, (2) the efficiency of reprogramming cells is usually low, and (3) the reprogrammed cells developed from a patient's own cells activate immune responses. These shortcomings present major obstacles for using reprogramming approaches in customised cell therapy. In this Perspective, the author synthesises past and present observations in the field of cellular reprogramming to propose a theoretical picture of the cellular memory disc. The current hypothesis is that all cells undergo an endogenous and exogenous holographic memorisation such that parts of the cellular memory dramatically decrease the efficiency of reprogramming cells, act like a barrier against reprogramming in the majority of cells, and activate immune responses. Accordingly, the focus of this review is mainly to describe the cellular memory disc (CMD). Based on the present theory, cellular memory includes three parts: a reprogramming-resistance memory (RRM), a switch-promoting memory (SPM) and a culture-induced memory (CIM). The cellular memory arises genetically, epigenetically and non-genetically and affects cellular behaviours. [corrected].

  17. Optimized Cellular Core For Rotorcraft, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Patz Materials and Technologies proposes to develop a unique structural cellular core material to improve mechanical performance, reduce platform weight and lower...

  18. Cellular Senescence: A Translational Perspective

    Directory of Open Access Journals (Sweden)

    James L. Kirkland

    2017-07-01

    Full Text Available Cellular senescence entails essentially irreversible replicative arrest, apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP. Senescent cells accumulate in various tissues with aging and at sites of pathogenesis in many chronic diseases and conditions. The SASP can contribute to senescence-related inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes, chronic diseases, geriatric syndromes, and loss of resilience. Delaying senescent cell accumulation or reducing senescent cell burden is associated with delay, prevention, or alleviation of multiple senescence-associated conditions. We used a hypothesis-driven approach to discover pro-survival Senescent Cell Anti-apoptotic Pathways (SCAPs and, based on these SCAPs, the first senolytic agents, drugs that cause senescent cells to become susceptible to their own pro-apoptotic microenvironment. Several senolytic agents, which appear to alleviate multiple senescence-related phenotypes in pre-clinical models, are beginning the process of being translated into clinical interventions that could be transformative.

  19. Respiring cellular nano-magnets.

    Science.gov (United States)

    Talib, Ayesha; Khan, Zanib; Bokhari, Habib; Hidayathula, Syed; Jilani, Ghulam; Khan, Abid Ali

    2017-11-01

    Magnetotactic bacteria provide an interesting example for the biosynthesis of magnetic (Fe 3 O 4 or Fe 3 S 4 ) nanoparticles, synthesized through a process known as biologically controlled mineralization, resulting in complex monodispersed, and nanostructures with unique magnetic properties. In this work, we report a novel aerobic bacterial strain isolated from sludge of an oil refinery. Microscopic and staining analysis revealed that it was a gram positive rod with the capability to thrive in a medium (9K) supplemented, with Fe 2+ ions at an acidic pH (~3.2). The magnetic behaviour of these cells was tested by their alignment towards a permanent magnet, and later on confirmed by magnetometry analysis. The X-ray diffraction studies proved the cellular biosynthesis of magnetite nanoparticles inside the bacteria. This novel, bio-nano-magnet, could pave the way for green synthesis of magnetic nanoparticles to be used in industrial and medical applications such as MRI, magnetic hyperthermia and ferrofluids. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Infiltrating giant cellular blue naevus.

    Science.gov (United States)

    Bittencourt, A L; Monteiro, D A; De Pretto, O J

    2007-01-01

    Cellular blue naevi (CBN) measure 1-2 cm in diameter and affect the dermis, occasionally extending into the subcutaneous fat. The case of a 14-year-old boy with a giant CBN (GCBN) involving the right half of the face, the jugal mucosa and the lower eyelid with a tumour that had infiltrated the bone and the maxillary and ethmoidal sinuses is reported. Biopsies were taken from the skin, jugal mucosa and maxillary sinus. The following markers were used in the immunohistochemical evaluation: CD34, CD56, HMB-45, anti-S100, A-103, Melan A and MIB-1. The biopsy specimens showed a biphasic pattern affecting the lower dermis, subcutaneous fat, skeletal muscle, bone, jugal mucosa and maxillary sinus, but there was no histological evidence of malignancy. The tumour cells were CD34-, CD56-, HMB45+, anti-S100+ and A-103+. Melan A was focally expressed. No positive MIB-1 cells were identified. The present case shows that GCBN may infiltrate deeply, with no evidence of malignancy.

  1. Efficiency of cellular information processing

    International Nuclear Information System (INIS)

    Barato, Andre C; Hartich, David; Seifert, Udo

    2014-01-01

    We show that a rate of conditional Shannon entropy reduction, characterizing the learning of an internal process about an external process, is bounded by the thermodynamic entropy production. This approach allows for the definition of an informational efficiency that can be used to study cellular information processing. We analyze three models of increasing complexity inspired by the Escherichia coli sensory network, where the external process is an external ligand concentration jumping between two values. We start with a simple model for which ATP must be consumed so that a protein inside the cell can learn about the external concentration. With a second model for a single receptor we show that the rate at which the receptor learns about the external environment can be nonzero even without any dissipation inside the cell since chemical work done by the external process compensates for this learning rate. The third model is more complete, also containing adaptation. For this model we show inter alia that a bacterium in an environment that changes at a very slow time-scale is quite inefficient, dissipating much more than it learns. Using the concept of a coarse-grained learning rate, we show for the model with adaptation that while the activity learns about the external signal the option of changing the methylation level increases the concentration range for which the learning rate is substantial. (paper)

  2. Re: Epigenetics of Cellular Reprogramming

    Directory of Open Access Journals (Sweden)

    Fehmi Narter

    2016-12-01

    Full Text Available EDITORIAL COMMENT Cells have some specific molecular and physiological properties that act their functional process. However, many cells have an ability of efficient transition from one type to another. This ability is named plasticity. This process occurs due to epigenetic reprogramming that involves changes in transcription and chromatin structure. Some changes during reprogramming that have been identified in recent years as genomic demethylation (both histone and DNA, histone acetylation and loss of heterochromatin during the development of many diseases such as infertility and cancer progression. In this review, the authors focused on the latest work addressing the mechanisms surrounding the epigenetic regulation of various types of reprogramming, including somatic cell nuclear transfer, cell fusion and transcription factor- and microRNA-induced pluripotency. There are many responsible factors such as genes, cytokines, proteins, co-factors (i.e. vitamin C in this local area network. The exact mechanisms by which these changes are achieved and the detailed interplay between the players responsible, however, remain relatively unclear. In the treatment of diseases, such as infertility, urooncology, reconstructive urology, etc., epigenetic changes and cellular reprogramming will be crucial in the near future. Central to achieving that goal is a more thorough understanding of the epigenetic state of fully reprogrammed cells. By the progress of researches on this topic, new treatment modalities will be identified for these diseases.

  3. Pulsed feedback defers cellular differentiation.

    Directory of Open Access Journals (Sweden)

    Joe H Levine

    2012-01-01

    Full Text Available Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable "polyphasic" positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a "timer" that operates over timescales much longer than a cell cycle.

  4. 12 CFR 269b.220 - Priority; acceleration of proceedings.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Priority; acceleration of proceedings. 269b.220 Section 269b.220 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL...; acceleration of proceedings. (a) A charge of “refusal to bargain” or a charge that, if sustained, would require...

  5. Survey of School Counselors' Perceptions of Graduate Training Priorities.

    Science.gov (United States)

    Sisson, Carol F.; Bullis, Michael

    1992-01-01

    Surveyed practicing school counselors (n=895) in Oregon to identify their opinions of educational priorities for graduate counseling training programs. Findings revealed that counseling theories, skills dealing with personal problems, development of counseling and guidance programs, consultation with teachers about individual students, and…

  6. 75 FR 78485 - Supplemental Priorities for Discretionary Grant Programs

    Science.gov (United States)

    2010-12-15

    ... success in college and careers, and a higher education system that gives every individual the opportunity... importance of improving the quality of education from ``cradle to career.'' Discussion: In this priority, we... projects in career and technical education may support the implementation of college- and career-ready...

  7. Priority therapeutic methods in hepatology, gastroenterology and urologic oncology

    International Nuclear Information System (INIS)

    Granov, A.M.

    1988-01-01

    The author briefly describes endovascular surgical methods; some of them were developed and used in clinical practice for the treatment of portal hypertension, liver cirrhosis and tumors, renal and bladder cancer. Besides, priority methods of endoscopic surgery employed in the treatment of peptic ulcer, are described

  8. Effectiveness of clean taxi priority incentive at Amsterdam Central Station

    NARCIS (Netherlands)

    van der Flier, A.S.; Dam, J.; van den Hoed, R.

    2017-01-01

    The municipality of Amsterdam wants to have an emission free taxi sector by 2025. In order to reach that goal, the city has taken a number of measures which favour clean taxis above conventional taxis. One of these measures is an innovative priority privilege scheme at the Amsterdam Central Station

  9. 77 FR 57495 - National Priorities List, Final Rule No. 55

    Science.gov (United States)

    2012-09-18

    ... set priorities and to move forward with studying and, where appropriate, cleaning up hazardous waste... agencies and the public is a two-way street.'' Northside Sanitary Landfill, Inc. v. Thomas, 849 F.2d 1516, 1520 (D.C. Cir. 1988) (citing Home Box Office, Inc. v. FCC, 567 F.2d 9 (D.C. Cir. 1977)). The commenter...

  10. 76 FR 27637 - Supplemental Priorities for Discretionary Grant Programs

    Science.gov (United States)

    2011-05-12

    ...) and college enrollment rates for students in persistently lowest-achieving schools (as defined in this... defined in this notice). Priority 5--Improving School Engagement, School Environment, and School Safety... may include improving the school setting related to student learning, safety, and health. (c...

  11. The OMERACT ultrasound task force -- Advances and priorities

    DEFF Research Database (Denmark)

    D'Agostino, Maria-Antonietta; Conaghan, Philip G; Naredo, Esperanza

    2009-01-01

    This article reports the most recent work of the OMERACT Ultrasound Task Force (post OMERACT 8) and highlights of future research priorities discussed at the OMERACT 9 meeting, Kananaskis, Canada, May 2008. Results of 3 studies were presented: (1) assessing intermachine reliability; (2) applying ...

  12. Model for setting priority construction project objectives aligned with ...

    African Journals Online (AJOL)

    A comprehensive model based on priority project objectives aligned with monetary incentives, and agreed upon by built environment stakeholders was developed. A web survey was adopted to send out a questionnaire to nationwide participants, including contractors, quantity surveyors, project managers, architects, and ...

  13. The brazilian nuclear submarine dossier: Navy's priority and its application

    International Nuclear Information System (INIS)

    Rosa, L.P.

    1990-01-01

    This work discusses the feasibility of the brazilian nuclear submarine. It is related to navy's remodeling and is considered as a priority. It would bring Brazil closer to developed countries. It considers the slip, itself, the weapon's system as well as the nuclear propulsion. (author)

  14. Integrated modelling of Priority Pollutants in stormwater systems

    DEFF Research Database (Denmark)

    Vezzaro, Luca; Ledin, Anna; Mikkelsen, Peter Steen

    2012-01-01

    The increasing focus on urban diffuse sources of Priority Pollutants (PPs) has highlighted stormwater as an important contributor to contamination of natural water bodies. This study presents an example of an integrated model developed to be able to quantify PP loads discharged by stormwater syst...

  15. Educational Priorities for Children with Cri-Du-Chat Syndrome

    NARCIS (Netherlands)

    Pituch, K.A.; Green, V.A.; Didden, H.C.M.; Whittle, L.; Lancioni, G.E.; Sigafoos, J.

    2010-01-01

    There are few data on the educational needs of children with cri-du-chat syndrome: a neurodevelopmental disorder that affects learning and development. We therefore designed an Internet survey to identify parents' educational priorities in relation to children's level of need/ability. The survey

  16. Global health strategies versus local primary health care priorities ...

    African Journals Online (AJOL)

    Global health strategies versus local primary health care priorities - a case study of national immunisation days in Southern Africa. ... should, therefore, focus its attention on diminishing the negative side-effects of NIDs and on getting the positive sideeffects incorporated in the integrated health services in a sustainable way.

  17. 15 CFR 700.20 - Use of priority ratings.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Use of priority ratings. 700.20 Section 700.20 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS...

  18. 15 CFR 700.21 - Application for priority rating authority.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Application for priority rating authority. 700.21 Section 700.21 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL...

  19. 15 CFR 700.5 - Special priorities assistance.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Special priorities assistance. 700.5 Section 700.5 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS...

  20. 15 CFR 700.3 - Priority ratings and rated orders.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Priority ratings and rated orders. 700.3 Section 700.3 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE...

  1. 15 CFR 700.15 - Extension of priority ratings.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Extension of priority ratings. 700.15 Section 700.15 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS...

  2. 15 CFR 700.51 - Requests for priority rating authority.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Requests for priority rating authority. 700.51 Section 700.51 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE...

  3. U.S. Public Libraries: A Snapshot of Priorities & Perspectives

    Science.gov (United States)

    OCLC Online Computer Library Center, Inc., 2012

    2012-01-01

    This new report details findings from a study OCLC conducted with libraries in mid-2011 to learn about their priorities, initiatives, thoughts on the future of their service points and the sources they use to keep up with developments in the library field. Most public library staff: (1) Anticipate that the top reason patrons are using their…

  4. 48 CFR 819.7004 - Contracting Order of Priority.

    Science.gov (United States)

    2010-10-01

    ... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Service-Disabled Veteran-Owned and Veteran-Owned Small Business Acquisition Program 819.7004 Contracting Order of Priority. In determining the acquisition strategy applicable... limited to SDVOSBs; (c) Pursuant to— (1) Section 8(a) of the Small Business Act (15 U.S.C. 637(a)); or (2...

  5. Twentenet: A LAN with message priorities, design and performance considerations

    NARCIS (Netherlands)

    Niemegeers, I.G.M.M.; Vissers, C.A.

    1984-01-01

    This paper discusses design and performance aspects of Twentenet, one of the few implemented LANs which offers a service based on message priorities. The medium access mechanism uses the CSMA/CD principle, however with a deterministic collision resolution method. These characteristics make Twentenet

  6. SOCIAL PRIORITIES OF FISCAL POLICY IN POST-CRISIS PERIOD

    Directory of Open Access Journals (Sweden)

    I. Lyutyy

    2014-01-01

    Full Text Available The article carried out a comprehensive study of the social priorities of fiscal policy in Ukraine. Efficiency of fiscal instruments in the system of state regulation of social processes in society. Defined the role of the budgetary impact on the social development of society.

  7. 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.

  8. 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...

  9. Simple Priorities and Core Stability in Hedonic Games

    NARCIS (Netherlands)

    Dimitrov, D.A.; Borm, P.E.M.; Hendrickx, R.L.P.; Sung, S.C.

    2004-01-01

    In this paper we study hedonic games where each player views every other player either as a friend or as an enemy.Two simple priority criteria for comparison of coalitions are suggested, and the corresponding preference restrictions based on appreciation of friends and aversion to enemies are

  10. A Two-Echelon Inventory System with Priority Shipments

    OpenAIRE

    Maqbool Dada

    1992-01-01

    A two-echelon system for spare parts is analyzed. The system allows the use of priority inventory pooling to expedite service when a stock-out occurs. First, a tractable aggregate model is derived. This model is then disaggregated to approximate the performance of the exact system. Results of computer tests are also presented.

  11. 8 CFR 207.5 - Waiting lists and priority handling.

    Science.gov (United States)

    2010-01-01

    ... Section 207.5 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS ADMISSION OF REFUGEES § 207.5 Waiting lists and priority handling. Waiting lists are maintained for each designated refugee group of special humanitarian concern. Each applicant whose application is accepted for filing by...

  12. 37 CFR 1.55 - Claim for foreign priority.

    Science.gov (United States)

    2010-07-01

    ... language translation of a non-English language foreign application is not required except: (A) When the...) If an English language translation is required, it must be filed together with a statement that the... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Claim for foreign priority. 1...

  13. Research priority setting for health policy and health systems ...

    African Journals Online (AJOL)

    Research priority setting for health policy and health systems strengthening in Nigeria: The policymakers and stakeholders perspective and involvement. ... Introduction: Nigeria is one of the low and middle income countries (LMICs) facing severe resource constraint, making it impossible for adequate resources to be ...

  14. 40 CFR Appendix A to Part 423 - 126 Priority Pollutants

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true 126 Priority Pollutants A Appendix A to Part 423 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS STEAM ELECTRIC POWER GENERATING POINT SOURCE CATEGORY Pt. 423, App. A Appendix A to Part 423—126...

  15. National Adult Student Priorities Report. Research Report, 2011

    Science.gov (United States)

    Noel-Levitz, Inc, 2011

    2011-01-01

    Serving the needs of adult learners in today's economic environment is becoming a greater priority for colleges and universities. Student satisfaction is considered a core element for higher education institutions serving traditional-age students. More colleges and universities are expanding this assessment activity to adult students as well. As…

  16. African Priorities for the UN Millennium Assembly by Sabelo J ...

    African Journals Online (AJOL)

    The second chapter is by Greg Mills on "Global Realities and African Priorities: A View from South. Africa". He assesses the ... He discusses the humanitarian crisis situation, drug abuse and trafficking, the ... With regard to refugees, he discusses the role of the UN and civil society in combating the refugee problem, and also ...

  17. Family Planning - A Priority Social and Health Action Programme for ...

    African Journals Online (AJOL)

    Family Planning - A Priority Social and Health Action Programme for. Africa and the Role of the Physician. Dr. A.A. Arkutu ... cern about che risk - benefit factor while ochers cite che spread of HIV infection as justification for not ... promote health and reduce che high levels of illness and mortality, especially among vulnerable.

  18. Planning a Family: Priorities and Concerns in Rural Tanzania ...

    African Journals Online (AJOL)

    Planning a Family: Priorities and Concerns in Rural Tanzania. T Marchant, AK Mushi, R Nathan, O Mukasa, S Abdulla, C Lengeler, JRM Armstrong Schellenberg. Abstract. A fertility survey using qualitative and quantitative techniques described a high fertility setting (TFR 5.8) in southern Tanzania where family planning use ...

  19. 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.

  20. 76 FR 19980 - Funding Priorities, Requirements, and Definitions

    Science.gov (United States)

    2011-04-11

    ... measuring appropriate concepts of interest for the age groups surveyed. Final Priorities, Requirements, and... Psychology. 32, 559-573. \\6\\ Smith, P.K. & Sharp, S. (1994). The problem of school bullying. In P.K. Smith...) The academic achievement of the ``all students'' group in a school in terms of proficiency on the...

  1. Deciphering priority areas for improving project risk management ...

    African Journals Online (AJOL)

    Deciphering priority areas for improving project risk management through critical analysis of pertinent risks in the Zambian construction industry. ... In a limited effort to address this deficiency in the body of knowledge, this article reports the results of a study conducted using 15 purposive semi-structured interviews and 198 ...

  2. Conservation Priorities for Terrestrial Birds in the Northeastern United States

    Science.gov (United States)

    Kenneth V. Rosenberg; Jeffrey V. Wells

    2005-01-01

    As part of the Partners in Flight (PIF) bird-conservation planning process, we assessed breeding land bird species according to seven categories of population vulnerability to derive a priority species pool in each of 12 physiographic areas that overlap the northeastern U.S. We then grouped species into the following habitat-species suites: (1) boreal-mountaintop...

  3. Priority Determination for AVC Funded R&D Projects.

    Science.gov (United States)

    Wilkinson, Gene L.

    As an extension of ideas suggested in an earlier paper which proposed a project control system for Indiana University's Audio-Visual Center (see EM 010 306), this paper examines the establishment of project legitimacy and priority within the system and reviews the need to stimulate specific research proposals as well as generating a matrix of…

  4. Data requirements and data sources for biodiversity priority area ...

    Indian Academy of Sciences (India)

    Unknown

    tions required for a priority areas analysis. An important ..... Analysis Project, etc. Even before bias can be assessed and decisions taken either to proceed with existing data, model expected data. (see below), collect new data, or reject the data, those data have to be ..... Caudill 1990). They are a form of artificial intelligence,.

  5. 12 CFR 627.2750 - Priority of claims-banks.

    Science.gov (United States)

    2010-01-01

    ...) All claims for taxes. (f) All claims of creditors which are secured by specific assets or equities of... accordance with priorities of applicable Federal or State law. (g) All claims of holders of bonds issued by... claims of holders of consolidated and System-wide bonds and all claims of the other Farm Credit banks...

  6. 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.

  7. Modelling Priorities of Financial Provision of the Social Sphere

    Directory of Open Access Journals (Sweden)

    Mamonova Hanna V.

    2014-01-01

    Full Text Available The article studies the modern state of the social sphere and conducts modelling of priorities of financial provision of the social sphere at the state level. Social sphere should be considered as the basis of development of the national economy. The goal of this article is the study of the modern state and modelling priorities of financial provision of the social sphere at the state level. The subject of the study is modelling priority directions of financial provision of components of the social sphere. Taking into account fast changes in the social sphere of the country and regular increase of social standards, the article identifies a necessity of changing priorities of the social policy, first of all, problems of financing the social sphere and formation of priority directions on improvement of this system. The article shows that the main problems of financial provision of the social sphere are: insufficient volumes of budget funds for financing the social sphere, financing practically all items of social expenditures in a smaller volume than it is required for the existing social support of the population and absence of mechanisms of ensuring quality of social services. The article offers to use the hierarchy analysis method for identifying immediate and priority directions of financing components of the social sphere. On the basis of the built directed communication graph the article presents a binary matrix of dependence of components of the social sphere and builds a hierarchy model of these components. As a result it is seen that the highest level of hierarchy is taken by science, then healthcare and social sphere are at the same level, then education, sports and at the lowest level are culture and art. The obtained results could be used when improving financing of the social sphere. In order to ensure efficiency of functioning of the social sphere it is necessary to improve the system of financing of its components on the basis of use

  8. Recent development of cellular manufacturing systems

    Indian Academy of Sciences (India)

    Cellular manufacturing system has been proved a vital approach for batch and job shop production systems. Group technology has been an essential tool for developing a cellular manufacturing system. The paper aims to discuss various cell formation techniques and highlights the significant research work done in past ...

  9. Reflections Lederberg and the 'Cellularity' of Bacteria

    Indian Academy of Sciences (India)

    Srimath

    He tried to observe bacterial mating and the details of conjugation at the cellular level [3]. (reproduced in the Classics section), processes that are still being investigated [4]. He made the important discovery that penicillin induces the formation of spheroplasts. The announcing. Lederberg and the 'Cellularity' of Bacteria.

  10. Cellular telephone use and cancer risk

    DEFF Research Database (Denmark)

    Schüz, Joachim; Jacobsen, Rune; Olsen, Jørgen H.

    2006-01-01

    BACKGROUND: The widespread use of cellular telephones has heightened concerns about possible adverse health effects. The objective of this study was to investigate cancer risk among Danish cellular telephone users who were followed for up to 21 years. METHODS: This study is an extended follow-up ...

  11. Immune cellular response to HPV: current concepts

    Directory of Open Access Journals (Sweden)

    Maria Alice Guimarães Gonçalves

    Full Text Available Although cellular immunity is essential for the elimination of human papillomavirus (HPV, the mechanisms involved are still poorly understood. We summarize the main mechanisms involved in cellular immune response to infections caused by HPV. Immunotherapies for HPV-related cancers require the disruption of T-cell response control mechanisms, associated with the stimulation of the Th1 cytokine response.

  12. On Elementary and Algebraic Cellular Automata

    Science.gov (United States)

    Gulak, Yuriy

    In this paper we study elementary cellular automata from an algebraic viewpoint. The goal is to relate the emergent complex behavior observed in such systems with the properties of corresponding algebraic structures. We introduce algebraic cellular automata as a natural generalization of elementary ones and discuss their applications as generic models of complex systems.

  13. Cellular Factors Shape 3D Genome Landscape

    Science.gov (United States)

    Researchers, using novel large-scale imaging technology, have mapped the spatial location of individual genes in the nucleus of human cells and identified 50 cellular factors required for the proper 3D positioning of genes. These spatial locations play important roles in gene expression, DNA repair, genome stability, and other cellular activities.

  14. Recent development of cellular manufacturing systems

    Indian Academy of Sciences (India)

    context of cellular manufacturing is primarily as an aid in identifying the part families to which production cells should be dedicated. Further analysis is required ... A number of researchers or investigators have used different types of similarity and dissimilarity coefficients for determining part families. In cellular manufacturing ...

  15. 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

  16. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Biaglow, J.E. (Case Western Reserve Univ. Medical School, Cleveland, OH); Varnes, M.E.; Clark, E.P.; Epp, E.R.

    1983-09-01

    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.

  18. Anks3 alters the sub-cellular localization of the Nek7 kinase

    Energy Technology Data Exchange (ETDEWEB)

    Ramachandran, Haribaskar; Engel, Christina; Müller, Barbara [Renal Division, Department of Medicine, University Freiburg Medical Center, Hugstetter Str. 55, 79106 Freiburg (Germany); Dengjel, Jörn [Department of Dermatology, University Freiburg Medical Center and Center of Biological Systems Analysis, Habsburgerstr. 49, 79104 Freiburg (Germany); Walz, Gerd [Renal Division, Department of Medicine, University Freiburg Medical Center, Hugstetter Str. 55, 79106 Freiburg (Germany); Center for Biological Signaling Studies (BIOSS), Albertstr. 19, 79104 Freiburg (Germany); Yakulov, Toma A., E-mail: toma.antonov.yakulov@uniklinik-freiburg.de [Renal Division, Department of Medicine, University Freiburg Medical Center, Hugstetter Str. 55, 79106 Freiburg (Germany)

    2015-08-28

    Nephronophthisis (NPH) is an autosomal recessive cystic kidney disease, and a frequent cause of end-stage renal failure in children. To date, 17 NPH-associated gene products (NPHPs) have been identified. Most NPHPs participate in large multi-protein complexes that localize to the cilium and/or basal body; however, the precise composition of these complexes and their biological function remain largely unknown. We recently observed that the ankyrin repeat protein Anks3 interacts with the NPH family member Anks6. Both Anks3 and Anks6 form complexes with multiple other NPHPs, suggesting that both proteins function in similar or overlapping signaling pathways. Here, we show that Anks3, but not Anks6 interacted with the NIMA-related kinase Nek7, and was heavily modified in the presence of Nek7, resulting in an approximately 20 kD increase in molecular weight. Although mass spectrometry revealed increased serine and threonine phosphorylation of Anks3 primarily within the N-terminal ankyrin repeats also required for Nek7 interaction, the molecular weight increase occurred even in the presence of a kinase-dead Nek7 mutant, indicating that this modification was not caused by Nek7-dependent Anks3 phosphorylation. Furthermore, the Anks3 modification was specific for Nek7, and did not occur in the presence of Nek8. Importantly, Anks3 retained Nek7 in the cytoplasm, suggesting that, Nek7 triggers the modification of Anks3, which in turn prevents the nuclear localization of Nek7. - Highlights: • Anks3 interacted with Nek7 kinase, and was heavily modified in the presence of Nek7. • Anks3 N-terminal ankyrin repeats, but not SAM domain required for Nek7 interaction. • Nek7 increased Ser/Thr phosphorylation of Anks3 primarily within ankyrin domain. • Interaction with Anks3 led to cytoplasmic retention and nuclear exclusion of Nek7.

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

    OpenAIRE

    T?th, Ren?ta; Alonso, Maria F.; Bain, Judith M.; V?gv?lgyi, Csaba; Erwig, Lars-Peter; G?cser, Attila

    2015-01-01

    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...

  20. Sonic hedgehog promotes somitic chondrogenesis by altering the cellular response to BMP signaling

    OpenAIRE

    Murtaugh, L. Charles; Chyung, Jay H.; Lassar, Andrew B.

    1999-01-01

    Previous work has indicated that signals from the floor plate and notochord promote chondrogenesis of the somitic mesoderm. These tissues, acting through the secreted signaling molecule Sonic hedgehog (Shh), appear to be critical for the formation of the sclerotome. Later steps in the differentiation of sclerotome into cartilage may be independent of the influence of these axial tissues. Although the signals involved in these later steps have not yet been pinpointed, there is substantial evid...